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Biomedical subjects

R Hata

Publications and source records attributed to R Hata.

At least 55 records · Page 3Linked to original sources
PubMed1994

Extracellular matrix regulates and L-ascorbic acid 2-phosphate further modulates morphology, proliferation, and collagen synthesis of perisinusoidal stellate cells.

Morphology, proliferation, and collagen synthesis of perisinusoidal stellate cells (fat-storing cells, lipocytes, Ito cells) varied according to the nature of the substratum. On a basement membrane gel, the stellate cells formed a mesh-like structure and proliferated slowly. On non-coated polystyrene and type I collagen-coated culture dishes, the cells spread well and extended cellular processes. The cell proliferation and collagen synthesis were more prominent on culture dishes coated with type I collagen than on polystyrene dishes. On each extracellular substrate, proliferation and collagen synthesis were stimulated by a long-acting vitamin C derivative, L-ascorbic acid 2-phosphate. These results indicate that morphology, proliferation, and collagen metabolism of the stellate cells are regulated by extracellular matrix and modulated further by L-ascorbic acid 2-phosphate.

Animals↗
PubMed1994

An ischemic opening of the blood-brain barrier may deteriorate brain stem auditory evoked potentials following transient hindbrain ischemia in gerbils.

To clarify the effect of vasogenic brain edema on the brainstem, the relationships between waveform changes in brainstem auditory evoked potentials (BAEP) and blood-brain barrier (BBB) disturbance following transient hindbrain ischemia were investigated. Hindbrain ischemia was induced in gerbils by bilateral occlusion of the vertebral arteries. The animals were divided into three groups subjected to 0, 5, and 30 min of bilateral vertebral occlusion (BVO-0',-5', and -30' groups; n = 4 in each group). Two hours after recirculation, Evans blue (EB) solution was injected into the saphenous vein. The brains were removed after 30 min of circulation, and all areas stained macroscopically by EB were noted and recorded. During hindbrain ischemia, BAEP disappeared within 3 min. In the BVO-5' group, BAEP reappeared and returned to normal within 10 min after reperfusion, whereas in the BVO-30' group, BAEP never returned to normal and finally disappeared within 30 min after reperfusion. In the BVO-5' group, no EB staining was visible. On the other hand, in the BVO-30' group, EB staining was seen in the medial part of the tegmentum in the midbrain in two animals, and around the vestibular nucleus in the lateral parts of the pons in three. These results demonstrate the close relationship between the reversibility of ischemia-induced changes in BAEP and BBB disturbance in the brainstem.

Animals↗
PubMed1994

A new gerbil model of hindbrain ischemia by extracranial occlusion of the bilateral vertebral arteries.

A new gerbil model of hindbrain ischemia was induced by extracranial occlusion of the bilateral vertebral arteries just before their entry into the transverse foramen of the cervical vertebra. Carbon black studies, performed at 5 min after occlusion, revealed that the pons-medulla oblongata, and the cerebellum were quite ischemic in all animals. Cardiovascular changes in mean arterial blood pressure (MABP) and heart rate were recorded until 30 min after occlusion, and revealed that the typical cerebral ischemic response (i.e., abrupt increase in MABP, bradycardia, and apnea) was elicited in all animals (n = 10). Thirty minutes after occlusion, animals (n = 4) were decapitated and immersion-fixed. Brain sections were stained with hematoxylin-eosin (HE) and also immunostained for microtubule-associated protein 2 in order to evaluate ischemic neuronal damage from 30 min of ischemia. By HE staining, ischemic lesions were detected bilaterally in the oculomotor, the trigeminal motor, the lateral vestibular, and the cerebellar interpositus nucleus. In addition, immunostaining revealed ischemic lesions in several other hindbrain areas. In conclusion, we could successfully establish a new gerbil model of hindbrain ischemia. Carbon black perfusion and hemodynamic studies revealed that severe and reproducible hindbrain ischemia was produced. By histopathological examination, we could also clearly demonstrate symmetrical ischemic lesions in several hindbrain areas.

Animals↗
PubMed1994

Effects of hemodialysis on cerebral circulation evaluated by transcranial Doppler ultrasonography.

BACKGROUND AND PURPOSE: The effects of hemodialysis on the cerebral circulation of humans and the correlation between changes in blood flow velocity in the basal cerebral arteries and those of several physiological variables influenced by hemodialysis have been inadequately studied. METHODS: Blood flow velocities were obtained from the middle cerebral artery and the basilar artery by transcranial Doppler ultrasonography in 27 patients receiving chronic maintenance hemodialysis immediately before and after the procedure. Changes in body weight, hematocrit, blood pressure, and arterial blood gases were recorded simultaneously. RESULTS: There was a significant reduction in mean flow velocity in the middle cerebral artery (P < .01) and the basilar artery (P < .01) after hemodialysis. We observed a significant negative correlation between the relative change in mean flow velocity and the loss of weight after hemodialysis, the amount of fluid removed, and the increase in hematocrit in the middle cerebral artery and the basilar artery. CONCLUSIONS: Hemodialysis and the associated physiological changes can significantly affect the cerebral circulation. Blood flow velocities in the middle cerebral artery and the basilar artery decrease significantly with hemodialysis. The loss of body weight, the amount of fluid removed, and the change in hematocrit significantly correlate with the change in mean flow velocity. The transcranial Doppler method can effectively monitor rapid changes in the cerebral circulation during potentially harmful procedures.

Adult↗
PubMed1994

[Therapeutic effect of lisuride maleate on post-stroke depression].

Twenty post-stroke depressive patients who obtained more than 11 points on Self-Rating Questionnaire for Depression, were treated with 0.075 mg/day lisuride maleate for 12 weeks. The drug effect on depression was evaluated quantitatively by the Hamilton Rating Scale for Depression. The relationships between brain CT or MRI and SRQ-D score were investigated in 24 subjects. More than 80% of post-stroke depressive patients improved after lisuride maleate treatment for 8 or 12 weeks. In particular, depressed mood, hypobulia, sleep disturbance, anxiety, etc. were significantly improved compared to the baseline condition. As for the relationships with CT and/or MRI findings, the group with moderate to severe brain atrophy had a significantly higher grade of depressive state than those without.

Aged↗
PubMed1994

Extracellular matrix regulates cell morphology, proliferation, and tissue formation.

The roles of extracellular matrix (ECM) components such as collagen, elastin, proteoglycan, and adhesive glycoprotein in the regulation of cell morphology, proliferation, and tissue formation were investigated. On a basement membrane gel, the perisinusoidal stellate cells (lipocytes, fat-storing cells, Ito cells) formed a mesh-like structure, proliferated slowly, and synthesized only a small amount of collagen. On polystyrene or type I collagen-coated culture dishes, the stellate cells spread well and extended cellular processes. The stellate cells proliferated better and synthesized more collagen on type I collagen-coated dishes than on polystyrene dishes. Co-cultures of hepatic parenchymal cells and fibroblasts formed a three-dimensional hepatic cord-like architecture in the medium supplemented with a long-acting vitamin C derivative, L-ascorbic acid 2-phosphate (Asc 2-P). Skin fibroblasts formed a three-dimensional dermis-like structure in the medium supplemented with Asc 2-P. Asc 2-P stimulated collagen synthesis of these cells. The stimulative effects of Asc 2-P on tissue formation were suppressed when collagen synthesis in these cells was inhibited. These data indicate that ECM can regulate cell morphology, proliferation and tissue formation. Regulation of cellular functions in other tissues such as mammary gland, thymus and prostate by ECM was also reviewed, and the molecular mechanisms of the regulation are discussed.

Adipocytes↗
PubMed1993

Induced resistance and susceptibility to cerebral ischemia in gerbil hippocampal neurons by prolonged but mild hypoperfusion.

Brief periods of non-lethal cerebral ischemia can induce resistance against subsequent lethal ischemia. In this study, asymptomatic gerbils after unilateral carotid artery ligation were subjected to 5 min of forebrain ischemia. The prolonged but mild hypoperfusion, by carotid occlusion, induced susceptibility at 1 day and tolerance at 30 days to lethal ischemia in the hippocampal neurons. The neuroprotective effect correlated well with induction of heat shock protein 72 in the hippocampal neurons. These results suggested that neuronal cells possess a cellular response to sublethal hypoperfusion and can survive forthcoming ischemic stress.

Animals↗
PubMed1993

Transcriptional activation of type I collagen genes by ascorbic acid 2-phosphate in human skin fibroblasts and its failure in cells from a patient with alpha 2(I)-chain-defective Ehlers-Danlos syndrome.

L-Ascorbic acid 2-phosphate (Asc 2-P), a long-acting vitamin C derivative, stimulated transcription of genes for pro alpha 1(I) and pro alpha 2(I) collagen in normal human skin fibroblasts after 8 h of treatment in the absence or in the presence of cycloheximide, indicating Asc 2-P stimulates transcription of type I collagen genes in the absence of protein synthesis. The transcriptional rate in these cells reached the maximum value after 40 h of treatment, and at that time it was three to four times higher than that of the control cells cultured in the absence of Asc 2-P. Steady-state levels of mRNAs for pro alpha 1(I) and pro alpha 2(I) chains were also increased to be three to four times higher than the control levels by treatment of the cells with Asc 2-P for 72 h. When the fibroblasts obtained from a patient with Ehlers-Danlos syndrome were treated with Asc 2-P, the derivative also stimulated transcription of the gene for pro alpha 1(I) chain and accumulation of mRNA for pro alpha 1(I) chain. On the other hand, Asc 2-P failed to stimulate transcription of the pro alpha 2(I) gene or an increase in mRNA for pro alpha 2(I) chain. Sodium ascorbate showed effects quite similar to those of Asc 2-P, when fibroblasts obtained from a normal control or the patient were cultured for 16 h with it. These results indicate the existence of cis-regulatory elements responsible for transcriptional activation by Asc 2-P or ascorbic acid in pro alpha 1(I) and pro alpha 2(I) genes of normal fibroblasts. These data also suggest some defect(s) of these elements in the pro alpha 2(I) gene of the patient with Ehlers-Danlos syndrome.

Ascorbic Acid↗
PubMed1993

Differential vulnerability in the hindbrain neurons and local cerebral blood flow during bilateral vertebral occlusion in gerbils.

Differential vulnerability in the hindbrain neurons was examined immunohistochemically during hindbrain ischemia in the gerbil. Hindbrain ischemia was produced by extracranial occlusion of the bilateral vertebral arteries just before their entry into the transverse foramen of the cervical vertebra. Local cerebral blood flow was measured by quantitative autoradiographic technique after 5 min of ischemia and was reduced to less than 5 ml/100 g per min in the cerebellum, the pons, and the medulla, indicating that severe and reproducible hindbrain ischemia was induced immediately after occlusion. For immunohistochemical investigation, four gerbils each were used for each ischemic period of 5, 10, 15, and 30 min. Immunohistochemical lesions, detected by the reaction for microtubule-associated protein 2, were visible in the lateral vestibular nucleus and the cerebellar interpositus nucleus even after 5 min of ischemia. These results suggested that these areas were more vulnerable than others, although blood flow was markedly reduced in various regions of the hindbrain. In contrast, areas related to respiratory or cardiovascular control were rather resistant to ischemia. The present study suggests that selective vulnerability during hindbrain ischemia depends mainly on different metabolic characteristics inherent to various neurons in the hindbrain.

Animals↗
PubMed1992

Simultaneous expression of type I procollagen mRNA and albumin in cirrhotic human liver.

The gene expression of human type I procollagen was investigated in cirrhotic human liver by using in situ hybridization with nonradioactive DNA probes. Using in situ hybridization can provide direct evidence for the cell type capable for type I collagen synthesis in tissues. T-T dimerized DNA probes were used and DNAs hybridized in situ were detected immunohistochemically using specific antibodies against T-T dimer. The data demonstrated that type I collagen is synthesized in hepatocytes and stellate cells in pseudolobules and in fibroblasts in Glissons capsules in cirrhotic human livers. We indicated hepatocytes morphologically and functionally by using immunohistochemical localization of albumin, which was used as a marker of hepatocyte, since albumin is synthesized exclusively by hepatocytes.

Adult↗
PubMed1992

The characteristics of blood-brain barrier in three different conditions--infarction, selective neuronal death and selective loss of presynaptic terminals--following cerebral ischemia.

We investigated the extravasation of serum albumin using immunohistochemistry in three different conditions, i.e., infarction, selective neuronal death and selective loss of presynaptic terminals following cerebral ischemia in gerbils. In selective neuronal death, which is typically found in the CA1 neurons of the hippocampus after 5-min bilateral cerebral ischemia, selective damage of postsynaptic components with intact presynaptic sites was demonstrated by immunohistochemical examination for microtubule-associated protein 2 and synapsin I, and albumin extravasation did not become apparent before postsynaptic structures were destroyed. In cerebral infarction, which was consistently observed in the thalamus after 15-min forebrain ischemia, massive albumin extravasation was visible early after ischemia due probably to the ischemic endothelial necrosis. In selective loss of presynaptic terminals, which was detected at the molecular layer of the dentate gyrus in the contralateral, nonischemic hippocampus after unilateral cerebral ischemia, immunoreaction for albumin was not visualized. Since endothelium and glial cells were intact in morphological aspects in selective damage of both pre- and postsynaptic sites, it was thought that extravasation was facilitated by the stimulation of endothelial cells and glial cells with unknown factors that were induced by the destruction of post- but not presynaptic elements.

Albumins↗
PubMed1992

Recombinant human superoxide dismutase can attenuate ischemic neuronal damage in gerbils.

The effects of recombinant human superoxide dismutase (r-hSOD) on ischemic neuronal injury were examined. Cerebral ischemia was produced in Mongolian gerbils by occluding bilateral common carotid arteries for 5 min. Preischemic treatment with r-hSOD clearly reduced hippocampal neuronal damages while postischemic treatment did not. This result suggests that oxygen free radicals play an important role in selective vulnerability to ischemia and r-hSOD has a potential clinical usefulness against cerebral ischemia.

Analysis of Variance↗
PubMed1992

[Surgical exploration for renal cyst: two-case report].

A 59-year-old male was admitted to our clinic for further examination of the calcified renal cyst discovered incidentally on medical workup elsewhere. CT showed a left renal cyst associated with calcification. Ultrasound-guided puncture of the renal cyst was not successful because of thickness of the cystic wall. Renal angiography showed hypervascularity of the cystic wall. Association of renal cell carcinoma could not be ruled out, therefore the exploration was performed. Histological examination revealed benign renal cyst with calcification. A 27-year-old male presented with the chief complaint of left flank pain. Following examinations by US, CT and MRI, a renal cyst associated with renal cell carcinoma was highly suspected. Subsequent exploration revealed cluster of cysts with a yellowish lesion a few mm in diameter. Frozen section revealed no malignancy, and cystic fluid was not hemorrhagic. Therefore as many cystic walls as possible were removed without nephrectomy. Histological examination of the permanent specimen revealed renal cell carcinoma. Renal cyst associated with renal cell carcinoma was regarded as rare clinical entity, but such cases are reported in increasing number in recent years. We report such cases and review the pertinent literature in this paper.

Adult↗
PubMed1991

'Ischemic tolerance' phenomenon detected in various brain regions.

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'ischemic tolerance'.

Animals↗
PubMed1991

Recombinant human interleukin-1 beta analogue as a regulator of hematopoiesis in patients receiving chemotherapy for urogenital cancers.

Ten patients with advanced urologic cancers who were scheduled to receive at least two courses of chemotherapy were enrolled in this trial. Fifty thousand units of recombinant human interleukin-1 (IL-1) beta analogue OCT-43 (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was administered subcutaneously only once or twice when severe neutropenia (less than 500/microliters) continued for 2 consecutive days. In eight patients, OCT-43 was not injected in the first course of chemotherapy as a control, but was injected in the second course. The durations of leukocytopenia (less than 2000/microliters) and neutropenia (less than 1000/microliters) were significantly shortened in the second course compared with those in the first course in those eight patients. Recovery of neutrophil number from the lowest number was also significantly faster in the second course. Thus, OCT-43 was considered to have hematopoietic activities. However, single or double injection of OCT-43 did not affect the numbers of eosinophilic or basophilic granulocytes, monocytes, or platelets. Adverse effects associated with OCT-43 injections were high fever and chills, but they were controlled by indomethacin.

Adult↗
PubMed1991

Epidermal growth factor inhibits transcription of type I collagen genes and production of type I collagen in cultured human skin fibroblasts in the presence and absence of L-ascorbic acid 2-phosphate, a long-acting vitamin C derivative.

Recombinant human epidermal growth factor (EGF, 2-10 ng/ml) stimulated growth and production of non-collagenous proteins, but inhibited production of collagen by 60% in cultured human skin fibroblasts. Type analysis of the collagen produced indicated that inhibition of the collagen production observed was mainly a reflection of a reduction in type I collagen. The accumulation of pro alpha 1(I) and pro alpha 2(I) mRNAs and the transcriptional activity of these genes were determined in human skin fibroblasts in order to investigate site(s) of regulation of type I collagen production by human EGF in the absence and presence of L-ascorbic acid 2-phosphate (Asc 2-P), a long-acting vitamin C derivative. Human EGF (10 ng/ml) used alone reduced the steady state levels of mRNAs for pro alpha 1(I) and pro alpha 2(I) chains and transcriptional activity of these genes in vitro by 45%. Asc 2-P (0.2 mM) alone, on the other hand, raised production of type I collagen and the steady state levels of mRNAs for pro alpha 1(I) and pro alpha 2(I) collagen chains as well as stimulated transcriptional activity of these genes. Human EGF attenuated these stimulative effects of Asc 2-P. These results indicate that human EGF regulates type I collagen synthesis at the transcriptional level in cultured fibroblasts in the presence and absence of Asc 2-P. The possibility that human EGF plays a role as a regulator of type I collagen genes in vivo was discussed.

Ascorbic Acid↗
PubMed1991

Hyperthermia-induced neuronal protection against ischemic injury in gerbils.

We investigated the effect of hyperthermic pretreatment before induction of ischemia using a gerbil model of 5-min forebrain ischemia. A single hyperthermic treatment 18 h before ischemia exhibited a partial protective effect, and repetitive hyperthermic pretreatments at 18-h intervals before ischemia showed clear protection against neuronal death in the CA1 area of the hippocampus, whereas single hyperthermic treatment 3, 6, 24, or 50 h before ischemia exhibited little protective effect. This transient and cumulative neuroprotective effect of hyperthermic pretreatment strongly suggested the involvement of stress reactions after hyperthermia in the protective mechanism against ischemic neuronal death.

Animals↗