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Biomedical subjects

Y Isogai

Publications and source records attributed to Y Isogai.

At least 19 recordsLinked to original sources

Effect of captopril on isoproterenol-induced cardiac hypertrophy and polyamine contents.

It is well known that isoproterenol (ISO) a nonselective beta adrenoceptor agonist induces cardiac hypertrophy. It can be assumed that, in addition to its direct cardiac effect, ISO has a cardiac trophic effect via stimulation of the renin angiotensin system. Synthesis of polyamines is facilitated in cardiac hypertrophy and polyamine levels are rapidly elevated prior to an increase in heart weight. In the present study, we investigated whether captopril (30 mg/kg body weight, daily) could attenuate cardiac hypertrophy and elevation of cardiac polyamine levels in rats, which effects were elicited by a chronic (1- or 2-weeks) and repeated administration of a small dose (0.5 mg/kg body weight) of ISO. Cardiac hypertrophy was assessed by an increase in the wet weight and RNA content of the heart. Polyamines were analyzed by HPLC. Captopril alone did not affect either heart weight/body weight ratio or cardiac contents of polyamines and nucleic acids at the end of the second week. In isoproterenol-treated rats, the above parameters, except for putrescine content on day 14, were significantly increased on both day 7 and day 14. Captopril slightly attenuated ISO-induced cardiac hypertrophy and significantly prevented the ISO-evoked increase in the contents of RNA, spermidine, and spermine at the end of the second week. These results suggest that the ISO-evoked increase in cardiac polyamines was mediated, at least in part, by the renin angiotensin system, which was stimulated by ISO.

Animals

Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension.

A middle-aged women with hypothyroidism, idiopathic portal hypertension and nephrotic syndrome is presented. This unusual clinical appearance could not be explained as SLE by serological examinations. Pathohistological examinations showed "Banti's liver", Hashimoto's thyroiditis and diffuse proliferative glomerulonephritis with severe tubulo-interstitial nephritis. Immunohistochemical studies revealed IgA deposits in glomeruli. Electron microscopic study disclosed peculiar lucent areas of rarefaction with osmiophilic particles in tubular basement membranes. This tubulointerstitial nephritis was considered to be related to the immunological mechanism involving thyroid gland, liver and kidney disorders. This case thus had a clinically rare combination of these three.

Female

Fabry's disease.

A 20-year-old man presented with generalized acquired anhidrosis and heat intolerance which was confirmed by a sweat test. Other clinical features included severe pain of the extremities and cutaneous angiokeratomas. On electronmicroscopy, granules specific for Fabry's disease were observed in the endothelial cells. Biochemical examination revealed a decreased level of serum alpha-galactosidase A. These findings confirmed the diagnosis of Fabry's disease.

Adult

Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit.

An electrophoretic variant of lactate dehydrogenase-A (M) subunit was discovered in a patient with multiple myeloma. DNA analysis of the variant allele revealed a nucleotide substitution (transition) of C to T at codon 314 (CGT-TGT), and this mutation resulted in the replacement of an arginine by a cysteine (R314C). This amino acid replacement affects the net charge of the subunit and makes the LDH-A variant have a faster electrophoretic mobility. The responsible missense mutation created a new restriction site, AGGCCT, which can be simply detected by endonuclease AatI digestion. In addition, four synonymous substitutions with no amino-acid replacements were found at codons 51, 119, 163 and 175 in the LDH-A gene from the patient.

Aged

Superoxide production by cytochrome b558 purified from neutrophils in a reconstituted system with an exogenous reductase.

Cytochrome b558, which is considered to be an essential component of the phagocytic superoxide (O2-)-generating system, was highly purified from porcine neutrophils. The isolated cytochrome was resolved into two polypeptides with molecular masses of 60-90 and 19 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. For enzymatic reduction of purified cytochrome b558, we utilized hepatic NADPH-cytochrome P450 reductase purified from rat liver microsomes. More than 80% of the cytochrome was reduced by incubation with the reductase and NADPH under the anaerobic condition, and was quickly reoxidized by the air. As indicated by measurement of oxygen consumption, the purified cytochrome catalytically reduced oxygen at a rate equal to approximately 30% of the activity of the phorbol myristate acetate-activated cells on the basis of cytochrome b558 content. Electron paramagnetic resonance study with a spin trapping agent 5, 5-dimethyl-1-pyrroline-1-oxide demonstrated that O2- is the exclusive primary product in the reduction of oxygen by the cytochrome. This gives direct evidence that cytochrome b558 functions as the terminal oxidizing enzyme in the O2- -generating system of neutrophils. This also establishes a new functional class of heme proteins that catalyzes one-electron reduction of molecular oxygen.

Animals

Effect of captopril on isoproterenol-induced myocardial ornithine decarboxylase activity.

Polyamines are thought to play an essential role in cellular hypertrophy and proliferation. Ornithine decarboxylase (ODC) catalyzes the first and probably the rate-limiting step in biosynthesis of polyamines. In this study, we evaluated the pathophysiological role of the renin-angiotensin system in isoproterenol-induced cardiac hypertrophy, using myocardial ODC activity as an indicator of cardiac hypertrophy. Isoproterenol caused an eight-fold increase of myocardial ODC activity in normotensive Wistar rats within 4 h after injection. Captopril suppressed the induction of ODC by isoproterenol to two-thirds of the control level. These results indicate that the renin-angiotensin system may participate in the induction of myocardial hypertrophy by isoproterenol.

Animals

Deficiency of osteoclasts in osteopetrotic mice is due to a defect in the local microenvironment provided by osteoblastic cells.

We have reported that osteoblastic cells are required for differentiation of osteoclast progenitors in splenic tissues into multinucleated osteoclasts. In the present study we examined the pathogenesis of the osteoclast deficiency in osteopetrotic (op/op) mice using a coculture system of spleen cells and osteoblastic cells. When spleen cells obtained from op/op or normal (+/?) littermates of op/+ parent mice were cocultured with osteoblastic cells obtained from calvaria of normal ddy strain mice, numerous tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) were formed in the presence of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. Most of the TRAP-positive MNCs bound [125I]salmon calcitonin. This suggests that there is no abnormality in the osteoclast progenitors present in the splenic tissues of op/op mice. When osteoblastic cells from +/? littermates were cocultured with normal spleen cells from ddy mice, TRAP-positive MNCs were similarly formed in response to 1 alpha,25(OH)2D3. In contrast, in cocultures of op/op osteoblastic cells with normal spleen cells, no TRAP-positive cells appeared, even in the presence of 1 alpha,25(OH)2D3. The op/op mutation was recently reported to exist in the coding region of the macrophage colony-stimulating factor (M-CSF) gene. Adding M-CSF and 1 alpha,25(OH)2D3 to the coculture with op/op osteoblastic cells induced the appearance of TRAP-positive MNCs with calcitonin receptors. These results clearly indicate that osteoclast deficiency in op/op mice is due to a defect in the local microenvironment in bone, in which M-CSF produced by osteoblastic cells plays a critical role in osteoclast development.

Acid Phosphatase

Comparison of color flow and 3D image by computer graphics for the evaluation of carotid disease.

Morphologic characteristics and hemodynamics in the carotid artery were investigated in patients with stroke by use of Doppler color-flow analysis and three-dimensional (3D) analysis by computer graphics. The 3D imaging of the carotid bifurcation was reconstructed from a series of transverse B-mode images. Comparison of color-flow and 3D images demonstrated that wall configuration in vivo, dilation, and curvature play an important role in reversal of flow and stagnation at the carotid bifurcation. Furthermore, 3D analysis is very useful in mapping the distribution of the atheromatous plaques. The analyses suggest that it is important to investigate the wall configuration of the bifurcation in vivo on flow patterns, especially flow separation and stagnation, in relation to the development of atheromatous plaques.

Arteriosclerosis

[Hemoglobin-oxygen affinity in acute exacerbation of chronic respiratory failure].

In order to study the effect of the decrease in P-Pi caused by low pH on hemoglobin-oxygen affinity, we measured P-Pi,2,3-diphosphoglycerate (2,3-DPG), and oxygen tension at 50% saturation (P50) in 36 cases with acute exacerbation of chronic respiratory failure with hypercapnia. The cases were classified into two groups by arterial blood pH values obtained on the day of admission. Group A: pH less than or equal to 7.35 and Group B: pH greater than or equal to 7.36. P50 was calculated by a modification of Severinghaus' equation developed by Yusa and Kohsaka, and it was corrected by applying the carboxy-hemoglobin (COHb) coefficient. On the day of admission (stage I), 2,3-DPG and P50 in both groups were slightly higher than in the control group. In Group A, a week after admission (stage II), these values decreased and became significantly lower than they had been at stage I. Especially 2,3-DPG in stage II was even lower than those of the control group. Approximately 14 days after admission, in stage III, it was found that these values had risen to the initial level at stage I. In Group A, similar changes were also observed for P-Pi. The value of P-Pi was low in stage II and recovered to the initial value in stage III. On the other hand, we found that the urinary excretion of phosphorus (U-Pi) increased at stage I in Group A. It was supposed that the increase in U-Pi at stage I caused a decrease in P-Pi, which caused the decrease in 2,3-DPG, in stage II.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate

[Skin peripheral perfusion pressure (SPPP) in the leg using a technique of 133Xe clearance method].

We developed a new technique for measuring skin peripheral perfusion pressure (SPPP) in the leg by 133Xe clearance method and studied the SPPP in 50 normal volunteers and 86 diabetic patients, including 16 diabetics with gangrene. The SPPP in normal subjects, diabetics without gangrene and diabetics with gangrene were 41.9 +/- 8.6 cmH2O, 30.2 +/- 12.7 cmH2O and 19.4 +/- 10.3 cmH2O, respectively. Our result revealed that the SPPP in diabetics with gangrene was significantly lowest in three groups. The decrease of the SPPP in the diabetics may be due to the steal phenomenon of the blood flow through the abnormally dilated arteriovenous shunt vessels caused by the diabetic neuropathy. The measurement of the SPPP is very useful to assess the impairment of peripheral circulation.

Adult

[An autopsied case of insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis].

A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti-ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case.

Chronic Disease

[Adjuvant chemotherapy for stage I and II non-Hodgkin's lymphoma--a seven-year follow up].

From 1975 to 1983, 51 patients of stage I (30) and II (21) of non-Hodgkin's lymphoma were treated with a combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone as an adjuvant therapy after radiation or operation. The following results were obtained. 1) Nine patients in stage I and 7 in stage II relapsed, so that 10 year-relapse free survival rates were 68% in stage I and 67% in stage II, respectively. 2) Three patients in nodal lymphomas, 7 in Waldeyer's ring lymphomas and 6 in extranodal lymphomas relapsed, so that 10 year-relapse free survival rates were 80%, 48% and 72%, respectively. 3) Ten year-survival rates were 86% in stage I and 70% in stage II. 4) Ten year-survival rates were 82% in nodal lymphomas, 62% in Waldeyer's ring lymphomas and 86% in extranodal lymphomas. 5) Ten patients relapsed within 1 year, 4 between 1-5 years and 2 after 5 years. Relapses occurred in other than primary sites in most patients. These results suggest that an adjuvant chemotherapy is useful for localized non-Hodgkin's lymphoma, but more intensive chemotherapy before local treatments is necessary.

Adult

[Central pontine myelinolysis followed by frequent hyperglycemia and hypoglycemia--report of an autopsy case].

A case of central pontine myelinolysis (CPM) followed by hyperglycemia and hypoglycemia was reported. The case was 53-year-old female. Diabetes mellitus was found when she was 32 years old, insulin therapy was started at 37 years of age. Since she was 50 years old, proteinuria and ankle edema had developed and she was admitted to The Keihin Hospital. The peritoneal dialysis (PD) was performed next year, followed by the hemodialysis (HD). In January 1978, strange movements and the disturbance of her consciousness were occurred during PD, then blood glucose level showed over 1,800 mg/dl and serum osmolarity was over 390 mosm/KgH2O. Then she was diagnosed as non-ketotic hyperosmolar coma. After that, during HD and PD, hyperglycemia (approximately 1,200 mg/dl) and hypoglycemia (approximately 40 mg/dl) developed frequently. She died soon after HD on 19th December 1979. The autopsy disclosed bilateral atrophic kidneys due to diabetic changes and atrophic pancreas. Gross neuropathological findings revealed a few small infarcts at the putamen and the globus pallidus, however, other area were observed to be normal. The most remarkable change in microscopical finding was nearly symmetrical demyelinative lesion in the center of the basis pontis. The nerve cells and axon cylinders were relatively well preserved in the demyelinative lesion. The hyaline degeneration was observed in the arterial wall, however, any arterial obstruction was not found. Recent studies would suggest that the electrolyte disturbance, such as hyponatremia, may lead to CPM, particularly when this disturbance was rapidly corrected. On the other hand, CPM induced by diabetic coma has been reported, however, its pathogenesis has been unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Demyelinating Diseases

[An autopsy case of meningeal carcinomatosis with vestibulocochlear nerve disturbance as the first manifestation].

A 54-year-old man initially complained of frontal headache, right ear pain and tinnitus in May, 1985. This was followed by right facial palsy and hearing loss, and he was admitted to our hospital. Physical findings revealed right trigeminal nerve disturbance, left facial nerve palsy and bulbar palsy. The spinal fluid showed pleocytosis, increased protein, decreased glucose, markedly increased carcinoembryonic antigen and adenocarcinoma cells. Gastric carcinoma was revealed by an upper GI series. He was treated with chemotherapy. However, he die in August, 1985. Nodular metastases were discovered at the right internal acoustic meatus and other areas. Microscopically, signet-ring cell carcinoma had diffusely infiltrated at the subarachnoid space.

Adenocarcinoma, Mucinous