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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 19 recordsLinked to original sources
PubMed1995

Demonstration of interleukin-3 receptor-associated antigen in the central nervous system.

We previously reported that interleukin-3 (IL-3) acts as a neurotrophic factor for cholinergic neurons. However, it has not yet been determined whether the action is derived from the interaction of IL-3 with IL-3 receptors. As the first step to study IL-3 receptors in the central nervous system, we examined the presence and localization of IL-3 receptor-associated antigen (IL-3RAA) in mouse and rat brain. Immunohistochemically, IL-3RAA, which is closely involved both in the IL-3 binding to IL-3 receptors and the tyrosine phosphorylation in the signal transduction for IL-3 in hematopoietic cells, was demonstrated in neurons throughout the brain. This was confirmed in primary cultured neurons and neuronal cell lines by immunocytochemistry and flow cytometry. The staining intensity varied among regions and the most intense immunoreactivity for IL-3RAA was found in large neurons in the magnocellular basal nuclei, pyramidal cells in the cerebral cortex, and neuronal cells in some nuclei of the brainstem. Not only cholinergic cell lines derived from the septal region but also other neuronal cell lines exhibited IL-3RAA immunoreactivity by flow cytometry. Therefore, we conclude that IL-3RAA is present in a wide variety of neurons in the brain including cholinergic neurons of the basal forebrain. Western blot analysis revealed that the candidates for IL-3RAA are 145, 100, and 50 kDa proteins both in neuronal and IL-3-dependent cell lines.

Animals↗
PubMed1995

Ultrastructural changes in the lung in Niemann-Pick type C mouse.

The biochemical and morphological aspects of BALB/c mice with many features of the Niemann-Pick disease type C in man (NP-C mouse) have been studied extensively. However, the pulmonary pathology has not been studied extensively and we describe here some unique ultrastructural features of the lung in the NP-C mouse. Ultrastructurally, macrophages in younger mice contained osmiophilic dense granules and annulolamellar structures, but larger multilamellar concentric structures increased in the macrophages of older mice. In contrast, endothelial cells and type I pneumocytes showed membrane-bound bodies with dense granules and vesicular or vesiculogranular structures as well as amorphous materials. Type II pneumocytes were unremarkable throughout. Our study suggests that endothelial cells and type I pneumocytes are the major site of metabolic derangement resulting in pronounced morphological changes with granular and round membranous structures in the lungs of NP-C mouse. Alveolar macrophages with multilamellar concentric structures may be a result of disturbed disposal of surfactant material from type II pneumocytes rather than that from storage material of type I pneumocyte.

Animals↗
PubMed1995

Peripheral nerve pathology in Niemann-Pick type C mouse.

The sciatic nerve of the mouse mutant with Niemann-Pick type C disease (NPC mouse) was investigated using light and electron microscopy, and teased-fiber preparations. As early as postnatal day 20, when clinical symptoms were not yet apparent, focal paranodal swellings with an accumulation of small myelin figures in the Schwann cell cytoplasm were noted. These paranodal changes were more pronounced in the distal segment and became progressively conspicuous with increasing age. The morphometric analysis revealed a hypomyelination of large myelinated fibers in the NPC nerves at 70 days, whereas an essentially similar histogram pattern was noted in both control and NPC nerves at 20 days, suggesting progressively defective utilization of cholesterol in the NPC nerves with age. Intraxonal accumulation of dense bodies was noted in older mice, but no segmental demyelination or Wallerian type of axonal degeneration was observed at any age. The changes noted in the paranodal regions in the NPC mouse closely resemble those found in rats treated with an inhibitor of cholesterol biosynthesis, as well as those seen in remodeling fibers during an early stage of peripheral nerve development. Thus, the morphological changes seen in the sciatic nerve of the NPC mouse may be an expression of perturbation in myelin maintenance as a result of defective cholesterol metabolism.

Animals↗
PubMed1995

Effect of the transmembrane gradient of magnesium and sodium on the regulation of cytosolic free magnesium concentration in human platelets.

1. To clarify the mechanism by which cytosolic free Mg2+ concentrations ([Mg2+]i) are regulated in human platelets, we investigated platelet membrane permeability to Mg2+ by altering extracellular Mg2+ concentrations, and tested the existence of a Na(+)-Mg2+ exchanger by manipulating the transmembrane Na+ gradient. 2. Platelet [Mg2+]i was 421 +/- 52 mumol/l in healthy men. [Mg2+]i remained constant during a 120 min exposure to nominally zero (low) or 5 mmol/l (high) external Mg2+ concentrations. 3. Preincubation of platelets with 10(-4) mol/l ouabain effectively decreased the transmembrane Na+ gradient. The ouabain-induced increase in [Mg2+]i was statistically significant after 30 min of exposure (14.6 +/- 2.0%) and reached 24.6 +/- 4.5% after 60 min. Similarly, the replacement of extracellular Na+ with N-methyl-D-glucamine significantly increased [Mg2+]i by 48.5 +/- 3.9% and 78.8 +/- 12.5%, respectively. 4. These results suggest that [Mg2+]i is well controlled in the presence of large transmembrane Mg2+ concentration gradients, and a Na(+)-Mg2+ exchanger may be involved in the regulation of [Mg2+]i in human platelets.

Blood Platelets↗
PubMed1995

Magnetic resonance imaging for the diagnosis of prostate cancer metastatic to bone.

OBJECTIVE: To examine the role of magnetic resonance imaging (MRI) in the evaluation of osseous metastasis in patients with prostate cancer. PATIENTS AND METHODS: A series of 36 patients with known prostate cancer, who were undergoing MRI and an isotope bone scan, were studied. RESULTS: Of 19 positive bone scans, MRI was read as negative for metastasis in one. Of eight equivocal scans, two MR images were interpreted as positive and six as negative. Of nine negative scans MRI was positive in one. Further MRI demonstrated additional metastatic lesions that were not shown by bone scintigraphy in six patients. MRI clearly indicated the areas of spinal cord compression in five patients with spinal metastases and associated myelopathy. CONCLUSION: MRI is helpful in the diagnosis of metastatic prostate cancer, especially when other radiographic examinations are inconclusive or spinal cord compression is suspected.

Bone Neoplasms↗
PubMed1995

Predictive factors in the response to interferon therapy in chronic hepatitis C.

Factors predicting the efficacy of interferon therapy were statistically analyzed on 111 patients with chronic hepatitis C. Of the treated patients (total doses of interferon; 96-468 MU), 35 (31.5%) had a long-term remission. On multivariate analysis, hepatitis C virus genotype (p < 0.0001), histological diagnosis (p < 0.05), fibrosis score of histological activity index (p < 0.01) and source of infection (p < 0.05) were found useful for predicting the response to interferon therapy. Our findings suggest that the outcome of interferon therapy can be predicted to some degree from pretreatment data, and that a new therapeutic strategy is necessary for the group of patients who are predicted to be nonresponders.

Adult↗
PubMed1995

Effects of L-arginine infusion on renal hemodynamics in patients with mild essential hypertension.

Previous studies have shown that endothelium-derived relaxing factor/nitric oxide plays an important role in the regulation of systemic and renal hemodynamics. The purpose of the present study was to determine whether endothelium-dependent renovascular relaxation was impaired in patients with mild essential hypertension who had normal renal plasma flow and glomerular filtration rate. We evaluated the effects of intravenous administration of L-arginine on blood pressure and renal hemodynamics in 13 patients with mild essential hypertension and 15 normotensive control subjects. L-Arginine infusion (500 mg/kg over 30 minutes) reduced mean blood pressure (from 82.5 +/- 2.5 to 76.3 +/- 2.6 mm Hg in hypertensive patients and from 106.1 +/- 3.0 to 97.5 +/- 2.9 mm Hg in control subjects; P < .001) and renovascular resistance (from 0.084 +/- 0.009 to 0.067 +/- 0.009 mm Hg.mL-1.min-1.[1.48 m2]-1 and from 0.105 +/- 0.010 to 0.093 +/- 0.011 mm Hg.mL-1.min-1.[1.48 m2]-1, respectively; P < .001). L-Arginine infusion increased renal plasma flow (from 602 +/- 36 to 698 +/- 40 mL.min-1.[1.48 m2]-1, P < .05) in normotensive subjects but not in hypertensive subjects, and glomerular filtration rate was unaffected in both groups. Although the L-arginine-induced reduction in mean blood pressure was similar in both groups, the decline in renovascular resistance was smaller in hypertensive subjects. The response of renal plasma flow was also smaller in hypertensive subjects. These findings suggest that dysfunction of the L-arginine-nitric oxide pathway exists in the renal circulation even in mild essential hypertension with normal renal plasma flow and glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Intravenous administration of L-arginine inhibits angiotensin-converting enzyme in humans.

The iv administration of L-arginine, a precursor of endothelium-derived relaxing factor/nitric oxide, is known to decrease blood pressure in humans by its direct vasodilatory effects. The purpose of the present study was to determine whether L-arginine infusion modifies the renin-angiotensin (Ang)-aldosterone system as well as blood pressure and renal hemodynamics. L-Arginine and saline vehicle were iv administered to 10 healthy male subjects in random order on different days. L-Arginine infusion (500 mg/kg over 30 min) decreased mean blood pressure (from 81.2 +/- 2.7 to 74.0 +/- 2.5 mm Hg; P < 0.001) and renal vascular resistance (from 0.085 +/- 0.007 to 0.074 +/- 0.006 mm Hg/mL.min; P < 0.01) and increased heart rate (from 60.3 +/- 2.7 to 69.7 +/- 2.1 beats/min; P < 0.001) and renal plasma flow (from 616.6 +/- 37.8 to 701.0 +/- 49.2 mL/min; P < 0.05). L-Arginine reduced serum Ang-converting enzyme activity (from 10.4 +/- 0.6 to 8.9 +/- 0.5 nmol/mL.min; P < 0.05) and plasma Ang-II (from 19.3 +/- 3.3 to 12.7 +/- 2.8 pg/mL; P < 0.001), but had no effect on PRA or the glomerular filtration rate. The saline vehicle did not alter any of these parameters. The iv administration of L-arginine (endothelium-derived relaxing factor/nitric oxide) may reduce the plasma Ang-II concentration by inhibiting Ang-converting enzyme. The mechanism by which L-arginine infusion decreases blood pressure can be at least in part explained by inhibition of the renin-Ang system.

Adult↗
PubMed1995

Systemic magnesium deficiency disclosed by magnesium loading test in patients with essential hypertension.

The present study was designed to determine whether magnesium (Mg) deficiency is present in patients with essential hypertension. We measured the retention of an intravenously administered Mg load (0.2 mmol/kg MgSO4 over 4 h), and serum and erythrocyte Mg concentrations in 17 inpatients with essential hypertension and in 15 normotensive controls. There was no significant difference between the two groups in erythrocyte Mg concentration (normotensives vs., hypertensives: 2.0 +/- 0.5 vs. 2.1 +/- 0.4 mmol/l cells), serum Mg concentration (normotensives vs. hypertensive: 2.1 +/- 0.2 vs. 2.1 +/- 0.2 mg/dl), or in urinary Mg excretion (normotensives vs. hypertensives: 65.8 +/- 25.5 vs. 73.7 +/- 26.7 mg/day). However, Mg retention was significantly higher in hypertensives than in normotensives (normotensives vs. hypertensives: 31.8 +/- 12.1 vs. 41.9 +/- 13.3%). These results suggest that a systemic Mg deficiency, which is undectectable by serum or erythrocyte Mg determination, may exist in patients with essential hypertension.

Adult↗
PubMed1995

Histological study of the circulatory system of human dental pulp from individuals under local anesthesia and electro-acupuncture.

A transmission electron microscopic (TEM) study was conducted on dental pulp obtained from patients under acupuncture or infiltration local analgesia. It was difficult to differentiate lymphatic circulation in the dental pulp that received infiltration anesthesia, because the vessels were constricted, congested, and showed stasis and thrombosis. On the other hand, the dental pulp that received acupuncture showed normal arterioles, capillaries, and venules, as well as some lymph capillaries and small efferent lymphatic vessels that measured about 8 microns and 100 microns in diameter, respectively. The lymphatic endothelial walls had many intercellular gaps, an imperfect basal lamina, and a few discontinuous pericytes. Between the openings in the lymphatic vessels, there were bundles of junctional filaments extending towards the dental pulp connective tissue. Therefore, the lymphatic system, which contains mainly B-3-alpha capillaries, is a leaky tissue for regulating fluid in the dental pulp.

Acupuncture Analgesia↗
PubMed1995

[Magnetic resonance imaging for the evaluation of prostate cancer metastatic to bone].

The response of bone metastatic lesions to endocrine therapy was assessed by repeated magnetic resonance imaging (MRI) and an isotope bone scan after an average period of 7.0 months (2-10 months) in 12 patients with prostate cancer. MRI used both T1-weighted spin echo technique and short TI IR (STIR) sequence. Of 7 patients with hormone-dependent cancer, the bone metastatic lesions resolved or became vague in all patients on STIR image, while in only 4 and 3 on T1-weighted image and bone scan, respectively. Of 5 patients with hormone-refractory cancer, the lesions progressed on both MRI and bone scan in all patients except one who had initially had diffusely metastatic lesions of systemic bone. The results indicate that STIR image of MRI is helpful for the therapeutic evaluation of bone lesions.

Adenocarcinoma↗
PubMed1995

[Study on prevention of flare-up phenomenon following initial LH-RH analogue administration: combination therapy with diethylstilbestrol].

To eliminate the initial testosterone (T) surge and prevent the risk of flare-up induced by the first administration of luteinizing hormone-releasing hormone (LH-RH) analogue, we examined the effectiveness of short-term combination therapy with diethylstilbestrol (DES). Sixteen previously untreated patients with prostate carcinoma (Stage C: 4 cases, Stage D2: 12 cases) were randomly assigned to 4 groups. Each group included 4 patients. Group 1 received DES (500 mg daily injection) for 7 days, staring before the first subcutaneous injection of luteinizing hormone releasing hormone (LH-RH) analogue (3.6 mg of Zoladex depot); Group 2 received 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, and moreover received a DES injection for 7 days; Group 3 received 500 mg of DES injection for 7 days simultaneously with the first injection of the LH-RH analogue; Group 4 was pretreated with 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, with additional DES injection for 3 days. In groups 1, 2 and 4 the level of T decreased during the 7 days of DES therapy, and at 3 days after the first injection of LH-RH analogue increased again. The mean T value in groups 1, 2 and 4 decreased by 33.2 +/- 27.6% (mean +/- SE), 20.5 +/- 20.8%, 13.2 +/- 9.8%, respectively, at the day of the first injection of LH-RH analogue, and increased by 75.2 +/- 21.6%, 70.7 +/- 63.4%, 56.7 +/- 46.4%, respectively, at 3 days after the first injection of LH-RH analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

[Pelvic kidney associated with staghorn calculus and renal pelvic cancer: a case report].

A 63-year-old man was admitted to our hospital with complaints of right lower abdominal pain and stone excretions. The patient was diagnosed as having a pelvic kidney associated with staghorn calculus and extended pyelolithotomy was to be performed. However, during the operation, a papillary tumor was found in the renal pelvis occupied with staghorn calculus. As the pathological examination of its frozen section was low grade transitional cell carcinoma, nephro-ureterectomy was performed. Pelvic kidney associated with staghorn calculus or renal pelvic tumor with stones is not rare, but pelvic kidney associated with staghorn calculus and renal pelvic cancer is extremely rare.

Carcinoma, Transitional Cell↗
PubMed1995

Assessment of platelet cytosolic concentration of free magnesium in healthy subjects.

We measured basal cytosolic concentration of free Mg2+ ([Mg2+]i) in platelets from 30 healthy volunteers by using mag-fura-2, a new fluorescent Mg2+ indicator. The mean [Mg2+]i was 381 +/- 22 mumol/L, with values ranging from 226 to 771 mumol/L. The day-to-day intrasubject coefficient of variation was relatively small (3.6%). [Mg2+]i was significantly higher in men than in women (430 +/- 38 vs 332 +/- 17 mumol/L, p < 0.03), and was not correlated with age. There was no significant relation between platelet [Mg2+]i and serum total Mg concentration. The results indicate that the gender but not age may decide intracellular Mg2+ status. In addition, the mechanisms that regulate [Mg2+]i may be independent of those that influence the extracellular concentration of Mg.

Adult↗
PubMed1994

Dose-dependent plasma clearance of human epidermal growth factor in rats.

Exogenously administered human epidermal growth factor (hEGF) shows a marked dose-dependent plasma disposition in rats. In the present study, total plasma clearance (CLtotal) of hEGF was examined from the viewpoint of hepatic blood flow and accessible EGF receptors in a dosing range of hEGF from 30 to 1000 micrograms/kg. In rats in which down-regulation of EGF receptors caused a reduction in their number (50% below the normal level) (group 1), the CLtotal of hEGF was decreased only at a medium dose (100 micrograms/kg) compared to those in normal rats. In rats in which hepatic intoxication with carbon tetrachloride caused 50% reduction of both EGF receptor number and hepatic blood flow (group 2), CLtotal was decreased at low and medium hEGF doses. The decrease at a low hEGF dose was proportional to the decrease in the hepatic blood flow. In rats with reduced hepatic blood flow caused by hypothermia (group 3), CLtotal was decreased at all hEGF doses examined, and the decrease at a low hEGF dose (50 micrograms/kg) was proportional to the hepatic blood flow. The decreases of CLtotal at a medium hEGF dose in groups 1, 2 and 3 were well accounted for by the decrease of hepatic blood flow and/or EGF receptor number in a well-stirred model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Decanoic acid induced enhancement of rectal absorption of hydrophilic compounds in rats.

The enhancing effect of decanoic acid (C10) on the rectal absorption of phenolsulfonphtalein (PSP) was analyzed with a pharmacokinetic model. The transfer index of PSP from the rectal lumen to the epithelial layer in the presence of C10 was proportional to the product of the C10 disappearance rate from the rectal lumen and its calcium ion sequestration capacity. The enhancement of rectal PSP absorption by different doses of C10 was also predictable by using a permeability index, Pa, of PSP, which was defined as a proportionality constant relating transfer index and the product value described above. The Pa values of various hydrophilic compounds with different molecular weights were also estimated from their rectal bioavailability in the presence of C10. A linear relationship was observed between Pa values and reciprocal values of the square root of individual molecular weight. These findings suggest that the Pa index is related to the permeant's diffusion coefficient through paracellular aqueous openings formed by C10.

Animals↗