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Biomedical subjects

K Isobe

Publications and source records attributed to K Isobe.

At least 325 records · Page 18Linked to original sources

Distribution of phenobarbital in serum, brain and other organs from pediatric patients.

The present study was performed to determine whether serum levels of phenobarbital were representative of their concentrations in the brains obtained from 11 autopsied patients, including premature and full-term babies, infants and children. Estimation of phenobarbital concentrations in plasma and organs was performed by high-pressure liquid chromatography. Brain phenobarbital concentrations correlated well with serum levels (r = 0.82, p less than 0.01, n = 11), giving a regression line with a slope of 0.75. It can be concluded that estimating the serum phenobarbital concentration during clinical pediatric practice gives a good indication of the brain concentration.

Body Fluids↗

Developmental changes in hepatic esterase activity towards chloramphenicol succinate and its Michaelis-Menten constant of liver, kidney and lung in human.

The hepatic esterase activities towards chloramphenicol succinate were determined in the tissues from 45 human subjects, including 18 electively aborted fetuses, 5 premature and 8 full-term newborn babies, 8 infants and 6 adults. The enzyme activities in the tissues from the fetuses and neonates were significantly lower compared with those obtained from the infants and adults. This suggests that the activity showed postnatal development. Kinetic studies of the esterase activity revealed that hepatic Km values were similar to those of the lung, but renal Km values were about 3 times higher than those of the liver and lung. In each organ, no age-related changes in Km values were observed. However, all the Vmax values in each organ showed developmental increases. Therefore, the liver plays the most important role in hydrolysis of chloramphenicol succinate when the weight of the organ is taken into consideration.

Adult↗

High-grade tumor-specific immunity induced by L1210 leukemia variants obtained from the culture of L1210 cells fused with Lesch-Nyhan fibroblasts.

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.

Animals↗

Kinetic study of photochemical and thermal conversion of bilirubin IX alpha and its photoproducts.

A kinetic study of the photochemical and thermal conversion of photoisomers, especialy peaks 0 and 3 [(EE)-bilirubin IX alpha and (EZ)- and (ZE)-bilirubin IX alpha], under anaerobic conditions, was performed by using reversed-phase high-pressure liquid chromatography. Peaks 0 and 3 are spontaneously, photochemically and thermally converted. Short-term photoirradiation of bilirubin gives a mixture containing not only the geometric isomers (EE)-, (EZ)- and (ZE)-bilirubin IX alpha, but also peak 2, (EZ)-cyclobilirubin IX alpha. On prolonged irradiation, cyclization and 15Z leads to 15E isomerization lead to gradual accumulation of two pairs of photoproducts: (EZ)-cyclobilirubin IX alpha A and B and (EE)-cyclobilirubin IX alpha A and B.

Bilirubin↗

Intact and subcellular form of thymocytes of rats are exceptionally immunogenic in mice for inducing anti-Thy-1 T cell-independent class 2 antibody responses.

Results of the present study show that the primary anti-Thy-1.1 antibody response to rat antigen in Thy-1.2 mice is induced exclusively by thymocyte antigen. Thy-1 antigens of brain and bone marrow, which expressed much Thy-1 antigen, were poorly immunogenic if at all. Brain Thy-1 antigen considerably inhibited the immunogenicity of thymocyte Thy-1. Moreover, we found that subcellular form of thymocytes induce as high antibody responses as intact thymocytes do. The subcellular thymocyte Thy-1 antigen behaved as TI-2 antigen, inducing a good response in athymic nude mice but not in CBA/N mice with a B cell defect. The significance of these findings is discussed in relation to the possible physiological activity of Thy-1 or Thy-1-linked molecules on thymocytes specifically mediating lymphocyte differentiation.

Animals↗

Control of T-cell-dependent antibody responses of mice to rat antigens by donor cell types.

Administration of rat red blood cells (RBC) into mice induced a rat antigen-specific T-cell-dependent primary antibody response that was detected by a plaque assay using rat RBC as a target. This response was not induced by rat thymocytes or rat spleen cells that should share rat-specific antigens with rat RBC. We then demonstrated that rat spleen cells but not rat thymocytes, which were administered with rat RBC, partially inhibit the action of rat RBC for induction of the anti-rat response. This inhibition required live donor FcR+ cells, and seemed to be specific to rat antigens common to RBC and spleen cells. The findings supported the idea that the control by donor cell types, which was originally shown to work for T-cell-independent antibody response [3,5], should be effective for T-cell-dependent response beyond the species barrier.

Animals↗

Vasospasm and regional cerebral blood flow (rCBF) in patients with ruptured intracranial aneurysm: serial rCBF studies with the xenon-133 inhalation method.

To clarify the relationship of vasospasm to the reduction of cerebral blood flow (CBF) and the delayed ischemic neurological deficit, serial rCBF studies with the use of the xenon-133 inhalation method were conducted in 35 postoperative patients with ruptured intracranial aneurysms. The CBF was calculated as an initial slope index (ISI) derived from the desaturation curve of each head probe, and the hemispheric mean value of the ISI (mean ISI) was calculated in both hemispheres. The mean ISI in the hemisphere ipsilateral to the operation was low compared to that of the contralateral hemisphere. In relation to the presence of vasospasm, angiographic findings were classified into the following five types: diffuse, peripheral, proximal-severe, proximal-mild, and no spasm. Patients with vasospasm of the diffuse, peripheral, and proximal-severe types showed a markedly decreased mean ISI, and vasospasm of the diffuse type caused the greatest degree of reduction. The mean ISI of the patients who developed delayed ischemic neurological deficit (DIND) due to vasospasm was significantly decreased (37.4 +/- 4.6) compared to that of the patients who did not develop DIND (52.2 +/- 5.6). None of 3 cases of no spasm and only 1 of 14 cases of proximal-mild spasm developed DIND. On the other hand, all of 4 cases of diffuse, 2 of 3 cases of peripheral, and 2 of 6 cases of proximal-severe spasm developed DIND. Thus, if these three types of vasospasm are joined together as severe vasospasm, 8 of 13 cases with severe vasospasm developed DIND. These results suggest that severe vasospasm causes a reduction of CBF and that the reduced CBF brings about DIND.

Adult↗

[CT scan in severe head injury with special reference to Glasgow coma scale].

CT scan demonstrates the invaluable information about the parenchymal lesions of head injuries. The parenchymal lesions were classified into 6 categories; 1) isodensity without mass effect: I(-), 2) isodensity with mass effect: I(+), 3)high density: H, 4) high-low density complex: H-L, 5) low density: L, 6) diffuse cerebral swelling: DCS. Glasgow coma scale (GCS) and outcome scale (GOS) were international practical scales for the evaluation of severity and prognosis of severe head injuries. One hundred and seventy-four cases with severe head injury were analysed. I(+), H and H-L were common findings in the group of GCS 3-6, and I(-) was in GCS 7-12 and GCS 13-15. H and H-L were not related with GCS. DCS was most common in GCS 7-12. Acute epidural hematoma was frequent in the group of GCS 13-15, and acute subdural hematoma was in GCS 3-6. The prognosis was significantly poor in the group of GCS 3-6, with the mortality of 72 percents. On the other hand, the prognosis was quite good in GCS 7-12 and GCS 13-15. There were few reports about the traumatic subarachnoid hemorrhage (SAH). SAH was one of the important risk factors in severe head injuries and it was frequently associated with I(+), H and H-L. The prognosis of the patients with SAH was most unfavorable in the presence of I(+). Number of analyses were reported about the traumatic intraventricular hemorrhage (IVH). IVH was also one of the powerful risk factors and this was commonly associated with H and H-L. The prognosis of the patients with IVH was very poor. Finally, the groups of the patients, whose prognoses turned out to be unexpected results from GCS on admission, were analysed. First, the age was an important factor. In the patients, whose prognoses were good in spite of low GCS, I(-) was a mostly common finding, while SAH, IVH and obscured cisterns, esp. basal and quadrigeminal, were less common. In the patients, whose prognoses were poor despite of favorable GCS, H and H-L were common findings. SAH and IVH were also common. The poor prognosis was induced by secondary systemic complications, such as pneumonia and meningitis, etc.

Adolescent↗

Postnatal development of circadian rhythm in serum cortisol levels in children.

High-pressure liquid chromatography was used to study the development of blood adrenocortical circadian rhythm in a total of 64 children, ranging in age from 1 month to 15 years. Patients with endocrine diseases, congenital anomalies, and diseases of the central nervous system were excluded from this study. Determination of corticosteroid concentration was possible with 20 to 100 microL of serum. Twenty-four hour patterns were determined at six-hour intervals. A distinct circadian rhythm with an amplitude comparable to that of an adult emerged at approximately 6 months of age.

Adolescent↗

Foetomaternal relationships of serum bile acid pattern estimated by high-pressure liquid chromatography.

The bile acid patterns in the maternal and umbilical vein and artery serum samples were analysed by a two-step chromatographic method involving group separation by piperidinohydroxypropyl-Sephadex LH-20 and high-pressure liquid chromatography using immobilized 3 alpha-hydroxy steroid dehydrogenase. Glycochenodeoxycholate predominates in the maternal blood and taurochenodeoxycholate in the umbilical blood. In cases where a free bile acid was detected in the maternal blood, the same bile acid was also demonstrated in the corresponding cord blood. The concentrations of taurocholate and taurochenodeoxycholate were found to be significantly higher in the umbilical artery than in the corresponding umbilical vein. Our data suggest that there is a bidirectional placental transfer of free bile acids and that there is a transfer of taurine-conjugated primary bile acids from the foetus to the mother.

Bile Acids and Salts↗

Control of primary IgM antibody responses to H-2 alloantigens by antigen-bearing live B lymphocytes.

Alloantigen-bearing (H-2d+) peripheral red blood cells, but not red cell-depleted H-2d+ spleen cells, induce primary IgM anti-H-2d plaque-forming cell responses. In this study it is reported that the primary antibody responses to H-2d+ peripheral red blood cells can be markedly suppressed by a subpopulation of H-2d+ spleen cells when they are injected simultaneously or a few days before injection of red blood cells. This suppression was antigen (H-2d)-specific, did not depend on T cells of either the donor or the recipient, and strictly required live donor cells. An energy-dependent action of the donor cell cortex and some proliferation of donor cells in the recipient seemed to be involved in the mechanism of suppression. The donor-suppressor cell type was largely present in the spleen but not in the bone marrow and thymus, and was present in the spleen of athymic nude mice. The suppressor cells displayed the properties of B lymphocytes: they adhered to the nylon wool but not to glass, were of relatively low density (rho less than 1.09), and were surface Ig+, Ia+, Fc receptor-positive but Thy-1-. H-2d+ suppressor-donor B lymphocytes might directly signal to antigen-specific recipient B cells competing with the signal provided by H-2d+ red blood cells for the B cell activation.

Animals↗

Studies on the designing of chemotherapy for gastric cancer in man, based on the tumor tissue concentration of anticancer agents.

5-fluorouracil analogs investigated in this study include a combination of uracil and Ftorafur (UFT), Ethyl (+/-)-t-butoxy-5-fluoro-hexahydro-2, 4-dioxopyrimidine r-5-carboxylate (TAC-278), and 5'-deoxy-5-fluorouridine (5'-DFUR). In a total of 45 patients with gastric cancer, tumor tissue level of 5-fluorouracil (5-FU) was determined at 2, 4, 6, 8, and 12 hours following the oral administration of drug, using a resected stomach specimen as material. As a result, it was demonstrated that oral administration of 200 mg/m2 of UFT maintained above 0.05 microgram/g (minimum inhibitory concentration: MIC) of 5-FU in tumor tissues over 12 hours in 11 of 13 patients. On the contrary, 133 mg/m2 of TAC-278, and 200 mg/m2 or 300 mg/m2 of 5'-DFUR (which is activated by thymidine phosphorylase in man) did not produce an effective 5-FU concentration in tumor tissues. Serum 5-FU level was high in order of TAC-278, UFT, and 5'-DFUR. Clinical response rates obtained with UFT (200 mg/m2 twice a day), or TAC-278 (133-200 mg/m2, 3 times daily) were 27.5% (49 of 178 cases), and 8.3% (3 of 36 cases, by Koyama et al.), respectively. Fisher's direct probability test revealed that there was a significant difference (p less than 0.05) between them in the response rate. It was considered that the measurement of concentration of anticancer drugs in tumor tissues might provide us useful information for the designing of chemotherapy of gastric cancer.

Antineoplastic Agents↗