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Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 145 records · Page 8Linked to original sources

An autopsy case of necrotizing ventriculo-encephalitis caused by cytomegalovirus in Hodgkin's disease.

A 59-year-old Japanese woman with Hodgkin's disease developed progressive dementia and died of pneumonia. The autopsy revealed necrotizing ventriculo-encephalitis caused by cytomegalovirus (CMV) infection, which was confirmed by immunohistochemical and electron microscopic examinations. It is suggested that CMV ventriculo-encephalitis could occur not only in patients with acquired immunodeficiency syndrome, but also in other immunocompromised hosts.

Autopsy↗

Na,K-ATPase expression in the developing brine shrimp Artemia. Immunochemical localization of the alpha- and beta-subunits.

Developing brine shrimp are a good experimental model for study of gene expression during development. Development is initiated on suspension of brine shrimp cysts in seawater. Only 48 hr are required for progression from cyst to the larval stage. We have localize the alpha- and beta-subunits in different cells by immunostaining as development progresses. Both alpha- and beta-subunits are first detected in epidermal cells in the trunk region at the emergence 2 stage (16-hr incubation). At the nauplius 1 stage (24 hr) the enzyme appears in the brain and epidermal regions, as well as in mesenchymal cells, with weaker staining in the salt gland. After further development (nauplius 2 stage, 36 hr) stronger staining appears in the salt gland and in the epidermal region. At the nauplius 3 stage (48 hr) the enzyme appears in the midgut mucosa. Co-localization of the alpha- and beta-subunits appears in all positive cells during development. In the epidermal and salt gland cells the enzyme is mainly localized on the basolateral membrane. The basolateral localization of the Na,K-ATPase in epidermal and salt gland cells suggests that Na+ is actively transported into the epidermal and salt gland cells and passively diffuses out from the apical region.

Animals↗

Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders.

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.

Animals↗

[Urinary tract infections after kidney transplantation].

Clinical significance of urinary tract infections (UTI) after kidney transplantation was studied in 57 cases. Of these patients, the UTI occurred in 63% of cases during follow-up after transplantation. Although the bacteriuria were observed more frequently in living-related donor (LD) group at pre-operation, cadaveric donor (CD) group showed significantly higher frequency in bacteriuria and UTI after transplantation. The initial UTI occurred within 4 weeks after transplantation in 86% of cases. The significant risk factors in the occurrence of UTI were presence of bacteriuria in post-operation, CD group, mismatch numbers in HLA, amount of steroid, and ages of donor and recipient. Of the bacteria isolated, about half were pathogens in UTI, which was a 2 times higher risk compared with the time of chronic hemodialysis. Gram negative rods were found to be major pathogen in UTI cases. The effect of UTI on graft survival was not obvious. However, of the patients who have bacteriuria at operation, 52% were found to have bacteriuria due to the same strain during follow-up. Therefore, bacteriological examination of urine at transplantation must be done carefully.

Adult↗

[A case of adult T-cell leukemia with a defective HTLV-I proviral DNA, in which the single T-cell clone appeared to have progressed from chronic phase to crisis].

A 39-year-old woman was first admitted to our hospital with increased white cell count on May, 1983. Physical examination showed only mild splenomegaly. Hematological examination revealed leukocytosis (14,600/microliters) with ATL cells (59%). Serum anti-HTLV-I antibody was positive. Examination of HTLV-I provirus in the abnormal T cells revealed the defective type. She was diagnosed as chronic type of ATL based on the clinical features. Cytogenetic study of the ATL cells revealed 47, xx, +4. For 12 months, she was followed without any therapy. WBC reduced to almost normal range and ATL cells decreased to 3 to 6% for 8 months. On May, 1985, she was readmitted to our hospital because of leukocytosis (32,200/microliters), and increased ATL cells (57%). She was diagnosed as crisis of ATL. Investigation of the proviral DNA and chromosome showed the same results as those of the chronic phase, indicating that ATL cells in both the chronic phase and the crisis phase originated from the same clone. She died after 3 months from massive diarrhea. Postmortem examination showed the extensive infiltration of leukemic cell in the small intestine.

Adult↗

Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus.

Neurotoxic effects of prenatal administration of dexamethasone were examined in the fetal rhesus monkey brain at 135 and 162 days of gestation (term is 165 days). In an experimental design mimicking human clinical trials, dexamethasone was given intramuscularly to pregnant monkeys on day 132 (single injection with doses of 0.5, 5, or 10 mg/kg maternal body weight) or on days 132 and 133 (multiple injections at 12-h intervals with 0.125 x 4, 1.25 x 4, or 2.5 mg/kg x 4). The fetuses were delivered by caesarean section on day 135 or day 162 and hippocampal slices were prepared for evaluation. Light and electron microscopic observation revealed decreased numbers of pyramidal neurons in the hippocampal CA regions and of granular neurons in the dentate gyrus associated with degeneration of neuronal perikarya and dendrites. Axodendritic synaptic terminals of the mossy fibers in the CA3 hippocampal region showed pronounced degeneration. Degeneration was dose-dependent and multiple injections induced more severe damage than single injections of the same total dose. Even the lowest dose (0.5 mg/kg, which is similar to the dose used in human clinical trials) produced these changes. Degenerative changes induced by dexamethasone treatment (5 mg/kg) on days 132 and 133 were also clearly evident in fetuses studied at 162 days. Therefore, caution is recommended in the use of prenatal corticosteroids in premature deliveries.

Animals↗

Disorders of bone metabolism caused by small bowel resection in rats.

Disorders of bone metabolism caused by resection of three quarters of the small bowel in rats were investigated biochemically and histomorphologically. Metabolic bone disorders developing 90 days after in 75%-distal-small-bowel resected rats were characterized by reduction in ash content of the femur and by the disappearance of the trabecular bone in tibial metaphysis. Biochemical studies showed significant decrease in serum Ca and 1,25-dihydroxyvitamin D concentrations in 75% distal small bowel resected rats. These data suggest that 75% distal small bowel resection impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorder in rats. On the other hand, 75% proximal small bowel resection causes no obvious metabolic bone disorders in rats, possibly because of the adaptation by the remaining part of the intestine.

Animals↗

The effects of topical diazoxide on hair follicular growth and physiology of the stumptailed macaque.

Diazoxide, an anti-hypertensive agent, has diverse pharmacologic effects; hypertrichosis, hyperglycemia associated with suppression of insulin release, and elevation of serum levels of androgens. Taking advantage of the hypertrichotic side effects of diazoxide, we examined the effect of topical application of the drug on hair regrowth in the bald frontal scalp of stumptailed macaques (Macaca arctoides); we also monitored systemic side effects. Using 7 adult stumptails, we applied diazoxide (5% solution in a vehicle) topically on the bald frontal scalp, once a day, 5 days per week. Two of seven macaques had vehicle alone applied. Hair growth was monitored by photographic recording (once every month) and by sequential analysis of folliculograms from biopsied skin (once every 4 months). We also examined body weight, hematology, blood pressure, heart rate, serum levels of testosterone and dihydrotestosterone, and glucose tolerance for a 4-month period. All 5 diazoxide-treated animals showed thickening and maintenance of the frontal hair during the entire treatment period (16 months). Analysis of folliculograms showed progressive enlargement of hair follicular size and acceleration of its cyclic growth from telogen to anagen phase and prolongation of anagen phase in all treated animals. Controls showed no consistent progressive changes of follicular growth. None of the animals treated with diazoxide showed abnormal changes in physical growth, cardiovascular function, serum levels of androgens, glucose tolerance (including insulin levels), or hematology.

Alopecia↗

Synthesis and antiinflammatory activity of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepinacetic and -oxepinacetic acids.

A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochemical features (C6a, C10a, and C2'). The 6a,10a-trans compounds exhibited considerable antiinflammatory activity, whereas the 6a,10a-cis compounds were inactive. Among the trans compounds, 6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepin-3-p ropionic acid (9a) and its oxepin analogue (13a) showed an antiinflammatory activity superior to that of indomethacin. The phenethyl ester (25) of 9a showed potent antiinflammatory activity, and its safety index (UD50/ED50) was over 14 times higher than that of indomethacin. The phenethyl ester (25) is the most favorable compound with high antiinflammatory activity and little ulcerogenicity.

Animals↗

The effect of topical minoxidil on hair follicular cycles of rats.

To explore an easily accessible and reproducible model for examining the effect of minoxidil on hair growth, we studied the effect of minoxidil on the natural hair cycles of rats from birth to 80 days of age. During the 1st and 2nd postnatal cycles, the hair follicles grew very rapidly and the size of anagen follicles were markedly enlarged. In the 3rd cycle (50 days to approximately 100 days of age), duration of the telogen phase lasted approximately 20 days. Topical minoxidil, 1%, 3%, or 5% solution, applied on the backs of the rats from 23 days (weaning) to 80 days, induced a remarkable shortening of the telogen phase in the 3rd cycle. Although the dose-dependent response was very minimal, rats treated with 3% or 5% minoxidil showed similar effects in the 4th cycle. Minoxidil, however, did not induce prolongation of the anagen phase, but increased the rate of DNA synthesis in the anagen bulb during the 2nd and 3rd cycles. These results suggest that minoxidil specifically stimulates the secondary germ of the telogen follicles, resulting in rapid progression to anagen follicles.

Administration, Cutaneous↗

[Spontaneous peripelvic extravasation: reports of two cases].

Spontaneous peripelvic extravasation must be distinguished from spontaneous rupture of the renal pelvis in urological emergency. The literatures revealed 42 cases of peripelvic extravasation and 35 cases of rupture of the renal pelvis in Japan. Most of them were caused by urolithiasis and malignant tumors. We report 2 cases of spontaneous peripelvic extravasation caused by urolithiasis, which were successfully treated conservatively.

Abdomen, Acute↗

Hippocampal damage associated with prolonged glucocorticoid exposure in primates.

In the laboratory rat and guinea pig, glucocorticoids (GCs), the adrenal steroids that are secreted during stress, can damage the hippocampus and exacerbate the hippocampal damage induced by various neurological insults. An open question is whether GCs have similar deleterious effects in the primate hippocampus. In fact, we showed that sustained and fatal stress was associated with preferential hippocampal damage in the vervet monkey; however, it was not possible to determine whether the excessive GC secretion that accompanied such stress was the damaging agent. The present study examines this possibility. Pellets of cortisol (the principal GC of primates) were stereotaxically implanted into hippocampi of 4 vervet monkeys; contralateral hippocampi were implanted with cholesterol pellets as a control. One year later at postmortem, preferential damage occurred in the cortisol-implanted side. In the cholesterol side, mild cell layer irregularity was noted in 2 of 4 cases. By contrast in the cortisol-exposed hippocampi, all cases had at least 2 of the following neuropathologic markers: cell layer irregularity, dendritic atrophy, soma shrinkage and condensation, or nuclear pyknosis. Damage was severe in some cases, and was restricted to the CA3/CA2 cellfield. This anatomical distribution of damage, and the cellular features of the damage agree with that observed in instances of GC-induced toxicity in the rodent hippocampus, and of stress-induced toxicity in the primate hippocampus. These observations suggest that sustained GC exposure (whether due to stress, Cushings syndrome or exogenous administration) might damage the human hippocampus.

Animals↗

Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure-activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acryl amides.

A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (3-pyridyl)acrylamide] against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase. Particularly, (E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (6-methyl-3-pyridyl)acrylamide (17p) showed an ED50 value of 3.3 mg/kg po in the rat PCA test, which was one-fifth of ketotifen and oxatomide. As compared with ketotifen and oxatomide, compound 17p (AL-3264) possessed a better balance of antiallergic properties due to inhibition of chemical mediator release, inhibition of 5-lipoxygenase, and antagonism of histamine.

Acrylamides↗

Acrylamide derivatives as antiallergic agents. I. Synthesis and structure-activity relationships of N-[(4-substituted 1-piperazinyl)alkyl]-3-(aryl and heteroaryl)acrylamides.

A new series of acrylamide derivatives (7-10) were synthesized. Antiallergic activity of these compounds was evaluated and their structure-activity relationships were examined. Compound 10d, N-[4-(4-diphenylmethyl-1-piperazinyl)butyl]-3-(3-pyridyl)acrylamid e, showed antiallergic activity equivalent or superior to that of ketotifen in the rat passive cutaneous anaphylaxis (PCA) test by oral administration. Compound 10d, unlike ketotifen, had more potent in vitro 5-lipoxygenase inhibitory activity than caffeic acid, whereas its in vitro antihistamine activity was weaker than that of ketotifen. In addition, its inhibitory activity against histamine release from rat mast cells was approximately two-thirds as potent as that of disodium cromoglycate (DSCG). Compound 10d is a promising agent for treating a variety of allergic diseases.

Acrylamides↗

A novel class of antiulcer agents. 4-Phenyl-2-(1-piperazinyl)quinolines.

The synthesis of a novel class of antiulcer agents, the substituted 4-phenyl-2-(1-piperazinyl)quinolines, and their pharmacological activities (inhibitory effects on hypothermia induced by reserpine and on gastric ulcers induced by stress or ethanol) are described. These compounds can be classified into three groups (a group predominantly effective on the stress-induced ulcer, one effective on both the stress- and ethanol-induced ulcers, and one selectively effective on the ethanol-induced ulcer), with regard to antiulcer activity. The inhibitory effect on stress-induced ulcer was found to be in close relation to the antagonism of hypothermia. The structure-activity relationships in these compounds are described. Among the compounds, 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate (9, AS-2646) showed a potent inhibition of stress-induced ulcer and gastric acid secretion, possively through action on the central nervous system, and it was selected for clinical evaluation.

Animals↗

Synthesis and antiallergic activity of N-[4-(4-diphenylmethyl-1-piperazinyl)butyl]-1,4-dihydro-4-oxopyridine-3 - carboxamides.

A new series of oxopyridinecarboxamide derivatives 3a--g and 5a were synthesized and evaluated for their antiallergic activity. 1,4-Dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxamides 3a and 5a exhibited potent antiallergic activity (inhibitory rates of 80.7 and 88.3%, respectively, at 20 mg/kg, p.o.) in the rat passive cutaneous anaphylaxis (PCA) test and also exhibited much more potent in vitro inhibitory activity than caffeic acid against the enzyme 5-lipoxygenase (5-LO). Their in vitro antihistamine activity, however, was weaker than that of ketotifen. Compounds 3a and 5a are viewed as promising candidates for antiallergic agents.

Animals↗