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Biomedical subjects

M Ohkido

Publications and source records attributed to M Ohkido.

At least 37 records · Page 2Linked to original sources

Genetic polymorphisms in the keratin-like S gene within the human major histocompatibility complex and association analysis on the susceptibility to psoriasis vulgaris.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. However, it has not yet been clarified if the HLA-Cw6 and Cw7 genes themselves are the susceptible gene related to this disease or if it is some other non-HLA gene in a linkage disequilibrium with these HLA-C alleles. The S gene, recently identified in the HLA class I region 160 kb telomeric of HLA-C, encodes a keratin-like protein and is expressed specifically in the granular layer of the epidermis. Therefore, it is tempting to speculate that the S gene is one of the strong candidate genes responsible for the pathogenesis of psoriasis vulgaris. Direct sequencing of the first and second exon of the S gene after polymerase chain reaction (PCR) amplification has allowed the identification of two diallelic polymorphic sites in exon I and seven diallelic polymorphic sites in exon 2, three among which result in amino acid exchanges, a Ser-Phe substitution at amino acid position 186, a Gly-Val substitution at position 393 and a Ser-Leu substitution at position 394. No significant difference in the dimorphic distributions of the S gene was observed between the patients with psoriasis vulgaris and healthy controls, suggesting that the susceptible gene for psoriasis is not the S gene itself.

Disease Susceptibility↗

[Multiple eccrine spiradenoma. Histological association with dermal cylindroma].

A case of multiple eccrine spiradenomata is reported. One of the tumours was histopathologically associated with dermal cylindroma, and immunohistochemical studies showed that the cylindroma cells differentiate towards the secreting portion of the eccrine sweat gland. The relationship among multiple eccrine spiradenomata, dermal cylindroma and multiple trichoepitheliomata is discussed.

Adenoma↗

Female sex hormone stimulates cultured human keratinocyte proliferation and its RNA- and protein-synthetic activities.

The present study was carried out to assess the effect of female sex hormones, i.e., estrogen and progesterone, on human keratinocyte proliferation, and its RNA- and protein-synthetic activities in a culture system. The presence of receptors for estrogen and progesterone and their messenger ribonucleic acids (mRNAs) in the cultured cells was also investigated. Human keratinocytes were cultured in the experimental DMEM-Ham's F12 medium containing various concentrations of estrogen or progesterone, which was followed by determining cell yields and [3H]thymidine incorporation. The keratinocytes were also tested for RNA- and protein-synthetic activities by measuring [3H]uridine and [3H]leucine incorporation. Both estrogen and progesterone receptors were determined by the enzyme immunoassay method using monoclonal antibodies, and mRNA expression for these hormone receptors was detected by in situ hybridization. Cell yields and [3H]thymidine incorporation increased gradually until 3 x 10(-10) M of both estrogen and progesterone, decreased thereafter until 3 x 10(-7) M, and peaked at 3 x 10(-10) M. [3H]Uridine and [3H]leucine uptake followed almost the same pattern as the cell proliferation, peaking at 3 x 10(-10) M of both hormones. Small amounts of estrogen and progesterone receptors were present in the cultured cells, and their mRNAs were found to be present in the cell cytoplasm. These results clearly suggest that sex hormones play an important role in human keratinocyte proliferation, and its RNA- and protein-synthetic activities, at least in part, via their hormone receptors.

Cell Division↗

Iontophoresis for enhancing penetration of dermatologic and antiviral drugs.

Iontophoresis is the process of introducing ionic drugs into the body for therapeutic purposes. Although iontophoresis has the potential for systemic therapy, it has mainly been used for local therapy at body surfaces. Many ionic drugs are available including lidocaine, epinephrine, methylprednisolone succinate, dexamethasone phosphate, several antivirals, various antibiotics, and other specific drugs. The use of an indicated ionic drug by iontophoresis offers a broad potential for promoting the development of more effective therapies in dermatology. Iontophoresis of ionized drugs provided a 20-60 fold increase in penetration over topical application. Iontophoresis for dermatological use requires that: a) a charged drug be placed at an electrode having a polarity the same charge as the drug, b) the condition or disease under treatment be at or near the body surface, and c) a modern, sophisticated source of direct current, with appropriate accessories, be used. The current source must have features that make it not only effective, but also safe for application to the patient. Modern systems for application of drugs by iontophoresis have features that make the process simple and efficient for use in practice. Iontophoresis has a long history of use, having been suggested for various therapies for many years in medicine, physical therapy and dentistry. Pilocarpine iontophoresis is a preferred method for cystic fibrosis detection. Also, lidocaine iontophoresis has been advocated to anesthetize the tympanic membrane before myringotomy. Anesthesia of the skin to a depth of 1.0 cm or more has been reported in double-blind studies of human volunteers. Local anesthesia by iontophoresis was reported to be effective for: 1) cutaneous cutdowns in patients requiring kidney dialysis, 2) delicate eyelid surgery, as the sole anesthetic, 3) preinjection topical anesthesia, and 4) shave biopsies of skin lesions. The use of iontophoresis for treating difficult cases of hyperhydrosis is quite popular among dermatologists. The present report emphasizes uses of iontophoresis in dermatology and is divided into discussion of studies using iontophoresis for postherpetic neuralgia, local anesthesia, antiviral therapy, and for corticosteroid therapy of nonspecific inflammatory lesions. Over 1250 patients have been treated for postherpetic neuralgia by corticosteroid iontophoresis at 6 medical centers with 60-80% of patients showing a major therapeutic response with return to a tolerable pain level. Double-blind studies of varicella zoster (active and postherpetic) and herpes simplex have proven that iontophoresis is a valuable modality for treating viral diseases of the skin. Many other uses for iontophoresis have been proposed in the literature that involve several hundred research papers, several textbooks and many book chapters. Review of the literature supports the concept that iontophoresis provides an optimal method for drug application in therapy of surface tissues.

Antiviral Agents↗

Ubiquitinated cytokeratin inclusions in lichen amyloidosus: an immunohistochemical analysis.

Eosinophilic hyaline inclusions were consistently seen in the perinuclear cytoplasm of suprabasal keratinocytes in lichen amyloidosus. The inclusions, negative with amyloid staining, were immunoreactive for ubiquitin and cytokeratin, and ultrastructurally showed aggregations of fine filaments of two sizes (central thin and peripheral thick). The thin filaments were the main component in the upper epidermal layer. Four monoclonal antibodies (AE1, AE3, KL1 and CAM5.2) and one antiserum (WSS) were used for characterizing cytokeratin expression. The AE1 antibody normally stained the basal cells, but in lichen amyloidosus basal staining mostly disappeared. Instead, groups of suprabasal keratinocytes were labeled, with AE1-reactive inclusions distributed therein. In contrast, the KL1 antibody, showing suprabasal staining, failed to react with the inclusions. The inclusions were weakly reactive with the AE3 and WSS antibodies, which stained all keratinocytes. The CAM5.2 antibody was unreactive. The subepidermal amyloid deposits were negative with all the antibodies. The inclusions were ubiquitinated especially in the granular layer. Immunoelectron microscopy disclosed that ubiquitin was more densely localized in the thin filaments than in the thick ones. This indicated that cytokeratin expression and metabolism are altered in the affected epidermis, and that ubiquitin functions in the process of degradation of abnormal cytokeratin filaments.

Adolescent↗

Anaphylactoid purpura with intestinal perforation: report of a case and review of the Japanese literature.

A 78 year old man suffering from anaphylactoid purpura complained of abdominal pain and bloody stools. Combined therapy with Prednisolone and cyclophosphamide had been given against nephrotic syndrome caused by purpura nephritis. Severe abdominal pain with symptoms and signs of pan-peritonitis necessitated laparotomy. Rectosigmoid perforation due to necrotizing angiitis (phlebitis) was also demonstrated histologically. The patient died of septicemia 18 days after surgery. Perforation of the alimentary tract rarely occurs in anaphylactoid purpura. Twenty similar cases were briefly reviewed from the Japanese literature.

Aged↗

Progressive facial hemiatrophy with localized scleroderma.

A 46-year-old woman who presented with progressive facial hemiatrophy (PFH) following localized scleroderma is described. The patient had a markedly deformed and depressed plaque surrounded by erythema on the right cheek. She also showed linear scleroderma with hair loss on the occipital area and morphea lesions on the neck and shoulder. Histological findings of the facial and other atrophic lesions were consistent with localized scleroderma. Therefore, the PFH and localized scleroderma may have had the same pathological background in this case.

Facial Hemiatrophy↗

[A case of psoriatic arthropathy complicated with clinical feature of ankylosing spondylitis].

UNLABELLED: A 25 years old man with psoriatic arthropathy complicated with clinical feature of ankylosing spondylitis was reported. 230 Japanese cases of psoriatic arthropathy were discussed. RESULT: 1) commoner in male 2) the cases that skin lesions were prior to arthritis and the cases that arthritis was prior to skin lesions were almost the same number 3) rheumatoid factor was seropositive in 17% of the cases 4) HLA-B27 was present in 9 of 50 cases and 7 of these 9 cases had central type arthritis 5) the cases had accompanied nail dystrophies in a high rate 6) concerning on skin lesion, many cases had atypical psoriatic lesion 7) 21.1% of the cases had central type arthritis 8) there were no certain effective therapy 9) prognosis of central type cases were relatively worse.

Adult↗

Possible involvement of oxidation of lipids in inducing griseofulvin photosensitivity.

Griseofulvin-sensitized photo-oxidation of lipids was examined in vitro. Iodometric determination and thiobarbituric acid assay proved peroxidation of squalene, cholesterol and red blood cell membrane lipids by UVA irradiation in the presence of griseofulvin. Simultaneous progression of Type I (non-singlet oxygen) and Type II (singlet oxygen) processes is likely because the oxidation products of cholesterol through both processes were identified by thin layer chromatography. These results suggest that lipids, especially membrane lipids, are one of the possible targets for induction of griseofulvin photosensitivity.

Cholesterol↗

Pigmented dermatofibrosarcoma protuberans (Bednár tumor). An autopsy case with systemic metastasis.

An autopsy case of pigmented dermatofibrosarcoma protuberans (Bednár tumor) with systemic metastasis is reported. No previous example of this tumor showing widespread metastasis has been reported in the literature. The patient, a 45-year-old man, developed a tumor on the right upper arm. The tumor recurred twice and metastasized to other parts of the skin, lungs and brain during the 8-year clinical course. The primary tumor contained melanin-laden tumor cells and showed a storiform growth pattern. Autopsy confirmed multiple metastatic lesions in the skin, lungs, brain, thyroid, pancreas, stomach, small intestine and thigh muscles. The recurrent and metastatic tumors lacked both melanin production and the storiform arrangement, and instead revealed "fibro-sarcomatous" change with a herring-bone or interlacing pattern of growth.

Adult↗

Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris.

In psoriasis vulgaris, the HLA class I Cw6 specificity has previously been recognized as the most commonly associated antigen serologically. This study was carried out to investigate whether or not the gene controlling the susceptibility to psoriasis vulgaris existed on the HLA, especially the HLA-C region. At first, we analyzed the restriction fragment length polymorphism (RFLP) of 13 patients with psoriasis vulgaris and 6 healthy controls who were all positive for at least one allele of HLA-Cw6. To characterize RFLP in psoriasis patients who did not have HLA-Cw6, 12 patients and 10 healthy controls who had HLA-Cw7 were also examined. Southern hybridization of genomic DNA demonstrated that DNA polymorphisms of the HLA-C antigen gene could not be found in any psoriasis vulgaris patient whether HLA-Cw6 or Cw7. However, a 4.5 kb BamHI fragment and a 3.1 kb PstI fragment were lacking in some healthy controls who had either HLA-Cw6 or Cw7. This study suggests that the presence of RFLP in the HLA-C gene is associated with psoriasis vulgaris. These specific fragments may help predispose individuals to psoriasis vulgaris, or may be essential for the development of the disease.

DNA↗

Chlorpromazine-sensitized photooxidation of squalene.

In connection with chlorpromazine-induced skin photosensitivity, chlorpromazine-sensitized photooxidation of squalene was studied in vitro. When squalene (in ethanolic solution or in an aqueous suspension) was irradiated with UV-A light in the presence of chlorpromazine, the yield of peroxidation products was greatly increased. Lines of evidence for the peroxidation were obtained by the iodometric determination and the thiobarbituric-acid method. Gas chromatography indicated that squalene was decomposed by the photosensitized reaction and the remaining amount was decreased exponentially with increasing fluence. The quenching effects of NaN3 and 2,5-dimethylfuran and the enhancing effect of D2O showed participation of singlet oxygen in the photosensitized reaction.

Chlorpromazine↗

Lipid peroxidative potency of photosensitized thiazide diuretics.

We examined the lipid peroxidative potency and photohemolytic activity of thiazide diuretics, especially penflutizide (PFZ), to determine the molecular mechanism of thiazide phototoxicity. Ultraviolet A irradiation of squalene in the presence of PFZ, hydrochlorothiazide, methiclothiazide, benzylhydrochlorothiazide, or trichlormethiazide induced in vitro peroxidation as measured by production of the hydroperoxides and thiobarbituric acid-reactive substances. Among the thiazides, PFZ showed the highest potency to photooxidize lipids. PFZ-photosensitized peroxidation of squalene was repressed by the presence of sodium azide or 2,5-dimethylfuran and was accelerated in a D2O suspension. These findings suggest the participation of singlet oxygen in PFZ photoperoxidation of squalene (type II mechanism). PFZ-photosensitized lysis of red blood cells (RBC) accompanied by formation of hydroperoxides in RBC membrane lipids was also noted. These results suggest that membrane lipids can be one of the target molecules of thiazide phototoxicity.

Benzothiadiazines↗