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Biomedical subjects

S Kai

Publications and source records attributed to S Kai.

At least 127 records · Page 7Linked to original sources

[Effect of butorphanol tartrate on cross-fostering in rats].

In the preceding study, neonatal deaths were observed when an analgesic, butorphanol tartrate (BT), was administered subcutaneously to female rats during the perinatal and lactating periods. In the present study, cross-fostering using CRJ:CD (Sprague-Dawley) rats was employed to clarify the cause of death. When the litters naturally delivered from dams receiving BT (25 mg/kg/day, s.c.) during the perinatal period were switched among one another within the BT-treated dams or placed with control (saline-treated) dams, the viability of newborns on postpartum day 3 was significantly lowered. Since some of the BT-treated dams were observed to neglect the delivery cares that were fundamental to dams such as removing amnions, umbilical cords and placentas, as well as gathering and lactating to newborns immediately after natural delivery, it was considered that death after cross-fostering was the result of the pups being emaciated before cross-fostering. This finding was supported by the fact that a significant elevation in the viability was revealed when the newborns Cesarean-delivered from BT-treated dams were placed with control or untreated dams. No significant effects of BT were observed on the viability and body weight of newborns at birth and on those of pups from postpartum day 3 through the weaning day.

Analgesics↗

[Physical dependence liabilities of butorphanol, a narcotic antagonist, and its main metabolites, norbutorphanol and hydroxybutorphanol].

After the intravenous injection of butorphanol or norbutorphanol in rats every 1 hr for 3 days, naloxone-induced body weight loss and withdrawal syndrome were observed to some degree. A slow-released emulsion containing each of the test drugs was injected subcutaneously in guinea-pigs, and naloxone was administered after 2 or 3 days. BT caused little jumping response even at a dose of 600 mg/kg, and the reaction was significantly weaker than that of pentazocine. No jumping responses were recognized in the cases of NB (600 mg/kg). In morphinized rats, the injection of BT or HB caused potent body weight loss, and these rats exhibited withdrawal syndrome which was more potent than that by pentazocine at the same dose. The body weight losses by the injection of NB and pentazocine were to the same degree, and these changes were significantly different from that of the saline control. BT inhibited the adenylate cyclase activity of the rat caudate nuclei, and the effect was weaker than that of pentazocine. NB showed a slight inhibition, and HB had no effect on the activity. These results suggest that the physical dependence liability of butorphanol is less than that of pentazocine, and the potent mu-antagonistic character of butorphanol is based on the liability. NB, a mu-agonist, makes dependence production possible. The ability of HB is negligible.

Animals↗

A case of severe aplastic anaemia successfully treated by retransplantation from the same donor.

A 16-year-old girl with severe aplastic anaemia was successfully treated with retransplantation of bone marrow from an HLA-identical sibling after rejection of the first transplantation from the same donor. Cyclophosphamide was used for the first transplantation and cyclophosphamide, 300 rad total-body irradiation and antilymphocyte globulin were used for the second transplantation. Permanent engraftment was achieved after the retransplantation with normalization of haemopoiesis, which has lasted for over 17 months. The patient is now in excellent clinical condition with minimal signs of chronic graft versus host disease.

Adolescent↗

Pluripotent, erythrocytic and granulocytic hemopoietic precursors in chronic granulocytic leukemia.

Using methylcellulose culture techniques, we investigated the behavior of committed and pluripotent hemopoietic precursors (CFUMIX) in marrow cells and blood from patients with chronic granulocytic leukemia (CGL) in the chronic phase whose marrow cells showed the presence of Ph1 chromosomes. The relative concentrations of the marrow precursors in CGL were nearly equal to those in control patients. The mean nucleated cell count in marrow fluid from the patients, however, was 6.3 times that of control values. As a result, the mean concentrations per unit volume of the hemopoietic precursors in CGL were significantly higher than those in control patients. Furthermore, the presence of erythropoietin (Ep) independent BFUE giving rise to erythropoietic bursts in the medium without the addition of Ep was demonstrable in marrow cells and blood. In the peripheral blood, the increment in numbers of CFUC, CFUE, BFUE, and CFUMIX in accordance with the leucocyte count was observed. The present results are consistent with the theory that the clonal expansion in CGL occurs at the level of pluripotent hemopoietic precursors and suggest that CFUMIX in CGL can differentiate into CFUE along the erythropoietic pathway and that a regulatory defect in CGL in present in both granulocytic cells and erythrocytic cells.

Adult↗

Mouse C3b/C4b inactivator: purification and properties.

Mouse C3b/C4b inactivator (C3b/C4bINA) was purified approximately 400 times from mouse serum. It is a beta-globulin and consists of 2 disulfide bonded chains of m.w. 60,000 and 35,000. Under nonreducing conditions, its m.w. is 95,000. It cleaves the alpha'-chain of cell-bound C4b into 3 fragments: alpha 2, alpha 3, alpha 4. The alpha 2 fragments remain bound to the cell surface (C4d), and the rest of the molecule (C4c) is released into the fluid phase. In fluid phase, C3b/C4bINA cleaves the alpha'-chain of C4b in a similar manner but only in the presence of mouse or human C4-binding protein (C4-bp). Mouse C4-bp and human C3b/C4bINA do not cleave human C4b, although mouse C4-bp binds to human C4b. This incompatibility suggests that C4-bp and C3b/C4bINA must interact to cleave fluid phase C4b. Mouse C3b/C4bINA also cleaves the alpha'-chain of human C3b in solution into 2 fragments in the presence of human beta 1H. Therefore, it is likely that mouse and human C3b/C4bINA are homologous proteins. A monospecific antiserum to mouse C3b/C4bINA has been prepared in rabbits. By crossed immunoelectrophoresis, this antiserum detects, in addition to the protein described above, a fast beta-globulin with a m.w. of approximately 200,000 and antigenically identical to C3b/C4bINA but enzymatically inactive. This protein could represent a precursor of C3b/C4bINA.

Animals↗

Pluripotent hemopoietic precursors in vitro (CFUMIX) in aplastic anemia.

When human marrow cells were cultured in a medium containing alpha-medium, methylcellulose, fetal calf serum, bovine serum albumin, erythropoietin, and leucocyte-conditioned medium, mixed colonies composed of erythrocytic cells and granulocytes were formed. The clonal nature of the mixed colonies was confirmed by the linear relationship between the numbers of cells plated and the number of colonies, and the absence or presence of Y-chromatin in the mixed colonies in a co-culture experiment with male and female cells. Using the methylcellulose cell culture techniques, the pluripotent hemopoietic precursors (CFUMIX) in marrow cells from 15 patients with aplastic anemia were assayed. In the control subjects of patients with iron-deficiency anemia, lymphoadenitis, reactive leucocytosis or Hodgkin's disease, 8 X 10(5) marrow cells in 4 dishes produced 12.7 +/- 6.9 (mean +/- SD) mixed colonies. On the other hand, 8 X 10(5) marrow cells from patients with aplastic anemia formed only 2.1 +/- 5.5 (mean +/- SD) mixed colonies. Furthermore, the marrow cells from 5 patients who were repeatedly receiving transfusions contained no CFUMIX which give rise to mixed colonies. The present results provided the first direct evidence that pancytopenia in most patients with aplastic anemia results from a reduced influx into the compartment of maturing hemopoietic cells from the compartment of pluripotent hemopoietic precursors.

Adult↗

Studies on the kinetics of hemopoietic stem cells and immune responses to the hapten-carrier conjugate.

The correlation between the kinetics of hemopoietic stem cells and immune responses to the hapten-carrier conjugate was investigated. The numbers of both pluripotent stem cells (CFU-S) and myeloid stem cells (CFU-C) in the spleen from mice immunized with the hapten-carrier conjugate were significantly greater than those of the control and the activity of colony-stimulating factor (CSF) in the serum of these mice was markedly elevated. The supernatant of short-term incubation of splenic T lymphocytes from these mice, when stimulated with carrier protein, had high levels of both activities of CSF and helper T cell factors. The study by gel chromatography showed that these factors are similar m.w. substances of 35,000 to 45,000 daltons. But analysis by ion-exchange chromatography demonstrated that they do not have identical biochemical properties. The present studies suggest that biologically active factors produced by T cells stimulated with carrier protein may induce the enhancing effect on the proliferation and differentiation of hemopoietic stem cells and immune responses to the hapten-carrier conjugate.

Animals↗

Studies on the immunopotentiating effects of a streptococcal preparation, OK-432. I. Enhancement of T cell-mediated immune responses of mice.

The effects of the anti-tumour agent OK-432 on the immune response to hamster erythrocytes (HRBC) and nucleated chicken erythrocytes (CRBC) were studied in inbred SL mice. Mice were treated repeatedly with OK-432 before immunization with erythrocytes in saline. The cytotoxicity of CRBC-primed spleen cells, as demonstrated by 51Cr release from labelled CRBC, was markedly increased by treatment with OD-432. The delayed footpad reaction to CRBC was significantly augmented by treatment with OK-432. These results in mice indicate that OK-432 can enhance the cellular immune responses which require the contribution of T cells. Such an activation of T cells by OK-432 was observed in the humoral immune response to a trinitrophenyl group. Augmentation of anti-hapten antibody production, suggesting the enhancement of helper T cell activity by OK-432, was noticed after immunization with trinitrophenyl conjugated to erythrocytes. Furthermore, this enhancement of helper T cell activity by OK-432 was confirmed by utilizing an adoptive transfer system. These results support the possibility that T cell activation may be one of the important effects of OK-432 as an immunopotentiator.

Adjuvants, Immunologic↗