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The effect of pyridoxine treatment of a homocystinuric patient on the urinary excretion of some sulfur-containing amino acids was studied and the following results were obtained. As a result of pyridoxine treatment, urinary homocystine decreased to a fairly great extent, and its unusual metabolites S.(3-hydroxy-3-carboxyn- propylthio) homocysteine (HCPTHC) and S-C8-carboxyethylthio homocysteine (j3-CETHC) increased to some extent. But its oxidation product (homocysteic acid) showed a tendency to decrease slightly. Urinary methionine and cystine increased to some extent, but cysteinehomocysteine mixed disulfide showed no remarkable change.

The mode of lymph flow from the breast to the regional lymph node was studied using 1llSAu colloid, to ascertain the concept of lymph node of Groups 1, 2, and 3. Lymph flow through the internal mammary nodes was found to be abundant. Especially so when 1llSAu colloid was injected into the lower half of the breast, there was observed more abundant flow than that to axillary lymph nodes. Therefore, it was concluded that regardless of the site of occupation of a tumor, internal mammary nodes should be con· sidered to be of Group 1. Lymph flow through the subclavian nodes proved to be always less than that to the axillary nodes or internal mammary nodes. The rate of the lymph flow appearance on the scintigram was about 20%. Whether the subclavian nodes should be classified as Group 1 or 2 should be further studied. The rate of supraclavicular node visualization was below 3%. Therefore, the supraclavicular nodes should be considered to be Group 2. When these results are applied to the current rule of handling of breast cancer, discrepancy occurs in the Stage number and R-numer.

By dividing at random 14 normal persons into 7 pairs of two individuals each, lymphocytes were isolated from their peripheral blood and taking one of the pairs as stimulating cells or antigens and the others as responding cells, mixed lymphocyte culture (MLC) was carried out. As for the method of MLC we used our MLC method of unidirectional mixed culture with a small amount of lymphocytes in additition of 1% (v /v) PHA.M and cultured for three days, and a widely used conventional method in which 3H.thymidine uptake was the parameter of the blastformation rate and cultured for seven days. In comparing the results of these two groups of MLC the data in six experiments out of the seven coincided. Namely, with 5x 104 cells each of stimulating cell group and responding cell group, it is possible to achieve satisfactory MLC, the culture can be done only for three days without requiring any special technique and the results can be readily evaluated. Therefore, MLC by our simple method would yield satisfactory results in clinics.

In order to study the viral etiology of human brain tumors, attempts were made to isolate cytopathogenic agents from human brain tumors by the tissue culture of tumor tissues and by the mixed culture of tumor tissues with HeLa cells. Five glioblastomas, a mixed form of glioblastoma and fibrosarcoma, two astrocytomas, two ependymomas, two meningiomas, an oligodendroglioma, a spongioblastoma polare and a choroid plexus papilloma were studied. In the tissue culture, besides the cells which appeared to be the tumor parenchymal cells, varying amounts of fibroblastic cells appeared in all the tumors tested and they increased with the prolongation of the culture period. In any of the tumors tested, no cytopathogenic agents were detected by either the culture of tumor tissues or the mixed culture of tumor tissues with HeLa cells. From the virological point of view, the significance of these negative results was discussed.

To obtain a useful rat liver cell line for in vitro carcinogenesis, two rat diploid epithelial cell lines were established from a 7-day-old male rat by the repeated colonial clone method. More than 80% of cells from each cell line have maintained normal diploid karyotype for over 30 months in vitro. The diploid cells were identi. fied as normal diploid karyotype by conventional Giemsa and trypsin. Giemsa techniques. They showed little difference in morphology and growth rate between early and late passages. Without cloning, they tended to be heterogenous in cell morphology, became heteroploid in chromosome and showed increased growth potential with time. Highly heteroploid cells which were derived from one of the lines produced ascites and solid tumors when inoculated into syngeneic rats intraperitoneally. Histologically, the tumors were diagnosed as poorly differentiated hepatocarcinomas. One of these diploid epithelial cell lines in early passage contained some activity of tyrosine transaminase and liver type aldolase and .glycokinase. Therefore, it is suggested that these epithelial cell lines represent liver parenchymal cells.

The establishment of a hamster lymphoma cell line was attempted. Simple mincing and trypsinization of lymphoma tissue resulted in a high degree of cell degeneration. The ascitic tumor cells produced by intraperitoneal transplantation of lymphoma tissue gave a better result. These ascitic cells grew and were cultured successively in medium consisting of RPMI 1640 and 20% fetal calf serum. Cells were round and grew in suspension. Accelerated cell growth was observed one month after starting the culture. In the stained preparations, cells were lymphoblastic. Cells were transplantable into new-born hamsters and produced tumors, but not in young adult hamsters.

Theta activity in EEG was found to be augmented in the frontal midline area in 5 young women while they played classical piano pieces and during related mental tasks. This activity was considered to be a frontal midline theta rhythm with the maximal amplitude mostly in Fz and of the frequency ranging from 5 to 7.5 Hz. This theta activity was observed to increase depending on the degree of the subjects' concentration on piano playing or related tasks. In bilateral parietal derivations, increases in the power value of alpha activity were observed in some subjects while they were listening to music, suggesting that alpha activity was involved in appreciation of music.

A 70-year-old woman with Waldenstroem's macroglobulinemia developed bilateral pleural effusions due to Cryptococcus neoformans. She was found to be a carrier of HTLV-I. It is speculated that the opportunistic infection occurred as the result of an impaired cellular immunity secondary to HTLV-I infection.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.

Thirteen patients with rectal carcinoma seen between December 1980 and December 1990 have been reviewed to determine the risk of lymph node metastasis and its implication for subsequent treatment. The mean age was 64 years (from 38 to 79; 9 males, 4 females). The site of the tumor was predominantly in the lower rectum (53.8 percent). The polypoid (I) and flat-elevated ulcerated (IIa + IIc) subtypes were detected in seven and six lesions, respectively. Sphincter-saving techniques were carried out in eight cases, and five cases required Miles' operation. Neither postoperative complications nor deaths were noted. The mean follow-up period was 57 months (6 to 133 months). No recurrence or distant metastasis was found during this follow-up. IIa + IIc subtype lesions with deep submucosal invasion at or beyond Smlc level were closely related with lymphatic and vascular invasion. Although this association was not necessarily accompanied by an increased number of involved lymph nodes, major surgical resection is suggested in such IIa + IIc cases due to an increased possibility for lymph node metastasis.

The taurine concentration and uptake in platelets obtained from normal pregnant women and gestosis patients with edema, proteinuria and hypertension (EPH gestosis) were investigated. The taurine concentration in platelets showed a marked increase in severe EPH gestosis compared with normal pregnancy or mild and moderate EPH gestosis, while the plasma taurine concentration did not change significantly. Taurine uptake in platelets paralleled the severity of EPH gestosis. The Vmax of the uptake in severe EPH gestosis was about 2.4 times higher than that in normal pregnancy or mild and moderate EPH gestosis, but no significant difference was seen in the Km value among these groups.

<P>Glycocalyx is suggested to play an important role in the pathogenesis of biomaterial-centered infection. Using an accurate and sensitive method to quantify glycocalyx and bacterial adherence, we have demonstrated that the producer of the most glycocalyx also exhibited the highest adherence index, whereas low producers exhibited the least (p less than 0.01). Additionally, at various concentrations the high producer had the greater tendency to adhere and grow on stainless steel wires and tubes (p less than 0.001). The adherence index, referred as the ratio of tritiated thymidine uptake on wires to colony forming units (CFU), was also the highest in high producers. The adherence index increased as the glycocalyx index increased. It was suggested that glycocalyx production enhanced the adherence of Staphylococcus epidermidis to biomaterials and caused persistent and intractable infections. In short, the glycocalyx index and the adherence index can be reliable indices of biomaterial-centered infection.

A rare case of primary retroperitoneal mucinous cystadenocarcinoma in a 44-year-old woman is reported. The cystic tumor was delineated by CT and echography. The tumor was removed intact in the presence of bilateral normal ovaries and demonstrated an infiltrating malignant process. This neoplasm may have arisen from a supernumerary ovary. The patient died of recurrence 4 months after surgery. A comparison of the known cases indicates that aggressive treatment by hysterectomy with bilateral salpingo-oophorectomy in addition to cyst extirpation may improve prognosis.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.

Reported clinical and experimental observations indicate that heart grafts in combined heart-lung transplantation are less frequently rejected than heart grafts transplanted alone. In order to elucidate the mechanism of this difference, twenty-eight inbred male Lewis rats receiving heterotopic allografts from inbred male Fisher rats were evaluated for surface markers of graft infiltrating lymphocytes (GIL) and peripheral blood lymphocytes (PBL) using flowcytometry. Monoclonal antibodies investigated in this study were W3/25 (anti-helper T lymphocyte), OX8 (anti-suppressor/cytotoxic T lymphocyte), OX39 (anti-interleukin 2 receptor), and OX6 (anti-MHC class II antigen). In the acute study, a heart transplanted group (n = 7) and a heart-lung transplanted group (n = 7) without immunosuppression were studied. In the chronic study, cyclosporine (10 mg/kg/day i.m.) were administered in the heart transplanted group (n = 7) and the heart-lung transplanted group (n = 7). Both in the acute and chronic studies, the proportion of W3/25 positive cells in GIL of heart grafts of the heart transplanted group was significantly higher than that of heart grafts and lung grafts of the heart-lung transplanted group. OX8 positive cell proportion in GIL of heart grafts and lung grafts of the heart-lung transplanted group were significantly higher than that of heart grafts of the heart transplanted group. These results lead us to speculate that suppressor T lymphocytes are an important distinguishing factor in the rejection processes of heart allografts and heart-lung allografts as observed in clinical experience.

Clinical features were studied in 125 patients with sarcoidosis (72 females and 53 males) diagnosed at Okayama University Hospital during a recent 10-year period. The age distribution had two peaks in patients in their 20s and the 50s. Over half of the patients were detected at health screening check and were asymptomatic, while the remaining were symptomatic. Twelve patients were in stage 0, 41 were in stage I, 54 were in stage II, 16 were in stage III, and 2 were in stage IV according to the chest x-ray findings. Serum angiotensin converting enzyme levels and serum lysozyme levels were elevated in 60% and 76% of the patients, respectively. The bronchoalveolar lavage fluid showed lymphocytosis, especially of helper T-cells. The clinical features of sarcoidosis appear to depend on the duration of the disease.

Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno-venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics.

The effects of cepharanthin (Ce), glycyrrhizin (G), verapamil (V), and G plus V on induced thermotolerance in NIH3T3 cells were studied. Cells were heated with or without the drug at 45 degrees C for 20 min (the first heating), incubated at 37 degrees C for 12h (the incubation period), and heated again at 45 degrees C for 0-210 min (the second heating). G and V were added throughout the experiment, while Ce was added throughout the experiment or during only the first or second heating, or the incubation period. The cells were harvested after the second heating to evaluate cell survival. In control experiments without any drug, thermotolerance developed and reached the highest peak in the cells incubated for 12h at 37 degrees C. However, thermotolerance in the control cells was suppressed by incubating them at 0 degree C, but developed by subsequent incubation at 37 degrees C. This suggests that the acquisition of thermotolerance by the cells required metabolic processes during the incubation at 37 degrees C. When each drug was present throughout the experiment, only Ce or the combined use of G and V was effective in reducing thermotolerance. Thermotolerance was also suppressed in the presence of Ce during the second heating. These results indicate that Ce reduces thermotolerance by enhancing thermosensitivity rather than by inhibiting the development of thermotolerance.