[Clinical studies on nephrotic syndrome after renal transplantation].
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Biomedical subjects
Publications and source records attributed to T Oikawa.
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We investigated the effect of quercetin on 3-methylcholanthrene (MCA) carcinogenesis in C57Bl/6 mice. We found that quercetin itself was not carcinogenic when administered i.m., even at a dose of 20 mg, throughout an observation period of 420 days. An i.m. administration of various doses of quercetin admixed with 1.0 mg of MCA, however, significantly shortened the mean latency periods for the development of local primary tumors compared with those of the group which had been given MCA alone. The shortening of latency periods was also found in the experiments using 0.1 mg of MCA after the administration of quercetin either admixed with MCA or fed with a diet containing it. Moreover, lung metastasis increased in mice given the mixture of MCA (0.1 mg) and quercetin compared with its occurrence in mice given MCA alone. A simultaneous administration of MCA and quercetin significantly increased the in vivo sister chromatid exchanges (SCE) formation of bone marrow cells when compared with its occurrence in the group given MCA alone. These results suggest that quercetin has an enhancing effect on MCA carcinogenesis and that this enhancement may be associated with such a genetic effect as an increased mutation rate in the host.
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Fundamental and clinical studies were carried out on sulbactam/cefoperazone (SBT/CPZ) in the field of pediatrics. The following results were obtained: A total of 185 clinical isolates that had been stocked at our department was employed to determine the minimum inhibitory concentrations (MICs) of SBT/CPZ against various bacterial species. SBT/CPZ showed strong antibacterial potency against E. coli, Salmonella, Klebsiella and P. mirabilis, and relatively strong potency against S. marcescens, P. aeruginosa and S. aureus. Antibacterial potency of SBT/CPZ was stronger than that of CPZ alone against E. coli, and it also showed strong activity against strains of Salmonella, S. marcescens and S. aureus, moderately or highly resistant to CPZ. SBT/CPZ was administered by intravenous bolus infusion to pediatric patients to determine the serum concentrations of SBT and CPZ. At a dose of 10 mg/kg the mean serum levels of SBT and CPZ were as follows; 17.8 micrograms/ml, 40.7 micrograms/ml at 15 minutes and 0.3 microgram/ml at 6 hours, respectively. The half-lives of SBT and CPZ in the serum were 1.05 hours and 1.76 hours, respectively. Similarly, at a dose of 20 mg/kg the mean serum levels of SBT and CPZ were; 31.9 micrograms/ml, 81.0 micrograms/ml at 15 minutes and 0.5 microgram/ml, 6.1 micrograms/ml at 6 hours, and the half-lives were 1.00 hour and 1.72 hours, respectively. At a dose of 40 mg/kg, only 1 case was determined. The serum levels of SBT and CPZ were 34.4 micrograms/ml, 74.8 micrograms/ml at 30 minutes and 0.2 microgram/ml at 6 hours, and the half-lives were 0.78 hour and 1.38 hours, respectively. SBT/CPZ was drip-infused intravenously over a period of 1 hour, and the serum concentrations of SBT and CPZ were determined. At the dose of 10 mg/kg or 20 mg/kg, the peak serum levels of SBT and CPZ were observed at 1 hour or at the end of drip infusion. At a dose of 10 mg/kg the mean serum levels of SBT and CPZ were 14.4 micrograms/ml, 33.7 micrograms/ml at 1 hour and 1.4 micrograms/ml, 4.6 micrograms/ml at 7 hours, respectively. The half-lives was 1.86 hours for SBT and 2.23 hours for CPZ, respectively. Similarly at a dose of 20 mg/kg, the mean serum levels of SBT and CPZ were, 22.2 micrograms/ml, 34.6 micrograms/ml at 1 hour and 0.5 microgram/ml, 2.8 micrograms/ml at 7 hours, and the half-lives was 1.17 hours and 1.75 hours, respectively. The urinary recovery rate was determined for the 6 hours period after administration.(ABSTRACT TRUNCATED AT 400 WORDS)
Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed in the field of pediatrics and the following results were obtained. The antibacterial activity of CTRX was determined against clinically isolated strains at our department. CTRX was definitely superior to CEZ and CMZ and almost equal or slightly superior to CTX in activity against Gram-negative bacteria, while the MIC of CTRX against Gram-positive bacteria was higher than that of CEZ and CMZ and about equal to that of CTX. The blood concentration of CTRX after one shot intravenous injection with 10 mg/kg was 67.98 micrograms/ml at 15 minutes, 51.96 micrograms/ml at 30 minutes, 37.51 micrograms/ml at 1 hour, 28.91 micrograms/ml at 2 hours, 20.71 micrograms/ml at 4 hours, 13.97 micrograms/ml at 6 hours and 6.45 micrograms/ml at 12 hours, while the half-life time was 3.74 hours. The blood concentration of CTRX after one shot intravenous injection with 20 mg/kg was 179.55 micrograms/ml at 15 minutes, 120.01 micrograms/ml at 30 minutes, 100.01 micrograms/ml at 1 hour, 53.75 micrograms/ml at 2 hours, 33.13 micrograms/ml at 4 hours, 26.41 micrograms/ml at 6 hours and 21.49 micrograms/ml at 12 hours, while the half-life time was 4.15 hours. The blood concentration of CTRX after intravenous drip infusion for 1 hour with 10 mg/kg was 19.54 micrograms/ml at 15 minutes, 27.19 micrograms/ml at 30 minutes, 36.57 micrograms/ml at 1 hour, 23.83 micrograms/ml at 2 hours, 19.69 micrograms/ml at 3 hours, 14.46 micrograms/ml at 5 hours, 11.02 micrograms/ml at 7 hours and 7.27 micrograms/ml at 13 hours, while the half-life time was 6.59 hours. The blood concentration of CTRX after intravenous drip infusion for 1 hour with 20 mg/kg was 61.72 micrograms/ml at 30 minutes, 108.1 micrograms/ml at 1 hour, 54.95 micrograms/ml at 2 hours, 35.68 micrograms/ml at 3 hours, 28.13 micrograms/ml at 5 hours, 20.51 micrograms/ml at 7 hours and 11.43 micrograms/ml at 13 hours, while the half-life time was 4.23 hours. There was noticed a tendency of the blood level being elevated by consecutive administration. The urinary recovery rate of CTRX ranged from 36.5 to 71.6%. The excretion rate of CTRX into the cerebrospinal fluid ranged from 5.2 to 11.6%. The excretion rate of CTRX into the pleural fluid was 31.0%. The clinical efficacy rate was 87.5% (excellent or good) in 8 children with infections treated with CTRX. The eradication of bacteria was observed in all of 5 cases bacteriologically evaluation.(ABSTRACT TRUNCATED AT 400 WORDS)
Somatic cell hybrids were prepared by fusion of a Rous sarcoma virus (RSV)-induced mouse tumor (CSA1M cl-11) with a Chinese hamster embryo lung fibroblast line (Wg3h X AGr X Ouar). Some hybrid clones showed rapid anchorage-independent growth and intracellular production of RSV-pp60src. Other hybrid clones showed slow anchorage-dependent growth and no production of such a protein. The former expressed both a common tumor-specific cell surface antigen(s) (TSSA) shared with other RSV-induced tumors and a private TSSA not shared with any other tumors; however, the latter lost the common TSSA and expressed only the private TSSA. These results suggest that the common and private TSSA on CSA1M cl-11 cells are independent genetic traits and only the common TSSA is coordinated with other expressions of the RSV src gene phenotype.
Basic and clinical studies were made on ceftazidime (CAZ) in pediatric field, and the following results were obtained. The antibacterial activity of CAZ against clinically isolated and maintained strains was examined. CAZ was unequivocally more active than CEZ and CMZ against Gram-negative rods, with MIC distribution similar to that of CTX, except for that for P. aeruginosa. The MIC of CAZ was lower than that of CTX for P. aeruginosa. Compared with the MICs of CEZ, CMZ and CTX, CAZ showed slightly higher MICs for Gram-positive bacteria. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ were 64.9, 36.9, 28.3, 14.7, 4.92 and 2.42 micrograms/ml, respectively, with the half-life of 1.27 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 10 mg/kg of CAZ were 16.6, 24.5, 41.4, 17.1, 5.38 and 2.62 micrograms/ml, respectively, with the half-life of 1.28 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 20 mg/kg of CAZ were 73.1, 60.8, 39.3, 17.3, 8.23 and 4.45 micrograms/ml, respectively, with the half-life of 1.42 hours. The blood concentrations of CAZ, at 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 20 mg/kg of CAZ were 55.1, 69.0, 32.1, 11.4 and 4.56 micrograms/ml, respectively, with the half-life of 1.27 hours. Urinary recovery rate of CAZ during the first 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ was 86.7%. CAZ was administered to 17 children with infections, and the clinical response was excellent or good in 94%. CAZ was bacteriologically effective in 14 patients, all bacteria having been eradicated in them. The bacteria were E. coli in 10 patients, H. influenzae in 2, P. aeruginosa in 1 and S. pneumoniae in 1. As for side effects, slight elevation in GOT was observed in 1 case and eosinophilia, in another case.
Simultaneous 24 hrs' polygraphic recording of the electrical potentials and the contractions of the stomach and duodenum was done in the unanesthetized state of mongrel dogs with chronically implanted electrodes and their interrelationship between these two organs was studied. The results obtained were as follows: In contrast to the diurnal rhythm of gastric activity after feeding, the frequency of the duodenal basic electric rhythm (BER) once increased immediately after feeding and thereafter gradually decreased during the fed state. A negative correlation was found with statistical significance between the frequencies of the gastric and duodenal BERs during the fed state. Tachygastria exhibiting the high frequency BER appeared in the antrum at the silent period of the fasting state, while any similar phenomena were not observed in the duodenum. In the fasting state, the interdigestive migrating contraction (IMC) occurred periodically and synchronously with each other of the two organs. Regarding each contraction, the duodenal contraction was inhibited at a strong contraction of the stomach. These results suggest that the BERs of the stomach and duodenum are not directly propagated to each other and that some reciprocal interaction between the two organs may come out in the fed state probably by reflexes via intramural nerve plexuses.
The karyotypes of 3 pristane (2,6,10,14-tetramethyl-pentadecane)-induced NZB mouse plasmacytomas producing IgA (plasmacytoma TEPC-3660), IgG3K (plasmacytoma TEPC-6583), and IgG2aK plus IgG3K (plasmacytoma TEPC-6906) were studied in early transplantation generations by the combined Hoechst 33258-quinacrine mustard banding method. The two IgG producers (TEPC-6583 and TEPC-6906) showed diploid chromosome number, whereas the IgA producer (TEPC-3660) showed hypotetraploid chromosome number. Banding analysis revealed that these 3 plasmacytomas consistently had the t(12;15) translocation with the specific breakpoints at 12F2 and 15D2. Taken together with the previous observation of t(12;15) in plasmacytomas of BALB/c and C3H mice, these results suggest that the t(12;15) is specific for murine plasmacytomas and that the putative gene(s) on the t(12;15) may participate in the genesis of murine plasmacytomas.
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A highly immunogenic variant of the murine L1210 leukemia cell (L1210/LN-1) for generation of tumor immunity has been obtained from culture of L1210 cells originally fused with human Lesch-Nyhan fibroblasts. In L1210/LN-1 cells, no human chromosomes were identified and chromosomes M1 and No. 1 carried by the parent L1210 cells were missing. L1210/LN-1 cells displayed an intermediate morphology between L1210 cells and Lesch-Nyhan fibroblasts. Most of the CDF1 mice that were inoculated with less than 2 X 10(6) L1210/LN-1 cells survived over 60 days without evidence of tumor, whereas the original L1210 cells killed all the mice tested in about 2 weeks. When inoculated with more than 5 X 10(6) L1210/LN-1 cells, CDF1 mice developed tumor. The CDF1 mice which rejected 2 X 10(6) L1210/LN-1 cells were protected very effectively against challenge of otherwise highly aggressive 1-5 X 10(5) L1210 leukemia cells; 40 out of 43 primed mice tested survived for 60 days or longer after the tumor challenge. Even the CDF1 mice primed with irradiated or mitomycin-treated L1210/LN-1 cells survived against a challenge of 10(5) L1210 leukemia cells. They were, however, not protected against P388 leukemia or Meth A sarcoma, indicating that the immunity was specific to L1210 leukemia. The immunity induced by L1210/LN-1 cells was transplantable by immune spleen cells into syngeneic recipients. Thus, the L1210/LN-1 cells we obtained seem to be very useful as an immunogen for generation of high-grade tumor-specific immunity against highly malignant L1210 leukemia.
Changes in the surface carbohydrate moieties of zonae pellucidae and naked vitelli isolated from unfertilized and fertilized hamster eggs were examined through potato agglutinin (STA)-mediated agglutination and binding of FITC-STA as a marker. The results indicated that the stereochemical properties of the saccharide residues within STA-binding sites on the outer surface of the zona pellucida, inner region of the zona pellucida, and the surface of the ooplasmic membrane were different in unfertilized and fertilized eggs, that part of the differences between the two kinds of eggs could be visualized with FITC-STA and that, on the basis of these data, if we use STA as a probe to analyze the surface change following fertilization, we may be able to analyze these changes to a substantial degree.
Infants with transient neonatal hypothyroidism, in whom TSH binding inhibitor immunoglobulin G (IgG) (TBII) were sequentially measured, are described. Their mother had been taking thyroid replacement for hypothyroidism due to nongoitrous autoimmune thyroiditis. IgGs inhibiting TSH binding were detected in maternal sera by radioreceptor assay. These IgGs also inhibited the adenylate cyclase response to TSH in human thyroid membranes. Three infants had frank hypothyroidism immediately after birth, and TBII were detected in two of them. In the two surviving infants, hypothyroidism was transient and improved when TBII disappeared from their sera. The profile of TBII in one patient corresponded to the IgG disappearance curve. These findings suggest that the transient neonatal hypothyroidism reported was caused by transplacental transfer of TBII.
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We compared the efficacy of intravenously, intramuscularly administered or intravenously infused over 45 minutes gentamicin (GM) by the experimental system in rabbits using diffusion chambers. Serum concentrations of GM obtained with 3 administration methods were different, while the peak values after intramuscular injection and intravenous drip infusion were similar. Similar concentration time curves of GM in the chambers were revealed after intramuscular injection and intravenous infusion. No marked difference in 3 administration methods was showed in the effects on the growth of P. aeruginosa in the chamber. Viable bacterial number in the chambers decreased when the GM concentration in the chamber was 4--5 times of MIC, and thereafter regrowth was observed after the decrease of GM concentration in the chambers to 2--3 times of MIC. About 8 hours were required for growth to the base line value. In the leucocyte containing chambers, viable bacterial number similarly decreased, but the rate of regrowth was slow. About 12 hours were required for growth to the base line value. The regrowth rate in the GM containing chamber was similar to that in the antibiotic free chamber. From this result, it is suggested that, when the antibiotic concentration in the chamber is 1--2 times of MIC, antibiotic does not show the growth suppressive effect and the activating effect on phagocytosis of leucocytes in the environment closed to the practical pathological condition such as this model. For the patients with qualitative or quantitative abnormal changes of phagocyte, short interval of drug administration might be needed. For this purpose, intravenous drip infusion under monitoring of serum concentration is more suitable than intramuscular injection, which might be accompanied with severe pain and contracture of injected muscle.
A transplantable myelomonocytic leukemia was established from a leukemia of a WKA/Hok rat which had been inoculated with Rauscher virus at birth. The tumor grew in ascites form in normal syngeneic rats and, after the middle stage of i.p. transplantation, leukemia cells consisting of a mixed population of monocytic and granulocytic cells were observed in the peripheral blood. A complement-dependent cytotoxicity test failed to demonstrate Rauscher virus-related antigen on the tumor cell surface. Membrane marker analysis revealed that most of the tumor cells possessed receptors for both complement and neuraminidase-treated sheep RBC. More than 90% of ascitic tumor cells displayed phagocytic activity and a positive nonspecific esterase reaction. Serum from rats bearing this tumor contained high levels of muramidase. Ultrastructurally, the tumor cells resembled both immature and mature cells of the monocyte-macrophage series. On serial transplantation into the peritoneal cavity, the tumor displayed consistent differentiation from undifferentiated blast cells to monocytes and cells indistinguishable from granulocytes. The karyotype analysis revealed that the modal number of chromosomes of the tumor cells was 81, and no structural abnormalities of chromosomes were observed after quinacrine mustard staining. This transplantable leukemia will provide a useful experimental model for the study of granulocyte-monocyte differentiation and for human myelomonocytic leukemia.
Latamoxef (LMOX) was used in the treatment and prophylaxis of infections in neonates and immature infants. The following results were obtained. Mean serum concentrations (bioassay) 30 minutes after a single intravenous injection of about 20 mg/kg of LMOX were 49.9 mcg/ml in neonates and 47.3 mcg/ml in immature infants aged 0--3 days, 54.1 mcg/ml in neonates and 60.6 mcg/ml in immature infants aged 4--7 days, 48.9 mcg/ml in neonates and 46.7 mcg/ml in immature infants aged 8--28 days and 62.1 mcg/ml in immature infants aged over 29 days. Six-hour values were 24.1 mcg/ml, 22.5 mcg/ml, 15.9 mcg/ml, 27.2 mcg/ml, 12.9 mcg/ml, 19.1 mcg/ml and 12.8 mcg/ml, respectively. Mean serum concentration half-lives were 6.70 hours in neonates and 8.16 hours in immature infants aged 0--3 days, 3.68 hours in neonates and 5.83 hours in immature infants aged 4--7 days, 3.06 hours in neonates and 4.47 hours in immature infants aged 8--28 days and 2.59 hours in immature infants aged over 29 days. Adequate clinical efficacy can be expected by the intravenous injection of LMOX in doses of 20 mg/kg 1--2 times daily, in neonates and immature infants aged 0--3 days, 20 mg/kg 2--3 times daily, in neonates and immature infants aged 4--7 days and 20 mg/kg 3 times daily, in neonates and immature infants aged 8--28 days. The clinical efficacy of LMOX was good in 5 cases of sepsis (including suspected cases), 5 cases of urinary tract infection, 2 cases of respiratory tract infection and 6 cases of intrauterine infection (including suspected cases). Only a case of respiratory tract infections due to P. aeruginosa was thought to be ineffective. Bleeding tendency was noted in 3 cases, which results from secondary vitamin K deficiency should be checked carefully during the administration of LMOX.