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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 163 records · Page 9Linked to original sources

Preexisting membranous nephropathy in allograft kidney.

A case of membranous nephropathy, preexisting in a donor kidney, will be reported. A 41-year-old man underwent a cadaver renal transplantation. An allograft biopsy specimen obtained during the operation showed spike formation on periodic acid-silver methenamine staining and deposition of IgG along the glomerular capillary loop on immunoperoxidase staining. Immunofluorescence staining for IgG remained in the specimens obtained on day 11 and after 4 weeks, but markedly decreased in the specimen obtained 7 weeks after transplantation. Electron-dense deposits also decreased in amount, but irregular thickening of the glomerular basement membrane with spikes, electron-lucent washout lesions, and small amounts of electron-dense deposits remained 20 months after the transplantation. These findings suggest that membranous nephropathy, as well as IgA nephritis and diabetic nephropathy, resolve after renal transplantation and that deposition of IgG markedly decreases within a few months after transplantation, but that complete histological restoration of the basement membrane needs at least a few years.

Adult↗

Effect of pretreatment with FTY720 and cyclosporin on ischaemia-reperfusion injury of the liver in rats.

The effect of pretreatment with FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride) or cyclosporin, or both, on neutrophil-mediated injury has been examined by use of a rat model of transient clamping of hepatic flow. Pretreatment with FTY720 alone or with cyclosporin induced a marked reduction of circulatory lymphocytes, whereas the use of these drugs in combination was very effective at suppressing the elevation of the number of peripheral polymorphonuclear neutrophils (PMN) after reperfusion. Pretreatment with cyclosporin, with or without FTY720, significantly reduced hepatic damage, whereas FTY720 alone tended to prolong hepatic damage. Pretreatment of cyclosporin alone, but not in combination with FTY720, significantly reduced the accumulation of PMN and led to lower myeloperoxidase levels in the damaged liver. In conclusion, pretreatment with cyclosporin, with or without FTY720, reduced hepatic damage after warm ischaemia-reperfusion, whereas pretreatment with FTY720 alone tended to prolong this damage.

Animals↗

IGF-1 regulates migration and angiogenesis of human endothelial cells.

Recent studies revealed favorable para- and/or autocrine effects of IGF-1 in the pathogenesis of diabetic complications. On the other hand, hyperglycemia is a risk factor for the development of diabetic vascular complications. In this study we examined the effects of high glucose and/or IGF-1 on cell migration and angiogenesis (tubular formation) by using human endothelial cells (EC) in vitro. First we examined cell migration by the two-chamber method. Chronic treatment with a high concentration of D-glucose strongly stimulated the cell migration, which was mimicked by PMA, a protein kinase C (PKC) agonist. The cell migration was also induced by IGF-1. The glucose-induced cell migration was blocked by PKC inhibitor, H7. IGF-1-induced cell migration was not blocked by PD98059, MAPK/ERK kinase (MEK) inhibitor or wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor. Next we examined the effects of high glucose and/or IGF-1 on the tubular formation of EC. The tubular formation was induced only when the cells were exposed to a combination of high glucose and IGF-1. The tubular formation was blocked by MEK inhibitor and PI 3-kinase inhibitor but not by PKC inhibitor. These results indicate that hyperglycemia and IGF-1, respectively, stimulate the EC migration, and tubular formation is induced by a combination of IGF-1 and hyperglycemia.

Androstadienes↗

Atypical Wegener's granulomatosis with positive cytoplasmic antineutrophil cytoplasmic antibodies, ophthalmologic manifestations, and slowly progressive renal failure without respiratory tract involvement.

A 68-year-old woman had microscopic hematuria and proteinuria since the age of 50. She also had hearing impairment, arthralgia, retinal embolism, peripheral arterial occlusion of the right foot and chronic renal failure during the course. At the age of 68, she had progressive renal failure and nephrotic syndrome with high titers of serum cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). No evidence of respiratory tract involvement was found. Methylprednisolone pulse therapy and low dose cyclophosphamide therapy ameliorated the renal failure and reduced the serum c-ANCA level. She, however, died on July 19, 1998 due to pulmonary fungal and pneumocystis carinii infection.

Aged↗

Image-guided epilepsy surgery.

Interactive image-guided techniques used in conjunction with three-dimensional images allow accurate planning and performance of a variety of neurosurgical procedures. The frameless stereotactic Viewing Wand System was used to provide real-time correlation of the operating field and computerized images in over 22 neurosurgical operations carried out for intractable epilepsy. The overall results of the surgery demonstrated favorable results, with class 1 + class 2 outcomes in 86.4% of the present series. Our experience shows that the Viewing Wand System is most helpful as an adjunctive navigational device in the microsurgical treatment of epilepsy.

Adolescent↗

cAMP enhances insulin secretion by an action on the ATP-sensitive K+ channel-independent pathway of glucose signaling in rat pancreatic islets.

Cyclic AMP potentiates glucose-stimulated insulin release by actions predominantly at a site, or sites, distal to the elevation of the cytosolic free Ca2+ concentration ([Ca2+]i). Glucose also acts at a site, or sites, distal to the elevation of [Ca2+]i via the ATP-sensitive K+ channel (K+ATP channel)-independent signaling pathway. Accordingly, using rat pancreatic islets, we studied the location of the action of cAMP and its interaction with the glucose pathway. Forskolin, an activator of adenylyl cyclase, raised intracellular cAMP levels and enhanced KCl-induced (Ca2+ -stimulated) insulin release in the presence, but not in the absence, of glucose. Thus, cAMP has no direct effect on Ca2+ -stimulated insulin release. The interaction between cAMP and glucose occurs at a step distal to the elevation of [Ca2+]i because forskolin enhancement of KCl-induced insulin release, in the presence of glucose, was demonstrated in the islets treated with diazoxide, a K+ATP channel opener. The enhancement of insulin release was not associated with any increase in [Ca2+]i. Furthermore, the interaction between cAMP and glucose was unequivocally observed even under stringent Ca2+ -free conditions, indicating the Ca2+ -independent action of cAMP. This action of cAMP is physiologically relevant, because not only forskolin but also glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pituitary adenylyl cyclase activating polypeptide exerted similar actions. In conclusion, the cAMP/protein kinase A pathway has no direct effect on Ca2+ -stimulated insulin exocytosis. Rather, it strongly potentiates insulin release by increasing the effectiveness of the K+ATP channel-independent action of glucose.

Adenosine Triphosphate↗

Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets: free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose.

Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive K+ channel (K(ATP) channel)-independent manner. In studying the mechanisms underlying this action, we used rat pancreatic islets and examined the effects of exogenous free fatty acids (FFAs), which are precursors of long-chain acyl-CoA (LC-CoA), on KCl-induced Ca2+-stimulated insulin release. Myristate, palmitate, and stearate augmented insulin release induced by 50 mmol/l KCl in the presence of 2.8 mmol/l glucose. Added acutely, their potency was weak compared with that of glucose-induced augmentation. The FFA-induced augmentation became much greater, however, when islets were preincubated with FFAs under stringent Ca2+-free conditions (with 1 mmol/l EGTA) before the KCl stimulation. Under these conditions, 16.7 mmol/l glucose augmented 13-fold insulin release induced by 50 mmol/l KCl, whereas palmitate or myristate (both at a free concentration of 10 micromol/l) produced 5.8- and 5.2-fold augmentations. Effects of FFAs and glucose were concentration-dependent. The temporal profiles of augmentation induced by 11.1 mmol/l glucose and 10 micromol/l palmitate were similar. Glucose and palmitate caused almost identical augmentation patterns for the initial 10 min of stimulation; subsequently, glucose augmentation was better sustained than palmitate augmentation. This suggests the existence of a longer-term glucose-specific signaling moiety that cannot be mimicked by FFAs. Our results provide direct evidence that FFAs can mimic the K(ATP) channel-independent action of glucose. Taking these results together with previous results, we conclude that glucose augments Ca2+-stimulated insulin release, at least in part, by increasing malonyl-CoA and cytosolic LC-CoA. However, one or more other glucose-specific signaling molecules are required for the full expression of augmentation.

Adenosine Triphosphate↗

Survival of rats undergoing continuous bile drainage depends on maintenance of circadian rhythm of bile secretion.

It is very difficult to collect bile secretions from animals for extended periods of time. We compared the use of saline or water as drinking fluids to sustain the animals, which were being continuously drained of bile. Complete bile drainage was performed in 16 male Wistar rats by surgical intervention. After surgery, 8 rats were given tap water, and the other 8 were given normal saline for water. The rats that received water rapidly lost weight after bile drainage, and all died within 8 days after the operation. In contrast, all rats that drank saline maintained their body weight and survived 14 days or longer after surgery. Serum biochemistry of the rats with water intake on the third day after bile drainage revealed hyponatremia, hypochloremia, and acute renal failure resulting in hyperkalemia. In contrast, electrolyte balance and renal function were normal in the rats with saline intake, and bile was secreted continuously with a circadian rhythm. These results clearly demonstrate that saline as drinking water is essential to the replacement of lost fluids and loss of electrolytes due to bile drainage. Further, saline proved efficacious for sustaining experimental animals undergoing continuous bile collection.

Acute Kidney Injury↗

Malignant intravascular lymphomatosis associated with venous stenosis. Case report.

This 55-year-old man presented with malignant intravascular lymphomatosis, a rare vascular disorder of the central nervous system characterized by proliferation of malignant lymphoma cells. The clinical manifestations were focal neurological signs and progressive dementia. Angiography demonstrated stenoses of the cortical veins. Postmortem examination revealed infiltration of tumor cells into the lumen and vascular wall, although the stenoses were caused primarily by fibrin thrombi. To the authors' knowledge this is the first case of malignant intravascular lymphomatosis associated with venous stenosis.

Angiography, Digital Subtraction↗

[A case of a traumatic anterior cerebral artery aneurysm following the penetration of the skull base by an iron rod].

A 61-year-old male fell from a position 1 m high when building a house. An iron rod, which protruded upward from a solid base in cement, penetrated this patient's neck 15 cm to the head and was successfully extracted by himself. On admission, he complained of headache and vomiting. General examination disclosed nasal bleeding, intraoral bleeding, and L figured skin laceration in the left side of his neck at the level of the thyroid cartilage. Mild disorientation (JCS2) was noted. Otolaryngological examination disclosed hyperemia on the left side of the vocal cord as well as at the dome of the superior pharynx. Plain skull film disclosed pneumocephalus and that a piece of bone fragment of the planum sphenoidale had penetrated the brain. CT demonstrated air in the subarachnoid space, ventricular hemorrhage, intracerebral hematoma in the right frontal lobe, and subarachnoid hemorrhage in the anterior interhemispheric fissure. CAG detected neither cerebral vascular abnormalities nor cerebral aneurysm. While staying in our department, he developed mild fever and CSF rhinorrhea. The diagnosis of bacterial meningitis was made from the CSF finding and was well controlled with conservative therapy. CSF rhinorrhea stopped spontaneously with conservative treatment. Sagittal MRI continuously demonstrated contusional hematoma in the base of the right frontal lobe just above the fractured planum sphenoidale and genu of the corpus callosum following the course of the intracranially invading iron rod. The right CAG on Day 10 demonstrated vasospasm on the A1 and a 1 cm sized saccular cerebral aneurysm at the proximal right fronto-polar artery. CAG on Day 17 again showed the persistent presence of the aneurysm. For the purpose of preventing delayed rupture of the aneurysm, radical surgical treatment was planned. Microsurgical dissection disclosed that the aneurysm was located just behind the elevated fracture of the planum sphenoidale. Severe arachnoid adhesion was noted around the aneurysm. The aneurysm was successfully clipped with preservation of the parent artery without inducing new neurological deficits. From the general, otolaryngological, neuroradiological, and operative findings, this aneurysm was diagnosed as a traumatic cerebral artery aneurysm following the penetration of the skull base by the iron rod. The CAG performed at 8 months postoperatively demonstrated the patency of the parent artery and that there was no recurrence of the aneurysm. An unusual case of a traumatic cerebral artery aneurysm following the penetration of the skull base by an iron rod was thus reported.

Accidents, Occupational↗

Novel V184E MEN1 germline mutation in a Japanese kindred with familial hyperparathyroidism.

We studied the MEN1 gene in a kindred where three patients (the proposita and two of her sons) were affected with hyperparathyroidism. By polymerase chain reaction (PCR)-based direct sequencing of 10 exons of MEN1, a novel germline mutation was identified in the proposita. This mutation, a T-to-A transition at codon 184 in exon 3, predicts an amino acid change from valine to glutamine (V184E). PCR-single-strand conformational polymorphism (PCR-SSCP) analysis of exon 3 followed by sequencing showed the same mutation in the two sons, and in two clinically normal granddaughters of an affected son. Since the T-to-A substitution segregated with the disorder in the kindred except for the granddaughters and it was not detected in 100 alleles from 50 normal individuals, the change observed in MEN1 is not a polymorphism, but causes familial hyperparathyroidism. Thus the two grandchildren with the mutation were diagnosed as presymptomatic carriers.

Adolescent↗

Increase in natural killer cell activity following living-related liver transplantation.

We monitored the serial changes of natural killer cell (NK) activity in eight recipients of living-related liver transplantation. The HLA types of all eight patients were haplotypically identical with those of their donors. Tacrolimus and methylprednisolone were used for immunosuppression. The NK activity before transplantation was 24.1 +/- 20.2% which is surprisingly low when compared with the value for normal individuals (67.7 +/- 13.2%, P < 0.01) or a liver dysfunction group (49.4 +/- 21.9%, P < 0.05). Serial changes in NK activity revealed a minimum of 6.1 +/- 3.6% 1 week after transplantation, gradually increasing to 49.2 +/- 12.5% at 2 months after transplantation. These results suggest that the diseased liver might play an important role in the suppression of NK activity.

Adolescent↗