Biomedical subjects
Publications and source records attributed to T Oikawa.
Using a panel of rat x mouse somatic cell hybrids and in situ hybridization, we determined the chromosomal location of the rat FOS gene locus. Southern blot analysis assigned this oncogene to rat chromosome 6. In situ hybridization confirmed this finding and mapped the gene more precisely to 6q21----q2.
This study was aimed to clarify the fate of the perfused drug and the characteristics of the serosal compartment. A portion of rat small intestine immersed in a solution regarded as the serosal compartment was perfused in situ and the permeability of drugs into the mesenteric venous blood and into the serosal solution were determined. The cumulative amounts of salicylamide (SAM) transported to the mesenteric venous blood and the serosal compartment were 19.7 and 45.8% of amount disappeared from the intestinal lumen, respectively and those of benzoic acid (BA) were 47.4 and 12.7%, respectively. The permeability of SAM into the serosal compartment was 2.8 times of that into the mesenteric venous blood, while the permeability of BA into the serosal compartment was only one fourth of that into the mesenteric venous blood.
A 1,040-g premature baby was diagnosed to have disseminated candidiasis and treated with amphotericin B (AMB) and 5-fluorocytosine. During the treatment, an unexpectedly large dose of AMB was infused unintentionally. AMB level was as high as 1.73 micrograms/mL soon after 5 mg/kg infusion instead of 0.5 mg/kg. However, it dropped rapidly to 0.83 micrograms/mL after 24 hours. AMB was detected in patient's serum at a higher level than minimal inhibitory concentration as long as one month after treatment was stopped. The patient showed liver dysfunction but no nephrotoxicity. The further studies are needed to establish safe and effective treatment regimen in premature infants with disseminated candidiasis.
Three cases of inner ear barotrauma with subjective symptoms and hearing impairment which were similar to the low tone sudden deafness were reported. Case 1 was a 34-year-old man who developed a hearing loss in the next morning of taking an airplane and recovered four days after. Case 2 was a 42-year-old man who developed a hearing loss 2 days after flying in an airplane and hearing loss have recurred 4 times in his right ear for 3 months. Eight months after recovery of previous recurrent attack, a hearing loss occurred in his left ear without flying and recurred twice for 3 weeks. Case 3 was a 25-year-old woman who developed a hearing loss in the right ear after 24 meter depth scuba diving and recurred 4 times for 40 days. Those three patients complained of no vertigo at any attacks and were treated conservatively. From previous reports and the onset and the course of hearing disturbance, acute low tone sensorineural hearing loss in case 1 and case 2 was thought to be caused by circulatory disturbance of the inner ear and in case 3 thought to be caused by inner ear window rupture. But, endolymphatic hydrops was also needed to be take into account in those three cases as a common possible cause. Inner ear barotrauma and so called labyrinthine window rupture were considered to be one of the diseases needed to differentiate from low tone sudden deafness without reference to mono-attack type or recurrent type.
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A case of IgD lambda type multiple myeloma that developed acute renal failure was presented. Histopathologic studies revealed apparent myeloma cast nephropathy with typical giant cells and light chain deposition along tubular basement membrane and inter-peritubular interstitium. Glomerular deposits of light chain were absent by electron and immunofluorescent microgram. The presented case showed a very uncommon histopathologic findings of unusual deposits of light chain, to tubulo-interstitium except for glomeruli, in addition to vertically rare IgD myeloma. A sixty-year old female who was suffered from acute renal failure and treated by hemodialysis for one month was admitted to our institute. Physical examinations revealed ill-apparent and emaciated uremic patient on admission. Laboratory and radiological studies demonstrated IgD lambda type monoclonal protein and numerous punched out appearance of skull bone. The diagnosis of IgD lambda myeloma was confirmed with aspiration bone marrow test. Anti-myeloma therapy of melphalan and prednisolone have started, however, fatal arrhythmia suddenly suffered the patient and resuscitation attempts failed to get any success one week after admission. Renal necropsy was performed and specimens were studied by light, immunofluorescent and electron microscope.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetics and clinical studies on cefsulodin (CFS) were conducted in neonates. 1. MIC's of CFS, sulbenicillin and gentamicin (GM) were determined using 7 strains of Pseudomonas aeruginosa clinically isolated from neonates and maintained as stock cultures. CFS was found to be nearly as active as GM. 2. When CFS 20 mg/kg was administered to a 12-day-old neonate by intravenous bolus injection, serum concentrations were 8.7 micrograms/ml before administration and 51.7 micrograms/ml at 30 minutes, 44.4 micrograms/ml at 1 hour, 38.6 micrograms/ml at 2 hours and 11.1 micrograms/ml at 6 hours after administration. The half-life was 2.5 hours. 3. CFS was administered alone or combination with other drugs to 3 neonates. The drug was clinically effective in 2 cases and slightly effective in another. Bacteriologically, one case was rated as decreased, another as replaced, and the remaining one as unchanged. 4. Neither side effects nor abnormal laboratory values attributable to CFS were found.
Type IV collagen was isolated from human kidney cortex according to the purification of mouse kidney type IV collagen (MKIVC) with minor modifications as described previously [Oikawa, T., et al. (1986) Chem. Pharm. Bull. 34, 789-797]. Chromatography of human kidney type IV collagen (HKIVC) on a column of DEAE-cellulose resulted in its separation into two fractions, i.e., one (HKIVC-1) passed through and the other (HKIVC-2) adsorbed to the column, similar to MKIVC. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Bio-Gel A-5m chromatography revealed that both HKIVC-1 and -2 differed from each other in the ratios of major and minor components. Amino acid analyses also demonstrated that there was a significant difference in the contents of several amino acid residues between both type IV collagens and their 80-kDa components, one of the major ones. These results indicate the possibility that there exist two forms of type IV collagen in human kidney.
Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and premature infants were conducted. The results are summarized as follows. 1. Intravenous administration of CMX at 20 mg/kg, via bolus injection or 1-hour drip infusion, produced at sufficiently high blood concentration. As it is the case with other cephem antibiotics, the half-life varied with age and tended to become shorter with aging. 2. There were intergroup differences in urinary recovery of the drug, but urinary concentrations were generally high. 3. In the clinical evaluation, 12 out of 15 cases which were evaluable for efficacy were rated "excellent" or "good". 4. Side effects were evaluated in 27 cases. A bleeding tendency was found in 1 case, eosinophilia in 1 case, elevated GOT in 1 case, and positive PIVKA II in 4 cases. It is, therefore, concluded that CMX is a highly useful drug for the treatment of bacterial infections in neonates and premature infants.
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The influence of cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CPDX-PR dry syrup was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of bacteria: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No notable changes were observed in fecal viable cell counts except that slight decreases of E. coli counts were observed on the days 3 to 5 after starting administration. The subjects in the pediatric study were 5 children with infections, 3 boys and 2 girls at ages from 1 year 1 month to 6 years 10 months, with their body weights ranging from 9.3 to 23.8 kg. CPDX-PR dry syrup was administered at a dose between 3.0 to 3.7 mg/kg, 3 times a day for 4 to 7 days. Although some variations of the fecal bacterial flora were noticed between subjects during the administration of CPDX-PR, no notable changes were observed in major aerobic and anaerobic bacteria such as Enterobacteriaceae, Enterococcus, Bacteroides and Bifidobacterium in 4 of the 5 cases. Large decreases in Streptococcus, Enterobacteriaceae, Bifidobacterium, Eubacterium and anaerobic cocci and an increase in Enterococcus were observed in the other case. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. Regarding Enterobacteriaceae, transitory bacterial replacement was observed within the genus. Fecal concentration of CPDX during the administration of CPDX-PR was extremely low or below the detectable limit except one specimen from a case in which intestinal bacterial flora showed remarkable changes. From the above, CPDX-PR appears to be a drug with a relatively small influence on the intestinal bacterial flora.
Pharmacokinetic and bacteriological studies were carried out on sulbactam/ampicillin (SBT/ABPC) in the field of pediatrics. The results obtained are summarized as follows: 1. A total of 248 clinical isolates were employed to determine minimum inhibitory concentrations (MIC) of SBT/ABPC against various bacterial species. SBT/ABPC showed stronger antibacterial activity against Gram-positive organisms than against Gram-negative rods. 2. The peak serum level of ABPC was about twice as high as that of SBT, and serum levels of ABPC and SBT declined with time. Both drugs showed almost the same trend of changes in concentrations. The half-lives of both drugs were about 1 hour. 3. The urinary recovery rates over 6 hours after administration were 52-80% for ABPC and 70-73% for SBT. 4. The effect of SBT/ABPC on coagulation system was examined. No case showed changes in PT, APTT, TT and HPT before and after administration of SBT/ABPC. Platelet aggregation during administration of SBT/ABPC was slightly faster than that before administration, suggesting that SBT/ABPC had no effect on platelet aggregation. Generally speaking, it seemed that SBT/ABPC was a safe antibiotic for bleeding. 5. The effect of SBT/ABPC on the intestinal bacterial flora in experimental animals was examined. Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve were reduced after administration of SBT/ABPC, suggesting that the intestinal bacterial flora was affected by the administration of SBT/ABPC more greatly than by the administration of ABPC alone. In a similar investigation being made with clinical cases, both aerobes and anaerobes showed great changes. Concentrations of the drugs in feces increased with increasing dosage, resulting in greater changes of the intestinal bacterial flora. Thus, the total number of aerobes and anaerobes was reduced. No diarrhea was observed in any subjects examined. From the above results, it appeared that SBT/ABPC was a safe and useful antibiotic for various bacterial infections in the field of pediatrics.
The amount of urinary calcium excretion is an useful marker for distinction between patient with preeclampsia and normal pregnancy of chronic hypertension has been reported. This study was performed to investigate the extent and the etiology of decrease in urinary calcium excretion in toxemia of pregnancy. The subjects in this study were 20 patients with severe toxemia of pregnancy (group T) and 20 subjects with normal pregnancy (group N). In these subjects, serum calcium (s-Ca), phosphate (s-Pi) and uric acid (s-UA) and urinary calcium (u-Ca), phosphate (u-Pi) and uric acid (u-UA) were measured. The values of u-Ca and u-Pi in the group T were significantly decreased than the group N (p less than 0.001, p less than 0.01). The values of s-Ca and s-Pi made no distinction between group T and group N. There was significant relationships between u-Ca and, s-UA (r = -0.70), clearance of UA (r-0.82), Ccr (r = 0.64), and FEca: Cca/Ccr (r = 0.87). These results indicated that the decrease of u-Ca was evident in severe toxemia of pregnancy. And the decrease of u-Ca has resulted from increase of tubular reabsorption. The change of u-Ca of patients with toxemia was studied. After the onset of toxemia, u-Ca was decreased rapidly (less than 50 mg/day) and u-Ca was restored to the normal range (more than 100 mg/day) promptly after delivery. The value of u-Ca was over 100 mg/day in the second pregnancy that developed on toxemia of pregnancy among the cases who has severe toxemia in the first pregnancy. However, toxemia of pregnancy have relapsed in the case with low u-Ca excretion of less than 100 mg/day during the second pregnancy.
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The influence of cefteram pivoxil (CFTM-PI), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFTM-PI in fine granular form was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable change was observed in the fecal viable cell count except that slight decrease in E. coli count was observed on days 2 to 5 after starting administration. The subjects in pediatric study were 5 children, 3 boys and 2 girls at ages from 6 months to 10 years 4 months, with infections. Their body weights ranged from 3.5 to 28.0 kg. CFTM-PI in fine granular form was administered at each dose of 3.0 to 3.8 mg/kg, 3 times daily for 5 to 11 days. During the administration of CFTM-PI, there were some variations in the change of the fecal bacterial flora noticed between subjects. Although Enterobacteriaceae tended to decrease and Enterococci tended to increase, other main aerobes and anaerobes were almost unchanged in most cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. In a 10 years 4 months old boy, the fecal concentration of CFTM, the active form of CFTM-PI, was 72.20 micrograms/g and a remarkable decrease of total anaerobe count was observed. In feces, CFTM-PI and CFTM were detected in 4 and 2 cases respectively, and their concentrations were 1.50 approximately 89.65 micrograms/g and 2.25 approximately 72.20 micrograms/g, respectively. beta-Lactamase activities in feces were positive in all cases. From the above, CFTM-PI is considered to be a drug with relatively less influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, we need to pay attention to fecal drug concentrations.
The significant inhibitory activity of medroxyprogesterone acetate (MPA) against mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was confirmed in female Sprague-Dawley (SD) rats, and was found to be independent of the estrogen receptor (ER) level. To facilitate elucidation of the mechanism underlying the antitumor activity of MPA against the rat mammary tumors (RMTs) regardless of ER status, the present study was conducted to determine whether or not a DMBA-induced RMT had the capacity to elicit angiogenic activity on tissue implantation into a rabbit cornea, and, if so, to determine whether or not the angiogenic activity of the RMT was inhibited by MPA. The RMTs obtained were classified into two groups based on the ER level; ER-positive and -negative groups. Both groups exhibited relatively strong angiogenic activity, the activity of the ER-negative group being significantly higher than that of the ER-positive one. The angiogenesis produced by both groups of RMTs was significantly inhibited by MPA, as judged from the results of the rabbit cornea assay. Similarly, MPA almost entirely suppressed not only the angiogenesis but also the growth of rabbit VX2 tumors without ER, included as a positive control as to the induction of angiogenic activity. In vitro experiments using neoplastic epithelioid RMT-1 and -2 cells cloned from DMBA-induced RMTs demonstrated that MPA had little or no suppressive effect on the growth of these epithelial cells. These results suggest that the inhibitory action of MPA toward the angiogenic activity of RMTs, at least in part, involves its antitumor activity toward the RMTs.
Expression of the rearranged c-myc oncogene and transformed phenotypes was investigated in 2 different types of somatic cell hybrid clones between a BALB/c mouse plasmacytoma line (S194) and normal allogeneic spleen cells or fibroblasts. In the parental S194 cells, one allele of the c-myc was rearranged and its 5'-flanking region was partially deleted by recombination with the immunoglobulin C alpha gene. Due to this recombination, S194 cells expressed approximately 20-fold higher than normal spleen or fibroblast levels of c-myc transcripts from the rearranged allele, which are smaller than normal germ-line 2.4-kb c-myc transcripts, but they expressed the same low levels of 2.4-kb c-myc transcripts from the non-rearranged allele as compared with normal spleen cells or fibroblasts. All the hybrid clones retained both the rearranged and the non-rearranged c-myc. The hybrid clones between S194 and normal spleen cells showed transformed phenotypes and expressed the same high levels of rearranged c-myc transcripts and low levels of the non-rearranged c-myc transcripts as the parental S194 cells. On the other hand, the hybrid clones between S194 cells and normal fibroblasts showing non-transformed phenotypes inhibited expression of the rear-ranged c-myc to undetectable levels but expressed the non-rearranged c-myc transcripts at low levels. A hybrid clone between S194 cells and normal fibroblasts showing transformed phenotypes also exhibited the same pattern of c-myc expression as the non-transformed hybrid clones. These results indicate that expression of the rearranged c-myc in S194 mouse plasmacytoma cells is modulated in different ways in different components of cell lineages, although the correlation between the levels of rearranged c-myc transcripts and the transformed phenotypes in the hybrid clones was not absolute.
Eggs were isolated from ovaries and oviducts of the golden hamster and the components of zonae pellucidae were examined using density gradient SDS-polyacrylamide electrophoresis. Zonae of ovarian eggs (ZP-OVA) had three major components corresponding to the so-called ZP-1, ZP-2, and ZP-3. Zonae of recently ovulated eggs collected from oviducts (ZP-OVI) had a 200-240 K component (ZP-O) in addition to the three components present in ZP-OVA. When ovarian and oviductal eggs were stained with FITC-conjugated B. simplicifolia-1 lectin (BS-1), which specifically binds to alpha-D-galactose- or alpha-N-acetyl-D-galactosamine-like terminal saccharide residues, ZP-OVI was intensely stained, while ZP-OVA was not. ZP-OVA gained the ability to bind to BS-1 after a brief treatment with oviduct extracts. These results suggest that biochemical properties of hamster zonae change after transport of eggs from ovary to the oviduct. The addition of the 200-240 K component of oviductal origin to preexisting zona components seems to be responsible for this change.