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Biomedical subjects

Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 649 records · Page 36Linked to original sources
PubMed1994

Autoantibodies to glutamic acid decarboxylase (GAD), 64,000-Mr islet cell protein (64K) antibodies and islet cell antibodies (ICA) in insulin-dependent diabetes mellitus with and without autoimmune diseases in Japan.

IDDM is known to be a heterogeneous disease which is frequently complicated with other autoimmune diseases (AID). We previously reported that IDDM patients with AID were characterized by late onset of diabetes, persistent ICA-positivity and increased association with DR9, while those without AID were characterized by rapid decline of ICA with duration of diabetes and increased association with DR4. The present study was performed to investigate the prevalence of autoantibodies to glutamic acid decarboxylase (GAD), autoantibodies to 64KDa islet cell protein (64K antibodies) and islet cell antibodies (ICA) in Japanese IDDM patients with and without AID. In short-duration diabetes (< 1 year), the prevalence of GAD antibodies, 64K antibodies and ICA were 100%, 100%, and 100%, respectively, in IDDM patients with AID, and 82%, 64% and 82%, respectively, in patients without AID. In long-standing diabetes (3-28 years), the prevalence of GAD antibodies were 76%, 48% and 33%, respectively, in IDDM patients with AID, and 48%, 28% and 16%, respectively, in patients without AID. The mean levels of GAD antibodies, 64K antibodies and ICA in IDDM patients with AID was significantly higher than in those without AID. Furthermore, the prevalence of GAD antibodies were detected more frequently than ICA and 64K antibodies in long standing IDDM patients. Our results demonstrate that the prevalence of GAD antibodies in IDDM patients were as high as those reported in Caucasians, and high levels of GAD antibodies were observed in IDDM patients with AID.

Addison Disease↗
PubMed1994

Survival of noncuratively resected lung cancer.

Out of 858 patients who underwent thoracotomy for primary lung cancer, 279 cases were classified as non-curative on the basis of intraoperative and/or post-operative examinations. The causes for non-curative resection were defined as follows: (I) absolutely non-curative resection, (1) palliative tumor extirpation (palliative), (2) remaining tumor in (a) lymph nodes (Ly rem), (b) chest wall or diaphragm (Ch/Dia rem), or (c) bronchial stump (Bro rem), (3) intrapulmonary metastasis (PM), (4) pleural dissemination or pleuritis carcinomatosa (P1/Diss), (5) metastasis in other organs (Meta); (II) relatively non-curative resection, (1) incomplete resection of lymph nodes (R0-1), (2) group 2b or 3 lymph node metastasis (2b Ly). The 5-year actuarial survival rate of the Bro rem group was 35.6%, being the best among the absolutely non-curative cases, followed by the PM group (33.7%), the Pl/Diss group (31.6%) and the Ch/Dia rem group (29.7%). The results of the Ly rem and Meta groups were poor at 5.4% and 0%, respectively. Those of the relatively non-curative group were 24.4% (R0-1 group) and 11.6% (2b Ly group). Non-curative resection is not the treatment of choice, but by analyzing the causes of non-curative resection, we may able to improve the prognosis of advanced cases of lung cancer.

Female↗
PubMed1994

Hepatic biliary transport after hepatocyte transplantation in Eizai hyperbilirubinemic rats.

The Eizai hyperbilirubinemic rat (EHBR) is a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Eizai hyperbilirubinemic rats have impaired canalicular excretory transport of organic anions, bile acid glucuronide and sulfate. Eizai hyperbilirubinemic rats, with and without a 68% partial hepatectomy, were treated by an intraportal injection of 1 x 10(7) wild-type Sprague-Dawley mutant rat hepatocytes. Serum bilirubin concentrations decreased significantly after hepatectomy and intraportal injection. Biliary excretion was demonstrated by biliary transport of indocyanine and sulfobromophthalein into the bile. These results indicate that hepatic transport of bile acid conjugates in Eizai hyperbilirubinemic rats can be restored by hepatocyte transplantation in conjunction with the recipient's excretory biliary system.

Animals↗
PubMed1994

Crystalline inclusions in the glomerular podocytes in a patient with benign monoclonal gammopathy and focal segmental glomerulosclerosis.

We report a case of a 40-year-old woman with benign monoclonal gammopathy who developed focal segmental glomerulosclerosis associated with widespread deposition of large crystalline inclusions in the glomerular podocytes. Electron microscopy showed that the crystalline structures were electron dense and needle shaped or polygonal. At a higher magnification, they were seen to be surrounded by unit membranes and to feature a longitudinal filamentous substructure. These inclusions showed positive immunohistochemical staining for kappa light chain. Clinically, the patient had shown nephrotic syndrome on the first medical examination, and later revealed chronic renal failure and monoclonal gammopathy of the immunoglobulin G kappa type, but no evidence of multiple myeloma or other lymphoproliferative diseases. This patient seems to have had a rare form of glomerular involvement associated with benign monoclonal gammopathy.

Adult↗
PubMed1994

Molecular analysis of Gpdh null mutations that arose in mutation accumulation experiments in Drosophila melanogaster.

In order to clarify the cause of null mutations in enzyme loci, the molecular structure of six null mutations in the Gpdh locus (encoding alpha GPDH: alpha glycerol-3-phosphate dehydrogenase (NAD+), E.C. 1.1.1.8; map position at 2-17.8) that arose in mutation accumulation experiments was examined. A restriction map analysis showed that five of the mutations are insertional mutations whereas the sixth is a deletion. The Gpdh regions of these null mutations were then cloned and sequenced. The inserted DNA fragments are all internally deleted P elements measuring 1.1 kb in length. Two are a KP element and two others are a HP element. All the insertions occur in the region near the initiation signal of transcription. The deletion encompasses the seventh and eighth exons over a length of 1.1 kb. These results therefore indicate that the null mutation rate at the Gpdh locus is largely influenced by P elements.

Animals↗
PubMed1994

Endoscopic ultrasonography in the diagnosis of extraluminal compressions mimicking gastric submucosal tumors.

We evaluated the diagnostic usefulness of endoscopic ultrasonography (EUS) in 19 patients with extragastric compression. In these 19 cases, the causes of the compression were normal organs or structures in 16 cases (splenic artery 7, spleen 5, normal pancreas two, gall-bladder one, colon one) and extraluminal tumors in three cases (two hepatic hemangiomas, one neurogenic tumor of the omentum minor). In 12 of these 19 cases, the site of the submucosal compression was located in the upper part of the stomach. All three tumors were confirmed by other procedures, and in the remaining 16 patients with compression by normal organs or structures, negative follow-up results (mean: 14 months) supported the absence of a true submucosal tumor. EUS was 100% accurate in the differentiation of an extragastric compression from a submucosal tumor, and in the identification of the compressing organ. EUS was also far superior to other procedures, such as ultrasonography and CT. It significantly shortens the diagnostic procedure, especially in patients with compressions by normal extraluminal structures, making other diagnostic modalities unnecessary.

Adult↗
PubMed1994

Retroviral delivery of DNA into the livers of transgenic mice bearing premalignant and malignant hepatocellular carcinomas.

To develop gene therapy for hepatocellular carcinoma (HCC), we infused mice through the portal vein with retrovirus carrying the Escherichia coli beta-galactosidase reporter gene under the transcriptional control of the viral long terminal repeat (LTR) and the promoter from the mouse multidrug resistance gene mdr1b. Two transgenic mouse HCC models were used, one bearing the human hepatitis B viral envelope protein and the other SV40 T antigen. These animals develop HCC with predictable pathological manifestations. The viral transduction efficiency appeared to depend upon the stage of the disease in the animals. The most efficient transduction occurred when the livers had developed microscopic nodular hyperplasia; in some cases as many as 0.01-0.1 copies/cell were transduced. The transduction efficiency was lower in the late stage of the disease when livers had a heavy tumor burden and in the early stage when no lesion was evident. Low viral transduction efficacy was also seen in nontransgenic animals but was significantly increased by partial hepatectomy. The expression of the reporter gene in these animals was very low, as determined by histological staining. These results suggest that hepatocarcinogenesis can enhance retroviral delivery of foreign genes into the liver. Further development by increasing the viral transducing efficiency and the level of expression of transduced gene is required.

3T3 Cells↗
PubMed1994

Glucosylceramide and glucosylsphingosine metabolism in cultured fibroblasts deficient in acid beta-glucosidase activity.

The metabolism of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) was studied using cultured fibroblasts deficient in acid beta-glucosidase activity. In fibroblasts from patients with Gaucher's disease, in vitro beta-glucosidase activities were 2.7-11.7% and 4.8-13.6% of control values when 4-methylumbelliferyl beta-D-glucoside and GlcSph were used as substrates, respectively. In spite of the enzyme deficiency, GlcCer and GlcSph, the natural substrates of the deficient enzyme, did not accumulate in the cells. When normal fibroblasts were incubated with conduritol B epoxide (CBE), a specific inhibitor of acid beta-glucosidase, the in vitro enzyme activities decreased dose-dependently (2.2-2.4% of control values at 50 microM CBE), and GlcCer and GlcSph accumulated in the cells at concentrations of CBE higher than 50 microM. To investigate the intracellular metabolism of GlcCer and GlcSph, either radioactive GlcCer or GlcSph was loaded onto cultured fibroblasts. In fibroblasts treated with a high dose of CBE (1 mM), the degradation of GlcCer and GlcSph was retarded (5-21% on day 7; normal range, 81-99%), while in fibroblasts from patients with Gaucher's disease, both the pattern and rate of the degradation of the lipids (83-97% on day 7) were almost the same as those seen in the control cells. These results indicate that in Gaucher's disease fibroblasts the intracellular metabolism of GlcCer and GlcSph is normal in spite of the deficiency in beta-glucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1994

The synthetic pathway for glucosylsphingosine in cultured fibroblasts.

The synthesis of glucosylsphingosine (GlcSph), a glucosylceramide (GlcCer) analogue devoid of fatty acids, in cultured fibroblasts was studied by using conduritol beta epoxide (CBE), an inhibitor of beta-glucosidase, and 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an inhibitor of glucosylceramide (GlcCer) synthase (glucosyltransferase). When CBE was added to the culture medium, the intracellular beta-glucosidase activity decreased, and both GlcCer and GlcSph accumulated in the cells. After the addition of PDMP, the concentration of GlcCer decreased, while the content of GlcSph increased. When CBE and PDMP were added together, the intracellular accumulation of GlcSph to decreased to less than when CBE alone was added. Based on these results, the synthetic pathway for GlcSph was thus considered to not only be through the glucosylation of sphingosine, but also through the deacylation of GlcCer. When GlcCer (d18:1, C12:0) was added to the culture medium, the intracellular accumulation of GlcSph (d18:1) was evident, and it was also more pronounced in the presence of CBE. In addition, when GlcCer (d18:0, C12:0) was used, apparent accumulation of GlcSph (d18:0) was also observed. In order to determine whether or not the deacylase of GlcCer is identical to acid ceramidase, a deacylase of ceramide, the same experiments were carried out using fibroblasts from two patients with Farber disease, in which acid ceramidase is genetically deficient. The accumulation of GlcSph in the Farber disease fibroblasts after the loading of GlcCer for 7 days was found to be one-fifth of the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗
PubMed1994

The capacity of dog lung to release prostaglandin I2 as a biochemical parameter for evaluating lung damage during preservation.

The release of prostaglandin I2 (PGI2) from the vasculature is thought to reflect damage to the vessels. Basal and bradykinin (BK)-stimulated release of PGI2 from isolated dog lungs after 6-hr preservation were investigated to evaluate lung damage after preservation. Maximal PGI2 release induced by BK decreased significantly after preservation at 24 degrees C (room temperature), but not after hypothermic preservation at 4 degrees C, although basal PGI2 release without BK stimulation did not change in either group of lungs after preservation. The function of allotransplanted lungs assessed by arterial oxygen tension was impaired by preservation at room temperature but not by hypothermic preservation. No differences were observed by light microscopy in either group in the pulmonary tissues, including the pulmonary artery, after preservation. In summary, damage to the lung after preservation may be reflected by the maximal PGI2 release from the lung after BK infusion. Therefore the maximal PGI2 releasing capacity induced by BK may be a useful biochemical parameter for estimating the viability of preserved lungs.

Animals↗
PubMed1994

Differences in endothelium-dependent relaxation in various arteries from Watanabe heritable hyperlipidaemic rabbits with increasing age.

1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A23187 was examined in aorta, coronary, basilar and renal arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls. 2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with vasoconstrictors, endothelium-dependent relaxation in response to ACh was attenuated with age compared to the heterozygous WHHL rabbits. A significant negative correlation was found between the total cholesterol content and the relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month old WHHL rabbits. 3. In the rings of basilar arteries, endothelium-dependent relaxations to ACh were not modified with age. Similarly, in the rings of renal arteries, the relaxation response to ACh was not changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at higher concentrations of ACh (10(-7) to 10(-6) mol/L). The contraction was endothelium-dependent and inhibited by indomethacin. 4. A23187-induced endothelium-dependent relaxations were also markedly attenuated in the aorta and significantly in the coronary artery with age. 5. Endothelium-independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages. 6. These findings indicate that in the aorta and coronary artery of the WHHL rabbit, the endothelium-dependent relaxation to ACh and A23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposition in the arterial wall) but is preserved in the basilar and renal artery.

Acetylcholine↗
PubMed1994

Virucidal effect of myeloperoxidase on human immunodeficiency virus type 1-infected T cells.

Myeloperoxidase is virucidal to human immunodeficiency virus type 1 (HIV-1) in the persistently infected CEM human T-cell line or in acutely infected human peripheral blood mononuclear cells, as judged by viral infectivity and P24 radioimmunoassay. HIV-1 was specifically inactivated by low doses of the human myeloperoxidase (1.4 to 14.3 mU/ml) and the cells were spared. A higher enzyme concentration (143 mU/m) was cytotoxic, but uninfected CEM cells and normal lymphocytes were resistant to > or = 143 mU of myeloperoxidase per ml. The enzyme was virucidal with the Cl- present in medium and did not require exogenous H2O2. Catalase, an antioxidant enzyme, partially inhibited the virucidal effect of myeloperoxidase. Hence, the H2O2 probably came from the HIV-infected cells themselves. These in vitro findings indicate that the myeloperoxidase system is capable of inactivating HIV-1 of infected cells.

Antiviral Agents↗
PubMed1994

Hepatic vascular response to anaphylaxis in isolated canine liver.

We determined the vascular response to anaphylaxis in isolated canine livers perfused with autologous blood at a constant pressure via the portal vein, with hepatic artery ligation to simplify the vascular system. We also studied the validity of the double occlusion pressure (Pdo) as a measure of the capillary pressure (Pc) in the isolated canine liver. Pdo was compared with Pc measured using the traditional isogravimetric method (Pc,i), and both parameters showed a strong correlation (Pdo = 0.34 + 0.90 Pc,i; r = 0.93; P < 0.01). This indicated that Pdo provided an accurate indication of Pc in the isolated liver. In livers with anaphylaxis induced by the intraportal injection of Ascaris suum antigen (5 mg; 1.0 +/- 0.03 mg/kg body wt), hepatic vascular resistance and Pc (assessed as Pdo) were increased transiently by 29-fold and 3.4 mmHg, respectively, along with a significant increase of liver weight. The ratio of presinusoidal to postsinusoidal vascular resistance decreased from 0.89 +/- 0.05 to 0.36 +/- 0.12, suggesting that hepatic venous constriction was predominant. In livers perfused in the antidromic direction from the hepatic vein to the portal vein, anaphylaxis caused marked presinusoidal vasoconstriction that was consistent with hepatic venoconstriction as well as a significant and sustained decrease of liver weight below the baseline. These results suggest that anaphylaxis produced hepatic weight gain because of an increase in sinusoidal pressure caused by hepatic venoconstriction. Such hepatic venoconstriction may play an important role in the development of portal hypertension and hepatic congestion associated with anaphylactic shock.

Anaphylaxis↗
PubMed1994

Enhancement of parasympathetic cardiac activity during activation of muscle metaboreflex in humans.

We measured the changes in heart rate (HR) variability estimated from the standard deviation of the R-R intervals to evaluate cardiac parasympathetic tone noninvasively before and during activation of muscle metaboreflex induced by postexercise muscle ischemia. Eight healthy male subjects performed sustained handgrip at 50% maximal voluntary contraction followed by forearm occlusion. Mean arterial pressure, cardiac stroke volume, and ratio of cardiac preejection period to left ventricular ejection time (PEP/LVET) were also measured. During the 2-min occlusion after 60 s of handgrip with voluntary respiration, HR variability and mean arterial pressure were significantly increased from baseline (54.4 +/- 6.1 to 80.1 +/- 12.8 ms and 81 +/- 1 to 99 +/- 3 mmHg, respectively) and PEP/LVET was decreased from resting level of 0.404 +/- 0.022 to 0.363 +/- 0.036. During occlusion and recovery, HR did not change from baseline level in any experiment. There was no influence of occlusion itself or of cessation of exercise per se on any parameters. Although overall enhanced HR variability was seen, probably due to lower breathing frequency and larger tidal volume, similar results were also obtained from an experiment with controlled respiration, showing that the increase in HR variability was not due to the changes in tidal volume or breathing frequency during occlusion. In conclusion, the HR variability is increased during activation of the muscle metaboreflex induced by postexercise muscle ischemia in humans. This finding shows that the parasympathetic cardiac tone is enhanced during activation of the muscle metaboreflex in humans and balances enhanced cardiac sympathetic activity to result in an unchanged HR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Probucol reduces renal injury in the ExHC rat.

To investigate the potential roles of oxidized lipoproteins and glomerular macrophages in the pathogenesis of lipid-induced glomerular injury, we examined the effects of administration of probucol on the development of renal injury in ExHC rats. ExHC rats are derived from the Sprague-Dawley strain and are highly susceptible to dietary hypercholesterolemic stimuli. We reported previously that ExHC rats fed a cholesterol-supplemented diet (HCD) develop proteinuria and characteristic glomerular lesions. These lesions include marked accumulation of numerous lipid-filled foam cells, which have a surface marker that identifies them as macrophages, within mesangial regions, as well as segmental clusters of foam cells that are associated with capsular adhesions, the destruction of glomerular tufts and glomerular sclerosis. ExHC rats were maintained on an HCD or on an HCD supplemented with 5% (wt/wt) probucol for 8 weeks. Probucol reduced the extent of renal injury, as evidenced by proteinuria and segmental glomerular lesions, in ExHC rats fed an HCD, in the absence of any significant reduction in plasma cholesterol levels. Both low-density lipoprotein and beta-very-low density lipoprotein isolated from the plasma of probucol-treated rats were found to be resistant to oxidative modification by cupric ions. Both the size and the number of foam cells within glomeruli in the probucol-treated rats were significantly reduced as compared to those of foam cells in the untreated rats. Probucol might reduce renal injury in ExHC rats by limiting the oxidative modification of lipoproteins and, subsequently, by restricting the foam cell transformation of macrophages within glomeruli and by inhibiting the recruitment of macrophages into glomeruli. The results of the present study may be interpreted to indicate that local glomerular oxidative modification of lipoproteins might occur in vivo, and both oxidized lipoproteins and glomerular macrophages may play important roles in the pathogenesis of lipid-induced glomerular injury.

Animals↗
PubMed1994

Hereditary nephrotic syndrome with progression to renal failure in a mouse model (ICGN strain): clinical study.

The clinical course of murine hereditary nephrotic syndrome (ICGN strain) was determined by examining 201 animals under different conditions. In the early stage, significant hypoproteinemia and hypoalbuminemia developed (p < 0.001) in parallel with a progressive rise in urinary protein concentration (p < 0.001). In the middle stage, the concentrations of total cholesterol, triglyceride, and beta-lipoprotein markedly increased (p < 0.01, p < 0.001, and p < 0.001, respectively), suggesting that type IIb hyperlipoproteinemia developed as in human nephrotic patients. Systemic edema appeared in 8 of 24 animals. In the terminal stage, both BUN and creatinine values greatly increased (p < 0.001), indicating rapid deterioration of renal function. The present study suggests that ICGN mice could be a useful model to study the pathophysiology of human nephrotic syndrome and its progression to renal failure.

Animals↗
PubMed1994

Transcriptional regulation of the human eosinophil peroxidase genes: characterization of a peroxidase promoter.

The molecular basis for commitment of progenitors to the eosinophil lineage and mechanisms by which eosinophil-specific genes are expressed and regulated during differentiation is unknown. Expression of eosinophil peroxidase (EPO) is restricted to the eosinophil lineage. To understand the mechanisms involved in transcriptional regulation of EPO gene expression, we cloned the region of the EPO gene upstream of the transcriptional start site and analyzed the cis-acting elements required for EPO promoter activity in an eosinophil-inducible leukemic cell line, HL60-C15. The -1.5 kb EPO-pXP2 promoter construct reproducibly expressed > 120-fold more luciferase activity than did promoterless pXP2, and a 12-fold decrease in promoter activity was obtained when sequences between -122 and -45 bp were deleted. To further characterize regulatory sequences important for promoter activity, we performed linker-scanning analysis on the -122 to -45 bp region and identified a number of positively and negatively acting elements in the promoter.

Eosinophil Peroxidase↗