To examine the clinicopathology of agglomerated bronchial epithelial cells, i.e. Creola body (CrB), in the sputum, the incidence of CrB stained by Papanicolaou's method was evaluated in 46 bronchial asthmatics and 10 patients with obstructive pulmonary diseases, and then was compared with the pathogenetic factors of bronchial asthma. CrB was observed specifically in the sputum of bronchial asthmatics. CrB-positive cases had asthma attacks for more than 4 days and a high incidence of eosinophils in the sputum, but not CrB-negative cases. The presence of CrB in the sputum tended to be high in non-atopic asthmatics with a low serum IgE level, but had no significant correlation with either the incidence of neutrophils in the sputum, the present age of patients, the severity of the disease or bronchial hyperresponsiveness to acetylcholine. These findings suggest that the involvement of histolesional factors such as persistent bronchial contraction and release of major basic protein from eosinophils in the airway may lead to the formation of CrB. Also the appearance of CrB may be a useful index for pre-serious stage of asthma.
To clarify the mechanism of Creola body formation in the sputum of bronchial asthmatics, guinea pigs were actively sensitized by intraperitoneal injection and provoked bronchial reactions by inhalation of aerosolized ascaris antigen. Then bronchoalveolar lavage fluid (BALF) and lung tissue were examined by cytological and histological analyses. Agglomerated bronchial epithelial cells (CrB) appeared in the BALF obtained from guinea pigs in the asthma model. The frequency of CrB in the BALF of guinea pigs in the asthma model tended to increase with increase in the number of daily antigen inhalation and eosinophils in the BALF. The histological findings of bronchi showed that infiltration of eosinophils and submucosal edema in the bronchi, hypertrophy and protrusion of the papillary formation of bronchial epithelial layer to the bronchial lumen, and also desquamation of the layer. These findings were mainly seen at the central bronchi in guinea pigs after 8 days of antigen inhalation. These findings suggest that CrB is formed by the epithelial tissue damage caused by the chemical mediators of eosinophils and also by chronic bronchospasm. Their appearance may be an index for organic tissue damage in the pre-serious stage of asthma.
We investigated the in vivo antitumor effect of recombinant human interferon-α, γ (IFN-α, γ) and/or recombinant human tumor necrosis factor-α (TNF-α) against human colon cancer cells (LoVo) transplanted into nude mice. LoVo cells were very sensitive to IFN-γ and slightly sensitive to IFN-α and resistant to TNF-α in vitro by dye uptake method. Intravenous administration of IFN-γ significantly inhibited tumor growth transplanted subcutaneously into nude mice, but IFN-α and/or TEN-α did not show any antitumor effect. Labeling index on staining with bromodeoxyuridine and mitotic index of LoVo cells treated with IFN-α, γ or TNF-α differed slightly from those of the control group. We previously reported that the synergistic antitumor effects on the three cell lines could be examined by the combined use of IFN-α and TNF-α and the mechanism of the synergism was arrested in the S phase of cell cycle of target cells. However in the case of LoVo cells, the combined use of IFN-α and TNF-α was not effective and did not arrest the cells in the S phase of cell cycle. Therefore, arrest in the S phase was suspected to be responsible from the synergistic antitumor activity of IFN-α and TNF-α on the sensitive targets.
Thirty nine reconstructive surgeries were performed in 37 cases of head and neck cancers from January, 1989 to August, 1991 in our department. The best functional results were obtained on deglutition, swallowing and phonation after intraoral and/or mesopharyngeal reconstruction using free radial forearm flaps. The free jejunal transposition procedure had the lowest complication rate. The rectus abdominus musculocutaneous free flap was used for nasal, paranasal reconstruction. Esthetics could be presereved by this reconstruction method due to milder postoperative atrophy and contraction. Eye sockets for the artificial eyes were made with eye conjunctiva in 3 cases of extended total maxillectomy with the orbital exenteration. The use of microvascular free flaps in this new plastic surgery resulted in the decrease of refusal of operations in maxillectomy cases.
A modified injection replica SEM method was introduced. Thorough injection of a resin mixture (monomeric methacrylate containing 1% benzoyl peroxide and 1% N, N-dimethylaniline) prior to the microwave treatment prepares good and fine blood vascular casts or replicas of brain, hypophysis, pineal body, thyroid gland and other organs. These casts sufficiently withstood ionbombardment and were useful for scanning electron microscopy. In this casting, preliminary perfusion fixation prior to the resin injection was always necessary because the mixture was toxic to the vascular walls and destroyed them.
The clinicopathologic findings and the prognosis of 154 patients without regional lymph nodes metastasis or distant metastasis (n(-) group) were compared with those in 134 patients with regional lymph nodes metastasis and without distant metastasis (n(+) group). The mean age of the n(-) group was significantly younger than that of the n(+) group (p<0.05) and there was no significant sexual preponderance. The proportion of the cases without lymphatic vessel invasion in the n(-) group was significantly higher than in the n(+) group (p<0.01). The proportion of the cases without venous invasion was significantly higher in the n(-) group than in the n(+) group (p<0.05). There was no difference in cumulative survival rate of patients in the n(-) group in respect to the background factors such as sex, tumor site, and venous invasion. However, the survival rate of patients whose cancer invasion was limited within the mucosa (m), submucosa (sm) and musclar propria (pm) was significantly better than that of patients who had subserosal or subadventitial penetration (ss(a1)), serosal or adventitial penetration (s(a2)) and cancer invasion adjacent organs (si(ai)) (p<0.05). The survival rate of patients with lymphatic vessel invasion was significantly higher than that of patients without lymphatic vessel invasion (p<0.05). That the poor prognostic factors in n(-) colorectal cancer patients are cancer penetration to/beyond ss(a1), or positive lymphatic vessel invasion.
A well-developed nervous branch supplying the upper lateral cutanea of the arm, which arose from the suprascapular nerve, ran beneath the acromio-clavicular joint and penetrated the deltoid muscle, is described. In usual cases, this branch is thin and sometimes referred to as the accessory upper lateral cutaneous branch of the arm (Murakami) (or subacromial cutaneous nerve, Yamada). Some unusual supraclavicular nerves, which penetrated the clavicular bone or ran under this bone, are also described.
Clinical and radiological studies were performed on 58 patients with rheumatoid arthritis (RA) who had sustained 64 femoral neck fractures. All but one patient were female, the mean age was 66.5 years, and mean duration of RA was 17 years. Only 3 hips showed rheumatoid changes. Sixteen fractures of 14 patients were spontaneous fractures without trauma. Ipsilateral total knee replacements were performed on 5 patients with spontaneous fractures. Results of treatment were analyzed on 47 fractures in 43 patients that could be followed up for more than 1 year (mean 42 months). Clinical results were evaluated by ability of ambulation and complications such as nonunion and avascular necrosis of the femoral head. All 4 fractures treated conservatively and 5 of 9 displaced fractures treated by internal fixation developed complications. Femoral head replacements had a high rate of proximal migration (23.8%) and distal migration (76.2%), and ambulation ability was lowered significantly in 10 patients with distal migration for more than 5mm. On the other hand, satisfactory results were obtained on all 6 fractures treated by total hip replacements (THR). THR is advisable for treatment of displaced femoral neck fracture in patients with RA.
TNF is a cytokine with the activity of a BRM (biological response modifier). TNF-α and TNF-β enhanced NK activity of peripheral blood mononucleocytes of a normal donor, but not in a cancer patient. ISS, a glycoprotein extracted from the ascitic fluid of a colon cancer patient with immunosuppressive properties, is also detected in large quantities in the serum of cancer patients. NK activity of a normal donor which was in an immunosuppressive state by the administration of ISS was not affected by treatment of TNF-α or TNF-β, but the suppressed NK activity was improved by the combination of TNF with IFN-α or IFN-γ. On the other hand, NK activity of a cancer patient treated with anti-IS antiserum which was obtained from serum of rabbit immunized by ISS was enhanced by both TNFs. These findings suggest that ISS suppresses the effect of TNFs on NK activity. Furthermore, the effect of TNF as a BRM is inhibited in cancer patients due to the high dose of ISS in the serum, and that the combination of TNF with other cytokines, such as IFN, is more effective than the single use of TNF, clinically.
Forty eyes in twenty-two cases in the active phase of retinopathy of prematurity were treated with laser photocoagulation. Thirty (93.7%) of the 32 eyes in type I and intermediate type were found in the cicatrical phase grade 1. In type II in which cryocautery was used as combination therapy, only 2 eyes (25.0%) were found in grade 1, 2 eyes (25.0%) in grade 2, 1 eye (12.5%) in grade 4 and 3 eyes (37.5%) in grade 5. All 21 eyes in which photocoagulation was performed up to the middle of stage 3 were found in grade 1 (100%). However, among 11 eyes in which photocoagulation were performed in late stage 3, 9 eyes (81.8%) were found in grade 1, and 2 eyes (18.2%) in grade 2. In conclusion, if adequate laser photocoagulation is performed in avascular areas at the middle of stage 3 of type I and intermediate type, treatment in cicatrical phase grade 1 is possible. Laser photocoagulation is clearly more effective than the xenon arc photocoagulation or cryocautery. However, in type II it is difficult to control the condition by photocoagulation alone, and early diagnosis followed by combination therapy using cryocautery is required.
Attitude of nurses and attendants toward mental disorders was studied by using questionnaire in Japan and Brazil. By factor analysis, three factors, negative attitude toward mental disorders and misunderstanding, positive attitude toward mental disorders and mental health ideology were extracted. The score of negative attitude toward mental disorders and misunderstanding was high in Brazil. This was suspected to be caused by poor knowledge about mental disorders. The score of positive attitude toward mental disorders was similar in Japan and Brazil. The score of mental health ideology was high in Japan. Mental health ideology is important to improve the attitude toward mental disorders both Japan and Brazil. It is important to spread knowledge about mental disorders in Brazil. In Japan, it is important to increase the interest in mental disorders.
The anticoagulant effect of nafamostat mesilate (FUT, a protease inhibitor) plus cepharanthin (CE) after small-caliber graft implantation into the canine jugular veins was compared with that of heparin (HE) or urokinase (UK). Twenty-four dogs were used in this study. Sauvage EXS Dacron grafts 5mm in diameter were implanted into external jugular veins. Immediately after implantation, continuous administration of drugs was started through posterior auricular veins. Coagulation tests were carried out serially during perfusion. Three hours after implantation, the grafts were removed and examined macro-and microscopically. The dogs were divided into 4 groups: 1) Control group; 2) UK group (2000u/kg/hr); 3) HE group (0.25mg/kg/hr); and 4) FUT plus CE group, FUT (0.3mg/kg/hr) plus CE (0.7mg/kg/hr). All grafts were thrombosed in the control group and UK group. However, no thrombus was found in the HE group and FUT plus CE group. Coagulation tests revealed that fibrinogen and AT-III decreased significantly in the UK group (p<0.05), ACT and APTT was gradually prolonged in the HE group (p<0.05), and there was no significant change in the FUT plus CE group. These findings suggest that FUT plus CE may not only decrease early thrombus formation, but may also maintain the balance of the coagulation system. The combination of FUT plus CE may be useful anticoagulant therapy during the postoperative period when the risk of bleeding remains.
We previously reported that alveolar lymphocytes in patients with active sarcoidosis are sensitized to Propionibacterium acnes (P. acnes) which may play a significant role in the induction of alveolitis in these patients. We further investigated the production of Interleukin-2 (IL-2), and the responsiveness to IL-2 of alveolar lymphocytes obtained from sarcoidosis patients and stimulated by P. acnes in vitro. In 21 untreated sarcoidosis patients, 7 treated patients and 13 control subjects, the mean IL-2 activity of fluid released from cultured alveolar lymphocytes was 9.8±15.7 (M±SD), 1.9±4.7 and 0.2±0.8u/ml respectively. The IL-2 activity of lymphocytes from untreated patients was significantly higher than that of control subjects (p<0.02). Neither peripheral lymphocytes in sarcoidosis patients nor in controls produced IL-2 stimulated by P. acnes. The responsiveness of alveolar lymphocytes to recombinant IL-2 was evaluated by 3H-thymidine uptake in the presence and absence of P. acnes. Lymphocytes stimulated by P. acnes showed a significantly increased uptake (3, 766±3, 929 dpm) compared to unstimulated lymphocytes (1, 123±968 dpm) obtained from 11 untreated sarcoidosis patients (p<0.02). On the other hand, the responsiveness of lymphocytes obtained from 6 control subjects was low regardless of stimulation by P. acnes. There was a significant correlation (p<0.05) between the P. acnes-induced production of IL-2 by alveolar lymphocytes and the blastogenesis of alveolar lymphocytes in untreated sarcoidosis patients. Our findings indicate that P. acnes stimulates IL-2 production and IL-2 receptor induction in alveolar lymphocytes from patients with active sarcoidosis. This study supported our hypothesis that P. acnes could be an antigen causing sarcoidosis.
The role of Propionibacterium acnes (P. acnes) isolated from a high percentage of patients with sarcoidosis by Dr. Honma, as a cause of sarcoidosis was examined. Interleukin-2 (IL-2) production and the responsiveness to IL-2 of alveolar lymphocytes stimulated by P. acnes were examined in vitro in a guinea pig model. The animals were divided into 4 groups, normal guinea pigs (group 1), guinea pigs intracutaneously presensitized with P. acnes and intratracheally challenged by saline (group 2), guinea pigs presensitized as above and intratracheally challenged with P. acnes (group 3), and guinea pigs presensitized as above and intratracheally challenged by P. acnes-pyridine extract residue (P. acnes-PER) (group 4). The production of IL-2 by alveolar lymphocytes stimulated by P. acnes-PER for 48 hours was determined using the method described by Gillis et al. The responsiveness of alveolar lymphocytes to IL-2 was evaluated by 3H-TdR uptake in the presence and absence of P. acnes-PER. The amount of IL-2 produced by alveolar lymphocytes was 0.6±1.1, 0.7±1.1, 21.2±27.9 and 329.4±294.1u/ml (M±SD), respectively, in groups 1, 2, 3 and 4. The value of IL-2 production in groups 3 and 4, the intratracheally challenged groups, was significantly higher than that in groups 1 and 2, the control groups (p<0.02, p<0.01). By contrast, the IL-2 production of peripheral lymphocytes in groups 1, 2, 3 and 4 was 0, 7.4±10.3, 8.6±15.7 and 9.3±8.9u/ml, respectively. The amount of IL-2 produced was about one-tenth that of alveolar lymphocytes. In the intratracheally challenged groups, the responsiveness to IL-2 of alveolar lymphocytes in the presence and absence of P. acnes-PER was 12, 514±12, 766 and 6, 611±7, 066 for group 3, and 12, 362±9, 414 and 5, 818±5, 494dpm, respectively, for group 4. The responsiveness to IL-2 of alveolar lymphocytes in group 4 was significantly increased by stimulation with P. acnes-PER (p<0.05), but that in groups 1 and 2, control groups, was not different. Our findings indicate that P. acnes-PER stimulated IL-2 production from alveolar lymphocytes and induced a functionally active state of alveolar lymphocytes to IL-2 in this guinea pig model. In conclusion, the role of alveolar lymphocytes in an animal model stimulated by P. acnes appears to be consistent with that obtained on the sarcoidosis patients we previously reported.
The estrogen binding activity in the human uterine cervix was measured, and the effect of natural and synthesized steroids on the activities was determined. To assay the estrogen binding activity, the sample was incubated with 10 nM [3H] estradiol-17β at 30°C for 2 hours. Then dextran-coated charcoal (DCC) was added to a final concentration of 0.5% to separate bound/free (B/F) estradiol. Estrogen binding activity was determined by subtracting the activity found in the heated sample from the corresponding activity in the untreated sample. For this purpose it was found appropriate to heat the sample at 40°C for 60 minutes. The dissociation constant obtained from the Scatchard plot analysis was: Kd=2.0×10-9M. A variety of steroids at the same molar concentration (1.0μM) were added to the sample to determine their effects on the estrogen binding activity. For binding with [3H] estradiol-17β, the synthetic estrogens were strongly inhibitory, the anti-estrogen agents were strongly to moderately inhibitory, the androdgens were moderately inhibitory, and the gestagens were moderately inhibitory. Danazol, which has been used for the treatment of endometriosis, was found to be as effective as androgens. All of those inhibitory effects occurred in a non-competitive manner.
An automated direct assay system using high performance liquid chromatography was developed for the measurement of Danazol; DA and its two metabolites, Δ1-2-hydroxymethylethisterone (Δ1-2-HME), and 2-hydroxymethylethisterone (2-HME), in biological fluid (human serum and ascites). Serum concentrations of these compounds were measured up to 24h following a single oral administration of 200mg of DA to 6 females with endometriosis. The maximum serum concentration of DA, Δ1-2-HME and 2-HME was 208, 44 and 58ng/ml, respectively. The serum half-life of DA, Δ1-2-HME and 2-HME was 7.9, 4.3 and 4.4h, respectively. The mean serum concentration of DA and its two metabolites at the the sampling time (2h after oral administration of 200mg of DA every 4 weeks) hardly changed in the patients administered 400mg/day of DA over a period of 16 weeks. DA and Δ1-2-HME were detectable in ascites 2, 4 and 8h after oral administration of 200mg of DA, and 2-HME was detectable in ascites at 4 and 8h. This system could quantify DA and its metabolites easily and simultaneously, and was considered to be valuable in the studies on the relationship between the pharmaco-kinetics and the clinical effects of DA.
The systemic blood flow distribution of cardiac output of adult dogs, the brain temperature of which was kept at 24°C by a simple hypothermia method under total spinal anesthesia was investigated. The systemic blood distribution was measured using a radioactive tracer microsphere (51Cr, 85Sr, 125I: 15±5μ in diameter) before total spinal anesthesia, after total spinal anesthesia and under deep hypothermia. Cardiac output was reduced to 83% of the control after total spinal anesthesia and to 38% of the control under hypothermia. The systemic blood re-distribution to each organ determined from the gamma-ray value of trapped radioactive microspheres tended, to be higher than the control value after the total spinal anesthesia in the brain, the heart and the kidney, but to be lower in the gastrointestinal tract. The systemic blood re-distribution to each organ except the liver decreased equally under hypothermia. That is, marked blood re-distribution accompanied by low cardiac output was not recognized. This method could be a safe and useful means for determining blood distribution during open heart surgery.
Two indicators (Risk score and Resection Index) for pulmonary and cardiac complications after lung resection were evaluated on 182 patients with bronchogenic carcinoma by quantitative technetium 99m macroaggregation albumin (MAA) perfusion scanning preoperatively and who then underwent lung resection. After surgery, the correlations between preoperative lung function and the development of postoperative pulmonary and cardiac complications (PPCC) were examined in each case. The Risk score consisted of eight parameters (%FVC, FEV1.0%, %MVV, %MMF, V50/HT, V25/HT, %peak flow, and %DLco), and a value of from 0 to 8 was assigned. In the patients with a Risk score of 0, PPCC occurred in 5 of the 71 cases, while complications were noted in 26 of the 94 patients with a Risk score from 1 to 5 and in 14 of the 17 patients with a score of over 6. The Resection Index was calculated from the predicted postoperative FEV1.0 from the quantitative 99m Tc MAA perfusion scan and the predicted FEV1.0, PPCC occurred in 20 of the 27 patients with a Resection Index of below 40%, 25 of the 131 patients with an index of 40% to 65%, and none of the 24 with an index over 65%. Both indicators had a good correlation with the occurrence of PPCC. These two indicators, the Risk score and the Resection Index, were clinically useful for predicting PPCC preoperatively and may help reduce the incidence of PPCC.
To assess the progress and limitation of chemotherapy in the treatment of small cell lung cancer in the elderly, we analyzed 218 patients in a protocol study between 1982 and 1990. There were 101 elderly patients (age of ≥66 years) and 117 non-elderly patients (age of ≤65 years). Response to chemotherapy with or without chest irradiation was similar for the elderly and the non-elderly; the complete response rate was 52% for limited disease (LD) and 33% for extensive disease (ED) in the elderly, and it was 68% for LD and 23% for ED in the non-elderly. Survival figures of the two groups were similar; the median survival time was 12.6 months for the elderly and 14.5 months for the non-elderly, and the 3-year survival rate was 14% for both groups. Hematologic toxicity was more frequent and severe in the elderly than in the non-elderly but the difference was not significant. Non-hematologic toxicity was comparable for the two groups, with an exception that the elderly showed a tendency of being predisposed to renal toxicity. In conclusion, elderly patients eligible for entry into a protocol study can benefit from intensive treatment just as younger patients can.
MRI is a valuable tool for diagnosing heart disease today. The cardiac blood flow is determined by an MRI image analysis and expert system. Image data are taken by a TV camera and digitalized. After gray level thresholding and region segmentation, the boundary of the regurgitant flow region is precisely extracted. Using this expert system, a doctor can easily make an accurate diagnosis of the valvular heart disease. This method should prove useful for the diagnosis of various heart diseases.