Okayama Igakkai Zasshi (Journal of Okayama Medical Association)

Studies on the pathogenesis of PIE syndrome

Part 1. Evaluation of cellular responses in bronchoalveolar lavage fluid of patients with PIE syndrome

Kyo SATO

1993 Volume 105 Issue 1-2 Pages 1-13
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_1

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The bronchoalveolar lavage (BAL) fluid of patients with PIE syndrome characterized by pulmonary eosinophilia was examined to determine the cellular response in the lungs. Evaluation of cellular components in the BAL fluid revealed an increased proportion not only of eosinophils but also of lymphocytes and neutrophils. In about half of the patients with PIE syndrome the level of eosinophilia was higher in the peripheral blood than in the BAL fluid. Patients with PIE syndrome were classified into prolonged PIE and PIE with asthma based on Crofton's classification. The percentage of neutrophils and eosinophils in BAL fluid were higher in patients with prolonged PIE than in PIE with asthma while the percentage of lymphocytes was higher in a group of PIE with asthma. On the other hand, the lymphocyte percentage in BAL fluid was higher in patients with PIE syndrome due to fungus antigen than in those with PIE syndrome due to drug allergy.
These findings suggest that various cellular components play important roles in the pathogenesis of PIE syndrome and that the accumulation of the effector cells in the lungs is regulated by an allergic mechanism.

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Studies on the pathogenesis of PIE syndrome

Part 2. The analysis of allergic and immunological mechanisms in PIE syndrome using Aspergillus antigen

Kyo SATO

1993 Volume 105 Issue 1-2 Pages 15-27
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_15

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Various allergic and immunologic mechanisms have been postulated in the pathogenesis of PIE syndrome. In this study, the immune response to Aspergillus antigen was examined in patients with the PIE syndrome of allergic bronchopulmonary aspergillosis (ABPA) and those with aspergilloma to elucidate the immune mechanisms which regulate the pulmonary changes in PIE syndrome.
The same Aspergillus species causes different clinical disease entities such as Aspergillus pneumonia, aspergilloma, ABPA and even hypersensitivity pneumonitis. The specific IgE against the Aspergillus antigen for the type I allergy existed in patients with ABPA but not in those with Aspergilloma. However, the prepicitating antibody for the type III allergy and enhanced lymphocyte blastogenesis against Aspergillus antigen for the type IV allergy were found in both the patients with ABPA and those with aspergilloma while pulmonary infiltration, dyspnea and the grade of peripheral eosinophilia correlated with the level of serum IgE and responsiveness of lymphocyte against Aspergillus antigen.
These findings indicate that the characteristics of the immune responses of the host play a crucial role in the pathogenesis of PIE syndrome.

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Colorectal carcinoma in aged patients over 75 years old: Clinicopathological study

Muneaki KURODA, Hiromi IWAGAKI, Nagahide MATSUBARA, Toshikazu KIMURA, ...

1993 Volume 105 Issue 1-2 Pages 29-33
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_29

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In a review of 358 patients with colorectal carcinoma resected at the department during the past 13 years between 1978 and 1990, 41 elderly patients over 75 years old were selected (served as aged group) and compared to younger patients under 74 years old (younger group) for clinicopathological features and prognosis. Elderly patients, who represented 11.5% of all cases, were predominantly females. There was no significant difference in the localization of the tumor, depth of invasion, lymphnode metastasis and lymphatic infiltration between the two groups. No siginificant difference was noted in macroscopic type, but a tendency of having type 5 was observed in the elderly group. The elderly group had a significantly smaller maximum diameter of the tumor. There was a lower tendency in the positive rate of vessel invasion in the elderly group. In the stage classification and the incidence of curative resection, there were no differences between the two groups. The cumulative survival rate after resection in the elderly group was relatively lower than that in the other group.

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Operative morbidity of elderly patients with gastrointestinal disease

Shigeo SHIIKI, Kazuhiko NAKAGAWA, Hiroshi SASAKI, Yutaka YAMASHITA, Ma ...

1993 Volume 105 Issue 1-2 Pages 35-41
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_35

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The operative morbidity and its relating factors were studied on 95 patients, 80 years old or older, operated for gastrointestinal (GI) diseases under general anesthesia at the department in a recent 11-year period. Among a total of 98 cases of GI diseases including 32 of gastric cancer, 17 of colorectal cancer, 16 of cholelithiasis and 33 of others, 108 procedures were performed for 38 gastric, 27 colorectal, 31 hepato-biliary-pancreatic and 12 other surgical conditions. Fifty-four operative complications occurred in 39 cases (41%), which were 13 respiratory, 11 delirium, 9 cardiovascular and 21 other complications. The respiratory morbidity rate was significantly high in males and significantly low in the cases receiving balanced epidural anesthesia. Postoperative delirium occurred more frequently in patients having an intraoperative blood loss of over 200 ml, and the cardiovascular morbidity rate was significantly high for an operative time of over 3 hours. The operative morbidity and 30-day operative mortality rate were significantly higher for emergency operations than for non-emergency operations. These findings suggest that, in the surgery for elderly patients and especially in an emergent situation, special care must be paid to decrease the quantity of bleeding and shorten the duration of operation by employing a proper procedure and anesthesia.

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Thermotolerance induction by benzalkonium chloride in NIH3T3 cells

Masahiro KURODA, Junichi ASAUMI, Koji NISHIKAWA, Seiryo TANAKA, Xian S ...

1993 Volume 105 Issue 1-2 Pages 43-48
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_43

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The ability of benzalkonium chloride to induce thermotolerance was examined in NIH3T3 cells. Benzalkonium chloride enhanced cytotoxicity as its concentration and administration period increased. The cell survival decreased to 50% of that in the non-treated group by 20min of treatment in 0.002% benzalkonium chloride. Thermotolerance developed during the culture after 20min of treatment with 0.002% benzalkonium chloride. Thermotolerance reached its peak at 15h after treatment and decreased subsequently. At 15h after treatment, the Do value at 45°C heating, a parameter of thermotolerance was 3.8-fold higher than that of the non-treated group. The thermotolerance induced by 0.002% benzalkonium chloride increased as its treatment period was prolonged. These findings suggested a relationship between thermotolerance induction and the cell membrane damage by benzalkonium chloride.

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Central nervous cells with strongly negatively-charged surface-coats

Takuro MURAKAMI, Takehito TAGUCHI, Aiji OHTSUKA

1993 Volume 105 Issue 1-2 Pages 49-53
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_49

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Light microscopy of tissue sections stained with cationic iron colloid (pH 1.0-2.0) and nuclear fast red or with this colloid and thionin revealed the presence of numerous neurons with a strong negative-charge or coated with sulfated proteoglycans such as chondroitin sulfates in the adult rat brain. These neurons were distributed mainly in the hippocampal subiculum, zona incerta, cerebral cortex (V lamina), medial cerebellar nuclei and certain other nuclei such as ventral pontine nuclei. In the hippocampal formation, the strongly negatively-charged cells seemed to be identical with the GABAergic inhibitory interneurons reactive to the lectin Vicia villosa agglutinin. The neurons, including the GABAergic Purkinje's cells, of the cerebellar cortex showed no reaction to the cationic iron colloid at pH 1.0-2.0. Many non-GABAergic large neurons of the ventral pontine nuclei were well reactive to the colloid at pH 1.0-2.0. These findings suggest that the cationic iron colloid at pH 1.0-2.0 mainly stains some subsets of GABA-ergic neurons, and additionally stains some non-GABAergic interneurons projecting long association or commissural fibers.

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The bone formating ability of 24R, 25 dihydroxyvitamin D₃ in hypophosphatemic mice

Tomoo YAMATE

1993 Volume 105 Issue 1-2 Pages 55-62
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_55

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The biological role of 24R, 25(OH)₂D₃ is still controversial, although 24R, 25(OH)₂D₃ has been reported to have peculiar effects particularly on the bone. To examine the biological effects of 24R, 25(OH)₂D₃ we administered Hyp mouse, which is a model for familial X-linked hypophosphatemic rickets in man, 1-10000μg/kg/day of 24R, 25(OH)₂D₃ or 0.01-10μg/kg/day of 1α, 25(OH)₂D₃ for 28 successive days by intraperitoneal injection.
24R, 25(OH)₂D₃ increased the body weight gain, bone size, bone formation and mineralization and reduced the serum alkaline-phosphatase activity, dose-dependently from 1 to 1000μg/kg/day without hypercalcemia.
Severe bone resorption and hypercalcemia were caused by 1 and 10μg/kg/day of 1α, 25(OH)₂D₃, which are considered to be equivalent to 1000μg/kg/day of 24R, 25(OH)₂D₃ in the affinity to the receptor of 1α, 25(OH)₂D₃. On the other hand, 0.1μg/kg/day of 1α, 25(OH)₂D₃ increased bone size, bone formation and mineralization to a similar degree as 1000μg/kg/day of 24R, 25(OH)₂D₃, but did not increase body weight gain, dry bone weight or bone mineral contents, did not reduce serum alkaline-phosphatase activity. At 0.1μg/kg/day, 1α, 25(OH)₂D₃ increased not only bone formation and mineralization but also bone resorption on Hyp mice.
These findings suggest that 24R, 25(OH)₂D₃ has peculiar biological effects on Hyp mouse rather than merely mimicking that of 1α, 25(OH)₂D₃ mediated by its receptor.

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Discriminant analysis and comparison between rheumatoid arthritis and osteoarthritis after measurement of determinants in the blood and synovial fluid

Kazuo MUNETOMO

1993 Volume 105 Issue 1-2 Pages 63-72
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_63

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Levels of rheumatoid factor(RF), β₂-microglobulin(β₂MG), C-reactive protein(CRP) and lipid peroxide(LP) in the blood and synovial fluid(SF) and erythrocyte sedimentation rate(ESR) of patients with rheumatoid arthritis(RA) and osteoarthritis(OA) were determined by clinical chemistry. These determinants were analyzed to discriminate RA and OA.
Differences in the average values of determinants in the blood and SF between RA and OA patients were calculated. Significant differences in the values of ESR, S-CRP, F-CRP and β₂MG between the two groups were observed.
In a discriminant analysis of RA and OA patients by an all possible selection procedure(APSP), nine parameters in blood and SF were used. In the analysis, S-BF, S-CRP, F-RF, F-CRP, F-β₂MG and ESR were selected as the group of the 6 most effective indices, which gave an 18.4% probability of misclassification. When S-RF and F-RF were excluded, and only 7 factors were used for discriminant analysis, the probability of misclassification was 21.2%. Probability of misclassification using measured values with females was less than that using males and females.

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Evaluation of anthracycline-anthraquinone analogues in the treatment of lung cancer using colony assay

Part 1. Comparison of antitumor activity of anthracyclineanthraquinone analogues in human lung cancer cell lines

Takeyuki NUMATA

1993 Volume 105 Issue 1-2 Pages 73-80
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_73

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In an attempt to evaluate the antitumor activity of new anthracycline-anthraquinone analogues; aclarubicin (ACR), tetrahydropyranyl adriamycin (THP-ADM), and mitoxantrone (MIT), these analogues were compared with adriamycin (ADM) in terms of 70% lethal dose by colony assay using five human lung cancer cell lines, which had been established and maintained in our laboratory. The human lung cancer cell lines tested were EBC-1, an epidermoid cancer cell line, ABC-1, an adenocarcinoma cell line, and SBC-1, -2, and -3, small cell cancer cell lines. In general, the EBC-1 established from a patient tumor showing resistance to ADM was the least sensitive to the drugs tested, and SBC-3 established from a patient tumor with no prior chemotherapy was the most sensitive to the drugs. In antitumor activity, both ACR and THP-ADM appeared to be superior to ADM and MIT, suggesting the clinical usefulness of these drugs in the treatment of lung cancer.

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Evaluation of anthracycline-anthraquinone analogues in the treatment of lung cancer using colony assay

Part 2. Comparison of cytotoxic effect of anthracycline-anthraquinone analogues in tumor specimens obtained from lung cancer patients

Takeyuki NUMATA

1993 Volume 105 Issue 1-2 Pages 81-86
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_81

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The drug sensitivity test using a human tumor clonogenic assay is an in vitro technique providing a high degree of accuracy for predicting the clinical response to anticancer drugs. The author applied this assay to compare the in vitro anticancer effects of four anthracycline-anthraquinone analogues against lung cancer. The drugs tested in the present study were adriamycin(ADM), aclarubicin(ACR), THP-adriamycin(THP-ADM) and mitoxantrone(MIT). A tumor was defined as sensitive, when the surviving fraction of colony-forming units was reduced 70% or more at a clinically achievable plasma concentration of these drugs in man. Tumor specimens from 100 individual patients were placed in culture. Forty-five specimens (45%) formed enough colonies to test drug sensitivity. Fourteen of the 31 specimens(45%) tested were found to be sensitive for ACR, 15 of 35 (43%) for THP-ADM, 10 of 30 (33%) for MIT, and 7 of 43 (16%) for ADM. These findings indicated that the activity of ACR and THP-ADM is stronger than that of ADM in the treatment of lung cancer.

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Studies on the pathogenesis of allergic gastroenteropathy

Part 1. Diagnostic application of abdominal ultrasonography during an antigen oral loading test

Yuji TOYOTA

1993 Volume 105 Issue 1-2 Pages 87-95
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_87

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Pathogenesis of allergic gastroenteropathy involves various antigen-mediated allergic reactions through a defensive mechanism of the digestive tract.
The conventional method of the diagnosis generally involves the exclusion-provocation test of causative food and the judgement based on only subjective symptoms. A diagnostic method based on objective parameters has not been established yet.
To establish an objective diagnostic method, ultrasonography was applied to 3 patients in whom chicken eggs and milk had been clinically diagnosed as the antigens during the oral loading test of appropriate antigen extract. After oral loading of the causative antigen extract, the gastric movements were observed by ultrasonography from 30 minutes before loading until 120 minutes after loading. The total number of peristaltic movements were then measured during every 30 minutes as an indicator of acceleration of gastric peristalic movements.
All 3 cases showed a marked acceleration of gastric peristaltic movements as well as several abdominal symptoms such as abdominal pain and diarrhea at 30 to 60 minutes after loading the antigen.
These findings indicate that this method may be useful in the diagnosis of allergic gastroenteropathy.

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Studies on the pathogenesis of allergic gastroenteropathy

Part 2. Existence of allergic gastroenteropathy caused by house dust

Yuji TOYOTA

1993 Volume 105 Issue 1-2 Pages 97-106
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_97

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Not only many food substances but also other substances such sa house dust(HD) may serve as causative allergens of allergic gastroenteropathy. To clarify the causative allergens and the pathogenesis of allergic gastroenteropathy, an oral loading test using HD, was applied to two patients with allergic gastroenteropathy caused by an unknown antigen, and with HD-sensitivity, and 24 bronchial asthmatics with or without HD-sensitivity, ther were examined using the ultrasonography of stomach reported previously.
Two patients with gastroenteropathy showed a positive skin test and IgE BAST to HD, although they had bronchial asthma in the past history. Peripheral blood eosinophils in the 1st and 2nd patients showed a high (max 78%) and slightly increased (9%) value. The precipitating antibody in the two cases was negative, but lymphocyte blastogenesis to HD was enhanced in one case. During the oral loading test using HD, both patients had abdominal pain at immediate and late phase and acceleration of gastric peristaltic movements was confirmed by ultrasonography. One of the 2 patients showed a strong gastrointestinal reaction during the delayed phase. LTC₄ and histamine were considered to be involved in the abdominal pain of these cases. One of the 12 patients with bronchial asthma and HD-sensitivity showed an immediate reaction in oral loading test without abdominal pain, suggesting a correlation of the hypersensitivity between the bronchi and the digestive tract, including 2 former cases.

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Myocardial function and metabolism after 24-hour preservation

A comparison of immersion vs perfusion and efficacy of PFC perfusate

Shingo SENO

1993 Volume 105 Issue 1-2 Pages 107-117
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_107

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To assess the viability of canine hearts after prolonged ex-vivo heart preservation, we evaluated the myocardial metabolism by determining the high energy phosphate(HEP) levels and respiratory function of isolated mitochondria(MRF). Furthermore, we calculated the mitochondrial score(MS) for semi-quantitative analysis of ultrastructural changes. These three indicators were compared with the left ventricular functioin (LVF) following orthotopic heart transplantation (H-TX). Forty two hearts, harvested from mongrel dogs, each weighing 8.5kg15kg, were divided into 3 groups: 24-hour immersion in modified Collins solusion (MC) (group A), 24-hour perfusion with MC (group B) and 24-hour perfusion with MC containing perfluorochemicals (PFC) (group C). After the 24-hour preservation, biopsies were obtained from 7 hearts in each group and HEP levels, MRF and MS were determined. The HEP levels, MRF and MS were significantly higher in group C than in group B and significantly higher in group B than group A. The cardiac function after H-TX revealed a similar tendency. These findings indicate that continuous hypothermic perfusion provides better protection than simple hypothermic immersion and that perfusion with an intracellular solution containing PFC preserves and protects an organ sufficiently before clinical heart transplantation.

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Studies on anti-HTLV-I antibody in interstitial lung diseases

Part 1. Western blot analysis for anti-HTLV-I antibody and HTLV-I related reaction in DPB and IIP

Katsumi UENO

1993 Volume 105 Issue 1-2 Pages 119-126
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_119

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By the immunofluorescent assay for the anti-HTLV-I antibody, the serum of many patients with diffuse panbronchiolitis (DPB) and idiopathic interstitial pneumonia (IIP) show two types of cytoplasmic fluorescence. One is a granular pattern in the MT-1 cell and diffuse pattern in the MT-2 cell. This is the typical pattern for the anti-HTLV-I antibody. The other is a diffuse pattern in the MT-1 and/or MT-2 cells. This pattern has been designated as HTLV-I related reaction. These serum reactions were investigated by Western blot analysis with an MT-2 cell lysate as antigen. Although about 20% of the patients with DPB and IIP were considered to be suffering from HTLV-I associated bronchiolo-alveolar disorder (HABA) because they showed the typical pattern of anti-HTLV-I antibody, only those patients with HABA were shown to have the antibodies against HTLV-I specific proteins (p19, p24, p28, pr53 and gp68). On the other hand, the patients with HTLV-I related reaction had neither the antibodies against any HTLV-I proteins nor the other protein components of MT-2. Thus, Western blot analysis revealed that antibodies against HTLV-I specific proteins were present only in the patients with HABA.

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Studies on anti-HTLV-I antibody in interstitial lung diseases

Part 2. Anti-HTLV-I IgG, IgM and IgA antibodies in HTLV-I associated bronchiolo-alveolar disorder (HABA)

Katsumi UENO

1993 Volume 105 Issue 1-2 Pages 127-134
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_127

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To study the pathogenesis of HTLV-I associated bronchiolo-alveolar disorder (HABA), Western blot analysis was performed using MT-2 cell lysate antigens on the serum of 6 patients with HABA, 7 patients with adult T cell leukemia (ATL), 14 asymptomatic carriers and 9 healthy controls. Five (83%) of the 6 HABA patients were positive for anti-HTLV-I IgA antibodies, although all 7 ATL patients and 11 of the 14 asymptomatic carriers were negative. All HABA and ATL patients and asymptomatic carriers were positive for anti-HTLV-I IgG antibodies. Four (67%) of the 6 HABA patients, 2 (29%) of the 7 ATL patients and 9 (64%) of the 14 asymptomatic carriers were positive for anti-HTLV-I IgM antibodies. Statistically there was little difference in the incidences of anti-HTLV-I IgG and IgM antibodies among HABA and ATL patients and asymptomatic carriers, but the HABA patients showed a significantly higher incidence of IgA antibody than the ATL patients and asymptomatic carriers. Since specific IgA antibodies are produced in the local infected mucosa and part of the IgA antibodies are transferred into the serum, in conclusion, the anti-HTLV-I IgA antibodies in HABA patients reflect the localization of HTLV-I in lungs which play an important role in the pathogenesis of HABA.

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Ultrastructural study of right ventricular myocardium in tricuspid regurgitation accompanying rheumatic mitral valvular disease

Shigeo IMAI

1993 Volume 105 Issue 1-2 Pages 135-151
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_135

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The pathogenesis of the tricuspid regurgitation (TR) accompanying the rheumatic mitral valvular disease was examined. In 42 patients (29 were rheumatic, 13 were non-rheumatic), the right ventricular myocardial biopsy specimens were obtained during surgery, with which the fraction of interstitial fibrosis (%Fib.) was calculated by light microscopy and myofibrillar degeneration was evaluated and scored by electron microscopy (EM-score). The relationship between the right ventricular morphology (%Fib. and EM-score) and the grade of TR was examined.
1) %Fib. was significantly higher in the rheumatic group than in the non-rheumatic group.
2) In the rheumatic group, %Fib. and EM-score were higher in proportion to the preoperative severity of TR.
3) After the change of the grade of TR was estimated in the early and distant postoperative periods in the rheumatic group, the patients were divided into two subgroups, one with worsened TR and one without worsened TR. Both %Fib. and EM-score were significantly higher in the worsened group.
These findings show that the right ventricular myocardial ultrastructural changes correlate significantly with the preoperative grade of TR and the postoperative change of TR. TR accompanying rheumatic mitral valvular disease may be caused not only by the secondary effect of back-pressure overloading to the right ventricle, but by the right ventricular myocardial ultrastructural changes due to the rheumatic disease itself and furthermore pressure and volume overloading to the right ventricular myocardium.

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Effect of exercise training on glucose tolerance and insulin sensitivity in rats receiving a high fat diet

Tomoko SHIMOMURA

1993 Volume 105 Issue 1-2 Pages 153-164
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_153

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The effect of exercise training on glucose tolerance and insulin sensitivity was studied in rats receiving a modern-westernized high fat diet, in which 42% of total energy was provided in fat.
Rats were either permitted to exercise actively (group E) or forced to be in the sedentary condition (group S) for the first two weeks. In the next 2 weeks, rats in both groups were subjected to either active exercise (group EE and SE) or the sedentary condition (group ES and SS). An intraperitoneal glucose tolerance test and insulin sensitivity test were performed at the end of the first and the second 2 weeks.
No significant difference was found among the groups in blood glucose levels after glucose challenge. However, the insulin levels in the groups E, SE and EE were significantly lower than those in the groups S, SS and ES, respectively. Sensitivity to exogenous insulin was higher in the group EE and SE than in the group ES and SS, respectively. The epididymal fat pads of the groups S, ES and SS were heavier than those of the group E, EE and SE, respectively.
These findings altogether showed that exercise training restrained the increase in the body fat of rats receiving a high fat diet and improved their sensitivity to endogenous and exogenous insulin. However, discontinuation of exercise rapidly lowered the insulin sensitivity. These findings suggest that continuous exercise is especially important for the prevention and treatment of diabetes mellitus, even under a westernized high fat diet.

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Protective effects of angiotensin converting enzyme inhibitors on ischemic rat heart: Possibility of pretreatment

Minoru NAITOH

1993 Volume 105 Issue 1-2 Pages 165-172
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_165

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The protective effect of angiotensin converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion injury was estimated in the isolated working rat heart. Male Wistar rats were divided into four groups and reared for 6 weeks: fed without ACEI (Group A), fed with Captopril 30mg/kg/day (Group B), fed with Captopril 60mg/kg/day (Group C) and fed with Enalapril 20mg/kg/day (Group D). Isolated perfused rat hearts were ischemic for 20min at 37°C and were reperfused for 30min at 37°C.
Addition of ACEI preserved cardiac output, prevented increase of coronary resistance and release of cardiac enzyme (CPK) in Group B, C, D hearts compared with Group A. These findings suggest that ACEI can protect the myocardium from ischemia and reperfusion injury by pretreatment.

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A clinical study of blood coagulation and fibrinolysis in vascular surgery in elderly patients

Akira SUGIYAMA

1993 Volume 105 Issue 1-2 Pages 173-184
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_173

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To evaluate the pathogenesis of bleeding tendency in vascular surgery in elderly patients, the serial changes in various parameters of coagulation and fibrinolysis were investigated perioperatively in 30 patients undergoing vascular surgery and in 18 patients undergoing general surgery (control).
The platelet count, platelet aggregability and plasminogen activity were lower in the group of vascular surgery than in the control group perioperatively. Thrombin-antithrombin III complex (TAT) and plasmin-α₂ plasmin inhibitor complex (PIC) levels were high during operation. Postoperatively, the TAT level gradually decreased but the D-dimer level was high postoperatively. Although platelet aggregability increased significantly with age in the group of general surgery, it tended to decrease in that of vascular surgery. TAT and PIC levels tended to increase but the α₂ plasmin inhibitor (α₂PI) and fibrinogen levels tended to decrease with age. In 22 patients undergoing graft replacement with abdominal aortic aneurysm, a negative correlation was observed between preoperative α₂PI and intraoperative blood loss. However, a positive correlation was evident between the preoperative PIC level and intraoperative blood loss.
These findings suggest that in vascular surgery, activities of coagulation and fibrinolysis increase and the postoperative hypercoagulable state is transient, although secondary fibrinolysis is stationary in a high level, and that in elderly patients with vascular disorders coagulating factor and anti-fibrinolytic factor tend to decrease.
Surgery may induce a bleeding tendency. Furthermore, α₂PI and PIC might be main factors in intraoperative blood loss.

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Studies on the mechanism of late asthmatic response using a technique of bronchoalveolar lavage

Part 1. Bronchial reaction after inhalation of house dust mite allergen in bronchial asthmatics

Kunihiro NAMBA

1993 Volume 105 Issue 1-2 Pages 185-193
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_185

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To investigate the mechanism of the late asthmatic response (LAR) which participates in intractable asthmatic attacks, humoral and cellular components at the sites of LAR were examined by bronchoalveolar lavage fluid (BALF) obtained after bronchial inhalation of house dust allergen. BAL examination was performed 2 hours after improvement of LAR, and leukotrienes (LTs) measured by high performance liquid chromatography.
The level of LTC₄ was significantly higher in BALF after LAR (p<0.05), and that of LTB₄ was also high at LAR.
The increase in the percentage of neutrophils, eosinophils and basophils were evident in BALF after LAR compared with the level in non-attack state and after IAR. However, little LTD₄ was detected in the BALF after LAR. On the other hand, the percentage of neutrophils and the LTB₄ level in peripheral blood showed a peak at 3 hours after bronchial inhalation of house dust allergen, and then decreased markedly during LAR.
These findings suggest that neutrophils, eosinophils, and basophils may release leukotriene-dominant chemical mediators which provoke an asthmatic attack in the late phase response.

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Studies on the mechanism of late asthmatic response using a technique of bronchoalveolar lavage

Part 2. Bronchial reaction after inhalation of Candida allergen in bronchial asthmatics

Kunihiro NAMBA

1993 Volume 105 Issue 1-2 Pages 195-204
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_195

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To clarify the mechanism of late asthmatic response (LAR) which is related to intractable asthmatic attacks, cellular and humoral components at the sites of LAR were examined by bronchoalveolar lavage fluid (BALF) obtained after bronchial inhalation of Candida allergen. BAL examination was performed 2 hours after the LAR attack. The differential cell count was obtained and the level of leukotrienes (LTs) in the BALF and peripheral blood determined by high performance liquid chromatography.
The percentages of eosinophils and basophil·mast cells and neutrophils were statistically high in the BALF after LAR compared with the level in the non-attack state (p<0.05, p<0.01). The level of LTC₄ was significantly higher in the BALF after LAR (p<0.01), and LTB₄ also showed a similar tendency at LAR. However, LTD₄ could not be detected in the BALF after LAR or in the non-attack stage. On the other hand, the percentage of neutrophils and LTB₄ level in circulating blood showed a peak before LAR, and then decreased markedly during LAR. Eosinophils also decreased significantly during LAR, but the plasma LTC₄ level increased significantly during LAR.
These findings suggest that neutrophils, eosinophils and basophil·mast cells play an important role in the pathogenesis of intractable asthma attack and LAR following release of leukotrienes.

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Effects of lithium carbonate on brain injury induced by complete global brain ischemia in dogs

Yutaka YAIDA

1993 Volume 105 Issue 1-2 Pages 205-216
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_205

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The efficacy of lithium carbonate (Li) in preventing ischemic brain injury was evaluated in 36 dogs in a vegetative state. The dogs were subjected to 18 minutes of complete global brain ischemia and divided into the following three groups; control group (n=12), L-I group (n=12), and L-II group (n=12). In the L-I and L-II groups, dogs were administered Li (10mg/kg) immediately after the end of ischemia (post-treatment). Only in the L-II group, dogs were administered Li (100mg/kg) orally one day before the ischemic insult (pre-treatment). In each group, neurologic outcome was evaluated for seven days after ischemia, and morphological changes in hippocampal CA1 pyramidal cells, small to medium-sized striatal neurons and cerebellar Purkinje cells were evaluated at day seven. In the L-II group, neurologic outcome was significantly better than that in the control group, and morphological improvement was recognized. Pre-treatment with Li might improve both neurologic and morphologic outcomes due to powerful inhibition of the stimulated phosphoinositide turnover during ischemia. These findings suggest that the stimulated phosphoinositide turnover during and immediately after ischemia might play an important role in brain injury induced by 18 minutes of complete global brain ischemia.

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The effects of MCI-186 for ischemic-reperfusion injury during cardiopulumonary bypass

Masahiko TAKEO

1993 Volume 105 Issue 1-2 Pages 217-226
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_217

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To determine the efficacy of MCI-186, a novel free radical scavenger, in ischemiareperfusion injury during cardiopulmonary bypass (CPB), the following experimental model was applied. Twenty-one mongrel dogs were subjected to 120 minutes of hypothermic global ischemia by aortic cross clamping with intermittent administration of a cardioplegic solution followed by 60 minutes reperfusion. They were assigned to three groups: group A(n=7), no drug was administered before reperfusion; group B(n=7), 1ml/kg of physiological saline was administered by bolus injection through the aortic root just before reperfusion; group C(n=7), MCI-186 (3mg/ml/kg) dissolved in physiological saline was administered in the same manner as group B. Cardiac function (left ventricular systolic pressure, cardiac output, left ventricular maximum dP/dt) after 60 minutes reperfusion expressed as a percent recovery of pre-ischemic state was superior in group C than in groups A and B. Release of lipidperoxide assayed by the TBA method as the difference between coronary artery and sinus were suppressed in the early phase of reperfusion in group C. Myocardial water content after 60 minutes reperfusion was also less in group C than in groups A and B. These findings suggest that administration of MCI-186 before reperfusion after ischemia is effective in protecting the heart from ischemia-reperfusion injury.

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Measurement of cyclosporine concentration using radioimmunoassay with a specific monoclonal antibody

Preparing for the liver transplantation program in Okayama University Medical School

Shinya SAITO, Kenichi SAKAGAMI, Tsuyoshi MATSUNO, Kunzo ORITA, Takao A ...

1993 Volume 105 Issue 1-2 Pages 227-229
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_227

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Cyclosporine, a new strong immunosuppressive agent, has dramatically improved the outcome of liver transplantation since its introduction to the clinical field in the 1980s.
Despite its efficacy, cyclosporine has a very narrow therapeutic window, which requires fine adjustment of the appropriate dose based on its concentration in the blood.
It will be necessary to obtain reliable data on a daily basis, when the liver transplantation program actually starts in the near future.
To address this problem, we examined the utility of the radioimmunoassay kit using a specific monoclonal antibody (CYCLO-Trac WHOLE-BLOOD, Baxter, Japan), compared with the data derived from a commercial laboratory service (SRL, Japan).
Each value of the cyclosporine concentration in the whole blood, measured by CYCLO-Trac correlated with that of SRL(p<0.0001). CYCLO-Trac was suggested to be useful in obtaining a reliable data on a daily basis within our hospital.

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[title in Japanese]

1993 Volume 105 Issue 1-2 Pages 231-239
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_231

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[title in Japanese]

1993 Volume 105 Issue 1-2 Pages 241-249
Published: February 27, 1993
Released on J-STAGE: March 30, 2009

DOIhttps://doi.org/10.4044/joma1947.105.1-2_241

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