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Biomedical subjects

H Uno

Publications and source records attributed to H Uno.

At least 181 records · Page 10Linked to original sources

Immunohistochemical demonstration of neuron specific enolase (NSE) on cutaneous nerves: comparative study using NSE and S-100 protein antibodies on denervated skin.

The presence of neuron-specific enolase (NSE) and S-100 protein, which are nerve specific proteins, was immunohistochemically investigated on the cutaneous nerves. NSE was found in the axons of the cutaneous nerve bundles and the terminal axons in the Meissner and Pacinian corpuscles of the normal human and macaque skin. S-100 protein was found in the Schwann cells, lamellar cells of the Meissner corpuscles, and inner core cells of the Pacinian corpuscles. After denervation of the ulnar nerve on macaque, NSE on axons of the cutaneous nerves and Meissner and Pacinian corpuscles was completely disappeared in the 5th digit. However, S-100 protein was still maintained in the Schwann cells and Meissner and Pacinian corpuscles in the same digit. From these results, we conclude that the comparative immunohistochemical staining of NSE and S-100 protein is simple and reliable method to demonstrate the cutaneous nerves in normal and pathological conditions.

Animals↗

Action of topical minoxidil in the bald stump-tailed macaque.

The effect of topical minoxidil (5% and 2% solutions) on hair regrowth was studied in the frontal bald scalp of 18 adolescent and adult stump-tailed macaques (Macaca arctoides). Gross observation of the hairiness and folliculogram analysis of the skin biopsy specimens have shown that minoxidil induces the enlargement of vellus follicles to the size of middle to terminal follicles (regrowth of hair effect), minoxidil maintains the terminal follicles in the prebald scalp of periadolescent animals (prevention of baldness effect), enlarged follicles regress after minoxidil is withdrawn, and hair follicular growth is once again stimulated when treatment with minoxidil is reinstituted. Hair regrowth was more prominent in the early stage of baldness among younger macaques than in baldness of longer duration in older animals. An in vitro study of 3H thymidine uptake revealed that the hair follicles in minoxidil-treated macaque skin showed significant enhancement of deoxyribonucleic acid synthesis in the follicular and perifollicular cells but not in the epidermal keratinocytes. Furthermore, the uptake of 3H minoxidil and its conversion to minoxidil sulfate (the active metabolite producing vasodilation) was relatively higher in the hair follicles than in the epidermis and dermis. Serum concentration of minoxidil was fairly constant 2, 4, 6, 15, and 24 hours after a single application (averaging 15 ng/ml with 5% minoxidil). Minoxidil's essential action in hair follicular growth may be as a potent vasodilator. However, a direct action on the hair follicle cannot be ruled out considering uptake and conversion of the drug to minoxidil sulfate within the hair follicle itself.

Administration, Topical↗

Synthesis and structure-activity relationships of 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives having narcotic agonist and antagonist activity.

Racemates and enantiomers of 1-substituted 4-[2-(3-hydroxyphenyl)-1-phenylethyl]piperazine derivatives (3-18) were synthesized, and their analgesic and other pharmacological activities and structure-activity relationships were investigated. The S-(+) enantiomers of 2a, 5, 7, 9, 10, and 15-18 had a stronger analgesic activity than their R-(-) enantiomers; analgesic activity of the strongest one [(S)-(+)-10] was 105 times as potent as that of morphine. The S-(+) enantiomers of these compounds had the opposite configuration to that of morphine with respect to its (C-9) asymmetric center but the same configuration to that of the tyrosine residue of Met5-enkephalin. The R-(-) enantiomers of 16 and 18 showed narcotic antagonist activity, but the S-(+) enantiomers did not. (R)-(-)-18 had analgesic and narcotic antagonist activities comparable to pentazocine but showed no significant physical dependence liability. From these results, it is suggested that these compounds show an uncommon enantioselectivity in comparison with morphine and its surrogates, and belong to a new series of compounds having a potent analgesic activity.

Analgesia↗

Effects of retinoic acid on the epidermal Langerhans cells and beta-glucuronidase activity in macaque skin.

Retinoic acid (0.5% in acetone) was applied topically to the back skin of five juvenile rhesus monkeys once a day for 7 successive days. Two control animals were given vehicle alone. Skin specimens were taken from each animal at 0, 1, 2, and 4 weeks. The tissues were prepared for both histology (1-micron plastic sections) and split epidermal sheets (after incubation with EDTA solution, 17 mM). The split epidermal sheets were stained with ATPase and anti-Ia antibody, and the number of Langerhans cells was counted. The activity of beta-glucuronidase in the split epidermis was assayed by Fishman's method. After one week of treatment, the epidermis showed marked acanthosis and hyperkeratosis. The Langerhans cells showed severe degeneration, and the number of cells had dropped to approximately one-third of the number in the control skins. Concomitantly, the activity of beta-glucuronidase in the epidermis had also decreased to one-third of the control levels. After withdrawal, the number of Langerhans cells and activity of beta-glucuronidase showed gradual recovery, and by the fourth week they were back to the ranges of pretreatment or control skins, but acanthotic change remained. The results suggest that retinoid applied topically to normal primate skin induces reversible degeneration and desquamation of the Langerhans cells, while the epidermis shows prolonged proliferative change.

Adenosine Triphosphatases↗

Substance P-induced histamine release in human cutaneous mast cells.

Substance P is an undecapeptide found in multiple sites throughout the central and peripheral nervous systems including small unmyelinated (type C) cutaneous nerve fibers. Previous studies demonstrated that antidromic stimulation results in substance P (SP) release from nerve endings, SP stimulates histamine release (HR) from rat mast cells in vitro, and intradermal SP in humans produces wheals identical to those induced by histamine. These studies suggest a possible role for SP as a link between neurologic events and cutaneous mast cell-mediated reactions. We therefore investigated SP-induced HR in an in vitro preparation of human skin mast cells. Human foreskin sections were incubated with varying concentrations of SP. Histamine was assayed using automated fluorimetry and release was calculated as a percentage of total tissue histamine. Substance P caused dose-dependent HR over a range from 10(-5) M (1.3%) to 5 X 10(-4) M (25.1%). Histamine release was optimal at 3 mM calcium and was blocked by pretreatment with calcium chelation. Naloxone failed to block HR. These studies suggest that HR from skin mast cells by SP may play a role in neural modulation of poorly understood inflammatory skin conditions.

Calcium↗

The effects of N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide, a 5 alpha-reductase inhibitor and antiandrogen, on the development of baldness in the stumptail macaque.

We used a primate model of male-pattern baldness to test the efficacy of a topically applied 5 alpha-reductase inhibitor and antiandrogen (4-MA) in the prevention of baldness. Six periadolescent stumptail macaques were given daily topical applications of either 4-MA in dimethylsulfoxide or dimethylsulfoxide alone for 27 months. The three control monkeys developed varying degrees of baldness, while the three 4-MA-treated monkeys retained their juvenile pattern of hair growth. The percentage of actively growing hair follicles in the frontal scalp did not change in the 4-MA-treated group [46 +/- 6 (+/- SE) vs. 48 +/- 4], while a significant decrease occurred in the control group (63 +/- 6 vs. 25 +/- 12; P less than 0.025). Skin 5 alpha-reductase activity was reduced in the scalp of the 4-MA-treated monkeys. We conclude that topical 4-MA can prevent the development of baldness in the stumptail macaque, a primate model of androgen-dependent baldness.

Alopecia↗

[A clinicopathological evaluation of AFP-positive gallbladder cancer--with special reference to two autopsy cases investigated by an immunological method].

We report on 2 autopsy cases of primary gallbladder cancer in which the serum AFP level was found to be above 1000 ng/ml. Both cases showed a hepatic metastasis and a moderately differentiated papillary adenocarcinoma. We investigated the primary and metastatic parts by means of an immunological technique and found them to be AFP positive. Gallbladder cancer cases at our hospital that have been evaluated as being AFP positive remain an object of our cancer as to its clinical pathological meaning.

Adenocarcinoma↗

Pulmonary stenosis with ventricular septal defect, common aorticopulmonary trunk, and dextroposition of the aorta: morphologic and qualitative physiologic effects in caffeine-treated chick embryos.

Effects of caffeine administration to Hamburger-Hamilton stage 19 chick embryos (3 days of incubation) were investigated. A morphologic study of the effect of caffeine on cardiogenesis showed that caffeine produced total cardiac malformations in the chick in a dose-related fashion. A maximum frequency of 70.6% was observed with 4.7 mg caffeine. Major malformations included common aorticopulmonary trunk and dextroposition of the aorta accompanied by ventricular septal defect with/without pulmonary stenosis. Qualitative analysis of cinegraphs following exposure of embryos to a single teratogenic dose of caffeine (3.5 mg/egg) produced marked alterations in cardiac function when compared with chick Ringer's controls. Within 3 minutes after exposure to caffeine, dilation of the common ventricle and weak ventricular contractility were observed and persisted for 1 hour. Dose-response data and microcinematographic observations suggest that caffeine induced cardiac anomalies by a direct toxic effect on the embryo rather than by altering cardiac cell function. Our data also suggest that pathophysiologic changes in cardiac function may play an important role in the pathogenesis of caffeine-induced cardiac anomalies in the chick embryo.

Abnormalities, Drug-Induced↗

Functional differences between human cutaneous mast cells and basophils: a comparison of morphine-induced histamine release.

Intravenous administration of morphine sulfate often produces urticarial and hypotensive reactions associated with elevations in plasma histamine. The source of this histamine and mechanisms controlling its release are poorly understood. Previous studies of morphine-induced histamine release compared human leukocytes to rat peritoneal mast cells. The effects of morphine on human cutaneous mast cells has not been examined. We studied in vitro histamine release from human basophils and human skin preparations containing cutaneous mast cells to evaluate their relative contribution to the pharmacologic effects of morphine. Human skin mast cell preparations showed dose-dependent histamine release over a morphine concentration range of 1.5 X 10(-5) to 4.5 X 10(-3) M, with peak release occurring at 5 X 10(-4) M, with peak release occurring at 5 X 10(-4) M. Clinically, morphine sulfate is usually injected as a 1.5 X 10(-2) M solution. Histamine release was calcium dependent and equivalent to that obtained with 3 and 10 mM strontium. Morphologic examination revealed degranulation and exocytosis occurring in morphine-stimulated tissue but not in specimens exposed to buffer alone. Lactate dehydrogenase levels did not increase following morphine incubation, thus supporting a noncytolytic mechanism of histamine release. Basophils, in contrast, showed no significant histamine release from exposure to morphine up to 10(-2) M. Concanavalin A, as a positive control in these same preparations, produced a mean histamine release of 21.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Basophils↗

Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices.

The effect of diarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. The addition of diarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. At three concentrations (10, 50 and 100 microM), increases in prostaglandin E2 formation induced by exogenous diarachidonin were 2-fold greater than those induced by exogenous arachidonic acid. Diacylglycerol or phosphatidic acid from egg lecithin had little or no effect on prostaglandin E2 production. Moreover, EGTA failed to inhibit diarachidonin-stimulated prostaglandin E2 formation, indicating that the stimulatory effect of diarachidonin is not mediated through the activation of endogenous phospholipase A2 (including phosphatidic acid-specific phospholipase A2). These results are discussed in the light of our former hypothesis that arachidonic acid release from kidney medulla phospholipids might occur through the sequential action of a phospholipase C coupled to diacylglycerol and monoacylglycerol lipases [Fujimoto, Akamatsu, Hattori & Fujita (1984) Biochem. J. 218, 69-74].

Acetophenones↗

[Studies on the pathogenesis of subacute thyroiditis].

UNLABELLED: Despite the fact that subacute thyroiditis (SAT) is a common disease, its pathogenesis is still uncertain. At present, viral infection is simply thought to be a possible pathogenic factor. In Caucasians and Chinese, however, a strong association has recently been found between HLA-Bw35 and SAT. Therefore, genetic factors are also thought to participate in the onset of SAT. In this study we have further attempted to clarify the pathogenesis of this disease in this regard. PROTOCOL: HLA typing for A, B and C loci (class I antigens) was performed on 89 patients with SAT (males: 7, females: 82) aged from 23 to 66 years, and DR and MT loci (class II antigens) were investigated in 55 patients. In 12 patients, viral antibody titers were measured as soon as possible after onset and two weeks later. The viral antibodies evaluated were those of Influenza A and B, Coxsackie A9, B1, B2, B3, B4, B5 and B6, Echo 3, 7, 11 and 12, Parainfluenza 1, 2, 3 and 4, and Adeno 8 virus. The following results were obtained: In class I HLA typing, the frequency of HLA-Bw35 in SAT was 67.4%, which was significantly (p less than 0.0001) higher than that in the control (14.1%). On the other hand, the frequency of Cw1 in SAT (14.6%) was significantly (p less than 0.01) lower than that of the control (32.1%), and that of Cw3 (65.2%) was significantly (p less than 0.01) higher than that of the control (46.5%). In class II HLA typing, the frequency of DRw8 in SAT was 38.2%, which was significantly (p less than 0.05) higher than that of the control (21.9%). Other antigens showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Genetic analysis of subacute (de Quervain's) thyroiditis.

A weak association between subacute (de Quervain's) thyroiditis and HLA-DRw8 (relative risk = 2.19, X2 = 3.86) was observed. However, the association was not statistically significant if p value was corrected. Since it was confirmed that the association of subacute thyroiditis with HLA-B35 was primary, and since this association was extremely strong, the two models (dominant and recessive) for the effect of an HLA-linked gene which has a major effect on the pathogenesis of subacute thyroiditis were tested by the method described by Thomson & Bodmer using the frequency of HLA-B35 in the patients. The data most fit to the recessive model for the HLA-linked major gene involved in subacute thyroiditis.

Genetic Linkage↗