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Biomedical subjects

S Hosokawa

Publications and source records attributed to S Hosokawa.

At least 19 recordsLinked to original sources

Effect of chronic L-dopa administration on serum luteinizing hormone levels in male rats.

We examined whether the repeated oral administration with a high dose of L-3-(3,4-dihydroxyphenyl)-alanine (L-DOPA) in 0.5% carboxymethyl cellulose increases serum luteinizing hormone (LH) levels in male rats. Serum LH levels were increased 4 h after a single administration of 1000 mg/kg L-DOPA to male rats, and returned to control levels within 8 h after administration. Four hours after a single administration, serum LH levels were significantly increased by L-DOPA at 1000 mg/kg, but not at 20, 100 or 200 mg/kg. Decreases in body weight and relative weight of the prostate were observed after 7 and 14 days of administration of 1000 mg/kg per day L-DOPA, but no changes were observed in weight of the testis, epididymis or seminal vesicle. The administration of L-DOPA at 500 or 1000 mg/kg per day for 7 or 14 days resulted in increased basal serum LH levels and decreased basal serum prolactin levels 24 h after the last administration. Serum testosterone levels tended to be higher in treated than in control rats. The levels of two metabolites of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in rats treated with 500 mg/kg per day tended to be slightly higher than those in control rats after 7 days of administration. Levels of DA, DOPAC and HVA were significantly increased after 7 and 14 days of administration of 1000 mg/kg per day and after 14 days of administration of 5000 mg/kg per day. The level of norepinephrine, but not its metabolite 3-methoxy-4-hydroxyphenylglycol, was significantly increased after only 7 days of administration of 1000 mg/kg per day. No significant changes were observed in levels of 5-hydroxytryptamine or its metabolite 5-hydroxyindole-3-acetic acid with administration of 500 or 1000 mg/kg per day. These findings suggest that a prolonged treatment with a high dose of L-DOPA in male rats induces release of LH from the pituitary, resulting in sustained elevation of LH levels in peripheral circulation.

3,4-Dihydroxyphenylacetic Acid

Species-specific mechanism in rat Leydig cell tumorigenesis by procymidone.

To clarify the mechanism of species difference in the induction of testicular interstitial cell tumor (ICT, Leydig cell tumor) between rats and mice, male Sprague-Dawley rats and ICR mice were fed procymidone at dietary concentrations of 700, 2000 or 6000 ppm and 1000, 5000, or 10,000 ppm, respectively, for 3 months. The Leydig cell functions were evaluated by serum testosterone and luteinizing hormone (LH) levels, testosterone levels in the testis, LH levels in the pituitary, the capacity of the testis to respond to gonadotropin stimulation, i.e., the production of testosterone in vitro, and by the testicular binding of labeled human chorionic gonadotropin (hCG). Measurement of testosterone and LH levels in rat serum, the testis, or the pituitary showed that both hormones were enhanced throughout the 3-month treatment period. The hypergonadotropism was associated with the increase of interstitial cell response to hCG in vitro for up to 3 months. As with rats, both serum and pituitary LH were increased in mice at 4 weeks but not at 13 weeks. However, in contrast to rats, no significant increase in testosterone was observed in mice either in vivo or ex vivo during the course of the study. This suggests a difference between the rat and mouse in the response of the Leydig cell to the LH stimulation associated with procymidone administration. These differences in the response of interstitial cells to procymidone may be the basis for the distinct species responses to procymidone-induced Leydig cell tumorigenesis. The sustained response of the Leydig cells to stimulation in the rat results in chronic hyperplasia and subsequent benign tumor formation, while the attenuated response of Leydig cells in the mouse is associated with neither hyperplasia nor neoplasia.

Administration, Oral

A possible mechanism for the increase in serum luteinizing hormone levels in male rats by oxolinic acid.

Oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3- quinolinecarboxylic acid), an antimicrobial agent, raises the serum levels of luteinizing hormone (LH) and increases the incidence of testicular Leydig cell tumors in male rats. In the present study the mechanism by which serum LH levels are raised in male rats receiving oxolinic acid was investigated. Aged Wistar rats were fed a diet containing oxolinic acid at 0 or 3000 ppm for more than 4 weeks. There was no effect of oxolinic acid on either the maximal levels of serum LH after castration nor on the serum levels of LH stimulated with 1 microgram/rat of luteinizing hormone-releasing hormone (LHRH). The concentrations of testosterone in serum and testis were not changed by the treatment of oxolinic acid. In the in vitro organ culture, the testes of rats receiving oxolinic acid released testosterone in the same manner as the controls, in the presence or the absence of human chorionic gonadotropin (100 mIU/ml). The oxolinic acid-stimulated serum LH was not increased further by the daily administration of L-dopa (500 mg/kg/day, po, 7 days) and was blocked by the injection of a dopamine antagonist, haloperidol (2 mg/kg, ip). In a microdialysis study, oxolinic acid increased the extracellular concentration of dopamine in the preoptic area of hypothalamus. These findings suggest that a high dietary level of oxolinic acid elevates LH release from the anterior pituitary with an increase in LHRH, in part, by the excitatory input of a dopaminergic system in the preoptic area of rat hypothalamus.

Animals

A patient with Schinzel-Giedion syndrome and a review of 20 patients.

The Schinzel-Giedion syndrome is characterized by severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations. So far, 20 patients have been reported. This is the first report of the syndrome demonstrated in Oriental patients. In surviving patients, severe growth and developmental deficiency is a common finding.

Abnormalities, Multiple

Effect of recombinant human erythropoietin (rHuEPO) on protein, zinc (Zn), nickel (Ni) and manganese (Mn) in patients undergoing chronic haemodialysis.

Serum protein, albumin, Zn, Ni and Mn concentrations were examined in thirty patients undergoing chronic haemodialysis and whose haematocrit levels had been maintained at 30% for two years with rHuEPO. Serum total protein, albumin, Zn, Ni and Mn concentrations significantly increased with time for two years with rHuEPO therapy. All patients showed improvement of appetite and a normal protein balance. Serum Zn, Ni and Mn levels increased with serum total protein. In conclusion, rHuEPO therapy is very effective for the increase of serum protein, albumin, Zn, Ni and Mn levels in patients undergoing chronic haemodialysis.

Adult

Silicon level in rats with chronic renal failure produced by 5/6 nephrectomy.

Serum, erythrocyte and renal tissue silicon levels in normal Wister rats and in rats with chronic renal failure were examined. The relationship between serum, erythrocyte and renal tissue Si levels, and markers of renal function (BUN, serum creatinine), markers of anemia (RBC, Hb, Hct) and markers of bone formation (serum calcium, phosphate) were studied. Serum and erythrocyte Si levels were directly correlated with the markers of renal function and with serum Pi and serum Ca x P, and inversely with the markers of anemia. Renal tissue silicon levels, on the other hand, correlated only with the markers of anemia.

Anemia

Transient cortical blindness following bypass graft angiography. A case report.

Transient cortical blindness, an uncommonly recognized complication of cerebral angiography, is an exceedingly rare event after cardiac catheterization and angiography. This report describes a sixty-two-year-old patient who had transient cortical blindness following bypass graft angiography. In this case, the authors showed that cortical blindness was associated with the breakage of the blood-brain barrier (BBB) and an increase in vascular permeability rather than with primary cerebral circulatory insufficiency. When the possibility exists that an excess volume of contrast medium may enter the cerebral circulation as in this case, that is, following a coronary artery bypass graft (CABG) using the internal mammary artery (IMA), precautionary measures may be necessary such as changing the type of contrast medium to be used or decreasing the volume injected. When cortical blindness occurs, it is a serious clinical problem whether transient or permanent. Therefore, the circumstances leading to this complication should be understood to determine suitable treatment and management.

Blindness

Differentiation of Langerhans cells from interdigitating cells using CD1a and S-100 protein antibodies.

The present study shows that Langerhans cells can be differentiated from interdigitating cells at the light microscopic level. Superficial lymph nodes and skin taken from necropsies and the lymph nodes of dermatopathic lymphadenopathy (DPL) were used for this experiment. Sections of lymph node and skin were embedded using the acetone, methyl benzoate and xylene (AMeX) method and dendritic cells were immunostained with anti S-100 protein antibody (S-100, and OKT-6 (CD1a) using the restaining method. Langerhans cells in the skin were positive for both CD1a and S-100. Dendritic cells positive for both CD1a and S-100, and dendritic cells positive for S-100, but not for CD1a were observed in superficial lymph nodes. In normal superficial lymph nodes, there were more interdigitating cells than Langerhans cells. The majority of the dendritic cells in the DPL were Langerhans cells. We conclude that the S-100 and CD1a positive cells are Langerhans cells, and the S-100 positive-CD1a negative cells are interdigitating cells.

Antigens, CD1

[Urinary tract abnormalities associated with anorectal malformations].

Anorectal malformation (ARM) is often associated with urological problems such as congenital urogenital anomalies, recto-urinary fistula, neurogenic bladder due to vertebral anomalies and operative complications. We analyzed 57 cases of ARM and discussed about the management of associated urogenital anomalies during neonatal and infantile period. The incidence of urogenital anomalies was 85.7% in high type, 65.5% in intermediate type and 38.1% in low type. Among these urinary tract anomalies, VUR was most common and was documented in 38.6% of ARM patients. Renal dysplasia, PUJ stenosis, megaureter and urethral stenosis was also common in these patients. Renal dysfunction was documented in 5 cases (2 in high type, 2 in intermediate and 1 in low type), mainly due to VUR and renal aplasia. These results show the need for evaluation of urinary tract during the neonatal and early infantile period even in low type ARM. The management of urinary tract anomalies associated with ARM is firmly related with the management of ARM itself, and we must be closely in co-operation with pediatric surgeons.

Abnormalities, Multiple

Role of the CYP2D subfamily in metabolism-dependent covalent binding of propranolol to liver microsomal protein in rats.

In vitro covalent binding of a chemically reactive metabolite of propranolol to microsomal macromolecules, which is presumed to cause inhibition of its own metabolism in rats, was diminished in liver microsomes from rats pretreated with propranolol. Covalent binding was suppressed by the addition of an antibody against P450BTL, which is a cytochrome P450 (P450) isozyme belonging to the CYP2D subfamily. SDS-PAGE of microsomal proteins after incubation with [3H]propranolol and NADPH indicated that the binding was non-selective but prominent at the molecular mass of approx. 50 kDa, corresponding to those of the P450 protein. The radioactivity peak was markedly but not completely diminished by the addition of reduced glutathione. In a reconstituted system containing P450BTL, NADPH-cytochrome P450 reductase (fp2) and dilauroylphosphatidylcholine, propranolol 4-, 5- and 7-hydroxylase activities decreased time dependently following preincubation with propranolol in the presence of NADPH, indicating time-dependent inactivation of P450BTL. The covalent binding of a reactive metabolite of [3H]propranolol to the proteins was also observed in this system. SDS-PAGE showed that among the three proteins in the reconstituted system, fp2 and P450BTL consisting of two polypeptides with molecular masses of 49 and 32 kDa, the binding was specific for a polypeptide corresponding to the P450 isozyme with a molecular mass of 49 kDa. In addition, the ratio of the amount of covalently bound radiolabelled materials to that of P450BTL which was estimated from each impaired propranolol hydroxylase activity under the same reconstitutional conditions was calculated to be approx. 1.0. These findings indicate that propranolol is a mechanism-based inactivator of a cytochrome P450 isozyme(s) belonging to the CYP2D subfamily.

Amino Acid Sequence

The correlation of serum luteinizing hormone levels with the induction of Leydig cell tumors in rats by oxolinic acid.

Studies were performed to examine the mechanism by which testicular Leydig cell tumors are induced in rats by administration of the antimicrobial agent oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid). In these studies, the effects of oxolinic acid on serum levels of luteinizing hormone (LH), testosterone, and prolactin and the binding of testosterone to prostatic androgen receptors were examined. In a long-term hormonal study, male Wistar rats were fed a diet containing oxolinic acid at 0, 100, 1000, or 3000 ppm for 104 weeks. A statistically significant increase in serum LH levels was observed at 1000 and 3000 ppm, but no dose of oxolinic acid had a significant effect on serum testosterone levels. Serum LH levels were no longer elevated above control levels within 2 weeks of cessation of the administration of oxolinic acid. Oxolinic acid was found to have no effect on the rate of clearance of exogenous LH from the circulation. Serum prolactin levels were decreased by the administration of oxolinic acid. The increase in serum LH induced by oxolinic acid was completely blocked by the intraperitoneal injection of the dopamine antagonist haloperidol (2 mg/kg). In addition, no significant affinity of oxolinic acid for androgen receptors was found in an in vitro study. These findings suggest that: (1) oxolinic acid induces Leydig cell tumors in rats by chronically stimulating the release of LH from the pituitary, (2) the mechanism of stimulating the release of LH involves facilitation of the dopaminergic systems in the hypothalamus-pituitary axis, and (3) oxolinic acid has no effect on androgen-mediated feedback inhibition.

Administration, Oral

Striatal 18F-dopa uptake and brain glucose metabolism by PET in patients with syndrome of progressive ataxia.

Striatal 18F-Dopa uptake and brain glucose metabolism were studied by PET with 6-L-[18F]flurodopa and [18F]fluorodeoxyglucose in 11 patients with syndrome of progressive ataxia. Five of the 11 patients were diagnosed as having cerebellar cortical degeneration (CCD), including 3 with late cerebellar cortical atrophy and 2 with Holmes type hereditary ataxia while 6 demonstrated olivopontocerebellar atrophy (OPCA). The caudate and putaminal 18F-Dopa uptake ratios to the occipital cortex in CCD showed no significant difference from those in the controls. On the other hand, those with OPCA decreased as compared to the controls. In addition, the cerebellar glucose metabolism in CCD decreased as compared to the controls, while that in the brainstem showed no significant decrease from the controls. The glucose metabolic rates both in the cerebellar hemisphere and in the brainstem in the OPCA patients decreased compared to the controls. The cerebral cortical, striatal and thalamic glucose metabolisms were normal in both the CCD and OPCA in groups. The appearance of a decreased glucose metabolism in the cerebellum is considered to be relevant in the genesis of cerebellar ataxia, even though their underlying diseases were different from each other. The differences in the glucose metabolism of the brainstem and in the nigrostriatal presynaptic dopaminergic function between CCD and OPCA as assessed by PET may be caused by differences in the pathophysiological mechanism between CCD and OPCA, and those differences appear to be useful when making a differential diagnosis of CCD and OPCA.

Adult

Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation.

The oxidative metabolism of bunitrolol, an adrenergic beta-receptor antagonist was examined in human liver microsomes fortified with an NADPH-generating system. The microsomal fractions (n = 11) showed bunitrolol 4-hydroxylase activities, which correlated well with CYP2D6 contents (correlation coefficient, r = 0.854), debrisoquine 4-hydroxylase (r = 0.953) and imipramine 2-hydroxylase (r = 0.976) activities. On the other hand, the bunitrolol 4-hydroxylase activity showed relatively poor correlations with CYP3A4 content (r = 0.552) and testosterone 6 beta-hydroxylase activity (r = 0.668). The bunitrolol 4-hydroxylase activity was significantly inhibited by quinidine, a selective inhibitor for CYP2D6. Polyclonal antibodies raised against rat liver microsomal cytochrome P450BTL, which is thought to belong to the CYP2D subfamily, effectively inhibited bunitrolol 4-hydroxylation. In contrast, polyclonal antibodies raised against human liver microsomal CYP3A4 did not show any inhibitory effect on the activity. These results suggest that CYP2D6 is involved in the bunitrolol 4-hydroxylase activity in human liver microsomes.

Adolescent

[Establishment of hyperbilirubinuria rat mutant--a new animal model for jaundice].

A new animal model for jaundice, a hyperbilirubinemic rat mutant (EHBR, Eizai hyperbilirubinuria rat), was established from Sprague-Dawley rats. Hyperbilirubinemia was inherited as an autosomal recessive trait. The gene manifesting jaundice was named "hyb". Homozygotes developed jaundice immediately after birth, and a high bilirubin concentration was detected in plasma and urine. The plasma bilirubin levels were high in the neonatal period, but they decreased from 6 to 10 weeks old. In male homozygotes, plasma bilirubin levels increased rapidly until about 40 weeks, and decreased thereafter. Female homozygotes showed slightly high plasma bilirubin levels until 56 weeks, then increased rapidly thereafter. At 72 weeks, the plasma bilirubin level of females was comparable to that of males. About 80 percent of the plasma bilirubin was conjugated. Plasma biochemistry demonstrated the increase of total cholesterol and total bile acid in the homozygotes. Histopathologically, the homozygote was characterized by brown pigment in the hepatocytes, and glomerular lesions with mesangial expansion. From these findings it was considered that EHBR might be a useful animal model for studying constitutional conjugated hyperbilirubinemia and bilirubin metabolism.

Animals

[Fetal genitourinary abnormalities associated with oligohydramnios].

After 16 weeks of gestation, amniotic fluid mainly consisted of fetal urine. Therefore, the association of oligohydramnios with fetal urinary tract abnormalities implies severe deterioration of renal function. The relationship of the kidney and amniotic fluid in pulmonary development has been investigated, and fetuses with oligohydramnios starting in the second trimester are considered to have uniformly fatal outcomes. We analysed underlying urological disorders, gestational age at presentation, and ultimate outcomes in 45 fetuses with severe oligohydramnios, and especially focused on clinical courses and prognosis of 7 surviving patients. Clinical and/or autopsy diagnosis included bilateral renal hypodysplasia in 20 patients, urethral atresia with/without prune belly deformity in 9, posterior urethral valve in 6, polycystic kidney disease in 4, hydrometrocolpos in 2, hereditary renal dysplasia in 2, and the others. The average gestational age at detection of severe oligohydramnios was about 30 weeks, ranging from 16 weeks in patient with urethral atresia. Urological disorders of 7 surviving patients consisted of 4 posterior urethral valves, one hydrometrocolpos, one hydronephrosis of the solitary kidney, and one bilateral megaureter. In these 7 patients severe oligohydramnios striated in the third trimester. Four patients required ventilator supports together with the administration of surfactant, but they were weaned in one to 4 days. There was no evidence of pulmonary hypoplasia on chest X-ray films. Urological emergency drainage was necessary in all patients on the day of delivery to 2 days postnatally. One patient with posterior urethral valve developed ESRF 6 months after birth. Two patients have a normal serum creatinine, but another 4 have slight elevation of SCr for their age.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

[Analysis of the preceding R-R interval and the coupling interval on premature ventricular contractions].

Premature Ventricular Contractions (PVCs) are one of the common arrhythmias. Although the analysis of the preceding R-R interval and the coupling interval on the Holter electrocardiogram, the Lorenz plotting method, has been used to characterize mature of PVC, this analysis has typically been performed without regard to the morphological classification of the electrocardiogram waveforms. Therefore, we performed the Lorenz plotting after a PVC classification. We analyzed 45 cases with more than 1,000 PVCs per day. Twenty-six of the cases with PVCs had no organic heart disease (idiopathic PVC); nineteen of the cases with PVCs had organic heart disease (PVC with disease). Each R-R interval was analyzed after classification based on the morphology of each QRS wave of the PVC. The computer generated a two-dimensional plot of the relationship between the preceding R-R interval of PVC and the following coupling interval. The forms of PVCs were monoform in idiopathic PVC and were mostly multiform in PVC with disease. The patterns on Lorenz plotting in idiopathic PVC had a tendency to be uniform with small standard deviations. In contrast, multiform PVCs tended to be highly variable with large standard deviations. The value of SD was 32.1 +/- 12.0 msec in idiopathic PVC, and that of the slope "a" was 0.048 +/- 0.051 in PVC with disease. Using the SD values and the slope "a" values, we were able to classify idiopathic PVC vs. PVC with disease with a 95% sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Effect of erythropoietin (rHuEPO) on trace elements and quality of life (Qol) in chronic hemodialysis patients.

In 30 patients undergoing chronic hemodialysis and whose hematocrit levels had been maintained at 30-50% for 2 years with recombinant human erythropoietin (rHuEPO) administration, changes of serum proteins, serum albumin levels, improvement of trace elements such as zinc (Zn), nickel (Ni) and manganese (Mn), and quality of life (Qol) were examined for 2 years. rHuEPO therapy significantly improved the protein nutritional status, as well as serum Zn, Ni and Mn levels; the concentrations of Zn ion (Zn++), Ni ion (Ni++) and Mn ion (Mn++) in serum were significantly elevated. Objective and subjective Qol of 30 patients showed significant improvement with rHuEPO therapy for 2 years.

Adult