In the present study, we investigated two patients with spontaneous rupture of the esophagus. One patient with the nature of the disease limited within the mediastinum (M type), was cured by means of the surgical primary closure. The other patient hadg hydrothorax and empyema after rupturing of the esosphgeal wall and mediastinal pleura (L type). Gaping occurred immediately after receiving the surgical primary closure. He was cured by resection of the ruptured portion. A recent survey in Japan revealed that mortality for the L type is significantly higher than that for the M type, the occurrence rate of gaping after the surgical primary closure is slightly lower than 50% in both the L and M types, and the occurrence rate for the spontaneous closure in the L type is low, slightly higher than 40% which is one half of that of the L type. It is important to detect the disease in early stage for the treatment of L type spontaneous esophageal rupture. In addition, suitable treatment for the removal and localization of mediastinitis and empyema is necessary.

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Among the three enzymes participating in the metabolic turnover of the folate cycle which has a close correlation to nucleic acid synthesis as well as sulfur amino acid metabolism, the activity of N^5-methyltetrahydrofolate homocysteine methyltransferase (MTHM) was measured in several areas of the brain and the spinal cord of two patients with amyotrophic lateral sclerosis (ALS) and of six controls died of non-neurological diseases. MTHM, which needs vitamin B_<12> as the coenzyme, catalyzes the conversion of N^5-methyltetrahydrofolate to tetrahydrofolate, the concentration of which was reported to be in significantly lowered values in the ALS cerebral cortex. In the controls, the MTHM activity was higher in the precentral gyrus than in the calcarine fissure area, and higher in the anterior horn than in the posterior horn of the spinal cord. In comparison between the brain and the spinal cord, the MTHM activity in the anterior horn was higher than that in the precentral gyrus. However, these differences were statistically not significant. In the ALS brain, the MTHM activity showed 62%, on the average, of the control values in the precentral gyrus, although this reduction did not exceed the mean minus two standard deviations of the control values. In the ALS spinal cord in which histopathological changes were markedly advanced compared to the brain, the reduction of the MTHM activity was obscure. This may be due to the proliferation of glial cells which also have this enzyme. More study will be needed to know whether the biochemical findings observed in the nervous tissue of the ALS patients lead to some primary changes relevant to the pathogenesis of this intractable disease.

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In order to investigate the central dopamine metabolism in schizophrenia, relationships between the changes of plasma HVA, serum prolactin, serum haloperidol and clinical effects were examined. Twenty nine schizophrenic patients were diagnosed according to the Research Diagnostic Criteria. Schizophrenic patients were treated with various doses of haloperidol during five weeks. Plasma HVA levels were measured by means of liquid chromatography with electrochemical detection. Serum levels of prolactin and haloperidol were assayed by radioimmunoassay. The clinical effects were assessed using the Brief Psychiatric Rating Scale. The mean plasma HVA levels before and during 1, 3 and 5 weeks following haloperidol treatment in 29 patients were significantly lower than those of 34 sex-and age-matched controls (Student's t-test, P<0.01). In case of the newly treated, unmedicated 15 schizophrenics, the pretreatment plasma HVA levels were significantly lower than those of the relapsed 14 schizophrenics who had not received any neuroleptics for at least two weeks (Student's t-test, P<0.05). The serum levels of prolactin were significantly increased with an increase in mean dose of haloperidol and serum levels at 1, 3 and 5 weeks, although there was a wide variation of inter-and intra-individual. Plasma HVA levels increased with improvement of anergia, thought disturbance and activation at 3 weeks. Anxiety depression improved with a decrease in serum prolactin levels in female patients at 1 and 3 weeks. There was a positive correlation between improvement of activation and serum haloperidol in male patients at 5 weeks. It is suggested that the central dopamine turnover may be decreased in schizophrenia and it may be resulted from the supersensitivity of postsynaptic receptor. The measurement of plasma HVA levels, prolactin and drug concentration in serum maybe useful indices of acute treatment in schizophrenia.

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A case of overlap syndrome with PSS and RA developed to pericardiomyocarditis and pleuritis, and subsequently the patient died suddenly although various treatments were tried. We reviewed her clinical course and laboratory data, and examined her autopsied tissues of heart and lung by light and immunofluorescence microscope. The histology of the heart showed remarkable picture of myocarditis with severe infiltration of mononuclear cells and myolysis of myocardium. The serous antibody titer to Echo virus type 11 was elevated to 32x and the immunofluorescence study of the lung beneath the involved pleura for Echo virus type 11 antigen revealed the specific staining with IgG and IgA in a few parts of the alveoler walls. However, no adequate pathognomonic lesions for PSS and RA were found in the myocardium and entire blood vessels so far as we examined. Accordingly, we presumed that her sudden death was due to viral myocarditis from Echo virus type 11. This case suggests that myocarditis, pericarditis, and pleuritis which occur during the clinical course of collagen diseases may not always be due to original diseases, but to viral origin.

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The recent change of progeny number or sibship size was analyzed in order to evaluate the opportunity for natural selection on fitness, especially on fertility. The data of 312 pedigrees obtained from the questionnaires to the medical students of two universities in Kyushu district as probands were used. The results are as follows : (1) The mean and variance of sibship size were nearly constant for the sibships of grandfathers, grandmothers, fathers and mothers, while those for the sibships of probands clearly decreased. (2) The index of opportunity for natural selection for the sibships of probands was half as much as those of grandfathers, grandmothers, fathers and mothers. (3) Significant correlations of sibship size were observed between the sibships of grand-fathers and those of grandmothers, but the reason was unknown. (4) There was no significant correlation of sibship size between parents and progenies. Therefore, the heritability of sibship size or progeny number was considered to be rather small.

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For the purpose of confirmation of the effect of s-NAG upon the arterial wall, we have attempted to make a series of experimental studies. As a control we have used the arterial wall of WKY. The results of a preliminary study are as follows : (1) An increase in activity of s-NAG was remarkable in the young age group of SHRSP which blood pressure was rising. (2) Histochemically, the activities of NAG became stronger with an increase in age. The enzymatic activities were extensive in the adult group with hypertension and arteriosclerosis, although meager in the young age groups mentioned above. Conclusively, these results suggest that the enzymatic activities of tissue-NAG has correlation to the occurence of arteriosclerotic damage in the vascular walls.

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Nine cases of bilateral breast carcinoma were investigated. Of these, 2 cases were simultaneous bilateral breast carcinoma and 7 were non-simultaneous bilateral breast cancer. The histological types in primary carcinoma and secondary carcinoma were identical in all 9 cases. Therefore, it can be thought that these cases were metastatic bilateral breast carcinomas. Primary carcinoma occurrence age was seen frequently in the thirties with 4 cases. In clinical stages, stage I had 2 cases ; stage II had 2 cases ; stage III had 3 cases ; and stage IV had 2 cases. In stage I, process in the 2 cases took some time before developing into secondary carcinoma and it can be said that prognosis was satisfactory in these 2 cases when comparison was made with cases that developed into secondary carcinoma at an early stage. The occurrence frequency of secondary carcinoma in breast carcinoma patients is not altogether high. However, it is most vital that follow-up examinations for metastasis be made postoperatively for the opposite breast as well as for total metastasis.

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The autologous or syngeneic mixed lymphocyte reaction is established as in vitro proliferation of T cells cocultured with autologous or syngeneic non-T cells. The in vivo functions of these T cells, however, have not yet been clarified. Meanwhile, it is of interest that graft versus host (GVH) diseases are accompanied by clinical and histological findings resembling several skin diseases such as lichen planus. Thus, I supposed that the changes like lichen planus might be caused by local autologous GVH reaction mediated by proliferation of self-reactive T cells. Based on this working hypothesis, I established several self-Ia reactive murine T cell clones and attempted to induce syngeneic GVH disease by injection of these cloned T cells into hind footpads of naive syngeneic mice. As a notable finding, some of these clones that showed self-Ia specific helper and cytotoxic activities in vitro evoked lichenoid tissue reaction when injected into syngeneic mice. Further examination demonstrated that keratinocytes became to express Ia antigens on their surface concurrent with lichenoid tissue reaction. It is tempting to speculate that spontaneous development of local autologous GVH reaction is the cause of lichen planus.

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Fluoride exists ubiquitously in water or foods and is known to prevent dental caries. Sodium fluoride (NaF) has often been used, as a source of fluoride, for prevention of dental caries by various means, such as a water fluoridation agent, an additive of teeth paste or as solution for mouth-rinsing. The concentration of NaF in practical usages ranges from 1 ppm (0.024 mM) to 2% (20, 000 ppm, 476 mM). It has been considered that fluoride has little hazardous effects within the limit of current Concentration of usages. Recently, however, it has been reported that NaF has a clastogenic effect on cultured human cells after treatment for 12 to 24 hours at the concentration of 1 mM, far below the one of current usages. As chromosome aberrations are not only serious injuries for cells but also one of presumptive causes of cancer or genotoxicity, it is important to investigate precisely whether it has clastogenic effects for cells after a short period of exposure. Experiments were designed to investigate the dependency on cell cycle stages of clastogenic effect of NaF by treating peripheral blood lymphocytes for one or three hours for component phases of the cell cycle. Lymphocytes treated in G_1 or G_2 phase, one to four hours after culture initiation or three hours before fixation, respectively, did not show elevated frequencies of chromosome aberrations, but they were inhibited to progress their cell cycles. NaF, however, induced chromosome aberrations for cells after treatment for one or three hours in their S phases. Significantly high frequencies of chromosome aberrations were observed at the concentrations of 10 or 20 mM. The results of present investigations showed that NaF has clastogenic effects even by one-hr-treatment at the concentration of 10 mM, which is about 1/50 of current usages. Clastogenicity does not directly mean carcinogenicity or genotoxicity, but considering that chromosome aberrations are serious genetic hazards for cells, the usage of NaF should be reconsidered.

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The effects of group-sizes on learning process, acquisition and retention, were investigated in adult rats. Group-sizes employed in the present study were as follow : Group I (slam condition) ; group-size of 6 animals in a cage, group II ; pair housing and group III (loneliness) ; individual housing. Adaptation procedure was carried out for 1 month in the above mentioned group sizes. Then the animals were trained in a two way shuttle box to test the acquisition. One month after the establishment of avoidance response, the animals were again tested in the shuttle box to evaluate the retention. Group II and III animals showed, respectively, the best and worst acquisition. The differences were statistically significant. The same tendency was observed in retention experiments, though the difference did not reach a statistically significant level. These results strongly suggest the inportance of group size in the learning process ; i.e., either slam condition or loneliness has advers effects on learning process, especially on acquisition of the conditioned behavior.

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The course of diabetic retinopathy was studied with special references to the correlation between the perfusing condition of retinal capillary network and the new vessel formation from the optic disc, the effect of photocoagulation therapy on the capillary network and the effect of lens extraction on the retinal changes. Following results were obtained : 1. An extention of the non-perfused area of retina, i.e. 60 percent of 6 DD zone, was profoundly related to the new vessel formation from the optic disc. This indicates that the advancement of the obstruction in capillary network is an important factor to induce papillary neovascularization. 2. Reopening and/or new vessel formation of retinal capillary in the capillary non-perfusing zone were observed a few months after photocoagulation therapy in most cases. Amoung 7 eyes which were followed up further for 13 to 24 months after therapy, 6 eyes revealed enlargement of the reopened and/or newly formed capillary network. These eyes remained well perfused also. However, the capillary network of one eye became nonperfused 22 months after photocoagulation. These findings indicate that the photocoagulation therapy improves the circulation of the damaged retinal capillary network on a long-term basis. 3. The deteriolation of diabetic retinopathy was more prominent in the eyes received intraocular lens extraction as a cataract surgery than in the non-operated eyes. Therefore, the retinal changes should be carefully followed after cataract surgery in the patients with diabetic retinopathy.

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This study was intended to throw light upon the thoughts on ageing and the conditions of health care in the Middle Ages. To begin with, character of the aged men and women who served as narrators of shikyo (Four Historical Stories), four representative historical stories, and lineage of the mountaineering ascetics were investigated. Secondly, working through such medieval literatures as Makuranososhi (Essays on the Court Life written by a Lady in Waiting), Ochikubomonogatari (Japanese Version of Cinderella Story), and Konjakumonogatarishu (Fables based on Buddhism), inquiries were made into the magical rites of mountaineering asceticism, the works of the physicians stationed at Tenyakuryo, medical office in the Imperial Court, and the relations between the physicians and the common people. As a result, it came to light that the Japanese of those days had high respect for the aged. Present historical studies of the development of health care revealed, furthermore, how medical services exclusively performed in the medieval Imperial Court were spread among common people. These findings are considered to be of some value as reference materials for the development and spread of modern medicine.

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