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Biomedical subjects

Y Yoshimoto

Publications and source records attributed to Y Yoshimoto.

At least 91 records · Page 5Linked to original sources

Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging.

Studies have suggested that the restorative effects of adrenal medullary chromaffin cell grafts in animal models of Parkinson's disease may be related to trophic factors contained within the chromaffin cells. Basic fibroblast growth factor (bFGF) is present in chromaffin cells and has been shown to exert trophic effects on dopaminergic neurons in vitro. Basic FGF was stereotaxically injected into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice which had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. MPTP treatment reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and striatal dopamine (DA) concentration in both the young and older mice 5 weeks later. Computerized image analysis of striatal DA fibers in young mice treated with bFGF showed significant recovery of DA fibers up to 600 microns from the injection site 5 weeks after MPTP administration. Striatal DA fibers in older mice treated with bFGF showed significant recovery only up to 300 microns from the injection site, and the degree of recovery was very limited compared with young mice. HPLC analysis of DA concentration revealed that striatal DA in young mice recovered significantly when treated with bFGF, but no significant recovery was observed in older mice. It is concluded that bFGF enhances the recovery of striatal DA systems from MPTP toxicity both in young and in older mice, but that such benefits are very limited in older mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Suppression of immunorejection against rat fetal dopaminergic neurons in a mouse brain by 15-deoxyspergualin.

In this study, the immunosuppressive effect of 15-deoxyspergualin (DSG) on the survivability of rat embryonic dopaminergic neurons grafted into the lateral ventricle of adult mice was investigated. DSG was administered daily in dose of 5 mg/kg for 2 weeks postgrafting, commencing on the day of transplantation, in the immunosuppressant-treated groups. Animals were then allowed to survive for 2 to 4 weeks after transplantation. Histological analysis revealed that most of transplanted rat fetal neural tissue was destroyed and scavenged in 2 weeks after transplantation in the non-immunosuppressed group. However, a large number of tyrosine hydroxylase (TH)-positive grafted neurons survived and grew postgrafting in the brain of the host administered with DSG even if they suffered from T lymphocyte infiltrations visualized by cytotoxic T cell immunohistochemistry. The results thus indicated that DSG is an potent immunosuppressant in neural transplantation as well as in transplantation of other organs in animals. It seems to be able to block, at least in part, the ability of mature specific cytotoxic T cells to lyse their targets.

Animals↗

Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurologic patients: a replication of neuroendocrine features of major depression.

A blunted thyrotropin (TSH) and an unaltered prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) are widely recognized in neuroendocrinology of depression. We studied effects of repeated TRH administration of 1 mg/day for 10 days on the pituitary-thyroid axis function and PRL secretion in 16 euthyroid patients with neurological disorders. Although levels of serum thyroid hormones and of nonstimulated PRL were not affected by the treatment, baseline TSH levels were markedly inhibited. A blunted response of TSH to TRH was found without a significant effect on a PRL response to TRH after long-term treatment with TRH in four patients in whom a TRH test was performed. These changes are similar to those in depressed patients. TRH administration in this manner replicates a lowered sensitivity of thyrotrophs of the pituitary with a normal responsibility of lactotrophs in depression.

Aged↗

Oscillation of intracellular free calcium in cleaving and cleavage-arrested embryos of Xenopus laevis.

Changes in the intracellular free calcium levels in the cortical region of cleaving Xenopus eggs were examined using semi-synthetic aequorin. We detected periodic oscillations in the free calcium levels accompanying the cleavage cycle as early as the first cleavage onward. The calcium levels began to increase at early interphase and were maximal during metaphase of mitosis. Eggs injected with colchicine to inhibit cleavage showed periodic oscillations in the calcium levels similar to those of normal eggs. This fact indicates that the furrowing process is not necessary for the periodic changes in the intracellular free calcium levels, but the changes are associated with the autonomous periodic cytoplasmic activity which controls cell cycle events.

Aequorin↗

Long-term effects of cografts of pretransected peripheral nerve with adrenal medulla in animal models of Parkinson's disease.

Trophic factor supplementation has been reported to enhance the survivability of grafted adrenal chromaffin cells. Because the content of nerve growth factor in the distal stump of a pretransected peripheral nerve increases markedly 1 day after transection, we injected cografts of adrenal medulla with pretransected peripheral nerve into the striata of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and performed follow-up histological and neurochemical analyses over a 12-month period. Adrenal medullary chromaffin cells cografted with pretransected peripheral nerve survived better than in adrenal grafts alone at 1, 3, and 12 months after transplantation. Host dopaminergic fiber recovery adjacent to the grafts was more prominent in mice with cografts than in mice with adrenal grafts alone at 1 and 3 months after transplantation. Twelve months after transplantation, however, there was no significant difference between the two groups of animals because of the natural recovery of intrinsic dopaminergic fibers from MPTP toxicity. Dopamine concentration in the striata of cografted mice was higher than in mice with adrenal grafts alone at 1 month after transplantation. At 3 and 12 months after transplantation, the natural recovery of dopamine concentration from MPTP toxicity was apparent in both groups of animals and no significant difference was observed between the groups. We conclude that adrenal medullary chromaffin cells can survive for at least 12 months after grafting when cografted with pretransected peripheral nerve. Cografts enhanced the recovery of the host nigrostriatal dopaminergic system up to 3 months after transplantation, but this enhancement was not apparent at 12 months because of the natural recovery of dopaminergic fibers from MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Temporal profile and significance of metabolic failure and trophic changes in the canine cerebral arteries during chronic vasospasm after subarachnoid hemorrhage.

To investigate the pathogenetic significance of metabolic failure observed in spastic cerebral arteries after subarachnoid hemorrhage (SAH), the temporal profile of alterations in the arterial content of high-energy phosphates was studied. A canine model of double hemorrhage was used. Constriction of the basilar artery was measured angiographically on Days 3, 5, 7, and 14 after SAH in separate groups of animals. Adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), guanosine triphosphate (GTP), guanosine diphosphate, creatine phosphate (CrP), and creatine (Cr) levels in the arteries were assayed using high-performance liquid chromatography. A time-dependent development of angiographic spasm was confirmed. A mild vasospasm was seen in the group studied 3 days after SAH, progressed in the Day 5 group, remained comparably severe in the Day 7 group, and resolved partially in the Day 14 group. The content of high-energy phosphates (ATP, GTP, and CrP) declined rapidly over the course of the study, and a significant reduction in ATP, GTP, and CrP was observed in the Day 3 group. Levels of ATP and CrP decreased further in the Day 5 and 7 groups. The decrement in GTP was completed in the early phase; a significant reduction took place in the Day 3 group, with no progression thereafter and no recovery through Day 14. Total adenylate (ATP + ADP + AMP) and total creatine (Cr + CrP) content diminished markedly over the course of the study. These results indicate that metabolic failure and trophic disturbance in the cerebral artery occurs with a rapid onset following SAH and progresses in close association with the development of vasospasm, suggesting a significant causal relationship with the pathogenesis.

Adenosine Triphosphate↗

Monoclonal gammopathy in atomic bomb survivors.

An analysis of monoclonal gammopathy in relation to radiation exposure was conducted on atomic bomb survivors examined between October 1979 and September 1981 and between June 1985 and May 1987. There was no overall increase in the relative risk of monoclonal gammopathy and only a suggestive increase in benign monoclonal gammopathy in the second survey which did not achieve statistical significance (P = 0.17). Thirty-one cases were detected among 8796 individuals studied in the first survey, whereas 68 cases were found among 7350 people in the second survey. Among the 31 cases found in the first survey, 9 individuals (29%) died before the second survey: 4 of cancer, 4 of vascular disease, and 1 of infection. Among the 8 individuals with benign monoclonal gammopathy examined in both surveys, 4 developed suppression of residual immunoglobulin(s), suggesting the progression of monoclonal gammopathy. The overall relative risks of monoclonal gammopathy in atomic bomb survivors in the two surveys were not significantly increased with increasing radiation dose. Only benign monoclonal gammopathy in 1985-1987 showed a suggestive increase with radiation exposure. The relative risk of benign monoclonal gammopathy in 1985-1987 was 2.64 in the group exposed to 0.01-0.49 Gy and 2.14 in the > or = 0.50-Gy group (95% confidence intervals = 0.90-8.82 and 0.69-7.31, respectively).

Female↗

[Studies on urinary apolipoprotein H in diabetics].

In order to elucidate the diagnostic significance of urinary apolipoprotein H (apo H), known as beta 2-glycoprotein I, urinary apo H levels were measured by a non-competitive enzyme immunoassay in diabetics without hypertension and Albustix-positive proteinuria. The relationships between urinary apo H levels and urinary albumin (Alb) levels as well as clinical profiles in diabetics were investigated. The mean urinary apo H level in 45 diabetics was 264.2 +/- 189.5 micrograms/g.cr, and significantly higher than that in 41 healthy subjects (120.6 +/- 84.8 micrograms/g.cr, p < 0.01). Diabetics were classified into three groups based on urinary Alb levels; 17 group I patients with normoalbuminuria (U-Alb < 15mg/g.cr), 12 group II patients, whose urinary Alb levels were in between normo- and microalbuminuria (15 < or = U-Alb < 30mg/g.cr) and 16 group III patients with microalbuminuria (30 < U-Alb < or = 300mg/g.cr). The mean urinary apo H level in group I patients, who were regarded as without nephropathy, was 199.2 +/- 109.0 micrograms/g.cr, significantly higher than that in normal subjects (p < 0.01). The mean urinary apo H levels in group II and III were 271.4 +/- 177.1 and 327.8 +/- 246.1 micrograms/g.cr, respectively. These values were also higher than in normal subjects (both of p < 0.01). Urinary apo H levels correlated positively with urinary levels of glycosaminoglycan (r = 0.382, n = 45, p < 0.01), which was regarded as an indicator of the anion loss from glomerular basement membrane to urine, and with urinary N-acetyl-beta-D-glucosaminidase activities (r = 0.378, n = 37, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Cool storage of fetal rat brain for neural transplantation].

The availability, storage and transportation of donor tissue are major practical problems associated with the potential use of grafted neural cell replacements in neurodegenerative diseases. The capacity to collect and maintain viable fetal neural tissue would facilitate possible clinical applications, and provide opportunities to study various neural diseases. In the present study, we examined the effect of cool storage on the survivability of intraventricular rat fetal ventral mesencephalic grafts (gestational days 15). In all experiments, fetal ventral mesencephalons were dissected out under a dissecting microscope in calcium-free magnesium-free buffer (CMF: 0.15 M NaCl, 0.008 M Na2HPO4, 0.0027 M KCl, 0.0015 M KHPO4, 0.026 M NaHCO3, with 0.1% glucose, 100 micrograms/ml streptomycin, 2.5 micrograms/ml fungizone). Fetal mesencephalic tissue was grafted into the lateral ventricle following pregraft refrigeration in calcium-free magnesium-free buffer at 4 degrees C. Fetal mesencephalic tissue was hibernated for 5, 12, 16, 20, 24, 28, 32 hours (group A, B, C, D, E, F and G, respectively). As a control group, fetal mesencephalic tissue was grafted into the lateral ventricle immediately after dissection. Grafted fetal mesencephalic tissue which had been hibernated for 16 hours or less survived well. There were no significant decreases in the size of grafts among group A, B, C and the control group. In group A, B, C and the control group, clusters of TH-positive neurons and dense networks of neuritic profiles within the grafts provided a morphological appearance reminiscent of the dendritic bundles that characterize the zone reticulate of the substantia nigra in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of transethmoidal encephalocele].

A case of a 3-year-old boy with transethmoidal encephalocele is presented. The patient was found to have bacterial meningitis, which responded well to an intravenous antibiotics therapy. No physical anomaly was evident on examination but plain skull X-ray film showed cloudiness of the left nasal antrum. Coronal CT scan disclosed a defect in the left cribriform plate and soft tissue mass in the left nasal cavity. MRI showed an anterior basal encephalocele protruding into the nasal cavity. Hypothalamic-pituitary system and the optic nerves appeared normal in the sagittal image. CSF rhinorrhea was confirmed by RI cisternography. An operation was performed transcranially. After a left frontal craniotomy, a unilateral bony defect in the cribriform plate and protrusion of the brain was observed subfrontally. The crista galli was intact. The herniated brain substance was transected and partially removed and the bony defect plugged by temporal muscle and covered by lyofirized dura. Microscopic examination of the herniated brain mass revealed gliosis and capillary proliferation. The patient recovered well and there has been no recurrence of CSF rhinorrhea or meningitis. Basal encephalocele is a very rare congenital anomaly. It is reported to constitute 1 to 10% of all encephaloceles. Incidence is estimated as 1 in every 35,000 to 40,000 live births. The anomaly is classified into two subtypes; transethmoidal (TE) and transsphenoidal (TS).(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

[Intrathecal dissemination of meningiomas; a case report].

A case of the cytologically verified intrathecal dissemination of benign meningiomas was reported. A 36-year-old man was admitted to our hospital because trans-sphenoidal surgery was planned for the repair of CSF rhinorrhea caused by a recurrent pituitary adenoma. The CT scan demonstrated incidental multiple tumors spread throughout in the pontomedullary and ambient cisterns. The head and spinal MRI showed more than fifteen small tumors in the posterior fossa and the thoracic spinal canal. CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body. Several comments were made on the mechanism of the intrathecal dissemination of the meningiomas.

Adult↗

The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents.

This study examines the effect of a novel immunosuppressive agent FK-506 (FK) on the survivability of embryonic (E14) rat ventral mesencephalic tissue after intracerebral grafting to the lateral ventricle of adult mice. The recipient mice were given FK in doses of 10 mg/kg or 1 mg/kg for 2 weeks postgrafting, at which time they were sacrificed and histologically processed except for one group of animals on the high dose (10 mg/kg). In this group most animals died from side effects of the drug during the following days. Only the mice receiving the high dose of FK displayed healthy grafts without signs of rejection.

Animals↗

Correlates of cortical bone mass among premenopausal and postmenopausal Japanese women.

Few studies have examined the multifactorial risk factors of bone mass in Asian populations. This cross-sectional study was designed to explore relationships between bone mass and environmental variables, including dietary and life-style factors, in Japanese women living in Japan. A total of 178 Japanese women completed the study: 89 premenopausal, ages 35-40, and 89 postmenopausal, ages 55-60. Midradial bone mineral content (MBMC) and bone mineral content per unit area, referred to as bone density (MBMD), were measured using single-photon absorptiometry. The major results of this investigation were the following: (1) The postmenopausal women differed significantly from the premenopausal women in having lower radial bone parameters, lower mean height, later age of menarche, and higher dietary intakes of carbohydrates, vegetables, and milk with a lower intake of caffeine. (2) Current protein intake was a positive correlate of MBMC in both groups. (3) Intake of vegetables (leafy green, yellow, orange, and white) and current milk intake were positively associated with MBMC in the postmenopausal women. (4) For the premenopausal women, irregular menstrual cycles was a negative correlate of MBMC, and for the postmenopausal women, years of menopause was negatively associated with MBMC and MBMD. Longitudinal studies are needed to establish more conclusively associations among diet, life-style, and reproductive history and bone mass of Japanese women.

Adult↗

The interferon family stimulates the secretions of prolactin and interleukin-6 by the pituitary gland in vitro.

The effects of interferon-alpha, interferon-beta 1 and interferon-gamma on the secretions of prolactin (PRL) and interleukin-6 by primary cultured rat anterior pituitary cells were examined. These three interferons caused dose-dependent increases in PRL secretion within 30 min, and dose-dependent stimulation of interleukin-6 were weaker than the effects of interleukin-1 and tumor necrosis factor-alpha. These results suggest that interferons regulate PRL secretion from the pituitary gland, and that there may be a pathway in which interferons stimulate PRL secretion through interleukin-6 release.

Analysis of Variance↗

Interleukin-6 stimulates gonadotropin-releasing hormone secretion from rat hypothalamic cells.

There are reports that both interleukin-1 beta and interleukin-6 (IL-6) stimulate the release of adrenocorticotropin through stimulation of hypothalamic corticotropin-releasing factor. We established a primary culture system for hypothalamic neurons producing gonadotropin-releasing hormone (GnRH) and examined whether IL-6 stimulated their GnRH secretion. We demonstrated immunohistochemically that some of these neurons contained GnRH-like immunoreactivity. In primary cultures of these GnRH neurons, we found that the calcium ionophore A23187 stimulated GnRH secretion in a dose- and time-dependent manner. These hypothalamic cells secreted IL-6 spontaneously, producing about 10 ng/l in 24 h, and their IL-6 secretion was significantly stimulated by E2 at 10(-9)-10(-8) mol/l. This stimulatory effect was observed within 3 h. IL-6 also stimulated the release of GnRH in a dose- and time-dependent manner, and these effects of IL-6 were significantly blocked by anti-IL-6 antiserum. These results suggest that the central action of IL-6 on the GnRH neurons may be an important physiological event in the hypothalamus.

Animals↗

Mortality among the offspring (F1) of atomic bomb survivors, 1946-85.

We compare the mortality in the years 1946-85 in a cohort of 31,159 children born to parents one or both of whom were exposed to the atomic bombing of Hiroshima and Nagasaki (a parental gonadal dose greater than or equal to 0.01 Sv) with that in a control group of 41,069 children. The average gonadal dose for the exposed parents was 0.435 Sv. The mean age of the cohorts was 28.8 years. In the greater than or equal to 0.01 Sv dose group 1,253 deaths were observed in the subset of children both of whose parents have been assigned DS86 doses. 3.2% were attributed to cancers, 72.9% to all diseases except neoplasms. These proportions in the 0 Sv dose group were about the same. Based on a linear relative risk model, no statistically significant increase in the mortality attributable to diseases other than neoplasms is noted following parental exposure, the excess relative risk being 0.030 (+/- 0.046) per sievert based on the DS86 doses (RBE of neutrons = 20). For fatal cancer, no statistically significant effect of parental radiation dose was also observed. An analysis based on the full sample, using not only the DS86 dose group but also ad hoc dose group, yields essentially the same results as the analysis restricted to the DS86 dose group.

Adult↗

Thyroid cancer: epidemiological study of thyroid cancer in A-bomb survivors from extended life span study cohort in Hiroshima.

We analysed thyroid cancers which were diagnosed clinically or detected at autopsy during 22 years (1958 to 1979) in a sample of 75,493 study subjects exposed in Hiroshima belonging to the extended LSS sample of the Radiation Effects Research Foundation. One hundred and twenty-five cases of clinical thyroid cancer (15 in males and 110 in females) were confirmed, giving a crude incidence rate per 100,000 person-years of 2.7 for males, 12.4 for females and 8.6 for both sexes combined. There was a significant increase of thyroid cancer with increase of atomic bomb radiation dose (thyroid tissue dose based on T65D) in females and in the sexes combined. This tendency was predominant in those exposed at less than 19 years of age. Compared to the control group, the relative risk in the greater than or equal to 0.50 Gy group was higher at 4.0 for males (not significant) and at 4.3 for females (p less than 0.01). Latent thyroid cancer was detected in 155 cases or 3.5% (2.5% for males and 4.5% for females) of the 4,425 cases that came to autopsy during the same period. Compared to the control group, the relative risk in the 50+ rad group was 1.7 for males (not significant), 2.0 for females (p less than 0.05) and 1.9 for both sexes combined (p less than 0.05). New data obtained from autopsy cases between 1950 and 1985 have been added.

Female↗