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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 451 records · Page 25Linked to original sources

Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.

Administration, Inhalation↗

Increased oxidative metabolism in cow tracheal epithelial cells cultured at air-liquid interface.

Airway epithelial cells cultured at the air-liquid interface possess highly differentiated functions and structures compared with the cells cultured under immersion. We examined the oxidative metabolism and glycolysis in cow tracheal epithelial cells on Days 3, 6, 10, and 13, cultured under three different conditions: (1) immersion culture on porous filters with apical and basolateral feeding (IM), (2) air-exposed culture on porous filters with basolateral feeding, i.e., air-liquid interface culture (AI), and (3) conventional immersion culture in plastic dishes with apical feeding (DI). Lactate production was less in AI than in IM and DI on Day 3 through Day 13, whereas cellular adenosine triphosphate content and basal O2 consumption were greater. Ouabain-sensitive and ouabain-insensitive O2 consumption, and the uncoupled O2 consumption were also greater in AI. Cytosolic lactate dehydrogenase activities on Day 10 were lower in AI, whereas alpha-ketoglutarate dehydrogenase activities were higher. The increased oxidative metabolism in AI was more pronounced at the late phase of culture (Days 10 and 13). In contrast, glycolysis remained elevated during the experiment in IM and DI. These data suggest that (I) AI begins to promote oxidative metabolism from growth phase by the provision of adequate oxygenation, and then further shifts to oxidative metabolism with differentiation; and (2) apical feeding may be responsible for the disturbance of the development of the oxidative metabolism.

Adenosine Triphosphate↗

[Structure of recombinant human serum albumin from Pichia pastoris].

The structure of recombinant human serum albumin derived from Pichia pastoris (rHSA) was analyzed in detail. Complete amino acid analysis was performed by the phenyl isothiocyanate precolumn labeling method. The amino terminal sequence was determined by the Edman degradation. The carboxyl terminal amino acid was determined by digestion with carboxypeptidase, and the carboxyl terminal peptide fragment was analyzed by electrospray mass spectrometry. The peptide fragments of rHSA digested with Lysylendopeptidase, Endoproteinase Glu-C, or Endoproteinase Asp-N were analyzed by electrospray mass spectrometry. The complete amino acid composition, the terminal sequences and the complete amino acid sequence of rHSA agreed with the primary structure deduced from its cDNA. The elution pattern of reduced and carboxymethylated rHSA digested with Lysylendopeptidase and the elution pattern of intact rHSA digested with pepsin were respectively similar to those of plasma-derived human serum albumin (pHSA). The pattern of CD spectrum of rHSA was identical in both shape and magnitude to that of pHSA. 1H-NMR spectra of rHSA and pHSA in deuterium oxide showed the same signal patterns in the observed region (delta 10.5-0.5 ppm). Cross peaks assigned to the alpha proton-beta proton of Asp-1 (delta 4.2/2.8 ppm) and the delta proton-epsilon proton of lysine residues (delta 2.8-3.2/1.4-2.0) showed the same cross peak patterns and chemical shifts in two-dimensional phase sensitive double-quantum filtered 1H-1H correlation spectra of rHSA and pHSA.

Amino Acid Sequence↗

Effect of CL316,243, a highly specific beta(3)-adrenoceptor agonist, on lipolysis of epididymal, mesenteric and subcutaneous adipocytes in rats.

To clarify whether a beta(3)-adrenoceptor agonist is more lipolytic in the visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by CL316,243, a highly specific beta(3)-adrenoceptor agonist (relative selectivities of 0, 1 and 10,000 for beta(1)-, beta(2)- and beta(3)-receptors, respectively) was investigated in adipose tissue from rats. White adipocytes were prepared from the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar rats (weighing about 150 g). Our findings showed that lipolysis of white adipocytes was stimulated both by the non-specific beta-adrenoceptor agonist, isoproterenol, and by the beta(3)-specific adrenoceptor agonist, CL316,243, but the lipolytic sensitivity to CL316,243 was about 10 times greater than that to isoproterenol in these three adipose tissues. Both isoproterenol and CL316,243 induced more noticeable lipolysis in the epididymal and mesenteric than in the subcutaneous adipose cells in terms of the pD2 value [-log mol l-1 for EC50 (the concentration of an agonist giving half of its own maximum stimulation)]. These findings show that CL316,243 is more lipolytic in the visceral adipose cells than in the subcutaneous adipose cells, although epididymal adipose cells showed a high lipolytic response close to those observed in visceral adipose cells. CL316,243 may therefore be especially useful for the treatment of visceral fat type obesity related to various diseases.

Adipocytes↗

Octreotide and bromocriptine suppress thyroid hormone levels and thyroid nodule in an acromegalic patient with nontoxic autonomous goiter.

An acromegalic patient with nontoxic autonomous goiter was sequentially treated with octreotide and bromocriptine. Before therapy, serum GH, PRL and insulin-like growth factor-I (IGF-I) levels were increased. Free T3 and free T4 were within the normal range with suppressed TSH levels, whereas 123Iodine-uptake of thyroid was 5.6% after 24 h. During treatment with octreotide and bromocriptine, serum GH, PRL, and IGF-I became normal and free T3 and free T4 were slightly but significantly decreased, but TSH levels remained very low. After thyroidectomy, thyroglobulin, free T3 and free T4 were further decreased, and the TSH levels were recovered to normal. These findings suggested that octreotide and bromocriptine inhibit the release of thyroid hormones from the autonomous thyroid gland directly or indirectly through the decline in IGF-I.

Acromegaly↗

Anti-obesity and anti-diabetic effects of CL316,243, a highly specific beta 3-adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of uncoupling protein and activation of glucose transporter 4 in white fat.

The anti-obesity and anti-diabetic effects of a highly specific beta 3-adrenoceptor agonist, CL316,243 (CL; beta 1: beta 2: beta 3 = 0:1:100,000), were investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and Long-Evans Tokushima Otsuka (control) rats. Daily injection of CL (0.1 mg/kg, s.c.) to these rats (10 weeks old) for 14 weeks caused a significant reduction in body weight (fatty, 27%; control, 15%), associated with a marked decrease in fat pad weight (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%) without affecting food intake. The levels of uncoupling protein mRNA and protein levels of uncoupling protein (UCP), as well as guanosine 5'-diphosphate-binding (a reliable index of thermogenesis) in brown adipose tissue, were lower in the fatty than in the control rats. However, after CL treatment, these parameters in brown adipose tissue increased significantly 2- to 3-fold in both groups. Furthermore, uncoupling protein was induced in white adipose tissue as well as in brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia during the glucose tolerance test, but CL ameliorated these parameters. These findings suggest that decreased thermogenesis in brown adipose tissue may be one of the causes of obesity in the fatty rats and that administration of CL prevents obesity by decreasing white fat mass, by activating brown adipose tissue thermogenesis, and by inducing uncoupling protein in white adipose tissue. Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity and by activating glucose transporter 4 in white adipose tissue and brown adipose tissue.

Adipose Tissue↗

The ventricular gradient and altered ventricular activation patterns.

The ventricular gradient vector was determined in normal persons and in cases with left and right bundle branch block (BBB) by means of the best fit method from body surface potential mapping data. Similar measurements were also made in cases with artificial ventricular pacing and the G vector during sinus rhythm was compared with that of the paced beats. Results indicated that the magnitude of the G vector in cases with BBB was smaller than in normal persons. The directional change in the G vector was found to be along the direction of the QRS change in the majority of cases with left BBB. In right BBB, the direction of the G change was variable but the angle between the QRS change was less than 90 degrees on average. Following right ventricular pacing a small increase of the G magnitude was observed acutely, which was opposite in direction to the QRS change. Possible mechanisms are discussed. The G changes in left and right BBB are considered to be based on certain chronic processes, different from those involved in the acute immediate effect of altered activation.

Adult↗

Pyogenic clavicular osteomyelitis associated with disseminated intravascular coagulation and acute renal failure in a patient with non-insulin-dependent diabetes mellitus.

Pyogenic osteomyelitis is often accompanied by diabetes, but the disease in the clavicula has rarely been reported. We describe an unusual case of a 53-year-old man with poorly controlled non-insulin-dependent diabetes mellitus who presented with pyogenic clavicular osteomyelitis and developed DIC and acute renal failure. A 67Ga scintigram revealed an abnormal accumulation of the isotope in the right clavicula, where magnetic resonance imaging (MRI) showed inflammatory changes. This suggests that a 67Ga scintigram and MRI are of clinical value for the early diagnosis of the disease. Antibiotic chemotherapy with gamma-globulin and gebexate mesilate, and hemodialysis almost cured his serious condition.

Acute Kidney Injury↗

Use of hepatic tumor index on color Doppler sonography for differentiating large hepatic tumors.

OBJECTIVE: Color flow patterns on Doppler sonography are nonspecific for differentiating various hepatic tumors. We previously reported that a tumoral peak systolic flow velocity of 0.40 m/sec or greater suggested a malignant hepatic tumor rather than a hemangioma. However, tumoral peak systolic flow velocity failed to differentiate hepatocellular carcinomas and metastatic tumors. In this study, we attempted to assess the value of the hepatic tumor index for differentiating hepatocellular carcinomas and other hepatic tumors. MATERIALS AND METHODS: Color Doppler sonography was performed in 80 patients with 108 hepatic lesions larger than 2.0 cm in diameter. The hepatic tumor index was calculated as the ratio of the tumoral peak systolic velocity to the peak systolic velocity of the right or left hepatic artery. RESULTS: Pulsatile color flow images were obtained in 42 of 48 hepatocellular carcinomas, 25 of 32 hepatic metastases, and 13 of 28 hemangiomas. The mean hepatic tumor indexes obtained from hepatocellular carcinomas, metastases, and hemangiomas were 1.14 +/- 0.37 (+/-SD), 0.63 +/- 0.22, and 0.60 +/- 0.17, respectively. The hepatic tumor indexes of hepatocellular carcinomas significantly exceeded those of metastases and hemangiomas (p < .01 in both cases). A hepatic tumor index equal to or greater than 1.0 was associated with 76% sensitivity, 92% specificity, and 82% accuracy in distinguishing hepatocellular carcinomas from hepatic metastases. In lesions with a tumoral peak systolic velocity of 0.40 m/sec or greater, a hepatic tumor index equal to or greater than 1.0 was associated with 91% sensitivity, 83% specificity, and 89% accuracy in distinguishing hepatocellular carcinomas from hepatic metastases. CONCLUSION: The hepatic tumor index on color Doppler sonography was useful in differentiating large hepatocellular carcinomas from hepatic metastases.

Adult↗

Effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients.

OBJECTIVE: To investigate the effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We measured body weight, waist-to-hip ratio (WHR), adjusted resting metabolic rate, fasting blood glucose, fasting serum insulin levels, insulin resistance index (fasting glucose x fasting insulin/22.5), and HbA1c levels before and after 12 weeks of obesity treatment in 61 obese women with type 2 diabetes. The MvaI polymorphism of the beta 3-adrenergic receptor gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of obese type 2 diabetic patients, those with the mutation (n = 24) had a higher WHR (P < 0.001), a lower adjusted metabolic rate, and higher blood glucose levels, serum insulin levels, insulin resistance index (P < 0.001), and HbA1c levels (P = 0.016). Furthermore, patients with the mutation had smaller decreases in body weight, WHR, insulin resistance index, and HbA1c levels after the weight-loss program compared with patients without the mutation (n = 37), even though food intake, exercise, and serum thyroid hormone levels were similar in both groups. CONCLUSIONS: These present findings show that the Trp64Arg allele of the beta 3-adrenergic receptor gene may predict difficulty in losing body weight, lowering WHR, and improving glycemic control and insulin resistance in obese patients with type 2 diabetes.

Adult↗

Serum autoantibodies against sulfatide and phospholipid in NIDDM patients with diabetic neuropathy.

OBJECTIVE: We investigated the presence of antisulfatide and antiphospholipid antibodies and the relationship between these antibodies and the results of quantitative tests of nerve function in NIDDM patients with diabetic neuropathy. RESEARCH DESIGN AND METHODS: Antisulfatide and antiphospholipid antibodies were measured in serum samples obtained from 68 NIDDM patients with diabetic neuropathy by an enzyme-linked immunosorbent assay (ELISA). Each patient was classified into one of three groups based on the combined neuropathy score (determined by the symptom score, the results of autonomic nerve function tests, and the vibration perception test), as follows: mild (n = 26), moderate (n = 22), and severe (n = 20). Nerve conduction studies were performed in a subgroup of 37 patients. RESULTS: The antisulfatide antibody was detected in 1 (4%) of 26 patients in the mild group, 4 (18%) of 22 patients in the moderate group, and 8 (40%) of 20 patients in the severe group (P < 0.01 vs. mild group). The antiphospholipid antibody was detected in none of the patients in the mild group, 8 (36%) of 22 patients in the moderate group (P < 0.001 vs. mild group), and 6 (30%) of 20 patients in the severe group (P < 0.01 vs. mild group). The threshold amplitude, determined by the vibration perception test, was significantly higher in antibody-positive patients than in antibody-negative patients: antisulfatide antibody, 55.9 +/- 46.8 microns (n = 13) vs. 22.9 +/- 13.7 microns (n = 55), P < 0.001; antiphospholipid antibody, 47.2 +/- 32.5 microns (n = 14) vs. 24.5 +/- 23.2 microns (n = 54), P < 0.01. The conduction velocity of the sural nerve was slower in the antisulfatide antibody-positive group (37.9 +/- 11.1 m/s, n = 12) than in the antisulfatide antibody-negative group (45.2 +/- 6.0 m/s, n = 19) (P < 0.05). CONCLUSIONS: These results suggest that autoimmune nerve destruction may be involved in diabetic neuropathy in NIDDM patients.

Aged↗

Beta 3-adrenoreceptor gene polymorphism: a newly identified risk factor for proliferative retinopathy in NIDDM patients.

Proliferative diabetic retinopathy is an important cause of visual impairment. We investigated whether the polymorphism of the beta 3-adrenoreceptor (beta 3-AR) gene, which is associated with insulin resistance and an earlier onset of NIDDM, was associated with proliferative diabetic retinopathy (PDR) in 215 Japanese NIDDM patients with a duration of diabetes of > or = 10 years. The polymorphism of the beta 3-AR gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The Trp64Arg allele of the beta 3-AR gene was significantly more frequent in the NIDDM patients with PDR (P = 0.002), but not in those with non-PDR (P = 0.151), than in NIDDM patients without diabetic retinopathy. Those with the mutation had an earlier onset of diabetes, a longer duration of diabetes, and higher current and maximal BMI values, compared with those without the mutation. Moreover, this mutation was also associated with higher serum triglyceride and decreased HDL-cholesterol levels. When adjustment was made for age, age at diagnosis, duration of diabetes, current BMI, systolic blood pressure, HbA1e, and serum lipids in a multiple regression analysis, a significant association was found between the Trp64Arg allele and diabetic retinopathy (P = 0.039). The Arg/Arg or Arg/Trp genotype was significantly associated with PDR, compared with the Trp/Trp genotype, with an odds ratio of 2.55 (95% CI 1.25-5.16). We concluded that the beta 3-AR gene polymorphism is a newly identified risk factor for PDR.

Aged↗

Cloning and molecular characterization of cDNA encoding a mouse male-enhanced antigen-2 (Mea-2): a putative family of the Golgi autoantigen.

The male-enhanced antigen-2 (Mea-2) gene was originally identified with a monoclonal histocompatibility Y (H-Y) antibody (mAb4VII). There is no report of the full length cDNA encode for Mea-2 product until this report. In this study, we isolated the full length mouse Mea-2 cDNA by screening a testis cDNA library with a PCR-amplified Mea-2 product, and direct PCR amplification of its upstream sequences from the cDNA library. The primary structure of the Mea-2 peptide, deduced from this nucleotide sequence, shows that it encode a 150 kDa protein, of 1325 amino acid residues, which contained five putative N-glycosylation sites and four leucine zipper motifs. A data bank search indicated that it has high homology with a human Golgi autoantigen (golgin-160) both in its nucleotides (78%) and amino acids sequence (83%). This suggests that Mea-2 gene product may encode a golgi structural protein. In situ hybridization analysis suggested that the Mea-2 gene is expressed in spermatids during spermatogenesis as already shown by Mea-1, suggesting that Mea-2 gene product as well as Mea-1 have also some role for spermatogenesis.

Amino Acid Sequence↗

Glucose metabolism in cat outer retina. Effects of light and hyperoxia.

PURPOSE: To determine the roles of oxidation and glycolysis with aerobic and anaerobic lactate formation in the glucose metabolism of the cat outer retina in light and darkness. METHODS: Blood was collected from a choroidal vein and from an artery, and veno-arterial differences in lactate concentration (Lac(v-a) were determined at increasing light intensities. Blood also was sampled under conditions of darkness, light, and hyperoxia and were analyzed for oxygen, glucose, and lactate concentrations with or without blood flow determinations. RESULTS: When the dark-adapted eye was subjected to increasing light intensities, there was a reduction in the Lac(v-a), indicating reduced glycolysis in the outer part of the retina as the rods saturated. In darkness, the mean lactate formation per retina was 0.409 mumol/minute, oxygen consumption was 0.198 mumol/minute, and glucose consumption 0.236 mumol/minute. In light, the corresponding figures were 0.253, 0.166, and 0.123 mumol/minute. Hyperoxia reduced lactate formation and increased oxygen consumption in light and in darkness. CONCLUSIONS: Approximately 80% of the glucose consumed by the outer retina is used primarily in aerobic lactate formation. Because it is more efficient, oxidation of glucose still accounts for most of the energy production in light and in darkness. Light reduces oxidation as well as aerobic and anaerobic lactate formation.

Adaptation, Ocular↗

Decreased pulmonary arterial endothelium-dependent relaxation in heartworm-infected dogs with pulmonary hypertension.

OBJECTIVE: To investigate the contractility of pulmonary arterial smooth muscle and the relation between pulmonary hypertension and endothelium-derived relaxing factor in canine heartworm disease. ANIMALS: 18 noninfected control and 9 heartworm-infected dogs. PROCEDURE: Mean pulmonary arterial blood pressure was measured in vivo, and tension of pulmonary arterial strips was measured by use of the isometric tension method. RESULTS: After phenylephrine (10(-5)M)-induced contraction of the pulmonary vascular smooth muscle, carbamylcholine chloride (CCh, 10(-6)M) caused more relaxation of the vascular smooth muscle of noninfected, dogs than that of heartworm-infected dogs. Furthermore, the degree of CCh-induced relaxation was inversely correlated with mean pulmonary arterial blood pressure in the noninfected and the heartworm-infected dogs. The CCh-induced relaxation was inhibited by pretreatment with NG-nitro-L-arginine methyl ester hydrochloride (10(-5)M), and in reversed dose-dependent manner by L-arginine (10(-4) to 3 x 10(-2)M). Sodium nitroprusside (10(-8) to 10(-5)M) caused a dose-dependent relaxation in all vessels, and there was no significant difference in the relaxation responses in both groups except at 10(-7)M for vessels with intact endothelium from noninfected dogs. CONCLUSION: The depression of endothelium-dependent relaxation is correlated with the pulmonary arterial blood pressure in heartworm-infected dogs, suggesting that the decrease is one of the essential factors for the genesis of pulmonary hypertension in canine filariasis.

Animals↗

Symptomatic porphyria secondary to hepatocellular carcinoma.

A 58-year-old woman gave a 6-month history of porphyria-like photosensitivity. Fractioned porphyrin analysis by high performance liquid chromatography revealed elevated concentrations of all urinary porphyrins and faecal protoporphyrin. Hepatocellular carcinoma had developed in an otherwise normal liver. Tumour tissue fluoresced strongly under fluorescence microscopy, exhibiting elevated activity of three haem-biosynthetic enzymes, delta-aminolevulinic acid (ALA) synthase. ALA dehydratase and porphobilinogen deaminase. This patient did not satisfy any of the criteria for inherited porphyria. The patient's symptoms were relieved after excision of the liver tumour. This strongly suggests that excessive porphyrin synthesis originated from the tumour tissue. Primary porphyria-like photosensitivity occurs as a paraneoplastic phenomenon, secondary to hepatocellular carcinoma.

Carcinoma, Hepatocellular↗