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Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 253 records · Page 14Linked to original sources

Altered production of nerve growth factor in aganglionic intestines.

Nerve growth factor (NGF), a target-derived neurotrophic molecule, is required specifically by sympathetic and dorsal root ganglion cells for their survival and maturation during embryonic and early postnatal development. In the present study, the NGF expression was studied both at the protein and mRNA level in normal and aganglionic intestines of Piebald-strain mice and also in 10 human specimens using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. In the aganglionic intestines of the mice, immunoreactive NGF was found on the giant nerve fibers in the submucosal layer, but not found in the mucosal layer. In the mRNA study, the signal for NGFmRNA was less intense in the aganglionic rectum of the congenitally megacolonic mice than in the rectum of the normal mice. In contrast, the distal dilated colon of the congenitally megacolonic mice had a more intense signal for NGFmRNA than did the colon of normal mice. The results obtained from human specimens were compatible with the findings in the Piebald mice; the distal colons harvested from the patients with Hirschsprung's disease (or its allied disease) had a uniformly more intense signal for NGFmRNA than did the normal colons. The results of this study may indicate that NGF production is altered in the aganglionic intestines and also in the "transitional zone" in Hirschsprung's disease. The altered production of NGF may be useful in increasing the accuracy of diagnosis of Hirschsprung's disease.

Animals↗

A high prevalence of human T-lymphotropic virus type I carriers in patients with antithyroid antibodies.

Human T-lymphotropic virus type I (HTLV-I) is a causative retrovirus of adult T-cell leukemia lymphoma and HTLV-I associated myelopathy/tropical spastic paraparesis. HTLV-I is also associated with some forms of pulmonary alveolitis, chronic arthropathy, polymyositis, and uveitis. In this study, the possible role of HTLV-I infection in the pathogenesis of autoimmune thyroid diseases with positive antithyroid antibody (ATA) to microsomal antigen or thyroglobulin was evaluated. In Fukuoka Prefecture or the northern part of Kyushu Island located in the southwestern part of Japan, the prevalence of patients with HTLV-I antibody was screened using the particle agglutination test and then was further confirmed either by the indirect immunofluorescence method or the western blot method. The observed prevalence in patients with thyroid disorders and the estimated prevalence calculated considering the sex- and age-specific prevalence among healthy blood donors (n = 16,008) were as follows: 19 (7.4%) vs 7.8 (3.0%) (p < 0.001) for ATA-positive chronic thyroiditis (n = 257), 21 (7.0%) vs 6.6 (2.2%) (p < 0.001) for ATA-positive Graves' disease (n = 298), 4 (4.3%) vs 2.1 (2.2%) (ns) for ATA-negative Graves' disease (n = 94), 1 (2.9%) vs 1.1 (3.1%) (ns) in ATA-negative hypothyroidism (n = 35), and 3 (1.8%) vs 5.0 (2.9%) (ns) for ATA-negative nodular goiter (n = 170). These findings thus suggest that HTLV-I infection may have some relationship to ATA-positive thyroid disorders.

Adult↗

Properties of the Na+/H+ antiporter in Vibrio parahaemolyticus.

The properties of the Na+/H+ antiporter in Vibrio parahaemolyticus, a slightly halophilic bacterium, were investigated using everted membrane vesicles. It appears that at least two Na+/H+ antiporters are present, one that is pH-dependent and one that is pH-independent. These two antiporters appear to correspond to the NhaA and NhaB antiporters of Escherichia coli, respectively. It seems that amiloride strongly inhibits the pH-dependent antiporter. Na+ is the best substrate for both of the two V. parahaemolyticus antiporters. Li+ is a poorer substrate and K+ is not a substrate. No K+/H+ antiport activity was detected in membrane vesicles of this organism. The Na+(Li+)/H+ antiport activity greatly increased with an increase in pH of the assay medium. pH did not affect the Km value of the Na+/H+ antiport, but it did increase the Vmax.

Hydrogen-Ion Concentration↗

Properties and sequence of the NhaA Na+/H+ antiporter of Vibrio parahaemolyticus.

A gene encoding an Na+/H+ antiporter was cloned from chromosomal DNA of the slightly halophilic marine bacterium Vibrio parahaemolyticus. The host was an Escherichia coli mutant that lacked both of the two major Na+/H+ antiporters, NhaA and NhaB. Untransformed mutant cells were unable to grow in the presence of 0.6 M NaCl or 0.1 M LiCl, but Na+ and Li+ were non-toxic to cells transformed with a plasmid carrying the antiporter gene. Membrane vesicles prepared from the original E. coli mutant did not show any detectable Na+/H+ (and Li+/H+) antiport activity. However, we observed high Na+/H+ (and Li+/H+) antiport activity in membrane vesicles prepared from the transformed cells. The activity increased greatly when the pH of the assay medium was increased from 7.0 and 8.5. This property is very similar to that of the NhaA Na+/H+ antiporter of E. coli. Drastic decreases in Km values for Li+ and Na+ were observed with membrane vesicles prepared from the transformed cells compared with those observed with V. parahaemolyticus vesicles. The amino acid sequence deduced from the nucleotide sequence of the cloned gene showed high homology (59% identity and 87% similarity) with the NhaA Na+/H+ antiporter of E. coli. Thus, we conclude that the gene we cloned and sequenced is the nhaA of V. parahaemolyticus. We also found that several regions of the NhaA protein showed sequence similarity with transport proteins from some other organisms. Such regions seem to be important for Na+ recognition, transport or amiloride binding.

Amino Acid Sequence↗

Prostaglandin E1 protects dog pancreas from ischemia-reperfusion injury.

Effects of prostaglandin (PG) E1 on ischemia-reperfusion (I-R) injury to the pancreas was evaluated using isolated in vivo perfused dog pancreas. Pancreatic endocrine and exocrine functions were stimulated with 10(-12) M cholecystokinin octapeptide (CCK-8). This amount of CCK-8 promoted production of insulin, glucagon, PGI2, and thromboxane (Tx) A2 in the pancreas. Sixty minutes of ischemia and subsequent reperfusion induced damage to pancreatic ductular, acinar, and beta cells. Intra-arterial administration of PGE1 at a dose of 0.5 microgram/kg/min throughout the experiment prevented the I-R injury, reducing plasma lipid peroxides, and elevating PGI2 without changing TxA2 in the pancreas. PGE1 thus appears to protect pancreatic function from I-R injury both by depressing the effect of free-radicals and by decreasing TxA2/PGI2 which predicts cell injury.

6-Ketoprostaglandin F1 alpha↗

The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas.

The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.

Amylases↗

Left ventricular volume and mass: Comparative study of two-dimensional echocardiography and ultrafast computed tomography.

This study was undertaken to define the accuracy of two-dimensional echocardiography in the determination of left ventricular end-diastolic and end-systolic volumes, stroke volume, ejection fraction, and mass when compared to ultrafast cine computed tomography in the same 56 patients. Single-plane and biplane modified Simpson's rule, single-plane and biplane ellipsoidal formula, bullet formula (biplane only), and biapical Simpson's rule methods were utilized. Linear regression analysis showed the strongest correlation with the modified biplane Simpson's rule (mean r = 0.897). In valvular heart disease (n = 12) and dilated cardiomyopathy (n = 6), the mean correlation coefficients for all methods were high (r = 0.894 and 0.911, respectively). The mean correlation coefficient for all methods in patients with prior myocardial infarction (n = 25) was relatively poor (r = 0.643). Intraobserver and interobserver variabilities for all methods were low (r = 0.980 and 0.965, respectively). It is concluded that calculations of left ventricular volumes and mass by two-dimensional echocardiography are accurate and reproducible in patients with a global effect on the left ventricle and were less acceptable in patients with segmental (ischemic) left ventricular involvement. The best measurement technique is a modified biplane Simpson's rule.

Adult↗

Nephrotoxic serum nephritis in nude rats: the role of cell-mediated immunity.

The role of T cell-mediated immunity in the early phase of nephrotoxic serum nephritis (NTN) was examined by transfer of pan T, CD8-positive, and CD4-positive cells. The disease was induced by transferring rabbit gamma-globulin (RGG)-sensitized T cells to nude (rnu/rnu) rats pretreated with a subnephritogenic dose (a dose insufficient to cause proteinuria) of nephrotoxic serum. Mild but abnormal proteinuria was detected, and macrophages showed significant accumulation in glomeruli. Transfer of not only RGG-sensitized CD4-positive cells but also CD8-positive cells separated by the T cell markers OX8 and OX38 using the panning method caused an increased accumulation of macrophages in isolated glomeruli. No host antibody against rabbit immunoglobulins was demonstrated either in glomeruli by immunofluorescence or sera by ELISA in the early disease phase. These findings support a pathological role of T cells in initiation of glomerular injury in NTN.

Animals↗

Studies on thermophile products. XI. Biological effect of antigen presenting inhibitor, isofatty acid-containing phosphatidylethanolamine, on mouse macrophages.

A new fraction, Fr. 8-A, which consists of a phosphatidylethanolamine with C14:0-C18:0 isofatty acids was obtained from Bacillus stearothermophilus UBT8038. The fraction inhibited major histocompatibility complex class II (Ia) antigen expression and antigen presentation on mouse macrophages. The effect of Fr.8-A on macrophage functions related to antigen presentation was investigated. Fr. 8-A increased arachidonate release, prostaglandin (PG) E2 release and nitrite production from peritoneal macrophages. It increased further the levels of PGE2, nitrite and tumor necrosis factor in the culture supernatant of the macrophages induced by the supernatant from concanavalin A-stimulated spleen cell cultures. Fr. 8-A augmented the activity of peritoneal macrophages to suppress Con A-stimulated T cell proliferation. Addition of either indomethacin or Ng-methyl-L-arginine had no effect on the augmentation of suppressor macrophage activity or the inhibition of antigen presentation by Fr. 8-A, while simultaneous addition of both inhibitors abrogated the effect of the fraction. These results indicate that Fr. 8-A inhibits Ia expression and antigen presentation, and augments suppressor macrophage activity at least partly via the activation of both cyclooxygenase and nitric oxide synthase pathways.

Animals↗

Lithium toxicity and Na+(Li+)/H+ antiporter in Escherichia coli.

The lithium ion (Li+) shows toxicity against Escherichia coli cells when present in a high concentration in the environment. Since Li+ is extruded from cells via a Na+(Li+)/H+ antiporter, this antiporter must be involved in the detoxification of Li+. Two Na+(Li+)/H+ antiporters (NhaA system and NhaB system) are known to be present in E. coli. We investigated the properties of the antiporters and the participation of these systems in the detoxification of Li+ using mutants lacking one of the antiporters, or lacking both of them. Although the affinity for Li+ of the two systems was almost the same, the Vmax value for Li+ transport of the NhaA system was about 12 times larger than that of the NhaB system. Wild type cells were unable to grow in the presence of 0.7 M LiCl. Although a wild type cell and a mutant lacking the NhaB system grew in the presence of 0.6 M LiCl, a mutant lacking the NhaA system did not. This second mutant grew in the presence of 0.1 to 0.2 M LiCl. A mutant lacking both the NhaA and NhaB systems could not grow in the presence of 30 mM LiCl.

Escherichia coli↗

Inhibitory effect of tuna peptide on endothelin production in cultured endothelial cells.

The effect of tuna muscle-derived angiotensin-converting enzyme (ACE) inhibitory peptide (tuna AI) on the production of potent contracting factor, endothelin-1 (ET), in the cultured bovine aorta endothelial cells (BAECs) has been investigated. ET production in the culture medium was measured by radioimmunoassay. BAECs spontaneously produced ET in a time-dependent manner for 4 to 24 h after incubation. Addition of tuna AI to the medium resulted in a time- and concentration-dependent decrease in the production of ET. The tuna AI-induced inhibition of ET production was blocked by B-3824 (bradykinin (BK) B2-receptor antagonist), NG-monomethyl-L-Arg and indomethacin, but not by angiotensin II receptor antagonist. While BK, sodium nitroprusside and platelet-derived growth factor (PDGF) significantly inhibited ET production, angiotensin II and interleukin-1 did not. Potent ACE inhibitory peptides among tuna AI analogues did not always inhibit ET production. The results suggest that tuna AI inhibits ET production at least in part via potentiation of PDGF expression in addition to potentiation of BK pathway.

Amino Acid Sequence↗

A family with hereditary high serum thyroxine-binding globulin.

A family with hereditary high serum thyroxine-binding globulin was studied. All the subjects studied were clinically euthyroid without goiter. The propositus (female), her mother and sister had high TBG, total T4 and total T3 with normal free T4, free T3 and TSH. Her father's thyroid function was within the normal range. Possible etiologic factors causing secondary hyper-TBG-nemia were ruled out in all the affected subjects. Isoelectric focusing demonstrated qualitatively normal microheterogeneity, ruling out possible TBG variations caused by liver diseases, estrogen therapy or pregnancy. Although the mechanism involved in the TBG increase awaits further investigation, it could be an abnormality in the gene controlling the synthesis of TBG.

Adult↗

Primary hypothyroidism manifested in childhood with special reference to various types of reversible hypothyroidism.

The clinical course of 15 patients with overt primary hypothyroidism manifested in childhood were studied. Nine female patients with goitrous hypothyroidism due to chronic thyroiditis showed almost normal height and became euthyroid spontaneously during iodine restriction. The other 6 nongoitrous patients (3M and 3F) (atrophic thyroiditis in 2, lingual goiter in 2 and probable hypoplastic thyroid in 2) showed physical growth retardation and remained irreversibly hypothyroid requiring replacement therapy. In the reversible group, the characteristic findings were high thyroidal radioactive iodine uptake (58 +/- 19%/24 h, N = 8) and positive perchlorate discharge test. Serum nonhormonal iodine levels were high in 4 of 6 patients measured. During the long-term follow-up period of 6 years in 6 patients, 2 patients remained euthyroid with normal growth and regular menstrual cycle and 4 patients became hypothyroid again (after eating seaweed in 1, despite iodine restriction in 2 and after the episode of painless thyroiditis in 1). Transient retardation of growth was observed during the second episode of hypothyroidism. In the irreversible group, one patient with blocking type TSH binding inhibitor immunoglobulin (TBII) became thyrotoxic 4 years later with the decrease in activity of blocking type TBII. These results suggested that reversible recovery of the thyroid function could be expected in patients with juvenile hypothyroidism due to chronic thyroiditis after (1) iodine restriction, (2) improvement of immunological perturbation, or (3) disappearance of blocking type TBII. However, careful follow-up is necessary, because hypothyroidism would recur again with transient retardation of growth in children.

Adolescent↗

P-A cephalometric analysis of nonoperated adult cleft lip and palate.

P-A cephalometric analysis was performed on the craniofacial morphology in 88 Brazilian men with nonoperated and operated cleft lip and palate. For the comparative study, these subjects were divided into the following four groups: (1) 31 nonoperated unilateral cleft lip and palate (UCLP), (2) 24 nonoperated bilateral cleft lip and palate (BCLP), (3) 16 operated UCLP, (4) 17 operated BCLP. Thirty Brazilian men without cleft lip and palate were used as control subjects. In comparison with the control subjects, nonoperated BCLP and UCLP showed remarkable facial deformity characterized by increased width of various facial parts. Facial morphology of surgically treated BCLP and UCLP, however, was very similar to that of noncleft subjects, apart from the immediate cleft region. There was no remarkable difference in the facial morphology between nonoperated BCLP and UCLP, except for the cleft width and the deviation of nasal septum base, while the only significant difference between operated BCLP and UCLP was in the cleft width.

Adolescent↗

Polysplenia accompanied by major cardiovascular anomalies with prolonged survival.

A 52-year-old female with polysplenia accompanied by major cardiovascular anomalies (a ventricular septal defect, atrial septal defect, persistent left superior vena cava, absent inferior vena cava with a hemiazygos connection and visceral heterotaxia) is reported. She underwent successful surgical treatment and showed prolonged survival.

Abnormalities, Multiple↗

Postpartum exacerbation of HTLV-I associated myelopathy/tropical spastic paraparesis followed by an episode of painless thyroiditis.

A 28-year-old woman noticed a progressive gait disturbance after her first delivery. At the age of 32, the gait disturbance improved during her second pregnancy, but became worse after delivery and eventually resulted in a scissoring gait. At the age of 34, she became transiently thyrotoxic and was diagnosed as having painless thyroiditis and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). The findings of this case suggest that the postpartum exacerbation of HAM/TSP was probably due to a rebound phenomenon after immunosuppression during pregnancy, and that the immunological abnormalities associated with HAM/TSP might have played some role in the development of painless thyroiditis.

Adult↗

Delayed cerebral ischemia manifesting as peduncular hallucinosis after aneurysmal subarachnoid hemorrhage--three case reports.

Three cases of peduncular hallucinosis occurred in patients with aneurysmal subarachnoid hemorrhage. All patients underwent early clipping of the ruptured aneurysms of the anterior circulation. Several days after onset of subarachnoid hemorrhage, the patients complained of vivid visual hallucinations associated with abnormal sleep-waking rhythms, suggesting a diagnosis of peduncular hallucinosis. The hallucinations disappeared with administration of an increased dose of dobutamine. These findings indicated that peduncular hallucinosis might be a manifestation of delayed cerebral ischemia after subarachnoid hemorrhage. No other possible cause of neurological deficits such as hydrocephalus, cerebral infarcts, or metabolic encephalopathies was identified. Damage to the ascending reticular activating system has been implicated in the pathogenesis of peduncular hallucinosis. Cerebral vasospasm in the perforating arteries of the ascending reticular activating system was probably the cause of the hallucinosis in our patients.

Adult↗

Biotransformation of a new synthetic retinoid, 4-[(5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (Am-80), in the rat. Structure elucidation of the metabolites by mass and nmr spectrometry.

1. The major metabolites of Am-80 in rat bile were examined by tlc-radiochromatography and hplc-radiochromatography after the intravenous administration of 14C-Am-80, and > 15 metabolites were detected. 2. Intact and Glusulase-treated bile were analysed by both tlc-radiochromatography and hplc-radiochromatography. As both samples gave similar patterns in both chromatography systems, we have concluded that neither glucuronide nor sulphate conjugates were present. 3. 2H3-Am-80 and 2H6-Am-80 were administered to rats, and the major metabolites in bile were detected and their structures elucidated by GC-MS. 4. The chemical structures of seven major biliary metabolites, including unchanged Am-80, were identified by mass and two-dimensional nmr spectrometry, and included 6-hydroxy-Am-80 (M-3), 7-hydroxy-Am-80 (M-4), 6-oxo-Am-80 (M-5), unchanged Am-80 (M-0) and the taurine conjugates of M-3 (M-1), M-4 (M-2) and M-0 (M-6).

Animals↗