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Biomedical subjects

Y Sumida

Publications and source records attributed to Y Sumida.

At least 55 records · Page 3Linked to original sources
PubMed1999

Differential involvement of small G proteins in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of cognitive function and memory in association with the wide-spread presence of senile plaques, neurofibrillary tangles and neuronal cell death. However, its pathophysiology remains unknown. GTP-binding proteins with molecular weights of approximately 20,000 are designated small G proteins. In the present study we quantitatively analyzed the small G proteins, Ras, Rap, Ral and Rab in brains removed at autopsy from controls and AD patients to examine whether small G proteins are equally or differentially affected in AD. Western blot analysis indicated that the protein level of Ras and RalB in both the cytosolic and membranous fractions and that of Rap2 in the cytosolic fraction was significantly decreased, while that of Rab8 in the membranous fraction was significantly increased in AD brains compared with controls. The protein level of other small G proteins was not different between control and AD brains. These results suggest a differential involvement of small G proteins in AD.

Aged↗
PubMed1998

Differential expression of rat brain bcl-2 family proteins in development and aging.

We have previously examined the involvement of the B cell leukemia-2 gene product (Bcl-2) family proteins (Bcl-2, Bcl-x, Bax, Bak, and Bad) in Alzheimer's disease (AD) and found that Bcl-2, Bcl-x, Bak, and Bad were upregulated. As AD is an aging-associated disease, in the present study we examined the developmental and aging-related changes in Bcl-2 family proteins in the rat brain. Immunoblot analyses of brain extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that the Bcl-2 protein level was highest at E19 and decreased after birth. Bcl-x levels remained high from E19 to 96 weeks. Bax levels were high from E19 to 2 weeks and decreased from 4 weeks onward. Bak levels were highest at E19 and decreased abruptly after birth. Bad levels were high from E19 to 2 weeks and decreased abruptly at 4 weeks. The present results suggest that the expression of each Bcl-2 family protein is differentially regulated during development and aging and that the changes in the senescent brains are different from those observed in AD.

Aging↗
PubMed1998

Differential expression of rat brain synaptic proteins in development and aging.

We have previously reported the differential involvement of synaptic proteins in Alzheimer's disease (AD). As AD is an aging-associated disease, in the present study we examined the developmental and aging-related changes in synaptic proteins such as synaptophysin, synaptobrevin, synaptotagmin, synaptosomal-associated protein 25 (SNAP-25), syntaxin 1/HPC-1 and drebrin in the rat brain. Immunoblot analyses of brain extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that the protein level of synaptophysin and synaptobrevin increased after birth, being highest at 24 weeks, and then decreased with aging. Synaptotagmin was detected at E19, with levels increasing after birth to 96 weeks. SNAP-25 levels were highest at 4 weeks, and then decreased with aging. Syntaxin 1/HPC-1 levels were high at E19 and 1 week, decreasing rapidly from 2 weeks onwards, and drebrin levels were highest at E19 and 1 week, and decreased during aging. The present results suggest that the expression of each synaptic protein is differentially regulated in development and aging.

Aging↗
PubMed1998

Alteration of myo-inositol monophosphatase in Alzheimer's disease brains.

myo-Inositol monophosphatase (E.C.3.1.3.25) catalyzes the hydrolysis of myo-inositol 1-phosphate in the presence of Mg2+ at a physiologic pH to form free myo-inositol, maintaining a supply that represents the precursor for inositol phospholipid second messenger signaling systems. In the present study the activity and protein level of myo-inositol monophosphatase were investigated in samples from normal human and Alzheimer's disease (AD) postmortem brains. The separation profile on Sephadex G-100 gel filtration chromatography revealed one major form of myo-inositol monophosphatase in crude extracts from both normal human and AD brains. In AD brains myo-inositol monophosphatase activity and its protein level were significantly higher than in control brains. The activity of myo-inositol monophosphatase per enzyme molecule was similar in control and AD brains. These results suggest that myo-inositol monophosphatase is upregulated in AD, probably reflecting compensatory mechanisms concerned with phospholipid metabolism.

Aged↗
PubMed1998

Differential expression of rat brain phospholipase C isozymes in development and aging.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. In the present study we examined developmental and aging changes in three PLC isozymes (beta 1, gamma 1, and delta 1) in the rat brain. Enzyme assays and immunoblot analyses after gel filtration chromatography of brain extracts from embryonic day 19 and postnatal 4- and 48-week rats indicated that gamma-specific activity was highest in fetal brain and decreased with aging, that beta 1-specific activity was high at 4 weeks but essentially undetected in fetal brain, and that delta 1-specific activity was high at both 4 and 48 weeks with faint detection in fetal brain. Our results suggest that the gamma 1 isozyme may be particularly involved in cell division and growth during the histo-genesis of the central nervous system, while beta 1 and delta 1 isozymes may take part in processes of its maturation and maintenance.

Aging↗
PubMed1998

Extrahepatic biliary cystadenocarcinoma arising from the left hepatic duct.

A 54-year-old man, who had no clinical symptoms, underwent a routine health checkup at our hospital. Abdominal ultrasonography disclosed a well demarcated tumor containing a solid portion occupying the dilated left hepatic duct and a cystic portion expanding into the parenchyma of the left hepatic lobe, with mild dilatation of the intrahepatic bile ducts. These findings were later confirmed by computed tomography (CT) and magnetic resonance imaging. Endoscopic retrograde cholangiography revealed a complete defect at the level of the left hepatic duct, while drip infusion cholangiographic-CT (DIC-CT) disclosed a defect of the left hepatic duct only, with the distal portions of the left intrahepatic ducts being visualized on the image. Hepatic angiography revealed light stains in the solid portion in the parenchymal phase. At left lobectomy, a multiloculated polyp-like tumor was found arising from the left hepatic duct and expanding into the parenchyma of the left hepatic lobe. Microscopically, all the lining cells in the cysts and the tumor cells in the solid portion showed the features of papillary adenocarcinoma. In this patient with extrahepatic biliary cystadenocarcinoma, DIC-CT was useful in identifying the site of origin of the tumor, and hepatic angiography was also useful in differentiating this rare malignant tumor from benign cystadenoma.

Bile Duct Neoplasms↗
PubMed1998

Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice.

Angiotensinogen gene-knockout (Atg-/-) mice lacking angiotensin II exhibit chronic hypotension. The present study was designed to investigate pathophysiology of Atg-/- mice from the renal functional view. Wild-type (Atg+/+) and Atg-/- mice at 10 weeks of age were housed in metabolic cages for 24-hour urine collection. When provided free access to water, Atg-/- mice showed an increased urine output and a decreased urine osmolality compared with Atg+/+ mice. Urinary excretion and plasma levels of vasopressin were significantly higher in mutant mice than in wild-type mice. On the other hand, urinary excretion of aldosterone in mutant mice was suppressed to the levels under the detection limit of the assay system. The mean plasma aldosterone level of Atg-/- mice was suppressed to 30% of that of Atg+/+ mice. Plasma levels of creatinine, endogenous creatinine clearance, and urinary electrolyte excretion were not different between these mice. In Atg+/+ mice, urine osmolality was markedly increased from 1929 +/- 21 to 3314 +/- 402 mOsm/kg during water deprivation, whereas this parameter in Atg-/- mice did not change significantly (from 1413 +/- 121 to 1590 +/- 92 mOsm/kg). Urinary vasopressin excretion increased during water deprivation from 0.24 +/- 0.04 and 0.70 +/- 0.08 to 0.42 +/- 0.06 and 2.31 +/- 0.35 ng/mg creatinine in wild-type and mutant mice, respectively. Histologic study revealed interstitial inflammation, and atrophic changes in the tubules and papilla in Atg-/- mice. In conclusion, a genetic deficiency of angiotensinogen produced an impaired urine concentrating ability and tubulointerstitial lesions, indicating the critical role of angiotensinogen in developing normal tubular function and construction.

Aldosterone↗
PubMed1998

Circulating levels of 7 S domain of type IV collagen and atrial natriuretic peptide in normotensive type 2 diabetic patients with or without retinopathy.

Thickening of the basement membrane and other structural alterations of the vascular walls occur frequently in patients with diabetes. The vascular response to atrial natriuretic peptide (ANP) is also altered in these patients. Abnormal vascular response in diabetes may be due to alteration of vascular physicochemical properties induced by accumulation of components of vascular basement membrane. The aim of this study was to evaluate the relationship between circulating levels of the 7 S domain of type IV collagen (7 S-collagen), and ANP in normotensive type 2 diabetic patients with or without retinopathy. Forty-one normotensive type 2 diabetic patients (n = 19 with and n = 22 without retinopathy) and 18 age-matched control subjects participated in the study. Serum 7 S-collagen and plasma ANP levels were measured by radioimmunoassays. Serum 7 S-collagen (4.4 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01) levels and plasma ANP (20.8 +/- 1.0 vs 15.5 +/- 1.0 pg/ml; p < 0.01) were significantly higher in diabetic patients than in normal subjects. Serum 7 S-collagen increased significantly in diabetic patients without retinopathy compared with normal subjects (4.1 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01). Diabetic patients with retinopathy showed significantly higher circulating concentrations of 7 S-collagen (4.6 +/- 0.1 vs 4.1 +/- 0.1 ng/ml; p < 0.01) and ANP (22.9 +/- 1.4 vs 18.9 +/- 1.3 pg/ml; p < 0.05) than those without retinopathy. There was a significant and positive correlation (r = 0.51, p < 0.01) between the circulating levels of 7 S-collagen and ANP in all patients. The results of this investigation showed that increased circulating levels of ANP correlate with the abnormal metabolism of the vascular basement membrane observed in diabetic patients with microangiopathy.

Atrial Natriuretic Factor↗
PubMed1998

Endocrinological abnormalities in angiotensinogen-gene knockout mice: studies of hormonal responses to dietary salt loading.

OBJECTIVE: Physiological roles of the renin-angiotensin system in maintaining blood pressure and sodium-water balance in angiotensinogen gene-knockout mice were evaluated with special reference to endogenous pressor substances. METHODS: Angiotensinogen-gene knockout mice and control mice were fed a 0.3 or 4% NaCl diet for 2 weeks. Systolic blood pressure and urinary excretions of electrolytes, creatinine, aldosterone, adrenaline, noradrenaline, dopamine and vasopressin were measured. RESULTS: About 60% of our angiotensinogen-gene knockout mice did not survive until weaning. These mice presented with hypotension and polyuria. Urinary excretion of aldosterone from such mice was significantly lower (not detected) than that from control mice (2.0+/-0.3 pg/mg creatinine). In contrast, urinary excretion of vasopressin from angiotensinogen-gene knockout mice (0.7+/-0.1 ng/mg creatinine) was greater than that from control mice (0.3+/-0.1 ng/mg creatinine), and those of adrenaline and of noradrenaline were similar for knockout and control mice. After salt loading (a 4% NaCl diet), angiotensinogen-gene knockout mice exhibited a significant increase in systolic blood pressure (from 68.3+/-2.9 to 95.9+/-5.9 mmHg), significant decreases in urinary excretions of adrenaline (from 65+/-8 to 40+/-7 pg/mg creatinine) and noradrenaline (from 467+/-48 to 281+/-41 pg/mg creatinine) and no change in excretion of vasopressin compared with such mice fed a 0.3% NaCl diet CONCLUSION: The present results with angiotensinogen-gene knockout mice confirm that the renin-angiotensin system plays fundamental roles in maintaining the blood pressure and sodium-water balance. Because the vasopressin and catecholaminergic systems may be altered by lack of angiotensin in angiotensinogen-gene knockout mice, these systems perhaps are not able to restore blood pressure and sodium-water depletion to normal levels in these mice.

Aldosterone↗
PubMed1998

Increased cardiac angiotensin II receptors in angiotensinogen-deficient mice.

Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT1-R) and type 2 (AT2-R), have been identified in the heart. However, little is known about the regulation of cardiac AT1-R and AT2-R by Ang II in vivo. Thus, we examined cardiac AT1-R and AT2-R in angiotensinogen-deficient (Atg-/-) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with 125I-[Sar1,Ile8]-Ang II in plasma membrane fractions. AT1-R and AT2-R were distinguished using their specific antagonists CV-11974 and PD123319, respectively. Total densities of Ang II-R and AT1-R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1+/-2.8 versus 18.8+/-2.1, 28.7+/-3.0 versus 16.9+/-2.3 fmol/mg protein, P<.01, respectively), and AT2-R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. Kd values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT1a-R) and AT2-R mRNA did not differ between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT1-R through translational and/or posttranslational mechanisms in Atg-/- mice.

Angiotensin II↗
PubMed1998

Effect of genetic deficiency of angiotensinogen on the renin-angiotensin system.

This study examined expression of renin-angiotensin system (RAS) component mRNAs in angiotensinogen gene knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg-/- mice were fed a normal-salt (0.3% NaCl) or high-salt (4% NaCl) diet for 2 weeks. Angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensin II type la receptor (AT1A), and angiotensin II type 2 receptor (AT2) mRNA levels were measured by Northern blot analysis. In Atg+/+ mice, activities of circulating RAS and renal angiotensinogen mRNA level were decreased by salt loading, whereas levels of renal and cardiac ACE; renal, brain, and cardiac AT1A; and brain and cardiac AT2 mRNA were increased by salt loading. Although activities of circulating RAS were not detected in Atg-/- mice, salt loading increased blood pressure in Atg-/- mice. In Atg-/- mice, renal renin mRNA level was decreased by salt loading; in contrast, salt loading increased renal AT1A and cardiac AT2 mRNA levels in Atg-/- mice, and these activated levels in Atg-/- mice were higher than those in Atg+/+ mice fed the high-salt diet. Thus, expression of each component of the RAS is regulated in a tissue-specific manner that is distinct from other components of systemic and local RAS and that appears to be mediated by a mechanism other than changes in the circulating or tissue levels of angiotensin peptides.

Angiotensinogen↗
PubMed1998

Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus.

To clarify the significance of the serum levels of tumor necrosis factor-alpha (TNF-alpha) in the mechanism of insulin resistance, we studied 12 obese patients with noninsulin-dependent diabetes mellitus (NIDDM). We evaluated the relationship of TNF-alpha levels with the visceral, subcutaneous, and total fat areas measured by computed tomography (CT), and with insulin resistance evaluated by the glucose infusion rate (GIR) observed during an euglycemic hyperinsulinemic clamp study. Controls consisted of 12 normal subjects and 12 nonobese patients with NIDDM. TNF-alpha levels were measured using a high sensitivity enzyme-linked immunosorbent assay. Following admission, all patients with NIDDM participated in a 4-week program of diet and exercise. After this treatment, we evaluated the relationship of the serum levels of TNF-alpha with the area of body fat, the GIR, and the resultant change in the TNF-alpha level. Serum levels of TNF-alpha in the obese patients with NIDDM significantly exceeded those observed in normal subjects (P < 0.01) or in the nonobese patients with NIDDM (P < 0.01). Serum levels of TNF-alpha in obese NIDDM patients showed a significant positive correlation with the area of visceral fat before (r = 0.662, P < 0.03) and after (r = 0.508, P < 0.05) the treatment; similar correlation was observed in all patients with NIDDM before (r = 0.537, P < 0.02) and after (r = 0.430, P < 0.05) the treatment. Serum levels of TNF-alpha in obese NIDDM patients showed a significant negative correlation with GIR after the treatment (r = -0.595, P < 0.05). Serum levels of TNF-alpha were significantly reduced in the obese patients with NIDDM after the treatment (P < 0.01), while those in the nonobese NIDDM patients were unchanged. These results suggest that serum TNF-alpha levels may play an important role in mechanism of insulin resistance associated with obesity.

Adipose Tissue↗
PubMed1998

Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice.

The present study investigates whether neuronal type nitric oxide synthase (N-NOS) in the macula densa participates in the regulation of renal renin expression during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of N-NOS and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg-/- mice compared with Atg+/+ mice. When mutant mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. These changes were paralleled by decreases in renal renin-immunoreactive areas and the levels of renin mRNA. On the other hand, salt restriction did not produce further significant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between these enzyme expressions and the levels of salt intake in wild-type mice. These results suggest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N-NOS and renin expressions are independent on angiotensin formation in Atg-/- mice.

Animals↗
PubMed1998

Significant decreased insulin secretion in a diabetic patient with clinically probable multiple sclerosis.

A 39-year-old man with chief complaints of aphasia, disorientation and acalculia was admitted to our hospital. He was diagnosed as a clinically probable case of multiple sclerosis (MS) and his symptoms improved while on steroid pulse therapy. The patient had been diagnosed as having diabetes mellitus 16 years before the onset of MS and his insulin secretion further decreased with time. Slight insulin resistance was observed during a euglycemic hyperinsulinemic clamp study. These results suggested that this patient developed diabetes mellitus mainly due to the decrease of insulin secretion.

Adrenal Cortex Hormones↗
PubMed1997

Serum 7S domain of type IV collagen levels in essential hypertension and hypertensive type 2 diabetic patients.

Metabolic alteration of Type IV collagen occurs in micro- or macrovascular basement membrane of diabetic patients. Hypertension, a risk factor for clinical progression of diabetic vascular disease, may influence this metabolic alteration. The object of this study was to evaluate the serum 7S domain of type IV collagen (7S-collagen) levels in patients with essential hypertension and in Type 2 diabetic patients with or without hypertension and to investigate the relationship between the type IV collagen metabolism and the arterial blood pressure. Serum 7S-collagen levels in 18 patients with essential hypertension were significantly higher than in 24 normal subjects (4.2 +/- 0.5 vs 3.6 +/- 0.4 ng ml(-1) p < 0.01). Serum 7S-collagen levels in 28 normotensive diabetic patients (4.2 +/- 0.5 ng ml(-1)) were significantly higher than in normal subjects (p < 0.01). The serum 7S-collagen levels were significantly higher in 22 diabetic patients with hypertension (4.8 +/- 0.6 ng ml(-1)) than in the other groups. There was a significant correlation between the serum 7S-collagen levels and the systolic blood pressure in cases with essential hypertension (r = 0.59, p < 0.001) and in all diabetic patients (r = 0.52, p < 0.001), suggesting that elevation of the systolic blood pressure may influence the type IV collagen metabolism of vascular basement membrane. We conclude that the metabolic alteration of basement membrane occurring in patients with diabetes mellitus may worsen in the presence of high systolic blood pressure.

Age Factors↗
PubMed1997

Effect of triiodothyronine on glucose transport in rat adipocytes.

The in vitro effect of thyroid hormones on glucose transport in insulin-stimulated muscle cells or adipocytes is still unclear. The objective of the present study was to assess the direct effect of 3,3',5-triiodothyronine (T3) on glucose transport and on the translocation of insulin-regulatable glucose transporter (GLUT4) in insulin-stimulated rat adipocytes. This evaluation was performed using an in vitro assay to avoid the well-known systemic effects of this hormone ( e.g.: hyperinsulinemia). Adipocytes were isolated from epididymal adipose tissue of Sprague-Dawley rats. Glucose transport assay and immunoblot analysis of GLUT4 were carried out in insulin-stimulated and unstimulated adipocytes after treating with or without T3. The results were as follows; 1) T3 inhibited the glucose transport in insulin-stimulated and unstimulated adipocytes in a dose-dependent manner. 2) T3 decreased the maximal response level (Vmax) but did not alter the sensitivity (Km) of glucose transport to insulin. 3) T3 did not affect the translocation of GLUT4 from the intracellular pool to the plasma membrane. We concluded that T3 inhibits the glucose transport in insulin-stimulated adipocytes in a post-receptor level without affecting the translocation of GLUT4 from the intracellular pool to the plasma membrane. This suggests that T3 acts by decreasing the intrinsic activity or the accessibility of GLUT4 in the plasma membrane.

3-O-Methylglucose↗