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Biomedical subjects

Y Yoshimoto

Publications and source records attributed to Y Yoshimoto.

At least 109 records · Page 6Linked to original sources

A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Cancer risk among in utero-exposed survivors.

The Radiation Effects Research Foundation (RERF) continues to conduct a follow-up study initiated some years ago of cancer mortality and incidence among the survivors of the atomic bombing of Hiroshima and Nagasaki exposed in utero. Although only 18 incident cases of cancer were identified in the years 1950-1984 (of which 5 cases were in the 0 dose group), cancer risk appears to increase significantly as maternal uterine dose increases. Only two cases of childhood cancer were observed among these individuals in the first 14 years of life; both had been exposed to greater than or equal to 0.30 Gy. All other cases developed cancer in adulthood, and the cancers they developed are, in the main, the ones known to be elevated in frequency among the postnatally exposed survivors. The estimated relative risk for cancer at 1 Gy (uterine dose) is 3.77. The results suggest that the in utero group may have a higher risk than that seen among exposed adults because the individuals exposed in utero have not reached the major cancer prone age. However, since the observed cases are too few to allow a site-specific review, further follow-up studies are required to determine if the observed increased cancer risk can definitely be attributed to A-bomb radiation, although there appears to be a significant dose-related cancer response.

Child↗

Mortality and cancer risk among the offspring (F1) of atomic bomb survivors.

The Atomic Bomb Casualty Commission (ABCC) and its successor Radiation Effect Research Foundation (RERF) has over the years conducted many studies to determine possible genetic effects of atomic bomb radiation among the offspring of atomic bomb survivors. Findings concerning mortality and cancer incidence of the offspring are summarized in this chapter.

Child↗

Effect of TNF-alpha on prolactin secretion from rat anterior pituitary and dopamine release from the hypothalamus: comparison with the effect of interleukin-1 beta.

The effects of human recombinant interleukin-1 beta and -6 and tumor necrosis factor-alpha (TNF-alpha) on the releases of PRL and dopamine were examined using monolayer cultures of rat pituitary cells and hypothalamic cells. The release of PRL from rat pituitary cells in 30 min was increased about 2-fold (p less than 0.05) by 10(5) U/l interleukin-1 beta, 10(5) U/l interleukin-6 or 100 micrograms/l TNF-alpha. TNF-alpha at 100 micrograms/l significantly increased PRL release within 5 min incubation and this effect continued throughout the next 30 min of incubation. Incubation for 5 min with TNF-alpha caused dose-dependent stimulation of PRL release. These cytokines did not modulate [3H]-dopamine release from primary cultures of hypothalamic cells. These results suggest that these cytokines stimulate PRL release directly at the pituitary gland, without modifying the release of dopamine from the hypothalamus.

Animals↗

[The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents--comparison with cyclosporin A].

The present study was performed to compare the immunosuppressive effect of FK-506 (FK) with cyclosporin A (CyA) in xenogeneic neural transplantation in rodents. The solid grafts of embryonic ventral mesencephalic tissue from 14-day rat embryos were transplanted into the right lateral ventricle of 20 mature male mice using a stereotactic approach, and the mice were sacrificed 14 days after transplantation. The removed brains, which were sectioned coronally, were stained with antibodies against glial fibrillary acidic protein (GFAP), Lyt-2 or tyrosine hydroxylase (TH) in addition to hematoxylin-eosin and Nissl stainings. The subcutaneous (s.c.) administration of FK at a dose of 10.0 mg/kg daily for 14 days enabled the neural xenografts to survive and grow (n = 5), although all of the neural xenografts treated with CyA at a dose of 10.0 mg/kg s.c. (n = 5) or FK at a dose of 1.0 mg/kg s.c. (n = 5) daily for 14 days and ones treated without such an immunosuppressive agent (n = 5) were rejected by immunological reactions. We conclude that FK is a more powerful immunosuppressive agent than CyA in xenogeneic neural transplantation as well as in cardiac and renal allograftings.

Animals↗

[Enzyme immunoassay of urinary apolipoprotein H and its application for detecting incipient diabetic nephropathy].

In order to elucidate the clinical significance of urinary apolipoprotein H (Apo H), otherwise known as beta 2-glycoprotein I, we first developed a non-competitive enzyme immunoassay (EIA) to quantify urinary Apo H levels. The measurable range of this assay was about 2 ng/ml to 100 ng/ml. The intra- and inter-assay coefficients of variation were 2.0 to 4.7% and 8.3 to 17.0%, respectively. These results indicated that this assay had high sensitivity and good reproducibility, and that it was useful for clinical study. We then determined urinary Apo H levels in 24 normal subjects and 36 diabetics using this assay. The mean urinary Apo H index (urinary Apo H/cr ratio), in 20 patients without proteinuria, who were regarded as patients without nephropathy, was 569 +/- 560 (X10(-3) mg/g.cr) and significantly higher than in normal subjects (252 +/- 147, p less than 0.01). The mean urinary Apo H index in 16 patients with overt proteinuria was 1,507 +/- 3,701 and also higher than in normal subjects (p less than 0.01). These results taken collectively indicate that urinary Apo H level using the EIA may be a new sensitive marker for detecting minor change of glomerular basement membrane in diabetics.

Adult↗

A case of acquired nystagmus alternans associated with acute cerebellitis.

A case of acquired nystagmus alternans (alternating nystagmus) is reported. The patient was a 14-year-old boy who presented with fever and headache, followed by dysbasia, truncal ataxia, and positional vertigo. Neuro-otological examinations revealed spontaneous downbeat nystagmus, bilateral gaze nystagmus and rebound nystagmus. Both cell count and protein volume were elevated in the cerebrospinal fluid, and a diagnosis of cerebellitis was made. About one month later, nystagmus alternans was observed, but it disappeared after 7 months. The presence of spontaneous downbeat nystagmus, rebound nystagmus, as well as cerebellar signs indicated that a cerebellar lesion was mainly responsible for the nystagmus alternans in this patient.

Acute Disease↗

Cancer risk among children of atomic bomb survivors. A review of RERF epidemiologic studies. Radiation Effects Research Foundation.

This article summarizes recent epidemiologic studies of cancer risk among the children of atomic bomb survivors conducted at the Radiation Effects Research Foundation. These children include two groups: (1) the in utero-exposed children (ie, those born to mothers who had been pregnant at the time of the bombings of Hiroshima and Nagasaki) and (2) the F1 population, which was conceived after the atomic-bombings and born to parents of whom one or both were atomic bomb survivors. Although from 1950 to 1984 only 18 cancer cases were identified among the in utero sample, cancer risk did appear to significantly increase as maternal uterine dose increased. However, since the observed cases are too few in number to allow a site-specific review, the increased cancer risk cannot be definitively attributed to atomic bomb radiation, as yet. For those members of the F1 population who were less than 20 years old between 1946 and 1982, cancer risk did not appear to increase significantly as parental gonadal dose increased. Follow-up of this population will continue to determine if the patterns of adult-onset cancer are altered.

Abnormalities, Radiation-Induced↗

Cortical alveolus breakdown in the eggs of the freshwater teleost Rhodeus ocellatus ocellatus.

Cortical alveoli and their breakdown in the eggs of the rose bitterling were morphologically investigated. Cortical alveoli of various sizes existed in multiple layers within the cortical cytoplasm of each egg. Two types of cortical alveoli were recognized--one possessed homogeneous contents; the other possessed heterogeneous contents with electron-less dense spots. The eggs were activated by a penetrating spermatozoon or by immersion in fresh water. The immersion of the eggs into fresh water induced a wave of cortical alveolus breakdown (CABD), which was propagated from the vegetal pole to the animal pole. When eggs were inseminated in fresh water, CABD progressed from both the vegetal and the animal poles of the egg, and was complete within about 20 min. The contents of the cortical alveoli were released into the perivitelline space through a large opening formed by the fusion of the plasma and cortical alveolar membranes. For a short time after CABD, the smooth inner surfaces of the cortical alveoli were readily discernible from the rougher original plasma membrane. About 30 min after immersion in fresh water, the inner surfaces of the cortical alveoli were indistinguishable from the original egg surfaces. Aequorin-injected eggs became luminescent immediately after their immersion in fresh water. The luminescence reached a maximum level about 15 min later and subsided after roughly 30 min. The result shows that increase in intracellular free Ca ions occurs during CABD.

Aequorin↗

Catecholaminergic afferents to the cat median eminence as determined by double-labelling methods.

The localization of dopaminergic and non-dopaminergic neuronal perikarya sending axons to the median eminence was investigated in the cat by using two colour double-immunostaining techniques. Unconjugated cholera toxin and wheat germ agglutinin were used as retrograde tracers and injected respectively into the median eminence and the neuro-intermediate pituitary of the same animal. As controls, cholera toxin was also injected into the arcuate (infundibular) nucleus or third ventricle. The retrograde labelling of one of the tracers was combined with tyrosine hydroxylase immunohistochemistry as a marker for dopaminergic neurons. The retrograde labelling studies of cholera toxin alone and the double-immunostaining of cholera toxin and wheat germ agglutinin on the same sections revealed that the cat median eminence receives major afferent projections originating in midline hypothalamic nuclear groups such as the anterior periventricular nucleus, the periventricular part of the paraventricular nucleus and the arcuate nucleus; minor afferent projections arise from the anterior hypothalamic area, the rostral part of the medial preoptic area around the organum vasculosum of the lamina terminalis and to a lesser extent from the posterior hypothalamic region. We further determine that the rostral part of the parvocellular arcuate neurons constitutes the main source of dopaminergic afferents to the median eminence in the cat brain.

Animals↗

Lower brainstem afferents to the cat posterior hypothalamus: a double-labeling study.

Using a double-immunostaining technique with cholera toxin (CT) as a retrograde tracer, the authors examined the cells of origin and the histochemical nature of lower brainstem afferents to the cat posterior hypothalamus. The posterior hypothalamus, in particular the lateral hypothalamic area, receives substantial afferent projections from: substantia nigra, peripeduncular nucleus, ventral tegmental area, periaqueductal grey, mesencephalic reticular formation, peribrachial region including the locus coeruleus complex, rostral raphe nuclei and the rostral part of the nucleus magnus. In addition, a moderate number of retrogradely labeled neurons was found in: Edinger-Westphal nucleus, nucleus reticularis pontis oralis, nucleus reticularis magnocellularis, caudal lateral bulbar reticular formation around the nucleus ambiguus and lateral reticular nucleus and the nucleus of the solitary tract. The posterior hypothalamus receives: 1) dopaminergic inputs from A8, A9 and A10 cell groups; 2) noradrenergic inputs from A6 and A7 pontine, as well as A1 and A2 bulbar cell groups; 3) adrenergic inputs from C1 cell group in the caudal medulla; 4) serotoninergic inputs from the rostral raphe nuclei (B6, B7 and B8 cell groups); 5) cholinergic inputs from the peribrachial region of the dorsal pontine tegmentum as well as from the nucleus reticularis magnocellularis of the medulla; 6) peptidergic inputs such as methionine-enkephalin, substance P, corticotropin-releasing factor and galanin that originate mainly in the mesencephalic periaqueductal grey, the dorsal raphe nucleus and the peribrachial region of the dorsal pontine tegmentum.

Acetylcholine↗

Interleukin 1 beta and tumour necrosis factor alpha stimulate the release of gonadotropin-releasing hormone and interleukin 6 by primary cultured rat hypothalamic cells.

The abilities of recombinant human interleukin 1 beta and tumour necrosis factor alpha to induce release of GnRH and interleukin 6 from primary culture of rat hypothalamic cells were examined. The effect of estradiol on the release of interleukin 6 by these cells was also tested. Both interleukin 1 beta and tumour necrosis factor alpha caused significant stimulation of GnRH secretion from the hypothalamic cells within 5 min. The hypothalamic cells secreted interleukin 6 spontaneously, and their secretion over 24 h was stimulated dose-dependently by interleukin 1 beta, tumour necrosis factor alpha and estradiol. These results suggest that interleukin 1 beta and tumour necrosis factor alpha stimulate the secretions of GnRH and interleukin 6 in the hypothalamus, and that these cytokines may be involved in the mechanism of GnRH secretion in the hypothalamus.

Animals↗

[Basic studies on glass ceramics. 3. Influence on calcification of osteogenic cells in vitro].

Two established osteogenic cell lines (NY, MC 3 T3-E 1) were used in vitro to determine the biocompatibility of glass ceramics and their effect on initial calcification of osteogenic cells. Morphological study of the cell under the phase-contrast microscopy and histochemical staining were applied as follows. First, glass ceramic granules were placed in 60 mm dishes, and cells were suspended in the dishes in alpha-MEM supplemented with 10% FBS (basic medium) or medium with 50 micrograms/ml of L-ascorbic acid added. After 8 or 14 day of culturing, calcium formation was tested by von-Kossa's staining. Also, alkaline phosphatase staining was performed by the azo-dye method. As controls, cultures in dishes without glass ceramic granules were stained at the same time. The results obtained in the experimental culture were as follows. 1. Phase contrast microscopy showed that contacts with glass ceramics did not cause cellular death or degeneration. 2. In both cell cultures with the glass ceramics the von-Kossa reaction was positive as early as the 8th day. 3. The alkaline phosphatase reaction on the 8th day occurred only in MC 3 T3-E 1. The reaction was localized on fibroblastic cells which proliferated three-dimensionally around glass ceramics, and on small polyhedral cells situated relatively for apart from the ceramics. 4. On the 14th day, the MC 3 T 3-E 1 formed large nodules around the glass ceramics, and they were stained uniformly positive by von-Kossa's method. The alkaline phosphatase-positive cells extended spoke-like forms. 5. In medium with L-ascorbic acid, growth of NY was inhibited, After being cultured for 14 days, abundant von-Kossa positive reaction was found around glass ceramics in both cells. In MC 3 T 3-E1 on the 8th days, the alkaline phosphatase reaction was stronger with glass ceramics than with basic medium only. On the contrary, in the control cultures of both cells there was negative von-Kossa reaction during the culture period. The above results showed that glass ceramic granules have the biocompatibility needed for bone grafts, and they facilitated calcification of MC 3 T 3-E 1 in culture.

Alkaline Phosphatase↗

Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors.

The risk of cancer (incidence) prior to age 20 years has been determined for children born to atomic bomb survivors and to a suitable comparison group. Tumor ascertainment was through death certificates and the tumor registries maintained in Hiroshima and Nagasaki. The rationale for the study stemmed from the evidence that a significant proportion of such childhood tumors as retinoblastoma and Wilms tumor arise on the basis of a mutant gene inherited from one parent plus a second somatic cell mutation involving the allele of this gene. Gonadal radiation doses were calculated by the recently established DS86 system, supplemented by an ad hoc system for those children for one or both of whose parents a DS86 dose could not be computed but for whom an ad hoc dose could be developed on the basis of the available information. The total data set consisted of (1) a cohort of 31,150 live-born children one or both of whose parents received greater than 0.01 Sv of radiation at the time of the atomic bombings (average conjoint gonad exposure 0.43 Sv) and (2) two suitable comparison groups totaling 41,066 children. Altogether, 43 malignant tumors were ascertained in the children of exposed parents, and 49 malignant tumors were ascertained in the two control groups. A multiple linear regression analysis revealed no increase in malignancy in the children of exposed parents. However, examination of the data suggested that only 3.0-5.0% of the tumors of childhood that were observed in the comparison groups are associated with an inherited genetic predisposition that would be expected to exhibit an altered frequency if the parental mutation rate were increased. There is thus far no confirmation of the positive findings that Nomura found in a mouse system.

Adolescent↗

Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors.

This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count.

Adult↗

[Cerebellopontine angle lipoma: a case report].

A surgical case of lipoma in the cerebellopontine angle in a 37-year-old man is reported. Cerebellopontine angle lipomas are very rare lesions that differ from other intracranial lipomas in that they typically present slowly progressive focal symptoms identical to those in other tumors of this location. The patient's chief complaints were left hearing disturbance and dizzy spells. Computed tomography showed a very low density lesion (-99.3 Hounsfield units) with no enhancement in the left cerebellopontine angle. Magnetic resonance imaging (0.15T) was subsequently performed. The relative T1 weighted image showed a lesion of high signal intensity in the left cerebellopontine angle. The tumor was adherent to both the brainstem and the cranial nerves involved. On dissection, it was quite hemorrhagic. The tumor could only be partially resected because of the embedded cranial nerves and vascularity. The authors review the literature on this rare tumor and discuss the clinical appearance. Radiological assessment including CT and MRI and management of this lesion were also discussed.

Adult↗

The children of parents exposed to atomic bombs: estimates of the genetic doubling dose of radiation for humans.

The data collected in Hiroshima and Nagasaki during the past 40 years on the children of survivors of the atomic bombings and on the children of a suitable control population are analyzed on the basis of the newly revised estimates of radiation doses. No statistically significant effects emerge with respect to eight different indicators. Since, however, it may confidently be assumed some mutations were induced, we have taken the data at face value and calculated the minimal gametic doubling doses of acute radiation for the individual indicators at various probability levels. An effort has also been made to calculate the most probable doubling dose for the indicators combined. The latter value is between 1.7 and 2.2 Sv. It is suggested the appropriate figure for chronic radiation would be between 3.4 and 4.5 Sv. These estimates suggest humans are less sensitive to the genetic effects of radiation than has been assumed on the basis of past extrapolations from experiments with mice.

Aneuploidy↗

Cells of origin of histaminergic afferents to the cat median eminence.

The exact origin of histaminergic neuronal perikarya sending axons to the median eminence and posterior pituitary was investigated in the cat by using two colour double-immunostaining methods: unconjugated wheat germ agglutinin or cholera toxin as retrograde tracers combined with histamine (HA) immunohistochemistry. HA immunohistochemistry revealed the presence of HA-immunoreactive terminal-like fibers both in the external layer of the median eminence and neural lobe of the pituitary. The double-labeling studies further demonstrated the histaminergic innervation of the median eminence and neural lobe by a few HA-immunoreactive neuronal perikarya located in the posterior hypothalamus.

Animals↗

Quantitative computed tomography of lumbar vertebrae in Japanese patients with osteoporosis.

Vertebral trabecular bone mineral density of both healthy Japanese subjects and Japanese patients with osteoporosis was measured by quantitative computed tomography (QCT) technique. The age-related reduction rate in vertebral trabecular bone mineral density of control females averaged 1.1% per year, from age 20 to 80, with an accelerated loss demonstrated after age 40. In the male controls, trabecular bone mineral density declined by an average of 0.9% per year. These values were found to be similar to the University of California at San Francisco (UCSF) QCT data (US Caucasians: 1.2% for female, 0.72% for male). Therefore, it appears that age-related rates of trabecular bone loss in the lumbar vertebrae may be similar for both Japanese and Caucasians. However, when compared to average values in UCSF QCT data of comparable age and sex, the mean values in Japanese appear to be approximately 10-20 mg/cm3 lower than Caucasian counterparts. All female patients with osteoporosis as evidenced by atraumatic vertebral fracture had QCT values below 50 mg/cm3. It is suggested that the Japanese may have lower trabecular bone mineral density than Caucasians but may also have a lower threshold for fracture of the vertebrae. Further studies are needed to establish the possible racial differences in vertebral trabecular bone mineral density, and to determine whether these possible disparities are related to genetic differences, or to differences in body size, dietary intake, physical activity or other lifestyle/environmental factors.

Adult↗