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Biomedical subjects

Y Fujioka

Publications and source records attributed to Y Fujioka.

At least 109 records · Page 6Linked to original sources
PubMed1993

MHC-linked diabetogenic gene of the NOD mouse: molecular mapping of the 3' boundary of the diabetogenic region.

To localize and characterize the MHC-linked diabetogenic gene of the NOD mouse, we studied the class III region of the MHC in the NOD mouse and related strains. Hsp70, Bat5, Tnfa and Tnfb loci were studied by microsatellite polymorphism analysis and/or restriction mapping. The CTS mouse had the same allele as the NOD mouse at the Hsp70 locus, but different alleles at the Bat5, Tnfa and Tnfb loci from those of the NOD mouse. Our previous studies indicated that in the CTS mouse, class II MHC was the same as that of the NOD mouse, but that class I MHC was different at both K and D loci, and that CTS MHC was diabetogenic in the presence of NOD background genes. These data map major genetic susceptibility to type 1 diabetes to the segment flanked by class I K and class III Bat5 loci. Moreover, since the diabetogenic effect of the CTS MHC is weaker than that of the NOD MHC, these data suggest the presence of a second MHC-linked gene or gene complexes that modulate susceptibility to type 1 diabetes outside this segment.

Animals↗
PubMed1993

Effects of naftidrofuryl oxalate on microsphere embolism-induced changes in tricarboxylic acid cycle intermediates of rats.

The present study was undertaken to determine whether naftidrofuryl oxalate, a cerebral vasodilator, may improve or attenuate microsphere embolism-induced damage to the mitochondrial tricarboxylic acid cycle. For this purpose, the intermediates in the tricarboxylic acid cycle were determined using cerebral cortex isolated from microsphere-injected rats with and without naftidrofuryl oxalate treatment. Seven-hundred microspheres, with a diameter of 48 microns were injected into the right hemisphere through the right common carotid artery. The presence of cerebral infarction on the 3rd day after the operation was confirmed by the development of triphenyltetrazolium chloride-unstained areas in brain sections. Succinate, fumarate, malate, citrate and alpha-ketoglutarate, but not oxaloacetate, contents were significantly decreased in the right hemisphere of rats on the 3rd day following microsphere embolism. In the left hemisphere, a similar but smaller decrease in these intermediates was seen. The rats, which showed typical stroke-like symptoms, were treated with 15 mg/kg naftidrofuryl oxalate i.p., twice daily for 2.5 days, resulting in a significant reversal of the intermediate content of both hemispheres toward the control and an increased in the triphenyltetrazolium-stained area of a coronal section of the right hemisphere relative to the untreated animals. The results suggest that naftidrofuryl oxalate attenuates the development of microsphere embolism-induced cerebral infarction and improves microsphere-induced impairment of the mitochondrial tricarboxylic acid cycle. The observed effects provided evidence for a possible site of action of the agent on ischemic brain energy metabolism.

Animals↗
PubMed1993

Histochemical demonstration of copper in LEC rat liver.

Livers of LEC rats were histochemically stained for copper according to the modified Timm's method, which includes trichloroacetic acid (TCA) treatment. TCA pretreatment was effective in removing zinc and iron, leaving as the major metal in the liver. Hepatocytes in 3-month-old rats were stained intensely by the modified Timm's method, both in frozen sections and in paraffin-embedded specimens. The centrilobular hepatocytes were usually stained, but positive cells were also randomly distributed in the hepatic lobes, showing a mosaic pattern. The staining was intensified in 8- compared to 3-month-old LEC rats. In contrast hepatocytes from LEA rats, the normal counterpart of LEC rats, were faintly stained for copper. Proliferating cholangioles found in older LEC rats were shown to lack copper deposition, and hepatocellular carcinoma showed less copper deposits than the hepatocytes surrounding the tumor. The copper staining was augmented in livers of LEC rats subjected to copper-loading, but was less intense in the livers treated with D-penicillamine. The staining intensity under the various experimental conditions showed good correlation with the copper concentration. Lysosomal deposition of copper in hepatocytes was demonstrated by electron microscopic analysis for copper. Thus the modified Timm's method was shown to produce valuable results in demonstrating copper in LEC rat livers, providing important information for an understanding of the mechanism of copper deposition and hepatic disease of the animal.

Animals↗
PubMed1993

Deficiency of holo-, but not apo-, ceruloplasmin in genetically copper-intoxicated LEC mutant rat.

Long-Evans Cinnamon(LEC) mutant rats exhibited less than 5% of normal levels of serum ceruloplasmin oxidase activity, but immunoblot analysis showed normal levels of immunologically detectable ceruloplasmin protein in sera from the mutant rats. Immunostaining of cryosections from the liver tissues with anti-ceruloplasmin antibody showed no significant difference between normal and LEC rats. Results from pulse labeling of ceruloplasmin for 3 hours with [35S]methionine in primary hepatocyte culture, followed by immunoprecipitation, SDS-PAGE and fluorography, showed only minor changes in ceruloplasmin protein synthesis and secretion. These results suggest that the mutation(s) does not affect ceruloplasmin gene expression, but results in a failure in the mechanism whereby copper is incorporated into newly synthesized apoceruloplasmin to produce oxidase active holoform.

Animals↗
PubMed1993

A microsatellite polymorphism in the human insulin receptor gene: a highly informative marker for linkage analysis.

To study genetic susceptibility to non-insulin dependent diabetes mellitus (NIDDM), association of insulin receptor gene, a candidate gene for NIDDM, with NIDDM was studied. A microsatellite polymorphism located in intron 2 of the human insulin receptor gene was detected by the polymerase chain reaction and used as a genetic marker. Eight different alleles were observed, indicating highly polymorphic nature of this marker. Although no association of this marker with NIDDM was observed in Japanese subjects, this marker will be useful for linkage studies of insulin receptor gene and genes located close to this gene on chromosome 19.

Alleles↗
PubMed1993

Lichenoid skin lesions as a sign of beta 2-microglobulin-induced amyloidosis in a long-term haemodialysis patient.

We report a case of beta 2-microglobulin-induced amyloidosis. The patient was a 40-year-old man suffering from non-amyloid nephropathy, who had been treated by haemodialysis for 20 years. Lichenoid skin lesions, consisting of groups of pin-head-sized shiny papules, were present on the arms and trunk. On histological examination, amyloid deposits were present, principally in the dermal papillae, but also around the sweat ducts and hair follicles. The amyloid displayed potassium-permanganate-resistant Congo red affinity, and green birefringence under polarized light. Immunohistochemically, beta 2-microglobulin was demonstrated in the lesions, confirming that they were a manifestation of beta 2-microglobulin-associated amyloidosis. Skin lesions of this type have not been reported previously in beta 2-microglobulin-associated amyloidosis.

Adult↗
PubMed1993

Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.

Angiotensin II↗
PubMed1993

A secondary amyloidosis associated with systemic lupus erythematosus.

Secondary amyloidosis associated with systemic lupus erythematosus has rarely been reported. A 57-year-old female had been diagnosed as having possible systemic lupus erythematosus, although her clinical course was not typical. About one year after the diagnosis, treatment was begun with prednisolone because of progressive renal dysfunction, thrombocytopenia and low serum levels of complements. Recurrent diarrhea and gastrointestinal bleeding soon developed, then amyloidosis was revealed in the stomach and duodenum. Postmortem examination confirmed systemic amyloidosis. We discuss the significance of this rare association of systemic lupus erythematosus and secondary amyloidosis.

Amyloidosis↗
PubMed1993

Squamous cell carcinoma showing lobar consolidation without collapse.

Most squamous cell carcinoma of the lung arises in the large bronchi and causes bronchial obstruction. We report a 74-year-old man with a squamous cell carcinoma of the lung whose roentgenogram revealed a lobar consolidation without collapse. A postmortem examination showed that the tumor cells filled the alveolar spaces completely without destroying the original architecture of the lung. The finding that tumor cells replacing alveolar epithelium, as in bronchioloalveolar cell carcinoma, was not seen throughout the lung. Airway obstruction by the tumor was not observed at any bronchus. These pathological findings seemed to explain the radiological findings.

Aged↗
PubMed1993

Fibromyxoma of the trachea.

A 53-year-old male with a small cell carcinoma of the lung was admitted to the Department of Respiratory Diseases, Nikko Memorial Hospital. During bronchofiberoptic examination of the cancer, a small nodule was discovered on the anterior wall of the trachea, about 8 cm below the vocal cord. Histopathologically, it was diagnosed as fibromyxoma of the trachea. Primary tumors of the trachea are very rare and fibromyxoma of the trachea is extremely rare. This is only the second report of a fibromyxoma on the tracheal wall. In this report its clinical manifestations were compared with those reported in the first case.

Carcinoma, Small Cell↗
PubMed1993

[The effect on age for the relationship between hypertension and glucose intolerance].

Recently, high frequencies of glucose intolerance and insulin resistance have been reported in patients with hypertension. However, both blood pressure and glucose tolerance are influenced by age. To investigate the effect of age on the interaction between blood pressure and glucose tolerance, we analyzed blood pressure and glucose tolerance in otherwise healthy subjects (n = 576) who underwent an oral glucose tolerance test and blood pressure measurement as a part of a healthy care program. The prevalence of DM and IGT were significantly higher in the hypertensive group than in the normotensive group. When the subjects were divided into three groups according to their age (less than 50 years old, between 50 and 60 years old and more than 60 years old), the prevalence of glucose intolerance (DM or IGT) was significantly higher in the hypertensive group than in the normotensive group in subjects under 50 years old, but not in subjects between 50 and 60 years old or over 60 years old. In the subjects classified as having normal glucose tolerance, the incremental area of glucose under the curve of 75g-OGTT was significantly higher in the hypertensive group than in the normotensive group. These data suggest that hypertension is associated with glucose intolerance in Japanese population and that age significantly affects this interaction.

Aged↗
PubMed1993

Investigation of the clinical value of assessing renal size on computed tomography in autosomal dominant polycystic kidney disease.

We examined relationship between serum creatinine concentration (Scr) and renal size on CT scans on 32 occasions in 25 patients with autosomal dominant polycystic kidney disease (ADPKD). As a result, a significant correlation was observed when the Scr was less than 5 mg/dl, as shown by the correlation coefficient (r) and P values of 0.803 and 0.0001, respectively. However, these values changed to 0.482 and 0.0093, respectively when 2 cases with Scr 6.2 and 6.4 mg/dl were included, and further changed to 0.005 and 0.9775 when an additional 4 cases with Scr 7.8, 9.9, 11.1 and 20.1 mg/dl were included. Renal size is therefore thought to be a useful parameter of renal function when the Scr is less than 5 mg/dl in ADPKD, but not when the Scr exceeds 6 mg/dl, and is regarded as useless for predicting the time at which dialysis would be required.

Creatinine↗
PubMed1993

[A study of trientine therapy in Wilson's disease with neurological symptoms].

D-penicillamine, an orally-administered chelating agent, is effective for Wilson's disease (WD). However 25% of WD patients showed serious adverse reactions to D-penicillamine cause this drug to be discontinued after months or years of treatment. For these cases, trientine-2HCl and trientine-4HCl, less toxic agents, are investigated. Three patients with WD, associated with neurological symptoms, were given either trientine-2HCl or trientine-4HCl. These patients had been on therapy with D-penicillamine. Severe adverse reactions had developed during the course of therapy, and D-penicillamine was discontinued, pancytopenia in case 1, nephrotic syndrome in case 2, and myasthenia gravis in case 3. Trientine-2HCl for case 1, and trientine-4HCl for cases 2 and 3 were instituted and continued. The neurological findings in all patients were extremely improved without side effects by trientine therapy. Though the chelating action on copper is weaker than that of D-penicillamine, it is efficient in improvement of the clinical neurological symptoms.

Adolescent↗
PubMed1993

[A case of degenerative type of progressive myoclonus epilepsy].

This report describes a patient with degenerative type of progressive myoclonus epilepsy (PME), who showed slowly progressive deterioration of the central nervous system; intellectual impairment, dysarthria, and involuntary movements, particularly action myoclonus and dystonia. The patient was a 19-year-old woman who had no hereditary factors. At the age of 4, she developed action myoclonus in the upper limbs bilaterally. Her condition became gradually worse, and at the age of 15, she was admitted to our hospital because of involuntary movement in the upper limbs. First physical examination revealed mild mental retardation, action myoclonus, dystonia, and delayed adolescence. As giant SEP characteristic of PME and Ramsay Hunt syndrome was found, she was tentatively diagnosed as having Ramsay Hunt syndrome without epilepsy, and delayed adolescence. Now, she is 19 years old, and unable to walk alone because of involuntary movements and paralysis. But she has not developed epilepsy. As she has not been compatible with progressive myoclonus epilepsy (PME) and progressive myoclonic ataxia (PMA) classified by Marseille Consensus Group, she has been diagnosed as having an atypical PME syndrome.

Adult↗
PubMed1992

D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper metabolism.

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D-penicillamine. D-Penicillamine is a copper-chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D-penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long-Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D-penicillamine-treated Long-Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in the liver.

Alanine Transaminase↗
PubMed1992

Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Base Sequence↗
PubMed1992

Non-arthritic rheumatoid valvulitis with coronary arteritis causing myocardial infarction.

Rheumatoid valvulitis occurring in an individual without arthritis has rarely been reported. A 62-year-old woman died after repeated myocardial infarction, with no articular symptoms but with a fever of unknown origin and a positive rheumatoid factor. Autopsy examination revealed granulomatous inflammatory lesions with rheumatoid nodules present in the aortic valve and the base of the left coronary artery. Wide-spread myocardial infarction was found in the septal and anterolateral walls of the left ventricle.

Aged↗