Ketosis is involved in the origin of prurigo pigmentosa.
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3-Hydroxybutyric Acid↗
Biomedical subjects
M Kawashima
Publications and source records attributed to M Kawashima.
Role of endothelin-1 in hyperpigmentation in seborrhoeic keratosis.
Seborrhoeic keratosis (SK) is a benign epidermal tumour with a varying degree of pigmentation. We have recently demonstrated that endothelin-1 (ET-1) is a strong keratinocyte-derived mitogen and melanogen for human melanocytes in UVB-induced melanosis. To clarify the role of ET-1 in hyperpigmentation in SK, we have used immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to see whether the production of ET-1 is accentuated in SK. Immunohistochemical analysis in SK (n = 7; acanthotic and deeply pigmented types) revealed marked immunostaining with anti-ET-1 in almost all basaloid and basal cells as compared with definite staining confined to basal cells in the perilesional normal controls. In parallel, RT-PCR of ET-1 mRNA demonstrated accentuated expression of ET-1 transcript in SK (n = 4) in comparison with that in the perilesional normal controls, accompanied by a similarly accentuated expression of tyrosinase mRNA. These findings suggest that ET-1 plays a part in the hyperpigmentation seen in SK.
Adult↗
Acral lentiginous melanoma (including in situ melanoma) arising in association with naevocellular naevi.
Acral lentiginous melanoma (ALM) occurring on the sole of the foot is the most common type of malignant melanoma in Asians, African and North American Blacks, but is relatively infrequent in Caucasians. According to the literature ALM is thought less likely to arise in a precursor naevus of any type or be associated with dysplastic naevi elsewhere on the skin. We present five cases of ALM (two invasive and three in situ cases) arising in association with pre-existing naevi on the foot in Asians and Caucasians. All patients were female, aged 35-66 years (mean = 47.8). Clinically, all five tumours demonstrated various shades of tan, brown and black, admixed with hypopigmented areas. Histologically, these melanomas showed a lentiginous character of the radial growth phase component with rare foci of pagetoid intra-epidermal spread. Invasive determal components in the form of epithelial and spindle cells were evident in two cases, with a measured depth of 1.7 and 0.85 mm, respectively. Pre-existing naevi, either dermal or junctional, were identified in all tumours. Clinical follow-up in all patients showed no evidence of recurrence or metastasis over a period of 4 months-5 years. These cases appear at variance with the general belief that ALM and ALM in situ arise de novo and rarely arise in precursor naevi. To the best of our knowledge, this is the first documented series of ALM in situ arising in association with pre-existing naevi. We conclude that ALM can arise in association with acral naevi.
Adult↗
Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency?
Previously, we demonstrated that there is a marked reduction in the amount of ceramide in the stratum corneum of both lesional and nonlesional forearms in atopic dermatitis (AD), suggesting that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin. In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to normal controls. In stripped stratum corneum and biopsied whole epidermis of patients with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl-14C]sphingomyelin as a substrate were markedly increased by 27- and 7-fold, respectively. Radio-thin-layer chromatography of the reaction products revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades SM to yield ceramides and phosphorylcholine (PC), most of the SM hydrolysis detected in AD were attributable not to the SMase but to a hitherto undiscovered epidermal enzyme, SM acylase, which releases free fatty acid and sphingosyl-PC (Sph-PC) instead of ceramides. The potential of this acylase-like enzyme to generate Sph-PC through SM hydrolysis was corroborated by thin-layer chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-performance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also detected by high-performance liquid chromatography-mass spectrometry after incubation of SM with atopic stratum corneum samples. On the other hand, the stratum corneum of patients with contact dermatitis or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layer chromatographic analysis. These findings suggest that SM metabolism is altered in AD, resulting in a decrease in levels of ceramides, which could be an etiologic factor in the continuous generation of atopic dry and barrier disrupted skin observed in AD.
Amidohydrolases↗
Apocrine cystadenoma arising on the ear.
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Aged↗
Molecular epidemiologic analysis of Japanese patients with molluscum contagiosum.
BACKGROUND: Molluscum contagiosum virus (MCV) causes molluscum contagiosum (MC) in both children and adults. Recent studies have revealed that the DNA of MCV can be classified into two major types by restriction enzyme cleavage patterns; however, the relationship between MCV types and the clinical features has not been fully understood. Our study was conducted to examine whether there are geographic differences in the incidence of MCV types and whether a correlation exists between MCV types and the age, sex, and clinical status of the patients. METHODS: Specimens were obtained from 171 Japanese patients. The total DNA was extracted and digested with the restriction enzymes, BamH I, Hind III, and Cla I, respectively. Specimens were then electrophoresed in agarose gels. The gels were stained with ethidium bromide and photographs were taken under transillumination. RESULTS: Six different cleavage patterns were observed; they were classified into two major types, MCV 1 and MCV 2, consisting of two MCV 1-variants, and MCV 2 prototype, and three MCV 2-variants. The ratio of MCV 1 to MCV 2 was 13:1. MCV 1 was commonly detected in children (98%) and adult women (92%). MCV 2 was more frequently isolated from adult men (44%) and from patients with human immunodeficiency virus (HIV) infection (75%). CONCLUSION: MCV types found in Japanese children and adult women were predominantly MCV 1 and less frequently MCV 2. This pattern is similar to that observed in European countries and Australia, suggesting a high frequency and world-wide distribution of MCV 1. The higher incidence of MCV 2 among adult men and HIV-positive patients may indicate that transmission routes of MCV 1 and MCV 2 is somewhat different, of which the latter may be in part by sexual contact.
Adolescent↗
Dermatofibrosarcoma protuberans of the sole.
A 42-year-old Chinese man presented with a dome-shaped, red, tender, bony-hard tumor on his right sole. Histological examination revealed tumor nests which consisted mainly of fibroblast-like cells with large, spindle-shaped nuclei and histiocyte-like cells extending from the upper dermis to the subcutaneous tissue. The tumor cells showed both a storiform and a cartwheel pattern. The location of a dermatofibrosarcoma protuberans on the plantar aspect of the foot is exceptional.
Adult↗
Effects of progesterone, estrogen, and androgen on progesterone receptor binding in hen oviduct uterus (shell gland).
The specific [3H] progesterone binding per milligram of protein of the cytosolic fraction of the hen uterus was found to have decreased at 1 and 4 h after the injection of progesterone (P4), but increased at 4 and 8 h after the injection of estradiol-17 beta (E2), and at 1 and 4 h after the injection of testosterone (T). The equilibrium dissociation constant obtained by Scatchard analysis was not significantly different between the hens receiving steroid injections [P4], E2, T, and dihydrotestosterone (DHT)] and controls. The maximum binding capacity was lower in hens injected with P4 and greater in hens injected with E2, T, or DHT than in uninjected hens. The results suggest that the cytosolic progesterone receptor binding in the hen uterus may be modulated by the sex steroid hormones.
Analysis of Variance↗
Mesotocin binding to receptors in hen kidney plasma membranes.
Radioligand assays were performed to demonstrate the presence of a receptor for mesotocin (MT) in the membrane fractions of the kidney of the hen. Specific [125I]MT bindings were decreased by the presence of Mg2+ and Ca2+, increased by the presence of EDTA, increased during the first 4 h of incubation and then reached a plateau, and increased with the increase in the protein concentration from 2.5 to 20 micrograms. The membrane fraction showed binding specificity to [125I]MT. The Scatchard plot revealed a curvilinear profile that indicated the presence of two classes of binding sites: a high affinity site and a low affinity site. The equilibrium dissociation constant was 0.08 +/- 0.01 nM (mean +/- SEM; n = 5) in the high affinity site and 0.87 +/- 0.08 nM (n = 5) in the low affinity site. The maximum binding capacity of the high and low affinity sites was 42 +/- 4 and 129 +/- 6 fmol/mg protein, respectively. The results suggest the presence of two distinct MT receptors in the kidney of the hen.
Animals↗
Periorbital oedema and erythema in systemic lupus erythematosus.
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Adult↗
[Health check on divers and compressed air workers].
We have conducted the health check of 3,554 compressed air workers and 1,821 divers, and also examined the incidence and severity of aseptic bone necrosis by using Roentgen pictures. We could classify 4,859 of 5,375 persons into four groups (A-D), based on our classification. We could also classify 4,205 of 5,375 persons that had had a bone X ray examination on the basis of the criteria described by Ota and Matsunaga (A-C). 4,859 persons belonged to four groups: class A (persons who can work, no limitations): 4,099 (84.4%), class B (persons who can work under conditions below 1.0 kg/cm2): 357 (7.3%), class C (persons who had better quit work under hyperbaric conditions, though they are not prohibited by regulations): 183 (3.8%), class D (persons who must be prohibited from working in a hyperbaric environment by laws of the Ministry of Labor): 88 (1.8%). About 90% of compressed air workers and divers (classes A and B) were permitted to work under hyperbaric conditions. Most of those belonging to classes C and D suffered from hypertension, cardiovascular disease and liver dysfunction. The incidence of aseptic bone necrosis was 11.1% (465 out of 4,205 persons). Eight persons (2.2%) belonged to criteria A which means poor prognosis. They were classified into class D. There is no differences between compressed air workers and divers in the incidence of aseptic bone necrosis.
Adult↗
Effect of 1,6-dihydro-2[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidineca rboxyli c acid on ethanol-induced microvascular injury in rats.
To disclose the cytoprotective mechanism of 1,6-dihydro-2[2-(2-methyoxypropoxy)anilino]-6-oxo-5-pyrimidinecarb oxylic acid (CAS 98772-05-5, MAR-99), the effect of this compound on the microvascular injury in gastric mucosa induced by 99.5% ethanol in rats was studied. In this experiment, it was found that the elevation of vascular permeability observed at the early state of ethanol-induced gastric mucosal injury was closely correlated with the combined action of histamine and slow reacting substance (leukotriene C4, LTC4). MAR-99 (0.3-10 mg/kg p.o.) prevented dose-dependently the increase in vascular permeability. Furthermore, MAR-99 (10 mg/kg p.o.) improved the decrease in the number of histamine containing cells and histamine content, and prevented the production of LTC4. These results suggest that MAR-99 exerts its anti-microvascular injury effect by regulating the release of histamine and the production of LTC4 in glandular stomach against ethanol, and this effect may contribute to the anti-lesion effect of this compound.
Animals↗
Induction of hepatic microsomal drug-metabolizing enzymes by methylsulphonyl metabolites of polychlorinated biphenyl congeners in rats.
The effect of methylsulphonyl (MeSO2) metabolites of 2,3',4',5-tetrachlorobiphenyl (tetraCB) (IU-70), 2,2',3',4',5-pentachlorobiphenyl (pentaCB) (IU-87), 2,2',4',5,5'-pentaCB (IU-101) and 2,2',3',4',5,5'-hexachlorobiphenyl (hexaCB) (IU-141), on the hepatic microsomal drug-metabolizing enzyme system was investigated in rats. The administration of 3-MeSO2-2,3',4',5-tetraCB (10 mumol/kg), 3-MeSO2-2,2',3',4',5-pentaCB (0.5 mumol/kg), 3-MeSO2-2,2',4',5,5'-pentaCB (0.5 mumol/kg) and 3-MeSO2-2,2',3',4',5,5'-hexaCB (2 mumol/kg) to rats significantly increased the contents of cytochromes P-450 and b5 and the activities of aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and benzo[a]pyrene hydroxylase. From these results, it is suggested that the 3-MeSO2 derivatives studied are possibly potent phenobarbital-like inducers of microsomal drug-metabolizing enzymes. On the other hand, 4-MeSO2-2,3',4',5-tetraCB, 4-MeSO2-2,2',3',4',5-pentaCB, 4-MeSO2-2,2',4',5,5'-pentaCB and 4-MeSO2-2,2',3',4',5,5'-hexaCB had almost no effect on both cytochrome contents and these enzyme activities. After 96 h, following administration of 2,3',4',5-tetraCB, 2,2',3',4',5-pentaCB, 2,2',4',5,5'-pentaCB and 2,2',3',4',5,5'-hexaCB (342 mumol/kg each), significant increases in contents of these two cytochromes and in activities of these enzymes were observed. The relationship between liver concentrations of 3-MeSO2-PCBs after administration of four PCB congeners and that after administration of their 3-MeSO2 derivatives, and increases in the contents of both cytochromes and activities of drug-metabolizing enzyme suggests that the 3-MeSO2 metabolites derived from PCBs studied play an important role in the induction of the drug-metabolizing enzymes by the parent PCB congeners.
7-Alkoxycoumarin O-Dealkylase↗
Characterization of hepatic microsomal cytochrome P-450 from rats treated with methylsulphonyl metabolites of polychlorinated biphenyl congeners.
The inducing potency of 3-methylsulphonyl(MeSO2)-2,2',4',5,5'-pentachlorobiphenyl (pentaCB), which was one of the major MeSO2 metabolites of polychlorinated biphenyls (PCBs) present in seal blubber, on the hepatic drug metabolizing enzyme activities was examined in comparison with that of the parent compound and phenobarbital (PB). The inducing fashion of the above enzymes and changes in the contents of PB-inducible P-450 forms by 2,3',4',5-tetrachlorobiphenyl (tetraCB) (IU-70), 2,2',3',4',5-pentaCB (IU-87), 2,2',4',5,5'-pentaCB (IU-101) and 2,2',3',4',5,5'-hexachlorobiphenyl (hexaCB) (IU-141), and their MeSO2 metabolites were investigated in rats. Administration at various doses (0.2-1.0 mumol/kg) of 3-MeSO2-2,2',4',5,5'-pentaCB produced nearly dose-related increases in the hepatic concentration of this methyl sulphone, in the contents of cytochromes P-450 and b5, and in activities of aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and benzo[a]pyrene hydroxylase of liver microsomes. Major PB-inducible forms, CYP2B1, CYP2B2, CYP3A2 and CYP2C6 were induced with four PCBs (342 mumol/kg) and their 3-MeSO2 metabolites (0.5-10 mumol/kg), indicating that 3-MeSO2 metabolites were strong PB-type inducers of hepatic drug-metabolizing enzymes. 3-MeSO2-2,2',4',5,5'-pentaCB was an especially strong inducer. On the other hand, four PB-inducible forms of cytochrome P-450 were not induced with the 4-MeSO2 isomers. The relation between liver concentrations of the corresponding 3-MeSO2 derivatives and induction of four PB-inducible forms of cytochrome P-450 after administration of four PCBs and their 3-MeSO2 derivatives further confirmed that the 3-MeSO2 metabolites played an important role in the induction which parent PCB congeners caused on the hepatic drug-metabolizing enzyme system.
Animals↗
Detection of inflammatory cytokines in psoriatic skin.
Recent investigations have revealed the involvement of cytokines in the pathogenesis of psoriasis. This study examined the amount of inflammatory cytokines--interleukin-1 (IL-1), interleukin-6 (IL-6) and granulocyte macrophage colony-stimulating factor (GM-CSF)--released into the supernatants of organ cultures of involved and uninvolved skin from psoriatic patients and normal skin from healthy individuals. Bioassays were employed to detect the activities of IL-1 and IL-6. Enzyme-linked immunosorbent assay (ELISA) methods were used to quantitate immunoreactive IL-1 alpha, IL-1 beta, IL-6 and GM-CSF. The activity of IL-1 in uninvolved psoriatic skin was found to be increased relative to that in involved and normal skin, while immunoreactive IL-1 beta was found only in involved skin. A neutralization experiment showed that bioactive IL-1 was mostly attributable to IL-1 alpha. Uninvolved psoriatic skin also secreted higher amounts of both bioactive and immunoreactive IL-6 compared with involved skin. Immunoreactive GM-CSF was detected in uninvolved skin only. These cytokines detected in uninvolved skin may have been released from epidermal or mesenchymal cells, since uninvolved skin contained fewer inflammatory infiltrates. Our results offer additional evidence that increased amounts of inflammatory cytokines in uninvolved skin may provide a preliminary condition and play important roles in the initial events in the evolution of psoriatic lesions.
Adult↗
Cellular distribution of the aquaporins: a family of water channel proteins.
A group of transmembrane proteins that are related to the major intrinsic protein of lens fibers (MIP26) have been named "aquaporins" to reflect their role as water channels. These proteins are located at strategic membrane sites in a variety of epithelia, most of which have well-defined physiological functions in fluid absorption or secretion. However, some aquaporins have been localized in cell types where their role is at present unknown. Most of the aquaporins are delivered to the plasma membrane in a non-regulated (constitutive) fashion, but AQP2 enters the regulated exocytotic pathway and its membrane expression is controlled by the action of the antidiuretic hormone, vasopressin. These pathways of constitutive versus regulated delivery to the plasma membrane have been reconstituted in transfected LLC-PK1 epithelial cells, indicating that the information encoded within the protein sequence is sufficient to allow sorting of newly synthesized protein into distinct intracellular vesicles. Finally, different members of the aquaporin family can be targeted to apical, basolateral or both apical and basolateral plasma membrane domains of polarized epithelial cells. This implies that signals for the polarized targeting of these proteins also is located in non-homologous regions of these similar proteins. Thus, future investigations on the aquaporin family of proteins will provide important information not only on the physiology of membrane transport processes in many cell types, but also on the targeting and trafficking signals that allow proteins to enter distinct intracellular vesicular pathways in epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Increased receptor-mediated phospholipase D activation and Ca2+ mobilization in peritoneal polymorphonuclear leukocytes from streptozotocin-induced diabetic rats.
Phospholipase D activation was investigated in peritoneal polymorphonuclear leukocytes from streptozotocin-induced diabetic rats. Stimulation of the cells with formyl-Met-Leu-Phe resulted in a time- and dose-dependent increase in phosphatidylethanol in the presence of ethanol, and this lipid formation in cells prepared from diabetic rats was enhanced as compared to that in the case of nondiabetic rats. Furthermore, the increase in the intracellular Ca2+ concentration was also enhanced in the stimulated cells from diabetic rats. Under the present conditions, N-acetyl-beta-glucosaminidase release and superoxide generation, which are known to be dependent on phospholipase D activation, were higher in the cells from diabetic rats than those in the cells from control rats. However, there was no difference in the dissociation constant and the number of binding sites for formyl-Met-Leu-Phe between the cells from diabetic and control rats. Phosphatidylethanol formation, N-acetyl-beta-glucosaminidase release and superoxide generation in response to ionomycin or 4 beta-phorbol 12-myristate 13-acetate were not enhanced in diabetic rat cells, as compared with those in control rat cells. These results suggest that receptor-mediated phospholipase D activation and Ca2+ mobilization are enhanced in diabetic rat polymorphonuclear leukocytes, which might be due to acceleration of receptor-mediated signaling.
Acetylglucosaminidase↗
Endometrial oestrogen and progesterone receptors and their relationship to sonographic endometrial appearance.
The present study was undertaken to evaluate a possible relationship between the endometrial concentrations of oestrogen receptor (ER) or progesterone receptor (PR), and the sonographic appearance of human endometrium. Sonographic assessments and aspirations of the endometrium at the time of or prior to ovulation were made in 48 cycles of 45 infertile women. Endometrial patterns were classified as A, triple line pattern, or B, not triple line, on the basis of echogenicity. We did not find a correlation between ER or PR and serum oestradiol or endometrial thickness. Furthermore, serum oestradiol concentrations were not correlated with endometrial pattern or thickness. The only significant correlations were found between the concentrations of ER and PR in the pattern A endometrium (r = 0.80, P < 0.01) and in the pattern B endometrium (r = 0.49, P < 0.05). There were no differences in the mean concentrations of ER and PR despite differences in endometrial pattern and thickness. However, PR was measured at > 800 fmol/mg protein in 12 out of 38 pattern A endometria, while PR was < 800 fmol/mg protein in all pattern B endometria. These data suggest that high PR expression in the pre-ovulatory period is related to an adequate endometrial growth and thereby increases the responsiveness of the endometrium to progesterone stimulation after ovulation.
Buserelin↗