Despite normal concentrations of serum eosinophilopoietic cytokines, blood eosinophilia was noted in patients with atopic dermatitis (AD) (n=32). Significant increase of EG₂⁺ “activated” eosinophil numbers that are mirrored in serum eosinophil cationic protein (ECP) levels in vitro, though not always in synchrony with total eosinophil counts, was also demonstrated. Functionally, AD-source eosinophils showed an enhanced MCLA-dependent chemiluminescence (MDCL) responsiveness to the eosinophilopoietic cytokines, with the characteristics that interleukin-5 (IL-5)-induced MDCL responses strongly correlated with EG₂⁺ eosinophil propor-tions, whereas both IL-3- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced MDCL responses rather significantly correlated with the degree of blood eosinophilia. Like other eosinophil-associated parameters (total eosinophil counts, EG₂⁺ eosinophil counts and serum ECP levels), those cytokine-induced eosinophil MDCL responses significantly increased in correlation to the AD severity. These results suggest that i) eosinophilopoiesis accompanying development of both IL-3- and GM-CSF-sensitive eosinophils within the bone marrow, and induction of IL-5-sensitive/EG₂-reactive eosinophils in the periphery may be regulated through inflammatory events in AD lesional skin; ii) it is unlikely that these eosinophil in vivo differentiation may be due to direct effect of locally synthesized three eosinophilopoietic cytokines; and iii) enhanced sensitivity of EG₂⁺ eosinophils for IL-5 may be responsible for elevated levels of serum ECP in vitro.

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The reliability of event-related potentials (ERPs) was studied in 10 healthy adults who were tested 8 times over 7-10 day intervals using a standard auditory oddball paradigm. The difference waveforms, obtained by subtracting the averaged waveforms for frequent trials from those obtained in rare trials, were designed to analyze the components of the ERPs, such as the P300, and to focus on the reliability of the probability effect on the ERPs. The between-session reliability (8 sessions) and the within-session reliability (order of blocks or of different visual procedures) were computed for the obtained difference waveforms. The between-session reliabilities, expressed as the intraclass correlations (r') for the P300 amplitude, area and latency, were 0.70, 0.61 and 0.65, respectively. The within-session reliability, presented as the Pearson correlation coefficients (r) for the three P300 measures were 0.43, 0.35 and 0.25 for different eyes. The values were 0.45, 0.39, 0.42 between the first and the second blocks (eyes-open) and 0.58, 0.47 and 0.29 (eyes-closed). These findings indicate that the P300 amplitude calculated from the difference waveforms may be the most stable marker for the between-session reliabilities. There were no significant differences in the P300 measures over the 8 sessions, suggesting that habituation may not occur with the difference waveform reflecting the probability effect on ERPs. The difference waveform may be useful in research on repetitive group ERPs.

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Lymphocytes with cytotoxic activity have been identified in sinusoids of rat liver. We investigated the effects of aging on the cytotoxicity of liver sinusoidal lymphocytes in the rat and attempted to identify the cells responsible for cytotoxicity using a Thyl monoclonal antibody. Natural Killer (NK) activity against YAC1 peaked at the age of 8 weeks, while cytotoxicity against NK-resistant Lymphokine Activated Killer (LAK)-sensitive P815 increased gradually with age. A cold target inhibition assay showed that lymphocytes cytotoxic for P815 and AH109 were also present in the liver sinusoids of aged rats. When these cells were fractionated by the Percoll discontinuous density gradient method, cytotoxic cells were found to comprise large granular lymphocytes (LGLs) rich in low- and middle-density fractions. Cytotoxicity against various targets increased when CD5(+) cells were removed using CD5-conjugated beads. Cytotoxicity against P815, AH109 and AH130 was decreased as compared with control lymphocytes when CD5(-) Thyl(+) lymphocytes were removed using CD5, Thyl-conjugated beads. Immunohistologic examination revealed Thyl(+) LGLs with rod-cored vesicles and electron-dense granules in the liver sinusoids. We consider that LAK-like cells with a Thy1 phenotype are present in the liver sinusoids and suggest that they have a broad range of cytotoxicity.

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Pancreatojejunal sutural insufficiency occurring after pan-creatoduodenectomy and countermeasures are discussed. In the Department of Surgery at Kurume University School of Medicine, 318 patients underwent pancreatoduodenectomies. The present study includes 15 of these patients, all of whom had pancreatojejunal sutural insufficiency. The frequency of sutural insufficiency was 4.7%. Five patients had bile duct cancer, 5 had cancer of the papilla of Vater, 2 had a carcinoma of the pancreatic head, 1 each had gallbladder cancer, chronic pancreatitis, and papillitis. Six (40%) of the 15 patients died during hospitalization. The presence or absence of sutural insufficiency was confirmed mainly by radiography and determining the properties and amylase levels of the drainage fluid. There was no significant difference due to the method of anastomosis. End-to-side anastomosis had a rate of 5 (5.9%) of 85 patients, while end-to-end had 10 (4.3%) of 233 patients. The sutural insufficiency was manifested as a major leakage in 6 patients and a minor leakage in 9. The degree of lymph node dissection was D₀ in 6.1%, D1 in 1.4%, D₂ in 4.8% and D₃ in 10.8%, with a high incidence of sutural insufficiency in D₃ patients. The pancreatic duct diameter was smaller than 4 mm in 10, 5-7 mm in 4 and over 8 mm in 1 patient. The intraoperative pancreatic findings were a soft pancreas in 8, slightly hard in 3, and hard in 4 patients. Fibrosis of the pancreas was normal to slight in 11 and moderate in 4 patients. Drainage by relaparotomy was performed in 4 of the 6 patients with major leakages to control sutural insufficiency, and the other 2 underwent continuous aspiration with an intraperitoneal drain inserted during the operation. The 9 patients with minor leakage underwent conservative treatment including continuous aspiration via an intraperitoneal drain inserted during surgery, fasting, intravenous hyperalimentation, and antibiotic administration. All of the patients with major leakage died from an associated occurrence of hepatic insufficiency, renal insufficiency, intraperitoneal hemorrhage or diffuse peritonitis during hospitalization. However, 8 of the 9 patients with minor leakage had some healing, and the 1 remaining patient developed a pancreatic fistula. The frequency of pancreatojejunal sutural insufficiency was high in patients with minimal pancreatic fibrosis, with soft pancreatic tissue without dilatation of the pancreatic duct, and with relatively good pancreatic function.

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To determine the morphologic characteristics of patients with sleep apnea syndrome (SAS), the facial skeleton, tongue area, soft palate area and upper airway area were examined on lateral cephalograms from 53 male patients with SAS. The SAS patients were divided into two groups according to their body mass index (BMI): Group N (BMI<25, N=23) and Group O (BMI≥25, N=30). Fifty non-snoring adult men were used as a control (Group C). The mean BMI of all 53 patients with SAS was 26.2±3.1 kg/m². The mean SNB was smaller in Group N (76.7±3.2°) than in Group C (78.4±3.0°). The mean airway area was markedly smaller in Groups N and O than in Group C. The tongue area was larger in Groups N (36.0±2.3cm²) and O (39.3±2.7cm²) than in Group C (33.3±3.4cm²). There was a positive correlation (R²=0.670) in all subjects between tongue area and body weight. There was also a positive correlation (R²=0.656) between tongue area and the distance between the ANS and the base of the epiglottis in the 103 subjects, the base of the epiglottis being shifted to a posteroinferior position as a result of the enlarged tongue. The findings suggest that micrognathia is a morphological characteristic of the Japanese patients with SAS. Micrognathia and enlargement of the tongue and soft palate due to obesity, were considered to be involved in the narrowing of the airway in SAS patients.

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Antineoplastons, which were firstly described by Burzynski, are naturally occurring peptides and amino acid derivatives which control neoplastic growth. We conducted a toxicological study of the Antineoplastons A-10 and AS2-1 in combination with other anticancer agents or radiation in 42 patients, 46 tumors with terminal stage cancer. Antineoplaston A-10 oral formulation and A-10 injectable formulation was administered in 14 and 25 patients respectively. The maximum daily dose was 10 g and 40 g, respectively and the longest term of administration was 610 days and 67 days, respectively. Antineoplaston AS2-1 oral formulation and AS2-1 injectable formulation was administered in 33 and 10 patients, respectively, the maximum daily dose was 12 g and 30 g, respectively, and the longest term was 1070 days and 25 days, respectively. The major adverse effects that may have been related to these agents as used in combination with other conventional chemotherapeutic agents or radiation were general weakness, myelosuppression, and liver dysfunction, but these effects were not seen when either Antineoplaston was administered alone. The minor adverse effects observed in single use of either Antineoplaston A-10 or AS2-1 were excess gas, maculopapullar rash, fingers rigidity, reduced cholesterol, reduced albumin, increased amylase, eosinophilia, increased alkaline phosphatase, headache, hypertension, palpitation, peripheral edema but these adverse effects did not limit to continuation of either agent. The evaluation of the usefulness of the Antineoplastons in combination therapy based on the imaging findings during the course of treatment revealed disappearance or measureable shrinkage of the tumor lasting more than one months as visualized by magnetic resonance imaging or computed tomography was seen in 15 tumors (32.6%). No increase in size of tumor for more than 3 months was observed in 8 (17.4%). The mean survival time of these patients was significantly longer than that in patients with tumors showing progressive increasing (17.52+3.31 months vs 4.80+0.65 months, p<0.005). Antineoplaston A-10 and AS2-1 are less toxic than conventional chemotherapeutics and they were useful in maintenance therapy for cancer patients.

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To clarify the relationship between daily performed dental practices and work-related physical complaints by dentists, we examined 16 male dentists who worked at their clinic in an urban district. Each subject answered a questionnaire concerning work-related complaints and was examined by a time study of daily actions. The electromyograms of back muscles were taken from ten different positions. Approximately 62% of the daily practice was occupied by the dental care work. The dental care postures were classified into 3 types according to the inclination of the body. The most common posture was a right-forward position. The prevalence of complaints including problems with eyes, hands and arms, neck and shoulders and low back differed among 3 types. The order of complaints was neck and shoulders, eyes, and low back. The amplitude of the electromyograms was increased by the extension of the muscles to lateral bending of 30°and internal rotation of 15°. These results suggest that the body positions of daily dental care practices cause an increase in work-related complaints in dentists.

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A chemiluminescence (CL) procedure was developed to determine the time course of the release of myeloperoxidase (MPO) from activated human neutrophils using two CL probes, luminol and MCLA. Luminoldependent CL (LDCL) and MCLA-dependent CL (MDCL) in a hypoxanthine (HX)/xanthine oxidase (XOD) system, both of which were completely inhibited by superoxide dismutase, were a linear function of the XOD concentration, with the relationship formula being LDCL=0.003×MDCL. Under the same conditions, MPO could enhance LDCL in a dose-dependent manner, without influencing MDCL. There was a linear correlation between the MPO concentrations and the values of (LDCL-0.003×MDCL) (coefficient of correlation=0.004). This correlation made it possible to determine the release of MPO in the neutrophil/stimulus system by simultaneously monitoring the generation of LDCL and MDCL. By this CL procedure, it was revealed that there were variations in both neutrophil MPO releasing patterns and levels depending on the stimulating agent used.

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A health diary was used for measurement of illnesses in the northeast rural area of Thailand during the month of November, 1992. Target population were villagers residing in 12 villages which were randomly selected from 2 districts in Khon Kaen province. Three hundred forty-five households (1690 subjects) were selected for the study from all households in those 12 villages. The sample represented 22.2% of all households. Each respondent was instructed how to record illness which may occur among family members during the observation period. Demonstration of recording was performed as well to ensure uniform reporting. Frequency of ill persons among the 1690 members of the selected 345 households was 299 persons (17.7%) in 333 episodes. The ratio of males to females for the reported illnesses was 1:1.18. The most common illnesses were common cold, fever, and abdominal pain, which occurred in 78, 59, and 47 episodes, respectively, followed by headache, and cough. According to the WHO international classification of diseases, diseases of the respiratory system were prevalent (26.1% of total episodes). Types of illness among age groups 0-1 years and 2-5 years were common cold followed by fever. The others two age groups; 16-45, 46-65 years were ill with abdominal pain as the first rank followed by common cold. Fever and common cold were the most frequent illness in age group 6-15 years and the elderly respectively.

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An educational intervention trial to increase calcium (Ca) intake was conducted on female college students taking a dietician course and the efficacy of the trial was assessed by a prospective cohort study. The one hundred and eight 18-or 19-year-old students were divided into two cohorts, i.e., a control group and an intervention group. The educational intervention was given to the intervention group only and both group received 3 surveys, before the intervention (baseline, BL), 1 week after the intervention (WAI), and 1 year after the intervention (YAI). The amount of Ca intake at BL did not differ significantly between the cohorts. The Ca intake of the control group did not change significantly in the 3 surveys. The intervention group significantly increased Ca intake at WAI and maintained a higher level of Ca intake at the time of YAI. These results suggest some efficacy of the educa-tional intervention to increase Ca intake in the female college students.

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An evaluation of the pulmonary vascular resistance and the reversibility of pulmonary vascular reaction in children with congenital heart disease is essential for determining the surgical indication and for assessing the long-term prognosis. We report the clinical efficacy, of low dosage inhaled nitric oxide and investigate the relationship between its effect and hemodynamic parameters in 18 patients with congenital heart disease. The patients were divided into 3 Groups; Group 1 consisting of 3 patients with Eisenmenger syndrome, Group 2 of 10 patients whose mean pulmonary artery pressure was more than 30mmHg, and Group 3 consisting of 5 patients whose mean pulmonary artery pressure was less than 30mmHg. High concentration (90%) oxygen, and also normal oxygen (21%) containing 10 parts per million nitric oxide were administered by cardiac catheterization. In Group 1, both the 90% oxygen and the normal oxygen with nitric oxide showed no affect on the hemodynamical variables. In Group 2, the pulmonary artery pressure and the pulmonary vascular resistance both significantly decreased with the 90% oxygen, and with the nitric oxide inhalation, but these decreases were not found in Group 3. In the 15 patients (of Groups 2 and 3 combined) who were considered to have reversible pulmonary vascular changes, significant correlations were found between the baseline pulmonary artery pressure and the magnitude of pulmonary vasodilation. No clinical evidence of toxicity was seen with the administration of the inhaled nitric oxide. These data suggested that inhaled nitric oxide, even in a low dosage, was a potent and selective pulmonary vasodilator in patients with congenital heart disease complicated with pulmonary hypertension. Since a positive correlation was found between the baseline pulmonary artery pressure and the magnitude of pulmonary vasodilation, this examination demonstrated potential efficacy for objective analysis in patients with pulmonary hypertension.

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The molecular mechanisms regulating epidermal differentiation and apoptosis have not been elucidated. Bcl-2, one of the candidate genes for suppressing apoptosis, was originally cloned from the breakpoint of a t (14;18) translocation present in many human B cell lymphomas. In this study, the influence of bcl-2 on apoptosis was observed in transfected keratinocytes. After transfection of pEF-BOS vector withlwithout bcl-2, the expression of coded protein and the viability under starved conditions were examined. The bcl-2-transfected keratinocytes had cytoplasmic positive staining with anti-bcl-2 monoclonal antibodies, however the vector only transfected cells were devoid of the reaction products. The viability of transfected keratinocytes under starved conditions, with a lack of epidermal growth factor and bovine pituitary extract, was maintained in bcl-2 trans-fected cells; while the vector only transfected cells showed apoptotic cell death. The present result indicates that bcl-2 suppresses apoptotic cell death under starved conditions due to a lack of epidermal growth factor and bovine pituitary extract.

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A Helium-Neon (He-Ne) laser with a wavelength of 632.8nm is known to have photobiological effects and is widely used for reducing the pain of herpes zoster and accelerating wound healing, however the cellular mechanism and effect of the He-Ne laser are poorly understood. The present study was designed to examine the influence of He-Ne laser irradiation on irritant and allergic contact dermatitis of the mouse ear and on histamine release from rat peritoneal mast cells. Irradiation was applied with a He-Ne laser (12.2J/cm²) at 1h, 10min, 5min and 0min before, and 5min, 6 hs and 24hs after a challenge of an irritated contact dermatitis (ICD) or allergic contact dermatitis (ACD) was made on the right ears of ICR-mice. Twentyfour hours after the challenge, the swelling of the ear was measured with a dial thickness gauge, and the anti-inflammatory effect of He-Ne laser irradiation was expressed as an ear thickness ratio (ETR). Although the laser did not decelerate the ETR from ICD, the allergic response was decelerated. Irradiation at 5min after the challenge of contact dermatitis increased the thickness ratio. Next, the influence of the He-Ne laser on histamine release from Wister-rat peritoneal mast cells was observed. The spontaneous his-tamine release was inhibited by laser irradiation, while substance P and compound 48/80-induced histamine release were not inhibited. From these results, it can be suggested that He-Ne laser irradiation has an anti-inflamma-tory effect on cutaneous inflammation.

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The patient was a 47-year-old female with chronic hepatitis B having antibody to HBe antigen (HBeAg). She was admitted to our hospital in March, 1994, because of acute exacerbation of chronic hepatitis B. Laboratory data revealed the elevated serum transaminase and DNA-polymerase levels, and decreased prothrombin activity. The histological examination of the liver showed chronic active hepatitis with severe hepatic necrosis. Point mutation of the precore region of HBV-DNA (pre-C mutant) was observed in clones from this case by polymerase chain reaction method. The patient was treated with recombinant interferon α-2a 9 MU daily for 2 weeks and thereafter 3 times weekly for 6 months. After interferon therapy, the pre-C mutant disappeared with the improvement of transaminase levels and prothrombin activity. These finidings suggest the possibility that longterm treatment with interferon therapy is effective for the acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg.

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We describe 4 patients with onset or aggravation of thyroid dysfunction induced by interferon (IFN) treatment of hepatitis type C. All 4 patients were females; 2 had hyperthyroidism and 2 had hypothyroidism during or after IFN therapy. The onset or aggravation of thyroid dysfunction occurred during administration of IFN in 1 patient and 4 weeks after the end of IFN therapy in the remaining 3 patients. The 2 patients who demonstrated hyperthyroidism were euthyroid and negative for thyroid autoantibodies before receiving IFN therapy. The remaining 2 patients who demonstrated hypothyroidism were positive for thyroid autoantibodies before IFN therapy. One of these patients had a slight decrease in thyroid function before IFN therapy. Anti-thyroid stimulating hormone (TSH) receptor antibodies became positive in all 4 patients. Since there may have been a causal relationship between IFN therapy and the onset or aggravation of thyroid dysfunction, IFN therapy should be administered with caution.

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