Biomedical subjects
Publications and source records attributed to N Hara.
We report a very rare case of anomalous origin of anterior choroidal artery. In our case anterior choroidal artery arises from internal carotid artery proximal to the posterior communicating artery.
Reviewing the outcome of 70 cases of clinically localized small cell lung cancer (SCLC) treated with combined modality treatment, we attempted to define the role of resection in this disease. The survival rate for all cases was 37 per cent at 2 years and 23 per cent at 3 years with a median survival time (MST) of 14 months. For 25 resected cases the overall 5-year survival rate was 37 per cent with an MST of 26 months. According to clinical staging, 5-year survival was 64 per cent for stage I and 20 per cent for stage II. However, none of the stage III cases achieved long-term survival, of over 3 years. In 45 non-resected cases, the overall response rate was 84 per cent with a 44 per cent complete response. The overall survival rate was 27 per cent at 2 years and 14 per cent at 3 years with an MST of 11 months. The 20 cases who achieved complete response had an MST of 26 months with 51 per cent alive at 2 years and 19 per cent at 5 years. Thus, we consider that lung resection is definitely indicated in cases with stage I and probably stage II SCLC. For stage III, however, particularly in cases with N2 disease, resection seems to offer no special benefit in favor of survival compared to combination chemotherapy and radiotherapy.
Plasma insulin clearance was studied in a patient with autoantibodies to the insulin receptor, manifesting persistent hyperinsulinemia associated with alternating hyper- and hypoglycemia. In the postabsorptive period, the plasma glucose level gradually decreased. To prevent the development of hypoglycemia, glucose was infused and the glycemic level was clamped at 50 mg/dl without insulin infusion. The plasma C-peptide level was below the detectable range during the clamp, indicating no appreciable secretion of insulin. The plasma insulin level declined exponentially with a markedly prolonged disappearance rate (half-time: 3.0 h) during the study. These results indicate that hyperinsulinemia in the postabsorptive period in this patient is attributable to the impairment of plasma insulin clearance through receptor-mediated mechanisms, and also confirm that the receptor plays the principal role in plasma insulin removal.
7B2 is a new protein isolated from human pituitary glands and distributed widely, particularly with high concentrations in the neuroendocrine tissues in the rat. We measured plasma 7B2 concentrations in 333 normal subjects, 20 patients with benign pulmonary disease and 111 patients with primary lung cancer (21 small cell carcinoma, 90 non-small cell carcinoma). A normal range for plasma 7B2 concentrations was defined as less than the mean + 3 S.D. value (110 pg/ml) based on plasma 7B2 concentrations in 333 normal subjects. Elevation of the plasma 7B2 concentration over the normal range was observed in 15 of 21 patients (71.4%) with small cell carcinoma, eight of 90 (8.9%) with non-small cell carcinoma and four of 20 (20%) with benign pulmonary disease. Plasma 7B2 concentrations correlated with the clinical course on chemotherapy in some patients with small cell carcinoma. Immunocytochemical studies revealed numerous 7B2-positive cells in the small cell carcinoma specimen, while 7B2 staining was not observed in the non-small cell carcinoma and the normal lung specimens. These findings suggest that 7B2 is secreted by the small cell carcinoma of the lung, which caused elevation of plasma 7B2 in these patients. 7B2 might be a possible plasma tumor marker for the small cell carcinoma of the lung.
We used a monoclonal antibody, YI 51, raised against human polymorphonuclear leukocytes (PMN) to induce superoxide anion (O2-) generation in cells. Although YI 51 alone played only a small part in inducing O2- generation in PMN, the amount of O2- generation induced in 5 X 10(5) PMN was 3.7 to 5.5 nmol/min when F(ab')2 fragments of rabbit anti-mouse immunoglobulin antibody were added as a cross-linking agent. This O2- -inducing activity was high compared with that of wheat germ agglutinin (WGA), insoluble immunoglobulin G immune complexes (IC), or phorbol myristate acetate (PMA). The binding of YI 51 and soluble immunoglobulin G IC to PMN was not reciprocally inhibitory, indicating that YI 51 does not interfere with ligand binding to the Fc receptor-binding site. In the absence of calcium ion (Ca2+), O2- generation induced by YI 51 decreased to 10 to 20% of that in the presence of Ca2+. In contrast, O2- generation in response to WGA, IC, or PMA under Ca2+-free conditions was not affected. When PMN were pretreated with low concentrations of PMA (10(-10) to 10(-9) M), the amount of O2- generation by the cells in response to YI 51 in Ca2+-free buffer was enhanced in a concentration-dependent manner. It also equaled the O2- generated by the cells in buffer containing Ca2+. In cells pretreated with PMA, the amount of O2- induced by WGA was enhanced two- to threefold over that in untreated cells. In contrast, there was no augmentation over untreated cells with stimulation by IC. These results suggest that YI 51, IC, and WGA induce O2- generation in human PMN in different manners.
The structural genes for the entire bacitracin synthetase 2 (component II) and for a part of the putative bacitracin synthetase 3 (component III) from Bacillus licheniformis ATCC 10716 were cloned and expressed in Escherichia coli. A cosmid library of B. licheniformis DNA was constructed. The library was screened for the ability to produce bacitracin synthetase by in situ immunoassay using anti-bacitracin synthetase antiserum. A positive clone designated B-15, which has a recombinant plasmid carrying about a 32-kilobase insert of B. licheniformis DNA, was further characterized. Analysis of crude cell extract from B-15 by polyacrylamide gel electrophoresis and Western blotting (immunoblotting) showed that the extract contains two immunoreactant proteins with high molecular weight. One band with a molecular weight of about 240,000 comigrates with bacitracin synthetase 2; the other band is a protein with a molecular weight of about 300,000. Partial purification of the gene products encoded by the recombinant plasmid by gel filtration and hydroxyapatite column chromatography revealed that one gene product catalyzes L-lysine- and L-ornithine-dependent ATP-PPi exchange reactions which are characteristic of bacitracin synthetase 2, and the other product catalyzes L-isoleucine-, L-leucine, L-valine-, and L-histidine-dependent ATP-PPi exchange activities, suggesting the activities of a part of bacitracin synthetase 3. Subcloning experiments indicated that the structural gene for bacitracin synthetase 2 is located near the middle of the insert.
Thrombosis-inducing activity (TIA) was detected in the peripheral blood of some patients with advanced lung cancer. When plasma from the patients was given intravenously to mice or to guinea pigs, the animals became immobile within 2 min and died at 3 to 30 min after the injection. Multiple thrombosis was found in the lungs and was considered to be the cause of the death. Thrombosis was not formed and the mice survived when heparin was given intravenously 5 min before the injection of the plasma. This TIA was present in plasma from 13 of 42 patients with lung cancer. On the contrary, only two of 32 with chronic lung diseases and two of 31 healthy control subjects had this activity in the plasma. The coagulation system in the 13 patients was considered to be chronically activated, as revealed by elevation of plasma fibrinogen levels, fibrin degradation product levels, and/or peripheral platelet counts. The TIA shared characteristics with tissue factor in that it was heat labile, nondialyzable through a dialysis membrane with a 10,000 molecular weight exclusion limit, sensitive to phospholipase C treatment, precipitated by 50% ammonium sulfate, and bound to concanavalin-A Sepharose.
Effects of adrenalectomy (AD) on ethanol-induced gastric injury and prostaglandin (PG) protection on the damage were investigated in rats and compared with those of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, and diethyl maleate (DEM), a SH depletor. Oral administration of 100% ethanol (1 ml) induced elongated bands of hemorrhagic lesions in the corpus mucosa of sham operated rats, and these lesions were significantly prevented by 16,16-dimethyl PGE2 (dmPGE2, 10 micrograms/kg, s.c.). AD markedly enhanced the mucosal ulcerogenic responses caused by ethanol and abolished the protective effect of dmPGE2; this agent rather worsened the lesions, which appeared throughout the corpus mucosa. AD by itself enhanced the microvascular permeability in the gastric mucosa without any effect on SH contents. These alterations caused by AD were significantly reverted by hydrocortisone treatment (10 mg/kg/day for 2 weeks, s.c.). On the other hand, a single injection of NEM (10 mg/kg, s.c.) similarly enhanced the vascular permeability, worsened the ethanol-induced lesion, and mitigated the protective effect of dmPGE2 without altering mucosal SH contents, while DEM (1 ml/kg, s.c.) significantly reduced the mucosal SH levels and the lesions. These results suggest that AD worsened the mucosal lesions induced by ethanol, probably by enhancing the microvascular permeability, and this action may be due to a lack of steroid secretion but is not directly related to a mucosal SH deficiency.
Eight hundred and twelve vital statistics death certificates, in which either the cause of death or complications was SMON, were selected from all the death certificates filed in Japan in a 13-year 6-month period from July 1972 to December 1985. In 411, or 50.6%, of these certificates, the SMON Research Committee had records of the clinical pictures as a result of the nationwide surveys conducted earlier. The epidemiological picture presented by the death certificates and the relationship between the information in these certificates and clinical records in nationwide surveys was observed. The results are summarized as follows: 1. The male/female ratio revealed in the 812 death certificates was 0.53, which is higher than those reported in nationwide surveys (0.4). 2. Although the yearly number of certificates was more than 70 in 1974 or before, it decreased year by year. The numbers in 1984 and 1985 were less than 50. 3. The leading underlying causes of death were; SMON in 44.0% of all the certificates, heart diseases in 10.3%, cerebrovascular diseases in 9.2% and malignant neoplasm in 8.6%. 4. The presence of clinical symptoms was compared between death cases and total cases reported by the nationwide surveys. Symptoms such as visual impairment and walking incapacity were seen more frequently in death cases. 5. From these results, it was suggested that the level of the severity of the disease at onset influences the long-term prognosis of the disease, although selection bias in the death certificates observed is unavoidable.
The purpose of the present study was to determine whether all patients with non-small cell lung cancer, clinically defined as stage 1 or 2, should have examinations to determine the presence of distant metastatic (M1) disease. The survival rates of patients who underwent the examinations and those who did not were compared. In all groups, the examinations had in no way positively affected survival. The 33 patients in whom distant recurrence had occurred within 12 months of curative operation, were then evaluated to establish the relationship between the recurrent site and the preoperative examination: negative scans on the examination failed to predict the low incidence of early distant recurrence. Those data suggest that the routine use of radionuclide or CT scans is of no benefit to asymptomatic patients with local, early disease.
We reviewed the brain metastases, after treatment, of 45 patients with limited small cell lung cancer who achieved complete remission by radiochemotherapy or curative operation. No patient received prophylactic cranial irradiation. The incidence of subsequent brain metastases was classified according to pretreatment staging as follows: two of 13 (15 percent) patients in stage I; two of ten (20 percent) in stage II; nine of 17 (53 percent) in stage IIIa; and four of five (80 percent) in stage IIIb. The brain metastases occurred from seven to 29 months after the start of treatment, and the median time of the occurrence was 13 months. Of 17 patients who developed brain metastases and who subsequently received cranial irradiation, there were two in whom relapse had occurred at no other site except the brain and who survived 26 and 79 months after the relapse, respectively. These data indicate that not all patients with limited SCLC achieving CR due to treatment necessarily benefit from PCI.
To elucidate the role of intracellular Ca ions in neuromuscular transmission, we investigated using frog neuromuscular preparations the effect of 1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA) on frequency augmentation-potentiation (formerly frequency facilitation), which have been shown to be useful in identifying the sites of actions of various cholinergic agents. Buffering of intracellular Ca ions by BAPTA was found to suppress only Ca-dependent component of frequency augmentation-potentiation (mo); its stimulation frequency dependent factor (k) remained unaffected. Depression by BAPTA treatment of the short-term facilitation of endplate potential (EPP) was the same in both the resting and augmented states. However, the effect of BAPTA was antagonized, but only partially, with the administration of Ca-ionophore, A23187. These suggest that Ca-buffering capability of the intracellularly loaded BAPTA was maintained during low frequency repetitive stimulation. In addition, the post-tetanic potentiation of miniature EPP frequency in Ca-free EGTA Ringer was practically unaffected with BAPTA treatment. Undoubtedly Ca ions were essential for transmitter release and short-term facilitation, but Ca ions were not solely responsible for all the changes of transmitter release. The contribution of transmitter mobilization to maintaining the synaptic transmission during repetitive stimulation should be reevaluated.
Standardised data on blood pressure, 24 hour urinary electrolyte excretion and other lifestyle factors were obtained in three Japanese populations as part of the INTERSALT study. Urinary sodium excretion and sodium/potassium ratio were significantly (P less than 0.01) higher in Toyama (a semi-rural area in central Japan) than in Tochigi (a rural area 100 km north of Tokyo) and Osaka. There were also significant (P less than 0.01) differences between the centres in diastolic blood pressure (highest in Toyama), although systolic pressure was similar in all three centres. Average potassium excretion was low (46 mmol/day), and the prevalence of both heavy alcohol drinking (greater than or equal to 300 ml/week) and smoking was high in men (33% and 61% respectively); compared with other countries, there were favourable levels of body mass index (mean 22.4 kg/m2). Despite a recent decline in sodium consumption in Japan, which has been accompanied by a fall in blood pressure levels, in the prevalence of hypertension and also in stroke mortality, average sodium excretion in the three centres was high compared to other countries (187 mmol/day). Applying overall INTERSALT regression coefficients to the Japanese data, suggested that further falls in sodium intake together with a modest increase in potassium intake and a reduction (in men) in the prevalence of heavy alcohol drinking could have an important impact on average blood pressures and the prevalence of hypertension. It can be expected that these nonpharmacological approaches to improved blood pressure levels will be accompanied by continued reductions in mortality from stroke.
A method for evaluation of adult health programs conducted by local municipalities (city, town and village) is elaborated. The evaluation is made from the three view points, which are the amount, the quality and the effects of the program. Although the limitation of the method, which uses information obtained from usual activity and is not enough to demonstrate the effects of the program, it is to be worthwhile for improvement of their programs.
The rate of second-case Kawasaki disease occurring among 1788 siblings of children with the disease was derived from data obtained from questionnaires mailed to the members of the Japanese Association of Parents of Children With Kawasaki Disease. Within 1 year after the onset of the first case in a family, the overall second-case rate was 2.1% for siblings, as compared to an overall incidence of approximately 0.19% in the general population of children 0 to 4 years of age in Japan in the epidemic year 1982. For siblings younger than 1 year of age, it was 8.4%, and for those between 1 and 2 years of age, it was 9.3%. More than half (54.1%) of the second cases developed 10 days or less after the first cases occurred.
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Adoptive immunotherapy for the experimental murine brain tumor was investigated by using lymphokine-activated killer (LAK) cells both in vitro and in vivo. Supernatants of 48-h culture medium of spleen cells from Wistar rats in the presence of concanavalin A were used as interleukin 2 (IL-2). LAK cells were generated by cocultivation of spleen cells from Fischer rats with IL-2 with the peak reactivity on Day 2 or 3 of culture. Lytic activity was observed against not only syngenic tumor cells but also allogenic and xenogenic tumor cells, while no lytic activity was observed against normal brain cells. The cell depletion test, dye exclusion test, and immunofluorescence method using monoclonal antibodies revealed that LAK cells partially belonged to the population of the activated T-cell group, but the precursor cells did not react with any monoclonal antibodies used. On the basis of these results in vivo study was performed. LAK cells and immune spleen cells were adoptively transferred to the rats i.v. or intratumorally (i.t.) on the seventh day after the inoculation of T9, a gliosarcoma induced by methylcholanthrene from Fischer rats, into the right basal ganglia. Then the survival rate and necrotic foci were compared between the groups treated with those cells and the control. The survival rate of the groups treated with LAK cells was significantly higher than that of the control (administered i.v.; P less than 0.01, administered i.t.; P less than 0.05). But the treatment with immune spleen cells was not effective. The incidence and area of necrotic foci in the tumors treated with LAK cells were greater than those of the others. Microautoradiography was also performed using [3H]thymidine-labeled LAK cells, which were administered i.v. to the models on the 14th day after the inoculation of T9. It was revealed that LAK cells accumulated in the lung shortly after the administration and then in the liver and spleen, especially in the white pulp. IL-2 inhibitor activity of the sera from the tumor-bearing rats was greater than that of normal rats (P less than 0.001), but it was depressed markedly by cyclophosphamide (P less than 0.01). The adoptive transfer of LAK cells may be one of the effective treatments of malignant brain tumor. The nature of IL-2 inhibitors is necessary to be clarified for more effective immunotherapy.
The effects of gastric distension on the morphology of acidified ethanol (AE) -induced mucosal lesions and on the protective action of 16,16-dm PGE2 were investigated in rats. AE (50% ethanol in 150 mM HCl) was given by gavage in the intact stomach or through a fistula prepared in the forestomach in the pylorus-ligated stomach. AE produced elongated bands of hemorrhagic necrosis within 1 hr in the former, while in the pylorus-ligated stomach the shape of lesions varied depending upon the volume of irritant. One milliliter produced bandlike lesions, whereas 2 ml or more induced widespread lesions; such volumes were observed to remove the mucosal folds. 16,16-dm PGE2 (0.3-10 micrograms/kg, subcutaneous) dose dependently reduced bandlike lesions in the intact stomach, but had no or little effect on non-band-like lesions in the pylorus-ligated stomach. This agent (10 micrograms/kg) had a slight effect on the reduction of PD caused by 10-min exposure of the stomach to AE (2 ml) in the intact stomach, while such effects were not apparent in the pylorus-ligated stomach. Oral gentian violet (2 ml, 0.3% w/v) produced bandlike staining of the mucosa in intact rats, but the effect was blocked by pyloric ligation. 16,16-dm PGE2 also significantly prevented the localized staining pattern seen in intact rats.(ABSTRACT TRUNCATED AT 250 WORDS)