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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 739 records · Page 41Linked to original sources

Characterization of high-affinity receptors for interleukin 5 on interleukin 5-dependent cell lines.

Interleukin 5 (IL-5) is a glycosylated polypeptide that acts as a key factor for B-cell growth and differentiation. We demonstrated previously that there are two classes (high and low affinity) of IL-5 receptors on murine chronic B-cell leukemic cells (BCL1-B20). Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a polypeptide of Mr 92,500. In this study, we analyzed characteristics of high-affinity IL-5 receptors on IL-5-dependent early B-cell lines (T-88 and T88-M), mouse myeloma cells (MOPC-104E), and BCL1-B20 cells. All cell lines had two classes of IL-5 binding sites, but T88-M cells bore the highest number of high-affinity receptors. The number of high-affinity IL-5 receptors on BCL1-B20 cells could be up-regulated 3-fold by lipopolysaccharide and down-regulated by IL-5. Disuccinimidyl tartarate crosslinking of 35S-labeled IL-5 to the receptors on the T88-M and lipopolysaccharide-stimulated BCL1-B20 cells revealed two major 35S-labeled components of Mr 92,500 and Mr 160,000, even when the binding of 35S-labeled IL-5 was carried out under high-affinity conditions (100 pM 35S-labeled IL-5). The Mr 92,500 component, but not the Mr 160,000 component, was detected in the lysates of MOPC-104E and T-88 cells, both of which bore a large number of low-affinity receptors and a limited number of high-affinity receptors. The results suggest that the Mr 92,500 component represents the complex of IL-5 with the low-affinity Mr 46,500 receptor, whereas the high-affinity receptor consists of the Mr 46,500 peptide and an additional peptide.

Adjuvants, Immunologic↗

Optimal serum trough levels of FK506 in renal allotransplantation of the beagle dog.

The present study was performed to estimate the optimal serum trough levels of FK506 (FK) for prophylactic use and for the treatment of acute rejection in renal allotransplantation of the beagle dog. The serum trough levels of an immunosuppressive dose of FK 1.0 mg/kg p.o. ranged from 0.1 to 0.4 ng/ml. The data indicate that the effective serum trough level is about 100 times lower than that of cyclosporine, as was already observed in previous in vitro studies. Combining treatment with a nonimmunosuppressive dose of cyclosporine of 2.5 mg/kg could lower the effective trough levels of FK. By the combining treatment, 2 out of 5 renal recipient dogs survived with well-functioning grafts as long as 60 days with the trough levels between 0.04 and 0.07 ng/ml. High-dose 5-day i.m. FK treatment of 0.5 or 1.0 mg/kg was effective in the reversal of acute rejection, with peak serum trough levels during successful rejection therapy ranging between 0.28 and 3.7 ng/ml. Two dogs died of malaise or pneumonia with peak trough levels of 2.25 and 2.78 ng/ml. Among the wide range of the effective trough levels for successful acute rejection therapy, those above 2.0 ng/ml seem to be toxic in some renal-transplanted dogs.

Administration, Oral↗

Effects of combination treatment with FK506 and cyclosporine on survival time and vascular changes in renal-allograft-recipient dogs.

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

Animals↗

Expression of proliferating cell nuclear antigen/cyclin in human keratinocytes.

The expression of proliferating cell nuclear antigen (PCNA), also called cyclin, in human keratinocytes was examined by using the serum obtained from a SLE patient and a murine monoclonal antibody against PCNA/cyclin. In the normal epidermis, few of the nuclei were labeled with anti-PCNA/cyclin. This was in contrast to the positive nuclear staining seen in active lesions of psoriasis. In a primary culture of human keratinocytes growing as a monolayer, 20%-30% of cells expressed PCNA/cyclin. SV40-transformed human keratinocytes showed positive nuclear staining in about 40% of the cell population. In stratified keratinocytes cultured in a high Ca++ medium, PCNA/cyclin expression was decreased and only the cells in the basal and suprabasal layers showed positive staining. These results indicate that the expression of PCNA/cyclin correlates with the proliferating state in human keratinocytes and may not be associated with the mechanism of differentiation in keratinocytes.

Antibodies, Monoclonal↗

Developmental retardation in children with refractory epilepsy.

It is controversial whether developmental retardation occurs in children with epilepsy and what causes the retardation if it occurs. The present study aims to reveal the factors associated with the retardation. The patients were 126 children who had been developmentally normal before the onset of epilepsy and had been followed for more than five years. Forty-eight of the 126 children showed mental retardation, and the remaining 78 had normal mental development at the follow-up. Developmental retardation was observed in children with onset before one year, known etiology, diffuse slow spike-wave or hypsarrhythmia on EEG, ingestion of six or more drugs and high blood levels of phenobarbital or phenytoin. Late onset of epilepsy, idiopathic or familial etiology, ingestion of five drugs or less and low blood level of phenobarbital or phenytoin were associated with normal development.

Adolescent↗

Ototoxic effects of a pseudodisaccharide aminoglycoside antibiotic, dactimicin, on the inner ears of guinea pigs.

The effect of dactimicin on the inner ear of guinea pigs was investigated by comparing it with the effects of ribostamycin, astromicin and amikacin. At doses of 200 and 400 mg/kg/day for 4 weeks, no pinna reflex loss was observed, but 2 animals receiving 400 mg dactimicin/kg/day showed unilateral loss of the outer hair cells in the cochlea and very scattered loss of the hair cells in the vestibular organ. At doses of 400 and 500 mg dactimicin/kg/day for 5 weeks, all surviving animals showed no abnormality of the outer hair cells, the inner hair cells and the spiral ganglion cells in the cochlea except for scattered unilateral loss of the outer hair cells and loss of the stria vascularis. Based on these observations, it is concluded that the ototoxicity of dactimicin on the inner ear of guinea pigs is the same as or a little stronger than that of ribostamycin, weaker than or the same as that of astromicin and weaker than amikacin.

Amikacin↗

Rat epidermal growth factors: purification and tissue content.

Rat epidermal growth factor (rEGF) was isolated from the submaxillary gland of male rat by reversed phase high performance liquid chromatography and ion exchange chromatography. The binding of purified rEGF to human carcinoma cells (A-431) and its tritiated thymidine uptake on rat epidermal fibroblast cells (FR) were almost the same as those of purified commercially available mouse EGF (mEGF). Antisera to rEGF was raised in rabbits and a radioimmunoassay (RIA) system was established. The assay range of the RIA was about 1.0 to 100 ng/ml. The within assay coefficients of variation were 5 to 10%, while the between assay coefficients of variation were 5 to 13%. The tissue content of rEGF of male rats (10 weeks old) was examined. As a result, the submaxillary gland was found to contain a very high concentration of rEGF (214 micrograms/g wet tissue) as predicted, and digestive tissues, stomach, intestine and duodenum contained 2.49, 3.57, 9.44 ng/g wet tissue, respectively. The amounts in prostate and seminal vesicle were relatively high, being 65.6 and 2,268 ng/g wet tissue, respectively. The amount in the submaxillary gland increased markedly after 7 weeks of age. These results suggest that EGF is an important factor in gonadal function.

Aging↗

[Mechanical contraction properties and roles in velar movements of tensor veli palatini muscle].

The present study was intended to clarify the mechanical contraction properties and to investigate roles in velar movements of the tensor veli palatini (TVP) muscle in dogs. The dogs used in the experiments were anesthetized intra-peritoneally with sodium pentobarbital. Experiment I: Tension of the TVP muscle was induced by stimulation to the motor nerve and was recorded: 1. The contraction time and half relaxation time of maximal isometric twitch of the muscle were 13.7 +/- 0.7 msec and 10.4 +/- 1.2 msec, respectively. 2. A clear summation of muscle contractions was obtained with stimulation at 20 Hz with maximal tetanic tension at 90 Hz. The tetanus twitch tension ratio was found to be 10.7 +/- 1.1. Experiment II: The role of the TVP muscle in velar movements was investigated from the standpoint of upper airway patency. In addition, the effect of fracture of the pterygoid hamulus and transection of the TVP muscle at the pterygoid hamulus on velar movements were also investigated. The results indicated the following: 1. Upon electrical stimulation of the motor nerve of the TVP muscle, the anterior part of the soft palate was displaced laterally with the subsequent expansion of the epipharynx. 2. Negative pressure in the nasal cavity was observed with the respiratory activity of the TVP muscle after tracheostomy, but not in the oral cavity. 3. Contraction of the TVP muscle decreased nasal airway resistance when intranasal airflow was confirmed at levels higher than 120 ml/sec. 4. After fracture of the pterygoid hamulus, contraction of the TVP muscle produced expansion of the epipharynx but less than that prior to the treatment. The fracture did not change nasal airway resistance. 5. After transection of the TVP muscle at the pterygoid hamulus, the contraction of the TVP muscle did not produce any velar movements. Neither expansion of the epipharynx nor changes in nasal airway resistance were observed.

Airway Resistance↗

[Experimental study on combination chemotherapy of UFT and calcium antagonist in gastric cancer].

The antitumor effect of combined use of UFT and verapamil, a calcium antagonist, was examined in gastric cancer transplanted to BALB/c athymic nude mice. Four experimental groups included Group I (Control) which was administered 3% Gummi Alabicum (p.o.), Group II (UFT) which was administered 64.8 mg/kg UFT (p.o.), Group III (UFT + verapamil) which was administered UFT and 10 mg/kg verapamil (s.c.) and Group IV (verapamil) which administered same doses of verapamil. All mice were sacrificed at the day of 12 and pathological and flow cytometric studies were performed to those tumors. At the day of 8, significant retardation of tumor growth was observed in Group II and Group III compared with Group I (P less than 0.05). The ratio of tumor retardation of Group III was more predominant than that of Group II at the day of 9 (p less than 0.05). However, no difference in pathological and flow cytometric changes was observed between Group II and Group III. Weight loss and death, as side effects, were found in Group II and III. It was assumed that this may be depend on the over dose of UFT or methods of administration. These results suggested that combination chemotherapy of UFT and verapamil was effective in the retardation of gastric cancer, however the doses of UFT and verapamil have to be reexamined in order to control the side effect.

Animals↗

[Severe postoperative pulmonary hypertensive crisis in a case of ventricular septal defect with Down's syndrome].

We encountered the episode of severe postoperative pulmonary hypertensive crisis in a case of ventricular septal defect with Down's syndrome. A 1 year 11 month old female with ventricular septal defect and pulmonary hypertension underwent open heart surgery. On the operative day after tracheal suction she experienced bradycardia, hypotension and pulmonary hypertension followed by shock condition. In spite of vigorous medical therapy clinical aspects were not improved. But only blood transfusion directly into the left atrium and administration of tolazoline hydrochlorides through pulmonary artery were very effective to improvement of hemodynamics and reduction of pulmonary hypertension. Moreover, after this episode pulmonary artery pressure showed elevation at the tracheal suction and the weaning from the respirator. We discussed the cause and treatment of postoperative pulmonary hypertensive crisis.

Down Syndrome↗

Potential usefulness of a cultured glioma cell line induced by Rous sarcoma virus in B10.A mouse as an immunotherapy model.

A cultured glioma cell line, SR-B10.A, which was derived from a brain tumor induced in an adult female B10.A mouse by Rous sarcoma virus (RSV), has been established. The morphological appearance of the tumor produced by s.c. inoculating SR-B10.A cells was analogous to an astrocytoma of human glioma. Glial fibrillary acidic protein as well as S-100 protein was positive in these SR-B10.A tumor cells. A population doubling time of the cultured cells was 18.5 hours. Chromosomal analysis revealed a defect in one of the sex chromosomes. Integration of RSV genome was proven to be positive in SR-B10.A cells. It was possible to generate cytotoxic effector cells in the syngeneic B10.A mouse against SR-B10.A. The tumor-bearing syngeneic hosts harbored a suppressor activity in the splenocytes. Although recombinant human tumor necrosis factor (rH-TNF) had no growth inhibitory effect on the SR-B10.A cells in vitro, the s.c. implanted and growing tumor regressed when rH-TNF was administered intratumorally several times. In addition, this anti-tumor effect was completely abrogated when the host mice were treated with wholebody x-ray irradiation prior to the tumor cells inoculation. In contrast, neither rH-TNF (i.v.) nor cyclophosphamide (i.p.) induced the regression of SR-B10.A, indicating that efficacy of the locally administered rH-TNF is dependent on the host immune mechanism. These results suggest that SR-B10.A is a potentially useful tumor model in evaluating efficacy of immunomodulators.

Animals↗

[A clinical evaluation of rush immunotherapy in adult patients with severe bronchial asthma].

Rush immunotherapy (RIT) using house dust (HD) antigen were performed in ten adult patients with chronic severe bronchial asthma who had mite allergy. All cases have reached to the maintenance dose of 10(-1) X 0.50 ml within 10 days and been able to introduce maintenance therapy smoothly. After the RIT, remarkable improvement of asthmatic symptom was seen in 4 cases and one of them was considered to be completely cured of the asthma. Although side effects such as local skin reaction, rhinorrhea and asthmatic attack were seen, severe side effect was not observed at all. IgE-RAST scores for both HD and mite were unchanged before and after RIT. On the other hand, the values of specific IgG4 for both HD and mite antibody were significantly increased 2 or 4 weeks after RIT. These results indicated that RIT can be performed safely and securely, and rapid immunological response as well as clinical effectiveness are able to be expected for adult severe asthmatics.

Adolescent↗