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The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.

Ferric nitrilotriacetate (Fe3+-NTA) solution showed maximum absorbance at pH 7.5. The iron was in ferric high-spin state and coordinated octahedrally with a relatively symmetric structure and also probably pentagonally. A spin trapping technique employing 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) yielded a DMPO spin adduct of unknown radical with three doublets (DMPO-Z) and a simple nitroxide radical (Y-NO.) in serum from rats injected intraperitoneally with Fe3+-NTA. When the Fe3+-NTA solution was diluted 500-fold with 50 mM NTA solution, DMPO-Z, Y-NO. and an additional signal, DMPO-OH were observed. The DMPO-Z signal was suppressed by a decrease in oxygen tension, alpha-tocopherol and 3-tert-butyl-4-hydroxy-anisole (BHA). The DMPO-OH signal was suppressed in the presence of ethanol and catalase. Fe2+-NTA solution hardly produced DMPO spin adducts. The Fe3+-NTA solution produced a strong DMPO-OH signal in the presence of H2O2. Rose Bengal solution, a singlet oxygen generating system, produced the same DMPO adducts. Fe3+-NTA reacted with oxygen in solution. The oxygen was activated and might be similar to singlet molecular oxygen. In the presence of H2O2, the Fe3+-NTA solution generated a hydroxyl radical. Fe3+-NTA itself generated free radicals, but Fe2+-NTA did not.

Methamphetamine (MA) toxicity in aggregated mice was studied by varying the number of mice and the proportion of MA treated mice kept in the same confined space. The lethality was measured 24 h after intraperitoneal injections of MA at doses ranging from 10 to 100 mg/kg. MA lethality, over a wide dose range (15 to 50 mg/kg), was higher in aggregated mice than in those maintained in isolation. The greater the proportion of MA-treated mice in aggregation was, the higher the MA lethality was. In aggregations of 10 mice, MA was lethal at lower doses than in aggregations of 5 mice. These results indicate that the lethality of MA is influenced by confinement and aggregation.

A series of clinical and pathological studies were performed on 74 cartilaginous bone tumors including osteochondromas, multiple cartilaginous exostoses, chondromas, chondromatoses, benign chondroblastomas and chondrosarcomas. Resection was adequate for the osteochondromas, and no recurrence was observed. Out of 14 multiple cartilaginous exostoses, three, all in flat bones showed malignant change. The predominant sites of chondroma were the finger and toe bones, and curettage and bone graft was adequate treatment. Neither recurrence nor malignant change was observed. Two cases of chondromatosis, one of Ollier's disease and one of Maffucci's syndrome, were included in our series. Leg length discrepancy and pathologic fracture were common problems in chondromatosis. Moreover, malignant change was suspected in a hemangioma of the Maffucci's syndrome patient. Benign chondroblastoma was treated by curettage and bone graft, with no recurrence. In our series, 4 primary and 3 secondary chondrosarcomas were observed. Metastasis was seen in only one case. Because of the discrepancy between the biological behavior and histological findings of cartilaginous bone tumors, the malignancy of tumors should be evaluated by clinical signs and symptoms as well as by histological findings.

In an attempt to evaluate high density lipoprotein (HDL) subfraction levels in liver diseases, HDL was separated by a precipitation method with dextran sulfate-Mg2+ from sera of 289 healthy adults and 50 patients with liver diseases. The HDL was subdivided into HDL2e and HDL3e by Utermann's polyacrylamide gel electrophoresis with lauric acid. Ultracentrifugally separated HDL2 and HDL3 roughly corresponded to HDL2e and HDL3e, respectively. Male and female groups had different distributions of HDL2e/HDL3e ratios. Among healthy males, 121 cases had ratios less than 1.0 (mean +/- SD = 0.72 +/- 0.39, n = 150), while among healthy females, the ratios were generally larger than those of males and varied widely from 0.2 to 6.6 (mean +/- SD = 1.77 +/- 1.05, n = 139). Low levels of HDL-cholesterol were found in patients with liver diseases, except those with mild alcoholic liver injury and intrahepatic cholestasis. Apparent decreases in HDL3e, but not in HDL2e, were found in all cases with liver diseases investigated, even in those who did not show decreases in the total HDL level, when male and female patients were analyzed separately. The analysis of HDL subfractions by the present method is simple and useful for the study on altered lipid metabolism in liver diseases.

<p>Type V collagen-degrading enzyme activity was detected as a metalloprotease acting at neutral pH in the human liver. Type V collagen extracted from human placenta and labeled with [1-14C] acetic anhydride was used as the substrate in the assay. Four major degradation products with relatively high molecular weights were observed upon polyacrylamide gel electrophoresis of the incubation mixture of type V collagen and liver homogenate. The significance of the measurement of this enzyme activity was discussed in relation to the clarification of the mechanism of liver fibrosis.</p>

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.

The anticancer drug sensitivity of human cancers was tested by the human tumor clonogenic assay (HTCA). Of 152 human cancer specimens tested, 63 (41%) formed more than 30 tumor cell colonies in control plates and could be used to evaluate the drug sensitivity of tumor cells. In 42 (93%) of 45 clinical trials in 24 patients, a parallel correlation was observed between the in vitro anticancer drug sensitivity measured by the HTCA and the clinical response of tumors to anticancer drugs. These results suggest that the HTCA is a good technique for the in vitro test of the anticancer drug sensitivity of human cancers.

Tissue reactions at the cement-bone and artificial implant-bone interface were examined light and electron microscopically in thirty-six patients who underwent revisory operation of hip or knee replacement. The reactions were classified into three types: inert tissue, active tissue with giant cell proliferation, and active tissue with predominant foamy cell proliferation. The third type of reaction was found only in total hip replacement with bone cement. No evidence of allergic reaction to implanted materials was found in any replacement, though active cellular infiltrations were observed around loosened prostheses especially in cemented arthroplasty. The tissue reactions always occurred around instable or loosened prostheses. Thus, the present study shows that mechanical instability is the primary cause of such undesired tissue reactions.

The proliferation of lymphocytes induced by Propionibacterium acnes (P. acnes) was measured by the in vitro incorporation of 3H-thymidine. The mean response rate of alveolar lymphocytes obtained by bronchoalveolar lavage was 2.23 +/- 0.89 in nine untreated sarcoidosis patients, 0.85 +/- 0.17 in five sarcoidosis patients given corticosteroids and 0.78 +/- 0.29 in 11 controls. The proliferation was significantly enhanced in the untreated patients compared to both the treated patients (p less than 0.01) and controls (p less than 0.001), but there was no significant difference in response rates between the treated patients and controls. The response rate of alveolar lymphocytes was significantly higher in four active patients (3.05 +/- 0.61) than in four inactive patients (1.77 +/- 0.44) (p less than 0.05) and in the controls (p less than 0.001). In sarcoidosis patients, the response rates showed a good correlation with activities of serum lysozyme (r = 0.695, p less than 0.01), and with percentages of lymphocytes in bronchoalveolar lavage fluid (r = 0.591, p less than 0.05). There was a low correlation between angiotensin-converting enzyme activities and the response rates (r = 0.508, p less than 0.1). Neither peripheral blood lymphocytes in sarcoidosis patients nor in controls showed any response to P. acnes, but alveolar lymphocytes of the untreated active sarcoidosis patients were sensitive to P. acnes. The lymphocytes activated by P. acnes may play a central role in the induction of alveolitis in sarcoidosis patients.

An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.

Accumulation of cyclic AMP elicited by glutamate was examined in slices from different cortical areas of rats 30 to 60 days after ferrous chloride solution was injected into the left sensorimotor cortex to induce an epileptic focus. In the anterior cortex of rats showing dominant electrographic spike activity on either side of the cortex, the glutamate-elicited accumulation of cyclic AMP was greater on the dominant side than on the other. In the anterior cortex of rats showing nearly equal spike activity on either side, the accumulation was greater on the side ipsilateral to the injection site than on the other. Different inhibitory effects of 3-isobutyl-1-methylxanthine on the elicitation of cyclic AMP accumulation by glutamate was observed in relation to the patterns of spike activity.

Using gas chromatography-mass spectrometry, we developed a sensitive and reliable technique to measure phenylacetic acid (PAA), an oxidatively deaminated metabolite of beta-phenylethylamine (PEA), in small amounts of cerebrospinal fluid (CSF). In a preliminary analysis, PAA concentrations in depressive patients were significantly lower than those in controls, while there were no differences in PAA levels between schizophrenic patients and controls. This suggests a possible link between the decreased PEA metabolism in the brain and the etiology of depression. However, further studies are needed to clarify the effects of neuroleptics and antidepressants on PAA levels in CSF, since the samples were obtained without regard to medication in the present study. In control subjects, a U-shaped distribution was obtained when the values of PAA were plotted as a function of age. There were no sex differences and no significant concentration gradients in CSF PAA levels.

The serum ceruloplasmin concentration was determined in cancer patients before and after radiotherapy, and after relapse of cancer, The ceruloplasmin concentration in patients who responded to therapy, decreased to the range of normal controls. In patients who did not respond to treatment, the ceruloplasmin concentration was more or less elevated. In patients with relapse of cancer, the ceruloplasmin concentration was higher than before treatment.

An adriamycin (ADM)-resistant subline was established by continuous exposure of the SBC-3 cells, a cell line of human small cell lung cancer, to increasing concentrations of ADM, followed by the cloning procedure. The resistant sublines (SBC-3/ADM) thus established were 30-fold more resistant to ADM than the parent SBC-3 cells, in terms of the 70% lethal dose determined by soft agar clonogenic assay. The doubling times of the SBC-3 and SBC-3/ADM cells were 36 h and 22 h, respectively. When transplanted into athymic nude mice, the parent as well as resistant cells formed tumors, and serial passage was successful. Although the transplanted tumors from the two cell lines were very similar in histology, the resistance of the SBC-3/ADM cells to ADM developed in vitro was maintained in serially transplanted tumors. The uptake studies with [3H]daunomycin revealed decreased influx and enhanced active efflux of the drug in the resistant cells, whereas cytogenetic analysis showed that the cell lines had an identical karyotype. These results indicate that ADM resistance may be attributed to alternations in membrane transport, resulting in reduced intracellular accumulation of the drug.

The concentrations of taurine in the fetal and neonatal organs, and the maternal organs, plasma and urine of rats between the 15th day of gestation and the 21st day after birth were determined using an automatic amino acid analyzer. In the fetal liver and brain and in the placenta, the taurine concentration was the highest of all ninhydrin positive compounds. In the fetal liver and placenta, the concentrations of taurine increased significantly with the gestational days. Concentrations of taurine in the brain were much higher in the fetus and neonate than that in the adult. Moreover, the total amount of taurine per fetus increased markedly after the 15th day of gestation, and near term, reached almost the same amount as in the adult rat liver. In contrast to this, a significant decrease was observed in the taurine concentration in the maternal liver and muscle near term. The concentration of taurine in the urine of pregnant rats decreased near term, but in the plasma of pregnant rats the concentration of taurine did not change during pregnancy.

Type IV collagen-degrading enzyme activity was measured in liver homogenate obtained from 10 patients with hepatocellular carcinomas. Type IV collagen, the enzyme substrate, was extracted from human placenta with pepsin digestion, and labeled with [1-14C] acetic anhydride. The homogenate was preincubated with p-aminophenylmercuric acetate to activate the latent form of the enzyme, and then the enzyme activity was measured at pH 7.5 by adding a substrate mixture. Referring to previous reports, the enzyme measured seemed to be a neutral metalloprotease. The enzyme activity of the homogenate was markedly reduced by omitting the p-aminophenylmercuric acetate pretreatment, indicating that the enzyme was present mainly in the latent form. The activity seemed to be higher in the peripheral portion of hepatocellular carcinoma than in the center. Further the activity was found to be the highest in a hepatocellular carcinoma patient with many metastatic nodules in the lung. The results might suggest that type IV collagen-degrading enzyme participates in tumor invasion and intrahepatic or remote metastasis.

Using a cell line (SBC-3/ADM) of human small cell lung cancer, which is 30-fold more resistant to adriamycin than the parent cell line (SBC-3), the activity of a variety of anticancer agents was analyzed by soft agar clonogenic assay to search for a means of circumventing drug resistance. The SBC-3/ADM cells were markedly resistant to some anthracycline antibiotics in comparison with the SBC-3 cells: 28-fold for daunomycin, 26-fold for 4'-epiadriamycin, 18-fold for THP-adriamycin, and 8.4-fold for aclarubicin. However, the cells were as sensitive to mitoxantrone, one of the anthraquinone derivatives, as the parent cells. The cells were resistant to structurally or pharmacodynamically unrelated compounds such as vincristine, mitomycin C, and an active form of ifosfamide, whereas they were susceptible to cisplatin to some extent. The in vitro radiosensitivity of both cell lines was also evaluated, and they were found to be equally sensitive to X-ray. These results suggest that mitoxantrone and cisplatin may exert sufficient activity for small cell lung cancer which has acquired resistance to adriamycin, and that consolidative chest irradiation may be clinically useful after combination chemotherapy including adriamycin.