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Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 235 records · Page 13Linked to original sources

Thromboxane A2 receptor antagonist (ONO 3708) protects from liver damage induced by cholestasis and ischemia-reperfusion.

The effect of a thromboxane (Tx) A2 receptor antagonist, ONO 3708, on cholestasis and injury related to ischemia and subsequent reperfusion (I-R) was investigated in the dog liver by assessing changes in insulin and glucagon metabolism. The left hepatic duct was ligated for 4 weeks to create a cholestatic lobe. Sixty-minute ischemia was induced by Pringle's procedure. ONO 3708 (200 micrograms/kg/min) was initiated 60 min before induction of ischemia and continued throughout the experiment. The rate of insulin metabolism was higher in the right noncholestatic lobe than in the left cholestatic lobe. There was no significant difference in the rate of glucagon metabolism between the right and left lobes. After induction of I-R, the rate of insulin metabolism, but not glucagon metabolism, decreased. The lipid peroxide level was higher and the glutathione level was lower in the cholestatic lobe than in the noncholestatic lobe. There was no significant difference in the alpha-tocopherol level between lobes. After induction of I-R, the lipid peroxide level increased and the alpha-tocopherol level decreased. There was no change in the glutathione level. I-R accelerated the release of 6-keto-prostaglandin (PG) F1 alpha, a stable metabolite of PGI2, and of TxB2, a stable metabolite of TxA2, from the liver. After I-R, cholestasis accelerated the release of TxB2, but not 6-keto-PGF1 alpha. I-R also increased the TxB2/6-keto-PGF1 alpha ratio. ONO 3708 reduced these metabolic changes in the cholestasis and after I-R. These findings suggest that ONO 3708 protects liver function, especially in the cholestatic lobe, from I-R-related injury by reducing peroxidation of lipids and the TxA2/PGI2 ratio, which predicts cellular damage, and by increasing levels of alpha-tocopherol and glutathione.

Animals↗

Human T-lymphotropic virus type I-associated uveitis in patients with Graves' disease treated with methylmercaptoimidazole.

Human T-lymphotropic virus type I (HTLV-I) is responsible for a certain form of uveitis [HTLV-I-associated uveitis (HAU)]. A previous history of Graves' disease has been reported in 9-17% of the patients with HAU. In this study, the prevalence of patients with either HTLV-I antibody or uveitis was evaluated in 819 consecutive patients with thyroid disorders between 1991 and 1992. Serum HTLV-I antibody was found in 25 of 392 patients with Graves' disease, 19 of 257 with chronic thyroiditis, and 3 of 170 with nodular goiter. Five of 25 HTLV-I-positive patients with Graves' disease developed HAU. All of these 5 patients had been treated with methylmercaptoimidazole (MMI). Within a few months before the onset of uveitis, 3 patients were hyperthyroid, and 2 were hypothyroid. In 2 of 5 patients, an exacerbation of uveitis occurred soon after the readministration of MMI for the relapse of hyperthyroidism. None of the 367 HTLV-I negative patients with Graves' disease nor 22 HTLV-I-positive patients with chronic thyroiditis or nodular goiter developed uveitis. It was therefore suggested that Graves' disease, thyroid dysfunction and/or MMI administration might be related to the development of HAU.

Adult↗

Effect of lithium on serum calcium level and parathyroid function in manic-depressive patients.

The purpose of this study is to find out whether hypercalcemia and hyperparathyroidism are rare or not in manic-depressive patients taking lithium carbonate. The subjects were 13 patients receiving lithium and 19 healthy subjects not receiving it as normal controls. Serum ionized calcium (Ca++), serum parathyroid hormone (PTH), urinary calcium and cyclic AMP(cAMP) were measured. Cervical ultrasonographic examination was also performed. The mean serum Ca++ level in the lithium administered group was significantly higher than that in the control group (P < 0.02). There was no significant difference between the serum PTH levels in the two groups. The mean urinary calcium level in the lithium administered group was below the normal range, but the mean urinary of cAMP level was within the normal range. Although a parathyroid cyst was found in one lithium administered patient on ultrasonographic examination, no swelling of the parathyroid gland was observed in the other patients in the lithium administered group or in any of the control subjects. In the present study, no distinct hyperparathyroidism was found in the patients in the lithium administered group. Lithium administration affects calcium metabolism in manic-depressive patients and hypercalcemia seems to be one of the complications needing attention at the time of lithium administration.

Adolescent↗

Aneurysmal dilatation of the pulmonary trunk with mild pulmonic stenosis.

We present the unusual case of a 72-year-old woman whose chest X-ray showed an abnormal left hilar shadow. A pulmonary angiogram revealed an aneurysm in the pulmonary artery with a diameter of 55 mm that extended from the main pulmonary trunk to its bifurcation. Mild pulmonic stenosis with a systolic pressure gradient of 18 mmHg across the pulmonic valve was recognized. Mild dilatation of the ascending aorta was also present. The pressure gradient across the pulmonic valve was lower than is typical for an aneurysmal dilatation, suggesting that this patient represented a case of idiopathic pulmonary artery dilatation. We suspected the presence of a congenital structural alteration common to the pulmonary artery and the ascending aorta.

Aged↗

Effect of iontophoretic patterns on in vivo antidiuretic response to desmopressin acetate administered transdermally.

The effects of concentration, amperage and duration on the antidiuretic response induced by iontophoretic delivery of desmopressin acetate (DDAVP) were examined using a diabetes insipidus model in rats. A higher current density brought about a larger and longer antidiuretic response. Prolonged iontophoretic duration caused an overdose. Repeated short iontophoretic treatments with lower current density maintained a constant response with a short lag time and a rapid disappearance of pharmacological response immediately after cessation of the final treatment. This type of iontophoresis substantially reduced the inter-subject variability of response as compared to the response using an intranasal route of administration.

Administration, Cutaneous↗

Transfer of copper and zinc from ionic and metallothionein-bound forms to Cu, Zn--superoxide dismutase.

Reactivity in transfer of copper (Cu) and zinc (Zn) to their binding sites of superoxide dismutase (SOD) was examined in vitro by the HPLC/atomic absorption spectrophotometry. Ionic Cu (cuprous and cupric ions) were incorporated more efficiently than the metal bound to metallothionein. Cu binds not only to the Cu-binding site but also to the Zn-binding site. Although Zn in the reaction medium and the metal bound to the Zn-binding site of SOD affected little the reactivity in binding of ionic Cu, they disturbed the reactivity of Cu bound to metallothionein to the Cu-binding site. Both ionic and metallothionein-bound Zn were transferred at a comparable efficiency to the Zn-binding site but not to the Cu-binding site. Co-existing ionic Cu but not metallothionein-bound Cu in the medium inhibited the binding of Zn to SOD. The results indicate that ionic Cu can be transferred to both Cu- and Zn-binding sites of SOD more efficiently than metallothionein-bound Cu, while both ionic and metallothionein-bound Zn are transferred only to Zn-binding site at a comparable efficiency.

Animals↗

[Right-sided infectious endocarditis due to methicillin-resistant Staphylococcus aureus resulting in ruptured abscess of the ventricular septum and sinus of Valsalva].

A 24-year-old woman presented with right-sided infectious endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA). This is the first report of right-sided infectious endocarditis caused by MRSA in Japan. The patient was admitted to the Jichi Medical School Hospital because of fever of unknown origin and disturbance of consciousness. Several months before, she had discontinued treatment for hyperthyroidism. Antibiotics effective against MRSA, vancomycin and flomoxef, were given intravenously, but a new heart murmur was detected. Echocardiographic study revealed vegetations attached to the tricuspid valve and abscess formation on the ventricular septum. The vancomycin dosage was increased and arbekacin sulfate was also given from the sixth hospital day. However, these antibiotics had very little effect and the abscess rapidly increased in size. Color flow mapping finally demonstrated intracardiac shunt flow through the ruptured abscess of the ventricular septum and sinus of Valsalva. She died suddenly, probably from heart failure. The prognosis of infectious endocarditis due to MRSA is poor and drug therapy often fails. Thus, surgery should be considered in the early stage.

Abscess↗

[Bone formation and mechanical properties of the cancellous bone defect site filled with hydroxyapatite granules].

We investigated the co-relationships of the granule size of hydroxyapatite with the amount of new bone formation and with mechanical properties at the bone defect site filled with hydroxyapatite granules. In this experimental study, cylindrical bone defects 6.4 mm in diameter and about 1 cm in depth were prepared in the bilateral femoral condyles and in the tibial condyles of large albino rabbits (body weight 5.1-7.3 kg), filled with three types of hydroxyapatite granules 0.3-0.6 mm, 0.6-1.0 mm, and 1.0-2.0 mm in diameter, and examined after 2, 4, and 8 weeks after sacrificing the animals. Two animals (4 limbs) each were examined for the same granule size and the same period after filling. Undecalcified sections of the tibia at the defect site were examined histologically, and the volume and surface of hydroxyapatite, the volume of new bone, the surface of the new bone in contact with hydroxyapatite, and the percent of this surface relative to the entire surface of hydroxyapatite were determined. Columnar specimens 6.0 mm in diameter and 5.0 mm in length were prepared from the defect sites of the femur, compressed at a deformation rate of 2.4 mm/min, and the failure stress, stiffness, and energy absorption were calculated from the load-deformation curve. The normal cancellous bone from 2 unoperated animals (4 limbs) and bone defect sites not filled with hydroxyapatite granules of 2 animals (4 limbs) were examined as controls. A greater amount of new bone was formed as the granule size was smaller. After 8 weeks, the failure stress and energy absorption were higher as the granule size was smaller, and the mechanical properties of the bone defect sites filled with 0.3-0.6 mm granules were similar to those of normal cancellous bone.

Animals↗

Molecular cloning of complementary DNA for a novel human hepatoma-derived growth factor. Its homology with high mobility group-1 protein.

A novel hepatoma-derived growth factor was purified from the conditioned medium of human hepatoma-derived cell line, HuH-7, by the assay of [3H]thymidine incorporation into Swiss 3T3 cells. Molecular cloning of a complementary DNA from the cDNA library of HuH-7 cells was done on the basis of the N-terminal amino acid sequence. This protein was acid- and heat-labile heparin-binding protein and inactivated by reducing condition. The cDNA is 2.4 kilobase pairs long, and the deduced amino acid sequence from cDNA contained 240 amino acids without a signal peptide-like N-terminal hydrophobic sequence. Heparin column-eluted fraction of the conditioned medium of Cos-7 cells transfected by the cDNA stimulated the DNA synthesis. Northern blot analysis revealed its ubiquitous expression in several tumor-derived cell lines, as well as in normal tissues. The primary sequence shares homology with the high mobility group (HMG)-1 protein (23.4% amino acid identity and 35.6% similarity). However, its hydrophobic profile was distinct from that of HMG-1 except for the C-terminal acidic region, and it contained no apparent HMG box motif. Immunofluorescence study showed that it is localized in the cytoplasma of hepatoma cells. These findings suggest that this factor is a novel heparin-binding protein, with mitogenic activity for fibroblasts.

Amino Acid Sequence↗

Batchwise purification of specific tRNAs by a solid-phase DNA probe.

A simple and efficient method for purifying a specific tRNA in a single microcentrifuge tube was developed. Oligodeoxyribonucleotides (about 30 mer) with sequences complementary to the 3' side of target tRNAs were synthesized with an aminohexyl linker at the 5' end, immobilized on a silica gel at a high concentration, and used as a solid-phase probe. A mixture of tRNAs was added to a suspension of the solid-phase probe in 2.4 M tetraethylammonium chloride and incubated for 10-30 min. Only a target tRNA hybridized with the immobilized probe at appropriate temperatures and was eluted out by heating. The solid-phase probe showed a large hybridization capacity (up to 17 A260 units/g dry gel) and specific and quantitative recovery of the target tRNA. The intactness of recovered tRNAs was ascertained by both Donis-Keller sequencing and aminoacylation experiments. These features show the usefulness of the solid-phase probe method as a reliable tool for purifying tRNAs whose gene sequences are known.

Base Sequence↗

Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects > 75 years of age.

Levels of lipoprotein (a) (Lp[a]) and various hemostatic factors were studied in 132 Japanese aged > 75 years (mean 83). The group consisted of 50 healthy persons, 36 hypertensive subjects, 31 patients with chronic cerebral infarction, and 15 with coronary artery disease. Lp(a) levels were slightly lower in the healthy "old old" subjects than in the 184 healthy younger adults (mean +/- SD: 10.7 +/- 7.9 vs 12.1 +/- 10.1 mg/dl). There were no gender-related differences in the Lp(a) levels of healthy adults and healthy old old subjects. Lp(a) levels were higher in the hypertensive old old subjects (14.6 +/- 15.4 mg/dl) and the old old patients with cerebral infarction (21.3 +/- 16.2 mg/dl) and coronary artery disease (26.5 +/- 20.4 mg/dl). The prevalence of subjects with high Lp(a) levels (> 30 mg/dl) was the greatest among old old patients with coronary artery disease (27%). Lp(a) levels in the 132 old old subjects showed positive correlations with sialic acid, fibrinogen, factor VII activity, and D-dimer levels. These results indicate a close association between Lp(a) levels and atherothrombotic disease as well as the characteristics of Lp(a) as an acute phase reactant in old old Japanese. Subjects with higher Lp(a) levels may develop cardiovascular disease later in life, whereas the remaining healthy old old subjects have lower Lp(a) levels.

Aged↗

Prostaglandin E1 protects liver from ischemic damage.

Studies were carried out to investigate the effects of prostaglandin E1 (PGE1) pretreatment on normothermic liver ischemia. Mixed-breed dogs were divided into three groups: a control group, a group with induced liver ischemia, and a group pretreated with PGE1 followed by induced liver ischemia. Liver ischemia was induced by the Pringle procedure for 60 min. PGE1 was administered intravenously to some dogs at a dose of 0.5 microgram/kg/min for 30 min prior to the Pringle procedure. Sham operations were performed without induction of liver ischemia in control animals. Insulin, glucagon, and glucose metabolic clearance rates were examined before and after the Pringle procedure in the control and experimental groups. Insulin and glucose metabolic clearance rates decreased 5 min after declamping in the ischemic group, while the glucagon metabolism was not affected, and lipid peroxide production increased. In contrast, hepatic insulin metabolism improved, and lipid peroxide production normalized in the ischemic group which was pretreated with PGE1. This study suggests that PGE1 prevents hepatic metabolic disturbances due to warm ischemia and subsequent reperfusion.

Alprostadil↗

Hypoglossal premotor neurons with rhythmical inspiratory-related activity in the cat: localization and projection to the phrenic nucleus.

Localization and projection to the phrenic (PH) nucleus were studied in a sample of premotor neurons that directly projected to hypoglossal motoneurons (XII Mns) and showed respiratory-related patterns of activity. The experiments were carried out in cats, under pentobarbital anesthesia. In the first part of the study, the retrograde double-labeling technique was used to reveal the existence of neurons projecting to both the XII and the PH nuclei. Injection of a fluorescent dye (fast blue, FB) into the XII nucleus and another (nuclear yellow, NY) into the PH nucleus retrogradely labeled, with either FB or NY, medullary reticular neurons mainly in the regions ventrolateral to the nucleus of the tractus solitarius (vl-NTS), ventrolateral to the hypoglossal nucleus (vl-XII), and dorsomedial to the nucleus ambiguus (dm-AMB) bilaterally. In addition, some neurons in these regions were labeled with both FB and NY. In the second part of the study, unitary activity was recorded extracellularly from medullary respiratory neurons. In the regions vl-NTS, vl-XII, and dm-AMB, inspiratory neurons were found which antidromically responded to stimulation of the XII nucleus. Some of them also responded antidromically to stimulation of the PH nucleus. Averaging of rectified and integrated XII and PH nerve discharges by spontaneous spikes of single inspiratory neurons in the vl-NTS and dm-AMB regions revealed a facilitation in either XII nerve discharge or both XII and PH nerve discharges after a short latency of monosynaptic range. It is concluded that in the vl-NTS and dm-AMB regions there are inspiratory neurons that are excitatory premotor neurons projecting to XII Mns showing the respiratory-related activity. Some of them have excitatory synaptic connections to XII and PH Mns via bifurcating axons.

Animals↗

Calcium regulating hormones and bone mineral content in patients after subtotal gastrectomy.

Twenty-nine men who had undergone Billroth I gastrectomy and 19 men who had undergone Billroth II gastrectomy were studied to examine the changes in their calcium regulating hormones and bone mineral content following surgery. The serum calcium and phosphate concentrations in the patients with Billroth I and Billroth II were normal. The Billroth II group had an elevated level of serum alkaline phosphatase and reduced bone mineral content. The 24,25(OH)2D concentration was reduced (P < 0.01) and 25(OH)D and 1,25(OH)2D concentrations were increased (P < 0.01, P < 0.05, respectively) in the Billroth II group. It was suggested by our study that the Billroth II patients had a reduced bone mineral content and an elevated 1,25(OH)2D concentration. Therefore, the pathophysiology of postgastrectomy bone metabolic disease is not due to vitamin D deficiency, but may instead be due to reduced calcium absorption in the intestine.

Aged↗

Effects of leukocyte and platelet depletion on ischemia--reperfusion injury to dog pancreas.

BACKGROUND/AIMS: Ischemia-reperfusion injury has been studied in various organs. Effects of leukocyte and platelet depletion on ischemia-reperfusion injury were evaluated using the isolated, perfused dog pancreas in vivo. METHODS: Pancreatic exocrine and endocrine functions were stimulated by an intra-arterial injection of cholecystokinin (10(-12) mol) and intravenous injection of glucose and arginine (1 g/kg body wt), respectively. The functions before and after 60 minutes of ischemia were evaluated in the no treatment and in the leukocyte and platelet depletion groups. RESULTS: Cholecystokinin increased prostaglandin I2 and thromboxane A2 production and stimulated exocrine pancreatic secretion. Glucose and arginine stimulated insulin and glucagon release from the pancreas. Sixty minutes of ischemia followed by 60 minutes of reperfusion damaged the pancreatic acinar and ductular cells. Ischemia of 60 minutes followed by 90 minutes of reperfusion damaged beta cells. Removal of leukocytes (97.6%) and platelets (99.4%) by using a filter throughout the experiment prevented the ischemia-reperfusion injury, reduced plasma lipid peroxide and thromboxane A2, and increased prostaglandin I2 levels. CONCLUSIONS: Leukocytes and platelets seem to damage the pancreas during ischemia-reperfusion by increasing the peroxidation of structurally important cell membrane lipids and reduced the thromboxane A2 prostaglandin I2 ratio, a predictor of cellular injury.

6-Ketoprostaglandin F1 alpha↗

Sacroperineal anorectoplasty using intraoperative ultrasonography: evaluation by computed tomography.

A new operative technique that uses ultrasonography during sacroperineal or sacroabdominoperineal anorectoplasty was performed on seven patients with an intermediate or high anorectal malformation. Ultrasonography was used for the purpose of making a pull-through tunnel under visual guidance. The results of this technique were evaluated by computed tomography scanning to find the anatomic position of the pulled-through rectum in relation to the anal sphincter muscle. Postoperative computed tomography scans showed that the rectum was correctly placed in the center of the sphincter muscle in all patients.

Fistula↗