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Biomedical subjects

T Shibasaki

Publications and source records attributed to T Shibasaki.

At least 163 records · Page 9Linked to original sources
PubMed1989

Effects of cyclosporine on puromycin aminonucleoside-induced nephrotic rats.

The effects of cyclosporine (CY) were determined to see whether CY has the potency of reducing urinary protein excretions due to puromycin aminonucleoside (PAN) in nephrotic rats which are the model of minimal change nephrotic syndrome (MCNS). CY had a marked reduction of urine protein excretion during treatment with this drug, but it was observed that an increment in urinary protein excretion was introduced within a few days after the withdrawal of CY. Immunological and histological studies were performed to know the mechanisms of reducing urinary protein excretion in PAN rats. Firstly, the lymphocyte subsets of peripheral blood were evaluated using monoclonal antibodies of W3/25 and MRCOX/8. We found that the W3/25/MRCOX-8 ratio increased to 3.2 +/- 0.3 in the PAN rats but significantly decreased to 2.8 +/- 0.3 with CY treatment. From these data it was impossible to decide whether the effect with CY had direct activity or not, because the interleukin-2 (IL-2) activity was not measured in rats. Secondly, polyethyleneimine (PEI) staining was performed to detect the sites of anion charge on glomerular basement membrane (GBM), and anionic dots on GBM in the CY-treated rats were clearly defined as nearly normal. Although there persist questions as to why nephrotic rats relapsed after the withdrawal of CY treatment, our results indicate that CY might reduce urinary protein excretion through immunological and non-immunological mechanisms.

Animals↗
PubMed1989

Induction of interstitial nephritis in rats by basement membrane of human origin.

A study was conducted to investigate nephritogenic tubular basement membrane antigens common to human and rat kidneys. Brown Norway (BN) rats were immunized with human renal basement membrane in complete Freund's adjuvant simultaneously with Bordetella pertussis vaccine. The immunized rats developed polyuria and increased levels of serum creatinine one week after the second immunization. Renal histology at this time revealed marked, acute tubulointerstitial nephritis with linear deposition of IgG and C3 along the tubular basement membrane and Bowman's capsule, but not along the glomerular basement membrane. Rats with this tubulointerstitial nephritis rapidly developed antibodies against renal antigens from normal BN rats such as tubular basement membrane and proximal tubule brush border, however antibodies to glomerular basement membrane appeared later. Western blotting using the same rat sera detected a 145-kDa antigen from 8 M urea-solubilized human renal basement membrane and 120-kDa, 135-kDa and 145-kDa antigens from 8 M urea-solubilized BN rat renal basement membrane. This suggests that renal basement membranes of human and rat origin have common antigens involved in the pathogenesis of tubulointerstitial nephritis.

Animals↗
PubMed1989

Experimental drug-induced allergic nephritis mediated by antihapten antibody.

Experimental drug-induced allergic nephritis (DIAN) was mediated by an antihapten antibody. It has been postulated that DIAN is induced by cellular and humoral mechanisms. We tried to induce DIAN in mice, where the mechanism depends on humoral immunity. The first attempt was made in mice actively producing antibodies against cephem antibiotics, i.e. cephalothin (CET). Acute interstitial nephritis (AIN), morphologically similar to human disease, was obtained by injection of a CET-protein conjugate into the renal cortex in mice producing anti-CET-IgE and IgG antibodies. AIN could also be induced when normal mice, passively given anti-CET IgG antibody, received a subsequent intrarenal challenge with CET-protein conjugate. These preliminary results indicate that IgG antibody has an important role in the genesis of DIAN. Further experiments were performed with monoclonal antibodies directed against haptens instead of antibiotics in order to clarify the Ig isotype concerned. In mice passively given anti-Dansyl-IgG2a or anti-NP-IgG2a monoclonal antibodies, a challenge with an appropriate hapten-protein conjugate into the renal cortex resulted in AIN. However, transfer of anti-Dansyl-IgE or anti-DNP-IgE monoclonal antibodies, followed by challenge, did not induce AIN. In the experimental systems described, the involvement of a cellular immune mechanism is excluded. The results suggest that IgG, but not IgE antibody, is essential for the induction of DIAN by humoral immune mechanism.

Animals↗
PubMed1989

Corticotropin-releasing factor potentiates the contractile response of rabbit airway smooth muscle to electrical field stimulation but not to acetylcholine.

We studied the effect of corticotropin-releasing factor (CRF) on airway smooth muscle functions in isolated rabbit tracheal segments under isometric conditions in vitro. The addition of ovine CRF synthesized by solid-phase methods did not cause muscle contraction, but it potentiated the contractile response to electrical field stimulation (EFS) at 5 Hz in a dose-dependent fashion, the maximal increase from the baseline response being 43.9 +/- 6.1% (mean +/- SE, p less than 0.001). This effect was not influenced by propranolol, phentolamine, indomethacin, pyrilamine, or (D-Pro2,D-Trp7.9)-substance P, but was completely inhibited by alpha-helical CRF, a CRF receptor antagonist. CRF (10(-7) M) also increased the responses to EFS at all frequencies of stimulation (1 to 40 Hz), so that the stimulus frequency required to produce a half-maximal contraction (ES50) decreased from 7.7 +/- 1.0 to 3.8 +/- 0.6 Hz (p less than 0.01). In contrast, contractile response to administered acetylcholine was not affected by CRF. CRF-induced potentiation of the response to EFS (5 Hz) was further increased from 44.5 +/- 5.4 to 144.6 +/- 11.1% in the presence of physostigmine and was abolished by atropine. These results suggest that CRF prejunctionally potentiates the vagally mediated contraction of airway smooth muscle through activation of CRF receptors on the cholinergic nerve terminals, likely involving the accelerated release of acetylcholine.

Acetylcholine↗
PubMed1989

The somatostatin analog octreotide inhibits the secretion of growth hormone (GH)-releasing hormone, thyrotropin, and GH in man.

The effects of the somatostatin analog octreotide on plasma GH, TSH, and immunoreactive GH-releasing hormone (IR-GHRH) were studied in 10 normal men. After morning sc administration of 50 or 100 micrograms octreotide or placebo, plasma GH, TSH and GHRH were measured frequently for 6 h. Plasma GH or IR-GHRH concentrations did not change after placebo injection, but plasma TSH levels gradually decreased, in conformity with a circadian rhythm during the morning. The mean plasma GH levels after sc injection of 50 or 100 micrograms octreotide declined, and no spontaneous GH pulses occurred for 5 h. Plasma TSH decreased rapidly after both doses of octreotide and was significantly lower than the level after placebo treatment from 90-315 min (P less than 0.05) and 60-360 min (P less than 0.05 or P less than 0.01), respectively. Plasma IR-GHRH levels also were significantly lower from 30-360 min (P less than 0.05) in the group given 100 micrograms octreotide compared with the value in the placebo group. We conclude that octreotide inhibits not only GH and TSH secretion from the pituitary, but also GHRH release from the hypothalamus and/or peripheral tissues. These findings suggest that somatostatin controls GH secretion not only by suppressing pituitary secretion of GH but also by suppressing GHRH release from the hypothalamus.

Adult↗
PubMed1989

[Changes in spinal evoked potentials following local cooling of the spinal cord in the cat].

Potentials evoked by stimulation of the ulnar nerve and the thoracic cord were recorded in the cervical cord of Nembutalized, curarized cats. The sites of the spinal cord stimulated or recorded therefrom were cooled, all together or independently, in 30 cats, and the effects of the cooling on the evoked potentials were investigated. In all cases, the peak latency tended to increase. On the other hand, the amplitude gradually decreased in the cats in which the stimulation site was cooled, gradually increased in the cats in which the recording site was cooled, and transiently increased when the whole area extending from the stimulation site to the recording site was cooled. In 20 cats, the effects of cooling on the anoxic spinal cord were studied. In the hypothermic cats, the evoked potentials disappeared in 24 min, and in the normothermic cats in 13 min. The difference was statistically significant (p less than 0.01). This indicates that cooling could counteract the effects of anoxia to a certain extent.

Animals↗
PubMed1989

[Relationship of nutrition and dietary habits to gingivitis, dental calculus deposit and dental plaque adhesion in high school students].

The purpose of this study was to assess the relationship of nutrition and dietary habits to gingivitis, dental calculus deposit and dental plaque adhesion in high school students. The subjects were 16 third-year students (7 males and 9 females) at a high school in Tokyo. Dietary investigation was made for 4 days from Sunday to Wednesday. Conditions of gingivitis and dental plaque adhesion were examined concerning the labial aspects of 6 anterior mandibular teeth and the condition of the dental calculus deposits of 4 mandibular incisors was examined with respect to their lingual surfaces, then index scores were given according to the severity. The results were as follows: 1) Investigation of nutritive intake revealed that intake of calcium, iron and vegetable in both sexes and intake of vitamins A and B2 in males were insufficient. 2) With regards to the regularity of meals, boys tended to have more unfavorable dietary habits compared with girls, namely, their frequencies of meals and eating between meals, and time of meal were more irregular. 3) The degree of gingivitis, calculus deposit and plaque adhesion were more severe in boys compared with girls. It was suggested that these serious conditions in boys resulted from improper nutrition and dietary habits. 4) A significant negative correlation was observed between the severity of gingivitis and the sufficiency rate of vitamin B2, light-colored vegetable and fat intake. 5) The results of assessing adequacy of nutrition and dietary habits showed that severities of gingivitis and dental calculus deposit were mild in the adequate group with significant difference from those in the inadequate group. 6) From the above, we can conclude that adequate nutrition and proper dietary habits are essential for the health of the periodontinum of high school students.

Adolescent↗
PubMed1988

Effect of alpha-methyl-p-tyrosine and an antiserum to rat growth hormone (GH)-releasing factor (GRF) on plasma GH secretory profile during a continuous infusion of human GRF in rats.

The effects of alpha-methyl-p-tyrosine (alpha-MT) and an antiserum specific to rat growth hormone-releasing factor (GRF) on growth hormone (GH) secretory profile during a 6-h continuous infusion of human GRF(1-44) NH2 were observed in unrestrained adult male Wistar rats. All rats were provided with two indwelling cannulae; one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for 0.9% NaCl or GRF infusion. GRF was administered by an infusion pump at a dose of 50 ng/kg b.wt./min ma GH levels during baseline period were low with little fluctuation. GH secretion was augmented significantly during continuous GRF infusion in control rats but interpeak intervals remained unaltered. When an antiserum specific to rat GRF was administered, episodic GH secretion was abolished. In these rats, pulsatile GH secretion indistinguishable from that of control rats was observed in the continuous presence of human GRF. Although alpha-MT inhibited episodic GH secretion, alpha-MT-treated rats exhibited high-frequency, low-amplitude episodic GH secretion and elevated baseline levels during the stimulation. There were no differences in the amount of GH secreted during GRF infusion between rats that had received either alpha-MT or antiserum to rat GRF. Since GH secretion to GRF is determined largely by somatostatin, the results suggest that phasic release of somatostatin plays an important role in determining the rhythmicity of episodic GH secretion, and that it is modulated by alpha-MT but not by the immunoneutralization of GRF.

Animals↗
PubMed1988

Fine structures of nerve fibers with corticotropin-releasing factor-like immunoreactivity in the rat lateral septum.

The fine structures of nerve fibers with corticotropin-releasing factor (CRF)-like immunoreactivity in the rat lateral septum were investigated by means preembedding immunoelectron microscopy. A number of CRF axon terminals formed synapses with cell bodies of non-immunoreactive septal neurons. They occasionally had broad terminal bulges whose subregions showed little or no immunoreactivity for CRF. CRF axon terminals were also in synaptic contact with non-immunoreactive dendrites or dendritic spines. Some dendrites with CRF were postsynaptic to non-immunoreactive axon terminals.

Animals↗
PubMed1988

Ontogeny and afferent connections of corticotropin releasing factor-like immunoreactivity in the rat neocortex.

The first set of the present experiments was designed to investigate the postnatal development of corticotropin releasing factor-like immunoreactivity (CRFI) in the rat cerebral cortex by means of cobalt-enhanced immunohistochemistry. Results showed the occurrence of CRFI fibres before cells in the developing rat cerebral cortex with and without colchicine treatment, suggesting that some CRFI cells in subcortical regions may project to the cerebral cortex. In the second set of experiments, ipsilateral double-labelled cells which contained both retrogradely transported horseradish peroxidase (HRP) and CRFI were observed in the zona incerta, subincertal nucleus, lateral hypothalamic area, perifornical hypothalamic area, and in the dorsal hypothalamic area after unilateral HRP injections into the cerebral cortex. These findings indicate the existence of corticopetal CRFI-containing projections arising from the above areas.

Animals↗
PubMed1988

CRF-containing neuron systems in the rat hypothalamus: retrograde tracing and immunohistochemical studies.

By employing a combination of the immunohistochemistry for rat corticotropin-releasing factor (rCRF) and retrograde tracing with biotinylated wheat germ agglutinin (b-WGA) injected into the posterior pituitary (group 1) or into the middle portion of the median eminence (group 2), functionally different populations of CRF neurons were identified in the rat hypothalamus. In the group 1 animals, WGA-labeling was seen not only in the posterior lobe but also in the intermediate lobe, in which CRF fibers exist. In these animals, WGA-labeling occurred for almost all large neurons in the anterior commissural, paraventricular (PV), and supraoptic (SO) nuclei, some of the neurons showing a slight immunoreactivity for anti-rCRF. Conversely, CRF positive neurons appeared in large numbers, some being labeled with WGA, in the caudal periventricular region (CPR), and in the dorsomedial to lateral hypothalamic area (DLH), especially in the latter. In the group 2 animals, WGA was disparsed throughout the subependymal, internal, and external layers of the medial portion of the median eminence, and was taken up by many small cells in the PV, almost half of the cells being immunoreactive for CRF. Slight WGA-labeling further occurred in some large neurons of the PV and SO, and in some cells of the DLH. It is concluded that hypophysiotropic CRF existing in the external layer of the median eminence originates from small neurons located in the PV, whereas CRF distributed in the posterior and intermediate pituitary originates from the magnocellular PV and SO, and from some neurons in the DLH and CPR.

Adrenalectomy↗
PubMed1988

Corticotropin releasing factor-containing afferents to the lateral septum of the rat brain.

Corticotropin releasing factor (CRF)-containing afferents to the rat lateral septum (LS) have been determined by means of cobalt-enhanced immunohistochemistry, tracing of retrograde transport of horseradish peroxidase (HRP), and by lesioning experiments. When unilateral lesions included the rostral part of the hypothalamus, CRF-like immunoreactive (CRFI) ipsilateral fibers in the LS decreased in number. Lesions in other brain regions did not cause alterations in the septal CRFI fibers. These findings suggest that the septal CRFI fibers originate in the rostral part of the hypothalamus. Furthermore, combined HRP and immunohistochemical staining on the same sections demonstrated double-labeled cells in two discrete areas within the rostral hypothalamus: one was the perifornical hypothalamic area (PeF) at the level of the paraventricular hypothalamic nucleus, and the other was the most caudal part of the anterior hypothalamic nucleus (AHc). These findings show that a large proportion of the CRFI projections to the LS have their origins in the PeF and AHc.

Animals↗
PubMed1988

Study on the mechanism of abnormal growth hormone (GH) secretion in anorexia nervosa: no evidence of involvement of a low somatomedin-C level in the abnormal GH secretion.

The response of plasma growth hormone (GH) to an iv injection of synthetic human growth hormone-releasing factor (hGHRF-44) (2 micrograms/kg bw) was studied in 23 patients with anorexia nervosa. The basal plasma concentrations of somatomedin-C (Sm-C) in these patients were also measured. Basal plasma GH levels were above normal in 8 out of 23 patients and an exaggerated GH response to hGHRF-44 compared to that in age-matched normal females was found in 9 patients. Mean basal plasma Sm-C concentration in the patients was 0.41 +/- 0.04 U/ml (mean +/- SE), which was in the low normal limit. When 6 patients were reexamined after their weight gain of 4-18 kg as well as their normalization of basal plasma Sm-C levels, their elevation of basal plasma GH level was lowered and the responsiveness to hGHRF-44 improved. However, there was no significant correlation between the Sm-C concentration and basal plasma GH level as well as the integrated GH response to hGHRF-44 expressed as the area under the curve (OhGH). These findings, therefore, suggest that some factor(s) other than the lowered plasma Sm-C level are involved in the mechanism of abnormal GH secretion in patients with anorexia nervosa.

Adolescent↗
PubMed1988

Effect of human growth hormone-releasing hormone on GH secretion in Cushing's syndrome and non-endocrine disease patients treated with glucocorticoids.

The GH response to 100 micrograms human growth hormone-releasing hormone (hGRH) given intravenously was evaluated in eleven patients with Cushing's syndrome who had been ill for more than one year and in six patients with non-endocrine diseases who were treated with glucocorticoid for one to twelve weeks. Extremely low to no response of plasma GH to hGRH injection was noted in all seven patients with Cushing's disease and in four patients with Cushing's syndrome due to an adrenal adenoma or carcinoma. In contrast, all six patients with non-endocrine diseases who were treated with glucocorticoid showed normal GH responses to hGRH. These results suggest that the diminished hGRH-induced GH secretion in patients with Cushing's syndrome might be caused by the prolonged period of hypercortisolemia.

Adult↗
PubMed1988

Involvement of corticotropin-releasing factor in restraint stress-induced anorexia and reversion of the anorexia by somatostatin in the rat.

The mechanism by which restraint stress induces suppression of food intake and the influence of intracerebroventricular (icv) administration of somatostatin on the anorexia induced by restraint stress were examined in the rat. Ninety minutes of restraint stress reduced food intake of rats to approximately 60% that of control. Anorexia induced by 90 min restraint stress was partially reversed by icv administration of alpha-helical CRF (9-41), a corticotropin-releasing factor (CRF) antagonist, and completely reversed by anti-CRF gamma-globulin. These results provide further evidence in support of the theory that CRF is involved in the inhibitory mechanism of food intake in restraint stress. ICV administration of somatostatin 14 and SMS 201-995, an analog of somatostatin, also reversed restraint stress-induced anorexia. It is, therefore, suggested that somatostatin may counteract the suppressive action of CRF on food intake in stress.

Animals↗
PubMed1988

Corticotropin-releasing factor reverses the effect of pentobarbital through a beta-noradrenergic mechanism in rats.

Corticotropin-releasing factor (CRF) has been shown to reverse effect of pentobarbital (PbNa) within the central nervous system. In this study, the mechanism of the antagonistic effect of CRF on PbNa-induced anesthesia and hypothermia in rats was examined. Intraventricular administration of CRF significantly shortened sleeping time and antagonized hypothermia induced by PbNa. Propranolol (148 micrograms, 0.5 mumol), a beta-blocker, completely reversed the CRF effect, although propranolol alone affected neither sleeping time nor rectal temperature. Phentolamine, an alpha-blocker, reversed the antagonistic effect of CRF on PbNa, though the same dose of phentolamine alone increased the sleeping time in the absence of CRF. Atropine, an anticholinergic agent, did not affect the ability of CRF to reverse the effects of PbNa. These results suggest that the ability of CRF to reduce some of the effects of PbNa may be mediated at least in part by brain beta-noradrenergic receptors.

Anesthesia↗