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Biomedical subjects

T Kodama

Publications and source records attributed to T Kodama.

At least 469 records · Page 26Linked to original sources

IgA nephropathy associated with hyper IgAnemia, psoriasis or pustulosis and ossification.

This is a report on two cases of IgA nephropathy associated with psoriasis vulgaris, having hyper IgAnemia (above 500 mg/dl) and ossification. Case 1 is a 47-year-old woman with a 7-year history of psoriasis vulgaris, and case 2 is a 57-year-old man with a 17-year history of this disease. IgA was 526 and 1,356 mg/dl, respectively. HLA analysis showed A2, A26 (10), Bw62 (15), Bw46, Cw3, DRw12 (5), and DRw8 in the former, and A2, A11, B13, Bw46, Cw11, DR4, and DRw8 in the latter. Renal biopsy specimens disclosed mild mesangial proliferative glomerulonephritis and moderate mesangial proliferative glomerulonephritis with predominant IgA deposition in mesangial area, respectively. A bone-scintigraphy revealed a high uptake of radioisotopes in the left shoulder, the vertebra, the sacroiliac joint, both sides of the knees and ankles, and the sterno-cost-clavicular area. An X-ray study showed ossification of the posterior longitudinal ligament (OPLL) in the former, and ankylosing spinal hyperostosis (ASH) in the latter. A review of the literature discloses three other case reports of hyper IgAnemia, IgA nephropathy, psoriasis or pustulosis, and ossification. The alertness of dermatologists, orthopedic surgeons, rheumatologists, and general practitioners will be required to attain to a more frequent diagnosis of the above combination.

Female↗

[The study of continuous arterial infusion chemotherapy with CDDP and 5-FU in patients with hepatocellular carcinoma].

Between Feb. 1992 and April in 1995, 22 patients with hepatocellular carcinoma (10, recurrence; 12, unresectable) received continuous arterial infusion of CDDP and 5-FU via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days as one course, and 4 courses were basally administered. Patients were divided into 2 groups (6 hours group and 24 hours group) according to the duration of the administration of 5-FU. There were no differences in efficacy rate between the 2 groups (6 hours group, 64%; 24 hours group, 62.5%), but CR (complete response) cases appeared in only the 6 hours group. There were no severe side effects in the 2 groups, but systemic side effects appeared in 6 hours group more often than in 24 hours group. Only in the 24 hours group, 2 patients had the narrowing and obstruction of hepatic artery which was suggested to be caused by intimal injury due to continuous administration of 5-FU. Continuous arterial infusion chemotherapy with CDDP and 5-FU seemed to be effective. Further study on adequate time and volume of administration including pharmacokinetics is needed to enhance the clinical effectiveness of continuous arterial infusion of CDDP and 5-FU.

Aged↗

Mac-1 expression and superoxide generation of the peripheral polymorphonuclear leukocyte following gastrectomy and esophagectomy.

The aim of this study was to evaluate the characteristics of the polymorphonuclear leukocyte (PMN) function after surgical stress. We investigated Mac-1 expression and superoxide generation by peripheral PMNs and serum granulocyte-colony stimulating factor (G-CSF) concentrations in 15 patients who underwent either gastrectomy (n = 8) or esophagectomy (n = 7). The serum G-CSF rapidly increased within 24 hours after operation. The maximum levels of serum G-CSF in the cases of esophagectomy were about 5-8 fold those of gastrectomy, although the increases in PMN counts within 24 hours of esophagectomy were lower than those after gastrectomy. Mac-1 expression and superoxide generation by PMN counts and serum G-CSF. After esophagectomy, Mac-1 expression on peripheral PMNs remained elevated through the 7th day after operation, while superoxide generation by PMNs in response to PMA declined to below preoperative levels after the 3rd day. These results suggest that, after major surgery such as esophagectomy, there is a discrepancy between Mac-1 expression and superoxide generation by the peripheral PMN despite a high level of serum G-CSF.

Aged↗

[A case of posterior fossa hypertrophic pachymeningitis with hydrocephalus].

A 52-year-old woman was admitted to our hospital because of nausea, headache, ataxic gait, and memory disturbance. CT scans and MRI showed a markedly enhanced lesion in the dura mater of the posterior fossa, edema in the right cerebellar hemisphere, occlusion of the transverse sinus, and hydrocephalus, suggesting hypertrophic pachymeningitis. Chronic otitis media and mastoiditis were also noted. Subjective complaints diminished after steroid administration. The patient underwent right suboccipital craniectomy and biopsy. The dura mater was markedly thickened, and the cerebellar surface was edematous. Histological examination revealed the thickened dura mater to be infiltrated by chronic inflammatory cells of forming lymphatic follicles and accompanied by Langhans giant cells. Inflammatory cells were not found in the cerebellar parenchyma, but were present in the subarachnoid space. Acid-fast stain, PAS and Grocott stain were negative. The cause of the hypertrophic pachymeningitis in this patient, may have been related to the chronic otitis media, but the patient's clinical course suggested that it might represent so-called "idiopathic hypertrophic pachymeningitis".

Cranial Fossa, Posterior↗

[Single administration toxicity studies of T-3761 in mice, rats and dogs].

Single dose toxicity studies of T-3761 were carried out in mice, rats and dogs, and the following results were obtained. 1. The approximate lethal dose of T-3761 were more than 5,000 mg/kg for mice and rats, more than 2,000 mg/kg for dogs with oral administration, and more than 5,000 mg/kg for mice and rats with subcutaneous injection. LD50 values with intravenous injection were 783 mg/kg for male mice, 832 mg/kg for female mice, 341 mg/kg for male rats, and 403 mg/kg for female rats. Two dogs given 200 mg/kg did not die but one of the two treated with 400 mg/kg died after intravenous injection. The approximate lethal dose for dog was 400 mg/kg. 2. Neither abnormal symptoms and macroscopic findings nor deaths were observed in mice and rats treated orally. Granuloma around precipitates of T-3761 at the injection site was seen in mice and rats injected subcutaneously. Slight increase of white blood cell count, serum GOT, CPK and urea nitrogen were transiently found in dogs treated orally. Neither abnormal macroscopic findings nor deaths were observed in dogs treated orally. 3. Decreased motor activity and irregular breathing were observed in mice and rats injected intravenously. In dying animals, tonic or clonic convulsions were observed. Vomiting, hyperemia of ophthalmic mucosa, edema of face, decrease of motor activity, salivation and decrease in body temperature were observed in dogs injected intravenously. At higher doses, scream and tachypnea were observed while injecting. Hematological examinations disclosed that increases in red blood cell count, white blood cell count, hematocrit and hemoglobin were found transiently. In biochemical examinations, increases in serum GOT, GPT, urea nitrogen and creatinine were found transiently. One dog intravenously injected 400 mg/kg, showed tonic convulsion and died.

Animals↗

[Three months oral repeated dose toxicity of T-3761 in rats].

A three months oral repeated dose toxicity study was carried out in rats at dosages of 1,500, 400, 100 and 25 mg/kg. The following results were obtained. 1. There was no dead rat caused by administration of T-3761. Soft feces were observed in male and female rats at 1,500 mg/kg. Body weight gain was slightly suppressed in male rats at 1,500 mg/kg. 2. Crystals which seemed to be test compound in the urinary sediment, were observed in male and female rats at 1,500 and 400 mg/kg. 3. There was no abnormality caused by administration of T-3761 in both hematological and ophthalmological examination. 4. Mild increase in total cholesterol (males and females in 1,500 mg/kg group, females at 400 mg/kg group), phospholipids (males at 1,500 mg/kg group) and A/G ratio (males and females in all treated groups) were observed. However, these biochemical changes were reversible in the recovery period. 5. Dilatation of the cecal lumen was observed in male and/or female rats at 1,500, 400, 100 mg/kg. However, no histological abnormalities were seen in the mucosa of cecum. 6. Blister and erosion were observed at articular cartilage of knee or hip joints in 2 of the 19 rats at 1,500 mg/kg, 1 of the 9 rats at 1,500 mg/kg of recovery study and 3 of the 10 rats at 400 mg/kg of recovery study. 7. No toxic dose level was regarded to be 100 mg/kg/day in this study.

Administration, Oral↗

[Three months oral repeated dose toxicity of T-3761 in beagle dogs].

A three months oral repeated dose toxicity study was carried out in beagle dogs at dosages of 300, 100, 30 and 10 mg/kg, respectively. The following results were obtained. 1. There was no death of animals during administration at any dose levels. A few to all animals in all T-3761 treated groups complained of pain at the time of extension of limbs. 2. Mild decrease of body weight was observed in 1 of the 10 animals at 300 mg/kg and 1 of the 8 animals at 100 mg/kg, respectively. 3. In urinalysis, crystals which seemed to be the test compound in the urinary sediment, were observed in 5 of the 10 animals at 300 mg/kg and 4 of the 8 animals at 100 mg/kg, respectively. 4. In blood biochemical examination, mild elevation of GPT was observed in 1 of the 10 animals at 300 mg/kg. Increase of A/G ratio was observed in males at 300, 100 and 30 mg/kg, and females at all dose levels. 5. In macroscopic findings at necropsy, blister and erosion were observed at articular cartilage of shoulder, elbow, hip, and/or knee joints in all animals at 300 and 100 mg/kg, 7 of the 8 animals at 30 mg/kg and 1 of the 8 animals at 10 mg/kg. 6. No toxic dose level was less than 10 mg/kg/day in this study.

Administration, Oral↗

[Reproductive and developmental toxicity studies of T-3761 in rats].

We carried out reproductive and developmental toxicity studies (i.e. fertility study, teratological study, and perinatal and postnatal study) of T-3761, a new quinolone derivative, in S.D. rats. T-3761 was administered orally at the dose of 60, 300 and 1,500 mg/kg/day as suspension in 5% acacia solution. 1. Fertility study T-3761 was administered to male rats for 9 weeks prior to mating and to female rats for 2 weeks prior to mating and until day 7 of gestation. In parent rats, soft stools, slight depression of body weight gain and increase in water intake were observed at the dose of 1,500 mg/kg. Cecum weight was increased at the dose of 300 mg/kg and more in male and at the dose of 1,500 mg/kg in female. No effects on reproductive performance were discernible in the T-3761 treated groups. In fetuses, external, skeletal and visceral examinations revealed no teratological abnormalities. Slightly retarded ossification, however, was observed at the dose of 1,500 mg/kg. From these findings, the no-effect dose of T-3761 in fertility study was considered to be 300 mg/kg/day for parent rats and fetuses. 2. Teratological study T-3761 was administered from day 7 to day 17 of gestation. In dams, soft stools, transient decrease in food intake, increase in water intake, depression of body weight gain and increase in cecum weight were observed at the dose of 1,500 mg/kg. In fetuses, slight increase in incidence of ventricular septal defect and slightly retarded ossification were observed at the dose of 1,500 mg/kg. In the postnatal examination, there were no effects in the T-3761 treated groups. From these findings, the no-effect dose of T-3761 in teratological study was considered to be 300 mg/kg/day for dams and next generations. 3. Perinatal and postnatal study T-3761 was administered from day 17 of gestation to day 21 of lactation. In dams, cecum weight was increased at the dose of 300 mg/kg and more. And soft stools, transient decrease in food intake, increase in water intake, transient depression of body weight gain and slight extension of gestation period were observed at the dose of 1,500 mg/kg. In the postnatal examination, there were no effects in the T-3761 treated groups. From these findings, the no-effect dose of T-3761 in perinatal and postnatal study was considered to be 300 mg/kg/day for dams and more than 1,500 mg/kg/day for next generations.

Animals↗

[Phototoxicity and photoallergenicity tests of T-3761].

Phototoxicity and photoallergenicity tests of T-3761 (oral or percutaneous administration) were carried out in guinea pigs. Phototoxicity test of T-3761 (oral administration) was done in rats, too. The following results were obtained. 1. Compared with comparative drugs in oral administration, phototoxicity of T-3761 was equal to that of ciprofloxacin, slightly stronger than that of nalidixic acid and weaker than those of ofloxacin, enoxacin, sparfloxacin and lomefloxacin. 2. A sensibility to phototoxicity of T-3761 in rats was weaker than that in guinea pigs. 3. Phototoxicity and photoallergenicity were not observed in application of T-3761 as 10% ointment. 4. Photoallergenicity was not observed in oral administration of T-3761.

Administration, Cutaneous↗

[Cytotoxicity and mutagenicity studies of T-3761].

We investigated cytotoxicity and mutagenicity of T-3761. The mutagenicity was evaluated using reverse mutation test with bacteria, chromosome aberration test with cultured cells and micronucleus test with mice. The following results were obtained. 1. Cytotoxicity test: The cell growth was examined using Chinese hamster (V79) cells. The 50% inhibition doses of T-3761 for cell growth (ID50) were 490 micrograms/ml (cultured for 24 hours) and 220 micrograms/ml (cultured for 48 hours). The inhibitory effect of T-3761 was 2-4 times lower than those of ciprofloxacin or norfloxacin and approximately equal to cephalothin. 2. Reverse mutation test with bacteria: The preincubation method with Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, and the induced mutation frequency (IMF) test with Salmonella typhimurium TA100, TA98 were performed. The number of revertant colonies were not increased in any strains treated with T-3761 in the presence or absence of S9 mix. 3. Chromosome aberration test: V79 cells were treated with 50-200 micrograms/ml of T-3761 for 24 or 48 hours, and were treated with 400-3,200 micrograms/ml of T-3761 for 6 hours with S9 mix. The number of cells showing chromosomal aberrations were not increased in any conditions tested for T-3761. 4. Micronucleus test: The male ICR mice were given a single (500-5,000 mg/kg) or five consecutive (150-1,500 mg/kg) oral administration of T-3761. The number of polychromatic erythrocytes with micronuclei were not increased at any dosage groups of T-3761. From these results, it is concluded that T-3761 has low cytotoxicity, and has no mutagenicity.

Animals↗

[Antigenicity study of T-3761].

Antigenicity studies of T-3761, a new quinolone derivative, were conducted and the following results were obtained. 1. By active systemic anaphylaxis test in guinea pigs, neither immunogenicity nor allergenicity of T-3761 was noted. 2. By homologous 4-hour passive cutaneous anaphylaxis (PCA) test using the serum obtained from these guinea pigs, neither immunogenicity nor allergenicity of T-3761 was noted. 3. The potential of IgE antibody production in mice was examined by heterologous 24-hour PCA test in rats. But neither the potential of IgE antibody production nor allergenicity of T-3761 was noted. 4. By passive hemagglutination assay, we analysed the antibody titer in rats and dogs serum obtained from three-month toxicity repeated dose studies (oral and intravenously administration). But the hemagglutination response was negative and specific antibodies were not detected.

Anaphylaxis↗

Molecular subtyping of clinical isolates of Escherichia coli from patients with lower urinary tract infections in Japan.

Crossed-field gel electrophoresis was used to analyse the chromosomal genomic DNA from 41 clinical isolates of Escherichia coli serotypes O-2, O-4, O-6 and O-75 from patients with lower urinary tract infections after digestion of the DNA with Not I and Xba I, respectively. Not I generated 28 distinctly different genomic profiles after crossed-field gel electrophoresis (CFGE) from 34 strains and Xba I generated 35 distinctly different genomic profiles from 41 strains. Not I failed to cleave the genomic DNA from one strain of E. coli serotype O-6 and from all of six strains of serotype O-75. Both enzymes were shown to have equal potential utility for detection of variability in CFGE profiles among 34 strains because both classified 34 of the 41 strains into 28 profiles in a similar manner. No examples of essentially identical restriction profiles among strains of different serotypes were obtained.

Bacterial Typing Techniques↗

Enzyme immunoassay of immunoreactive progastrin-releasing peptide(31-98) as tumor marker for small-cell lung carcinoma: development and evaluation.

Previously, using recombinant human progastrin-releasing peptide (ProGRP)(31-98), we developed a RIA for ProGRP(31-98) and demonstrated that the determination of serum ProGRP(31-98) was a reliable marker for small-cell lung carcinoma (SCLC) (Miyake et al., Cancer Res 1994;54:2136-40). Aiming for a more convenient assay system, we have now developed and evaluated a highly sensitive and specific ELISA for ProGRP(31-98). Only 50 microL of nonextracted serum is needed, and results are obtained in only 2 h. Intraassay and between-day CVs were 1.7-4.6% and 4.2-6.8%, respectively. The log-log calibration curve was linear to 1000 ng/L, and analytical recovery was 91.5-108.7%. The detection limit of this assay, 1.9 ng/L, means that basal concentrations of ProGRP(31-98) were detectable in all healthy subjects. The cutoff value, based on the mean + 3 SD of concentrations in 247 healthy subjects, was set to 45.1 ng/L. Serum concentrations exceeded this value in 18 of 25 SCLC patients, similar to the frequency of increased values found by RIA previously. In contrast, the frequency of increased serum ProGRP(31-98) in patients with nonmalignant pulmonary diseases or non-SCLC was quite low: 0% and 5.0%, respectively. Such results may justify a clinical trial for evaluating this ELISA for the diagnosis and monitoring of SCLC patients.

Amino Acid Sequence↗

Pulmonary metastasis of renal cell carcinoma resected sixteen years after nephrectomy.

A 50-year-old man underwent a left nephrectomy for renal cell carcinoma of the clear cell type in February, 1978. He was examined using computed tomography in September, 1993, and was found to have a small coin lesion in his right lung. A fine needle aspiration biopsy failed to disclose any tumor cells. He underwent a video-assisted thoracoscopic biopsy of the right lung in February, 1994, 16 years after his nephrectomy. The resected specimen contained a coin lesion measuring approximately 1 cm in diameter, and the lesion was microscopically diagnosed as a renal cell carcinoma of the clear cell type metastatic to the lung. The patient is doing well with no signs of re-recurrence six months after the resection of the metastatic lesion. To our knowledge, the time interval between his nephrectomy and resection of the metastatic lesion is the longest ever reported in Japan.

Biopsy↗