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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.

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 concentration and uptake of taurine in the umbilical and adult blood platelets were studied. Taurine was the most abundant free amino acid in both umbilical and adult blood platelets. The taurine concentration in umbilical blood platelets (2.30 pmoles/10(4) cells) was significantly lower than that of adult blood platelets (3.27 pmoles/10(4) cells) in contrast to the reverse relationship in taurine concentrations in umbilical and adult blood plasma. No other amino acid showed such significant difference in the concentrations between umbilical and adult blood platelets. Taurine uptake into umbilical blood platelets was temperature sensitive and sodium-dependent in a manner similar to that of adult blood platelets. The uptake conformed well to Hanes-plot. The Vmax of the uptake into adult blood platelets was about 3.6 times higher than that of umbilical blood platelets, but no significant difference was seen in the Km value between the two groups.

To evaluate urinary albumin index (UAI), the relationship between albumin excretion rate (AER) in the urine stored for 24 h and UAI in the urine collected arbitrarily on the morning of the same day was studied in 123 inpatients. The patients were admitted to our hospital from September 1, 1988 to August 31, 1989, consisting of 67 non-insulin dependent diabetics (Group 1), 40 patients with collagen disease (Group 2), and 16 patients with primary renal disease (Group 3). The relationship between log(e) AER and log(e)UAI was plotted on a graph. Pearson's rank correlation coefficients of Groups 1-3, Group 1, Group 2, and Group 3 were as follows: r = 0.725, r = 0.691, r = 0.855, and r = 0.611, respectively. The formula obtained by using Pearson's rank correlation coefficients to estimate log(e)AER from log(e)UAI in 123 cases of Groups 1-3, 67 cases of Group 1, 40 cases of Group 2, and 16 cases of Group 3 were: log(e)AER/log(e)UAI = 0.815, log(e)AER/log(e)UAI = 0.860, log(e)AER/log(e)UAI = 0.830, log(e)AER/log(e) = 0.722, respectively. In the present study, log(e)UAI was found to correlate well with log(e)AER. As AER is generally accepted to be the most reliable index to know the stage of albuminuria, UAI is considered to be clinically useful.

An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer cell line, SBC-3, was developed by continuous exposure to increasing concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross-resistant to teniposide, adriamycin, vinca alkaloids, 4-hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross-resistant to cisplatin, while the subline showed a collateral sensitivity to bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of one half and topoisomerase II activity to an extent of one eighth in comparison with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC-3/ETP was significantly lower in comparison to the SBC-3. An overexpression of MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of the protein, MRK16. These results indicate that a decreased activity of topoisomerase II is the major factor for the development of etoposide resistance, and that an overexpression of the MDR1 gene is responsible, in part, for the development of resistance to the drug and some structurally unrelated compounds such as adriamycin and vinca alkaloids.

A new dynamic CT method for evaluating the portal blood flow is described. Thirty healthy volunteers were injected with non-ionic hypo-osmotic iodine contrast medium to estimate the portal blood flow. Time density curves (TD-curves) for the abdominal aorta and the main trunk of the portal vein were determined on the basis of data obtained by dynamic CT. From the TD-curves, portal blood flow coefficient and circulation time to flow into the portal vein (P-P time) were calculated. More detailed data of the TD-curves could be obtained by the new dynamic CT than by the previous methods. Subjects were simultaneously studied by an ultrasonic pulsed Doppler method which has been clinically accepted. There was a significant correlation between our dynamic CT method (portal blood flow coefficient) and the ultrasonic pulsed Doppler method concerning the measurement of portal blood flow. Therefore, it may be concluded that this CT method is reliable and clinically acceptable.

Left atrial plication (LAP) following Kawazoe's method was performed on eight patients with mitral valve stenosis associated with a giant left atrium. To investigate the effect of LAP particularly on left ventricular function, the preoperative and postoperative left ventricular function in these patients were compared. The data were also compared to that of the non-left atrial plication (non-LAP) group with left atrial dimension of 60 mm or over. In the LAP group, there were significant differences between preoperative and postoperative data in the following parameters; New York Heart Association (NYHA) class, cardiothoracic ratio, mean pulmonary arterial pressure (PAP), left ventricular end-diastolic pressure (LVEDP), left atrial dimension, stroke volume index, ejection fraction and cardiac index. On the contrary, in the non-LAP group, there were significant differences between preoperative and post-operative data in the following two factors; NYHA class and PAP. The size of the left atrium in the non-LAP group remained unchanged over the course of long-term follow-up. Despite severe clinical symptoms and severely reduced cardiac function of the patients in the LAP group, cardiac function in all patients improved satisfactorily. This suggests that left atrial plication has a considerably beneficial effect on left ventricular function, and therefore, may be recommended for patients with a giant left atrium.

The influences of ventricular pacing at a rate of 70 beats/min (bpm) on the systemic and coronary hemodynamics, myocardial metabolism, and cardiac work efficiency were evaluated in five patients with bradycardia. The results were compared to those obtained in six normal subjects at rest. In order to elucidate the effects of a relatively high rate of ventricular pacing, cardiovascular and metabolic variables were also obtained at 120 bpm in the normal subjects. It was observed that the patients eventually benefited from ventricular pacing at a rate of 70 bpm and improved in systemic hemodynamics. Although coronary hemodynamics and myocardial metabolism were accelerated, the cardiac work efficiency was not improved. A pacing rate of 120 bpm in the normal subjects did not appear to accelerate systemic hemodynamics, but adverse accelerations of coronary hemodynamics and myocardial metabolism were observed, and the cardiac work efficiency was remarkably reduced as a result. Our observations indicated that the coronary reserve capacity was very important for ventricular pacing, and suggested that an undue increment of the pacing rate not only might be meaningless but also might induce ischemic angina. Therefore, we should be cautious in using a rate-responsive pacing mode, particularly in determination of the upper limit of pacing rates, although many benefits with this pacing mode have recently been advocated.

To investigate the role of Kupffer cells in complement activation, we used a rat model of acute hepatic injury induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). In in vivo study, minimal histological changes were observed after i.p. GalN (200 mg/kg) single administration. Complement hemolytic activity (CH 50) decreased to 70% of its initial value 2-3 h after i.p. LPS (1.5 mg/kg) single administration. Massive hepatic necrosis was induced by simultaneous administration of GalN and LPS. After 2-3 h, CH 50 decreased to 70% of its initial value, and deposition of C3 fluorescence (C3) was observed in Kupffer cells. After 4 h, GPT was greatly increased (1286 +/- 240 IU/l), CH 50 was further reduced, and C3 was observed on hepatocyte membranes and in the cytosol. In in vitro study, we used hepatocyte cultures and co-cultures of hepatocytes and Kupffer cells to investigate the participation of GalN, LPS, complement, and Kupffer cells in hepatic cell necrosis. We found no increase of LDH (% leakage) when LPS and complement were added to the medium (22.7 +/- 5.7%). A moderate increase was observed with the addition of GalN (33.2 +/- 2.6%). A remarkable increase was observed only with the addition of GalN, LPS, and complement to the co-culture (50.0 +/- 8.8%). These results suggest that Kupffer cells activated by LPS are very important in promoting acute hepatic injury by complement.

The percentages and absolute numbers of gamma delta T cells per CD3 positive cells (T cells) in four different compartments, namely peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis (RA) and in peripheral blood from healthy controls were studied by two color flow-cytometric analysis. The percentages (mean +/- SEM = 6.3 +/- 0.8%, n = 22) and absolute numbers (70 +/- 11/microliters, n = 22) of gamma delta T cells in peripheral blood from RA patients were not different from those of 22 age-matched healthy controls (7.5 +/- 0.9%, 81 +/- 17/microliters, respectively). The gamma delta T cells in peripheral blood from 50 RA patients were, however, significantly decreased in negative correlation with the value of CRP as a marker for inflammation, although they had no correlation with the titer of rheumatoid factor as an autoantibody. The percentages of gamma delta T cells in synovial fluid from 10 patients (3.3 +/- 0.5%, n = 10) or in synovial membrane from 5 patients (4.2 +/- 1.9%, n = 5) and in bronchoalveolar lavage fluid from 6 patients (3.6 +/- 0.8%, n = 6) were not different from those in peripheral blood from the same patients. Thus, gamma delta T cells are not the dominant infiltrating T cell subset in the inflammatory sites of RA patients.

A case of biliary cystadenocarcinoma that occurred in a 45-year-old woman is reported. Ultrasonography and computed tomography clearly revealed papillary projections in the cyst of the liver. Percutaneous transhepatic cystography showed connection between the cyst and the common bile duct. The tumor was surgically resected and proved to be a mucinous papillary adenocarcinoma arising from a biliary cystadenoma. The patient is doing well 4 years after surgery. Interestingly, this is the first reported case of a biliary cystadenocarcinoma in the liver with markedly diminished excretion of indocyanine green.

The present study was undertaken to determine whether a biventricular bypass system operated in an independent variable rate (VR) mode can maintain the entire circulation. Two pusher-plate pumps which incorporated the Hall effect position sensors were used to bypass the right and left ventricles in 10 sheep under fibrillation. The flow distributions of the pump output to the carotid and renal arteries were investigated every 6 h using ultrasonic blood flow meters for 24 h in 5 animals, and the controllability of the VR mode was evaluated in 5 long-term experiments. The carotid artery flow ratio to the pump output decreased significantly from 4.7 +/- 0.8% before the bypass to 2.7 +/- 0.9% after 24 h. However, the renal artery flow ratio did not change throughout the experiments. In the long-term experiments, the animals were kept alive from 3 to 48 days (mean 15.6 days). The mean pump output had been maintained at more than 90 ml/min/kg for the first 7 days. After the surgery, the pump driving conditions were not readjusted in any experiment. The results indicate that the biventricular bypass system operated in the independent VR mode automatically maintains the entire circulation at a satisfactory level.

To test the hypothesis that the endothelium-derived relaxing factor (EDRF) contributes to coronary vasodilation induced by myocardial ischemia, we examined the effect of NG-nitro-L-arginine (a potent and selective inhibitor of EDRF release) on the coronary reactive hyperemic response in the open-chest dogs. Intracoronary infusion of NG-nitro-L-arginine at a coronary plasma concentration of 5 x 10(-5) M had no effect on hemodynamics and myocardial oxygen metabolism, but attenuated repayment of the flow debt by an average of 20.4% and 20.0% following coronary occlusion for 10 sec and 20 sec, respectively. Concomitant infusion of NG-nitro-L-arginine at the same concentration and 8-phenyltheophylline (a potent adenosine receptor blocker) at a coronary plasma concentration of 10(-5) M further attenuated flow debt repayment following 10 sec and 20 sec of coronary occlusion by 47.7 and 59.4%, respectively. These results indicate that EDRF plays a significant role in the coronary reactive hyperemic response and may cause vasodilation independently of adenosine-mediated vasodilation following coronary occlusion.

Bronchial asthma was classified by the pathophysiology and by the mechanism of onset of the disease. Forty asthmatics who had serum IgE levels lower than 200 IU/ml were evaluated by two classification methods. 1. In asthma classified by a score based on clinical findings and examinations, the characteristics of the findings and examination results were compared among three asthma types, i.e., Ia. simple broncho-constriction type, Ib. bronchoconstriction+hypersecretion type, and II. bronchiolar obstruction type. Type Ib patients, in addition to manifesting hypersecretion, had a significantly higher proportion of eosinophils in the bronchoalveolar lavage (BAL) fluid compared to other asthma types. Significantly decreased values for ventilatory parameters and an increased proportion of BAL neutrophils were found in type II compared with other asthma types. 2. In a new classification by mechanism of onset, asthma was classified into three types according to the degree of participation of IgE-mediated reactions associated with specific IgE antibodies and serum levels of total IgE: asthma induced by definite IgE-mediated reaction (atopic asthma), possible IgE-mediated reactions (asthma), and asthma induced by non-IgE-mediated reaction (asthma syndrome).

Cytotoxic anti-thyroid microsomal autoantibodies are highly prevalent in sera of patients with Graves' disease, but in Graves' disease thyroid tissues rarely show destructive changes. We postulated that this might be due to membrane-associated complement regulatory proteins which protect target cells from injury by complement activation. We, therefore, investigated the expression of membrane attack complex inhibitory factor (MACIF) and decay accelerating factor (DAF) in the thyroid tissues from patients with Graves' disease, Hashimoto's thyroiditis, thyroid adenocarcinoma and normal human thyroid tissues. We found a high level of expression of MACIF and DAF in Graves' thyroid tissues. Using the membrane immunofluorescence and cell-ELISA techniques, we also investigated the factors which enhanced the MACIF and DAF expression in cultured thyroid cells. Thyroid stimulating hormone, phorbol 12, 13-dibutyrate and thyroid stimulating autoantibody enhanced the MACIF and DAF expression. These findings suggest that the membrane complement regulatory proteins increase in response to the thyroid stimulating factors such as thyroid stimulating autoantibody in Graves' disease and that this increase then protects the cells from damage due to complement activation by thyroid autoantibodies.