Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 109 records · Page 6Linked to original sources

PubMed1994

Evaluation of 3-[18F]fluoro-alpha-fluoromethyl-p-tyrosine as a tracer for striatal tyrosine hydroxylase activity.

3-[18F]Fluoro-alpha-fluoromethyl-p-tyrosine (3-F-FMPT) was evaluated as a tracer for CNS tyrosine hydroxylase (TH) activity in rodents and in a rhesus monkey. Results of in vitro experiments using rat striatal homogenates showed that the introduction of fluorine into the 3-phenyl position did not significantly alter the ability of FMPT to act as a TH-activated L-aromatic amino acid decarboxylase (L-AAAD) inhibitor. These studies further showed that 3-F-FMPT-induced L-AAAD inhibition was dose-dependent. Furthermore, striatal homogenates prepared from rats pretreated with the potent TH inhibitor alpha-methyl-p-tyrosine was found to have diminished 3-F-FMPT-induced L-AAAD inhibition. However, despite these promising in vitro results, the biodistribution of this compound in mice showed low brain uptake and fast clearance through the kidneys. A PET study using a Rhesus monkey injected with 3-[18F]F-FMPT confirmed the results obtained in mice, i.e. negligible brain uptake but high localization in the bladder. We conclude that 3-[18F]F-FMPT would not be useful as a tracer for cerebral TH activity.

Animals↗

PubMed1994

Minoxidil sulfation in the hair follicle.

The in vivo model which may be the most accurate for the ability to predict hair growth in humans, and which was utilized in the preclinical development of minoxidil, is the adult stumptailed macaque. Previous reports have suggested that the enzyme activity which accounts for the activation of minoxidil, i.e., minoxidil sulfotransferase, is present in skin. We have demonstrated that scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity, and further with dissection of that scalp skin into epidermis, dermis and hair follicle, most of sulfotransferase activity was present in the follicle. Sulfotransferase activity in the hair follicle in freeze-dried scalp skin sections from 9 stumptailed macaques ranged from 47 to 84% of the total (mean 61 +/- 12%). Much less minoxidil sulfotransferase activity was measured in the epidermis (mean 18 +/- 11%, with a range of 2-37%) and the dermis (mean 21 +/- 8%, with a range of 4-35%) of these scalp sections. These results indicate that the scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity and this activity is largely localized in the hair follicle which may account for its ability to stimulate hair growth in this animal model.

Animals↗

PubMed1994

The effects of finasteride (Proscar) on hair growth, hair cycle stage, and serum testosterone and dihydrotestosterone in adult male and female stumptail macaques (Macaca arctoides).

Finasteride, a 5 alpha-reductase inhibitor, was administered orally (1 mg/kg.day) for 6 months to six male and five female stumptail macaques. Vehicle was given to five male and five female animals over the same period of time. Hair weights in a defined 1-in.2 area of frontal scalp were measured periodically every 1-2 months, and serum was collected for measurement of testosterone and dihydrotestosterone. In addition, scalp biopsies were taken before and 6 months after treatment to evaluate the micromorphometry of hair follicles. Results showed that both male and female serum dihydrotestosterone levels were significantly reduced (60-70%) by finasteride treatment. Both males and females showed statistically significant increases in mean hair weight over the treatment period compared to controls (P = 0.034). In addition, there was a statistically significant increase in mean follicle length (measured histologically in scalp biopsies) compared to baseline in the finasteride-treated animals (P = 0.028). These data show that an inhibition of 5 alpha-reductase in the stumptail macaque can reverse the balding seen with age in both the male and female animals.

Animals↗

PubMed1994

Effect of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) and Wistar (WF/NCr) rats.

A previous report indicated that progesterone pretreatment can markedly reduce cadmium (Cd) toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on Cd toxicity in male Fischer (F344) and Wistar (WF) rats. A single subcutaneous injection of 10 or 30 mumole (CdCl2)/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. Moreover, when F344 rats were pretreated with progesterone (100 mg/kg, sc, at -48, -24, and 0 hr) and then given cadmium (20 mumole CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing 53% mortality. Progesterone pretreatment had no effect on cadmium-induced lethality in WF rats or on testicular lesions in either strain. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated F344 rats given cadmium as compared to rats given Cd alone. Progesterone did not induce increases in hepatic or renal metallothionein (MT) and hepatic or testicular MT-I mRNA levels in F344 rats. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated F344 rats were doubled. This increase in TCBP provided no protection against cadmium toxicity in the testes. These results indicate that, in contrast to previously reported data for mice, progesterone pretreatment increased the lethality of cadmium in male F344 rats and had no effect on cadmium-induced testicular toxicity in F344 and WF rats.

Animals↗

PubMed1994

Bulky plasmacytoma of the bone with intracranial invasion.

A 56-year-old man with left anterior chest pain showed two well-defined tumors in the left anterior chest wall and left parietal region. A large osteolytic lesion in the parietal bone and several punched-out lesions in the temporal bone were revealed by a skull X-ray examination. He showed monoclonal gammopathy (IgG, kappa type) and Bence Jones proteinuria, but no proliferation of plasma cells was observed in the bone marrow. The tissue specimens from both lesions consisted of abnormal plasma cells, indicating plasmacytoma. Although a bulky intracranial plasmacytoma was present, the patient did not exhibit intracranial hypertensive symptoms, or neurological abnormalities.

Bence Jones Protein↗

PubMed1994

A case report of serologically diagnosed pulmonary anisakiasis with pleural effusion and multiple lesions.

The second known human case of pulmonary anisakiasis is reported. A 22-years-old man living in Hyuga City, Miyazaki Prefecture, Japan, developed high fever, respiratory distress, and pleural effusion after consumption of raw fish. Although his total white blood cell count increased to approximately 10,000-20,000/mm3, eosinophilia was not observed. The total IgE level in his serum markedly increased up to 3,599 IU/ml. Since the patient was suspected to have a parasitic disease, immunoserologic tests were carried out. Screening tests using a multiple dot-enzyme-linked immunosorbent assay (ELISA) and an Ouchterlony double-diffusion test showed that his serum and pleural effusion had the strongest reactivity against crude antigen of Anisakis type I larvae, together with weak cross-reactivity against several other nematode antigens. Since extragastrointestinal anisakiasis was strongly suspected, this diagnosis was confirmed by a microplate-ELISA and Western blot analysis using a monoclonal antibody.

Adult↗

PubMed1994

Pharmacological profiles of contractile endothelin receptors in guinea pig hilar bronchus.

Characterization of the receptors mediating contractions to endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin S6c (STXc), or IRL 1620 in isolated epithelium-denuded hilar bronchus of guinea pig using as antagonists BQ-123 (ETA receptor-selective) and Ro 46-2005 (ETA/B nonselective) was investigated. ET-1, ET-3, STXc, and IRL 1620 produced only contraction, and their concentration-response curves were obtained at the same concentration range (10(-10)-10(-7) M). The potency order was the following: STXc = ET-3 = ET-1 > IRL 1620. BQ-123 (10(-5)M) had no marked effect on the contraction induced by ET-3 or STXc, whereas it attenuated the response induced by high concentration of ET-1 (3 x 10(-8)-10(-7)M). The contraction induced by IRL 1620 was antagonized by BQ-123 (3 x 10(-6)-10(-5)M). Ro 46-2005 (10(-5)M) failed to inhibit the responses to ET-1 and ET-3. Ro 46-2005 (10(-5)M) slightly, but significantly, shifted the concentration-response curve for STXc to the right (pKB = 4.94 +/- 0.10, n = 7), and the maximum response was potentiated to about 127%. The curve for IRL 1620 was shifted in parallel by Ro 46-2005 (3 x 10(-6)-10(-5)M) to the right (mean pKB = 6.35 +/- 0.09, n = 8). These results suggest that ETB receptors primarily mediate contraction to ET-1, ET-3, STXc, and IRL 1620, and the relative inhibitory activities of ET antagonists vary with the agonist used. However, ET-1 and ET-3 might also activate non-ETB receptor or unknown mechanisms.

Animals↗

PubMed1994

Niacin attenuates acute lung injury induced by lipopolysaccharide in the hamster.

Lipopolysaccharide plays a major role in the development of lung injury induced by Gram-negative bacteria, but a protective agent to attenuate the LPS-induced lung injury has not been found. The aim of this study was to examine the effects of niacin on LPS-induced acute lung injury. We administered LPS (Escherichia coli) 0.01 mg.100 g-1 body weight, transtracheally into the lungs of hamsters. Niacin (250 or 500 mg.kg-1 body weight) was injected intraperitoneally 24 h before, and 1 h after the LPS administration. LPS treatment increased wet/dry lung weight, albumin content and neutrophil counts in bronchoalveolar lavage fluid. In hamsters treated with niacin, wet/dry lung weight, albumin content and intra-alveolar cell counts were normal. Nicotinamide adenine dinucleotide (NAD) was significantly decreased in lung tissue of hamsters treated with LPS alone, but was increased in hamsters treated with LPS and niacin. Histopathological examination revealed that niacin-treated LPS-administered hamsters had lungs with no or occasional inflammatory cell infiltration in alveolar spaces, in contrast to the lungs of LPS-treated hamsters, which were infiltrated with numerous inflammatory cells. We conclude that niacin attenuates LPS-induced acute lung injury, probably, in part, by preventing the depletion of NAD.

Animals↗

PubMed1994

[Evaluation of inhibitory effect of isoflurane on the hypoxic pulmonary vasoconstriction response in dogs].

The effect of isoflurane on hypoxic pulmonary vasoconstriction (HPV) was examined using the separately ventilated left lower lobe lung model in dogs. When the HPV was induced with anoxic gas ventilation of the left lower lobe, the magnitude of HPV inhibition by isoflurane of 2 MAC was predominant, as assessed by the index of pressure-flow curve which is a novel indicator of pulmonary vascular tone in the left lower lobe. However, isoflurane 2 MAC attenuated the HPV by only 16%, as assessed by indices of the changes in left lower lobe blood flow rate and PaO2. This weak HPV inhibition, as shown by the latter parameters, may result from the net effect of isoflurane-induced HPV inhibition and secondary HPV enhancement due to decreases in cardiac output and pulmonary arterial pressure by isoflurane. However, none of the parameters showed inhibition of HPV when the HPV was induced by collapse of the left lower lobe. This discrepancy in the results may be caused by a lack of isoflurane reaching the hypoxic lobe when the HPV is induced with atelectasis. These results show that potency of HPV inhibition with isoflurane depends on the method of induction or evaluation of HPV, and that inhibition of HPV response with isoflurane at clinical concentrations is negligible in an atelectasis-induced HPV, in which no isoflurane is directly reaching the hypoxic lobe.

Animals↗

PubMed1994

Investigation of type IIC von Willebrand disease.

Type II von Willebrand disease (vWD) is characterized by qualitative abnormality of von Willebrand factor (vWF). It is characterized by the absence of the largest, or the largest and intermediate-size plasma vWF multimers. Type IIC vWD is a very rare variant subtype. We report the tenth case of type IIC vWD who is a 32-year-old Japanese with a history of lifelong mild bleeding problems. The multimeric analysis of vWF of the patient's plasma revealed that the multimers were composed of the increased smallest multimer and progressively decreased larger multimers, with each multimer replaced by a single band instead of a normal triplet structure. The family study highly suggested that the propositus is the first case of homozygote for type IIC vWD gene, although previous studies have suggested that type IIC vWD is due to double heterozygosity of two different mutant genes. The patient's von Willebrand factor antigen showed a slight response to 1-deamino-8-D-arginine vasopressin (DDAVP), whereas his ristocetin cofactor showed no response. The patient responded very well to an intermediate-purity factor VIII concentrate, and then underwent cholecystectomy without bleeding problems.

Adult↗

PubMed1994

[Psoriasis exacerbated by alpha-interferon therapy in a case of chronic myelogenous leukemia].

A 49-year old male with chronic myelogenous leukemia (CML) and psoriasis was admitted for interferon treatment. He was given 6 MU of human lymphoblastoid interferon (HLBI), a natural alpha-interferon, daily for 1 month followed by 3 MU every other day for 1.5 months and twice a week for 1 month. Because HLBI administration showed no favorable effects on the hematological findings and because of the exacerbated psoriasis of the patient, it was discontinued. Subsequently his psoriasis improved to the initial findings observed at the admission. We reported a case of CML in which psoriasis was exacerbated during interferon therapy.

Humans↗

PubMed1993

Effect of L-ascorbic acid pretreatment on cadmium toxicity in the male Fischer (F344/NCr) rat.

Some studies have indicated that cadmium-induced lethality and selective injurious effects to specific tissues, such as testes or liver, can be prevented by pretreatment with the antioxidant L-ascorbic acid (ascorbic acid). However, the basis of this tolerance is unclear. We examined the effects of ascorbic acid pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. Cadmium treatment alone (25 mumol CdCl2/kg, s.c.) proved lethal, causing a 93% mortality within 72 h, but in rats pretreated with ascorbic acid (2 g/kg, s.c. 24, 12 and 1 h) cadmium-induced lethality was nearly prevented. Hepatic lesions, including hepatocellular necrosis, induced by cadmium were at least partially ameliorated by ascorbic acid pretreatment. Ascorbic acid pretreatment had no effect on cadmium-induced testicular lesions nor on cadmium content in testes, liver, kidney and urine. Ascorbic acid alone modestly increased hepatic metallothionein (MT), but not renal MT and had no effect on induction of hepatic or renal MT by cadmium. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) in rats exposed to cadmium alone decreased markedly. Moreover, the level of TCBP decreased unexpectedly in ascorbic acid pretreated rats as compared with control. These results indicate that ascorbic acid pretreatment decreases the toxicity of cadmium in the rat without markedly modifying its toxicokinetics or markedly stimulating MT synthesis.

Animals↗

PubMed1993

The age of biosenescence and the incidence of cerebral beta-amyloidosis in aged captive rhesus monkeys.

Autopsy surveillance of 186 rhesus monkeys aged 20 to 36 years revealed that development of major geriatric diseases such as emphysema, coronary sclerosis, and cancer increased rapidly after the age of 25 years, and nearly 70% of the monkeys in each cohort group died by 30 years. According to our 12-year longitudinal survey, the age of biosenescence in captive rhesus monkeys begins around 25 years and the maximum longevity is 36 years. The incidence of cerebral beta-amyloidosis associated with plaque formation and cerebral angiopathy was observed in 51 brains of rhesus monkeys aged 25 to 36 years. Lesions were found in 31 of 51 aged brains (60%) and 6 monkeys over 34 years of age were all severely affected. Despite the size of the plaque, nearly all of them showed immunopositive beta-amyloid. Cerebral angiopathy coexisted in 10 of 31 plaque-positive brains. The basal prefrontal gyrus was the most common site and contained the highest density of plaques, followed by the amygdala region. The amyloid in the liver, spleen, adrenal and pancreatic islets in visceral amyloidosis showed no positivity to the beta-amyloid demonstrated in the brain. As in aged human brains, the incidence of age-dependent cerebral beta-amyloidosis in captive rhesus monkeys showed great individual variation.

Aging↗

PubMed1993

Alterations in populations of GST-p-immunoreactive single hepatocytes and hepatocellular foci after a single injection of N-nitrosodiethylamine with or without phenobarbital promotion in male F344/NCr rats.

The fate of placental glutathione S-transferase (GST-P)-immunoreactive hepatocytes, detectable in livers of rats soon after treatment with N-nitrosodiethylamine (DEN), was examined sequentially with or without phenobarbital (PB) promotion. Group 1 male F344/NCr rats were administered a single i.p. injection of 200 mg DEN per kg body weight at 5 weeks of age. Group 2 rats were given 500 ppm PB in the diet two weeks after the DEN treatment. Groups of six rats were sequentially sacrificed 16, 42, 70, 126 and 238 days after DEN injection. In DEN-treated rats, GST-P immunoreactive hepatocytes (single cells and multiple cell foci) were detectable 16 days after DEN, the total numbers decreasing by day 70 and thereafter rising again. In the early stages the proportion of single immunoreactive hepatocytes was prominent, but with time a gradual increase in small GST-P+ hepatocellular foci and larger foci became evident. Feeding of PB to rats for 16-238 days after a single DEN injection resulted in increases of both single cells and foci, especially foci composed of more than three hepatocytes. The growth response was increasingly pronounced with time. Adenomas or carcinomas were only observed at 126 or 238 days. Numbers of GST-P+ foci far exceeded the numbers of foci visible in hematoxylin-eosin (H & E) stained sections, and a few H & E foci were negative for GST-P. Many GST-P+ foci smaller than ten cells were composed of histologically normal hepatocytes. Almost all GST-P+ foci identifiable in H&E stained sections were larger than ten cells, consisted of clear cells (in both groups) or mixed (clear-eosinophilic) cells in PB-exposed rats, and appeared to be evenly distributed throughout the three zones of the liver. These results suggest that the promotive effect of PB is most evident as an increase in larger hepatocyte populations composed of more than three GST-P+ hepatocytes, rather than in increasing the populations of single GST-P immunoreactive cells. PB may cause clonal expansion of these single GST-P reactive hepatocytes. This study provides evidence for the hypothesis that some of the GST-P reactive hepatocytes are initiated cells.

Animals↗

PubMed1993

The tonotopic representation in the auditory cortex of the guinea pig with optical recording.

We examined spatio-temporal characteristics of the tonotopic representation in the auditory cortex of the anesthetized guinea pig with a multichannel optical method using voltage-sensitive dye. The response latencies increased, and the response field in the cortex became small when the stimulus intensity levels were decreased. Low frequencies were represented rostrally and high frequencies caudally. The two fields responding to different frequencies at higher intensity levels gradually overlapped as time after stimulus onset increased, though these response field did not overlap at the beginning of the response. These findings indicate that tonotopic representation varies dynamically with time after stimulus onset.

Acoustic Stimulation↗

PubMed1993

Effect of progesterone pretreatment on cadmium toxicity in the male Fischer (F344/NCr) rat.

A previous report has indicated that progesterone pretreatment can markedly reduce cadmium toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. A single sc injection of 20 mumol CdCl2/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. However, when rats were pretreated with progesterone (100 mg/kg, sc, -48, -24, and 0 hr) and then given cadmium (20 mumol CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing a 53% mortality. Progesterone pretreatment had no effect on cadmium-induced testicular lesions in surviving rats. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated rats given cadmium as compared to rats given cadmium alone. Progesterone pretreatment had no effect on the distribution of cadmium to liver, kidney, or testes. Progesterone pretreatment also had no effect on the cadmium-induced increases in hepatic or renal metallothionein (MT) or hepatic or testicular MT mRNA levels. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated rats were doubled. These results indicate that, contrary to previously reported data for the mouse, progesterone pretreatment increased the lethality of cadmium in male Fischer (F344/NCr) rats and had no effect on cadmium-induced testicular toxicity. The mechanism by which progesterone enhanced cadmium toxicity, especially cadmium-induced hepatotoxicity, deserves further study.

Animals↗

PubMed1993

Effect of sevoflurane on hypoxic pulmonary vasoconstriction in the perfused rabbit lung.

BACKGROUND: In vitro studies have shown that isoflurane, enflurane, and halothane inhibit the hypoxic pulmonary vasoconstriction (HPV) with essentially the same potency. The aim of this study is to compare the effects of sevoflurane and isoflurane on HPV in constant-flow perfused rabbit lungs. METHODS: Constant-flow perfused lungs from Japanese white rabbits were tested. The lungs were divided into three groups: isoflurane alone (n = 6), sevoflurane alone (n = 6), and sevoflurane with ibuprofen pretreatment (n = 6). Baseline HPV responses were measured as the pulmonary arterial pressure increased after changing inspired oxygen concentration from 95% for 15 min to 3% (with 5% CO2) for 5 min without anesthetic administration. Next, three different concentrations of anesthetics were added to the inspired gas for 15 min in random order. The HPV response in the presence of anesthetic was expressed as a percentage of the pressor response in the absence of anesthetics, and dose-response relationships were calculated using the nonlinear least-squares method. RESULTS: Isoflurane and sevoflurane both depressed the HPV response in a dose-related manner. The half-inhibition values (ED50) of HPV with isoflurane and sevoflurane were 0.85 +/- 0.22 MAC and 1.00 +/- 0.12 MAC (mean +/- SD), respectively, and were not statistically different. Ibuprofen pretreatment did not alter ED50 and slope of dose-response curve, although the absolute value of pressor response in the sevoflurane group with ibuprofen pretreatment was greater than that in the sevoflurane alone group at every concentration of sevoflurane. CONCLUSIONS: Sevoflurane inhibits the HPV response in a dose-related manner, and its potency is similar to that of isoflurane in vitro. Cyclooxygenase products do not mediate the inhibition of HPV by sevoflurane.

Anesthetics↗

PubMed1993

Chemical agents and peptides affect hair growth.

During the past decade we have examined both the therapeutic and the prophylactic effects of several agents on the macaque model of androgenetic alopecia. Minoxidil and diazoxide, potent hypotensive agents acting as peripheral vasodilators, are known to have a hypertrichotic side effect. Topical use of both agents induced significant hair regrowth in the bald scalps of macaques. The application of a steroid 5 alpha-reductase inhibitor (4MA) in non-bald preadolescent macaques has prevented baldness, whereas controls developed it during 2 years of treatment. The effects of hair growth were determined by 1) phototrichogram, 2) folliculogram (micro-morphometric analysis), and 3) the rate of DNA synthesis in the follicular cells. These effects were essentially a stimulation of the follicular cell proliferation, resulting in an enlargement of the anagen follicles from vellus to terminal type (therapy) or a maintenance of the prebald terminal follicles (prevention). A copper binding peptide (PC1031) had the effect of follicular enlargement on the back skin of fuzzy rats, covering the vellus follicles; the effect was similar to that of topical minoxidil. Analyzing the quantitative sequences of follicular size and cyclic phases, we speculate on the effect of agents on follicular growth. We also discuss the triggering mechanism of androgen in the follicular epithelial-mesenchymal (dermal papilla) interaction.

Animals↗