Biomedical subjects

H Shinkai

Publications and source records attributed to H Shinkai.

At least 73 records · Page 4Linked to original sources

PubMed1997

Gene expression of types I and III collagen, decorin, matrix metalloproteinases and tissue inhibitors of metalloproteinases in skin fibroblasts from patients with systemic sclerosis.

Cultured fibroblasts from patients with systemic sclerosis (SSc) and normal individuals were examined for gene expression of types I and III collagen, decorin, matrix metalloproteinases (MMP) MMP-1, MMP-2, and MMP-3, tissue inhibitors of metalloproteinases (TIMP) TIMP-1 and TIMP-2, urokinase- and tissue-type plasminogen activators (u-PA and t-PA). Fibroblasts from patients with early stage SSC (less than 1 year duration of disease) exhibited higher levels of types I and III procollagen, decorin, MMP-1, MMP-3, TIMP-1, and PAs than those from normal individuals. The gene expression of procollagen alpha 1(I) and TIMP-1 mRNAs were increased, but those of decorin, MMP-1, MMP-2, and MMP-3 were decreased, in fibroblasts from SSc patients with mid-stage SSc (2 to 4 years duration) as compared with those from normal individuals. In contrast, no significant difference in gene expression was found between fibroblasts from normal individuals and from patients with late-stage SSc (more than 6 years duration). These results suggest that gene expression of collagen, decorin, and degrading factors is dynamically modulated during fibrillogenesis. The responses of procollagen alpha 1(I) mRNA to IL-1 and TGF-beta were lower in fibroblasts from SSc patients with early and mid-stage disease, but not in those from patients with-late stage disease, than in control fibroblasts, which indicates that these cytokines may be involved in the earlier phases of fibrosis in SSc.

Adult↗

PubMed1997

Differential regulations of matrix metalloproteinases and tissue inhibitors of metalloproteinases in dermal fibroblasts by dibutyril cyclic AMP.

The influence of dibutyril cyclic AMP (dbcAMP) on the gene expression of matrix metalloproteinases (MMP)-1, MMP-2, MMP-3, tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was investigated in human skin fibroblasts by northern analyses. The treatment of dbcAMP increased MMP-1 and MMP-3 mRNA levels but decreased TIMP-1 mRNA levels in time and dose dependent manners. Procollagen alpha 1 (I), MMP-2 and TIMP-2 mRNA levels were unaltered by this reagent. Our data indicate that dbcAMP potentially enhances the degradation of extracellular components of connective tissue.

Bucladesine↗

PubMed1997

Gene expression of matrix metalloproteinase-1 (interstitial collagenase) and matrix metalloproteinase-3 (stromelysin-1) in basal cell carcinoma by in situ hybridization using chondroitin ABC lyase.

The gene expression of matrix metalloproteinase-1 and -3 was examined in basal cell carcinomas by in situ hybridization using digoxigenin-labelled riboprobes. Nodulo-ulcerative basal cell carcinomas demonstrated the gene expression for both metalloproteinases but superficial basal cell carcinomas did not present any transcripts for them. Transcripts for matrix metalloproteinase-1 (interstitial collagenase) were demonstrated densely in stromal cells among tumour masses, and those for matrix metalloproteinase-3 (stromelysin-1) were detected only in more advanced cases. Neither were expressed in tumour cells. The two metalloproteinases were produced by stromal cells according to the tumour invasion process, in which various growth factors, cytokines and inflammatory factors, which could regulate gene expressions of matrix metalloproteinases, were involved. It was also found that hybridization signals were enhanced by treatment with chondroitin ABC lyase, which digested abundant glycosaminoglycans in basal cell carcinoma. The procedure for the digestion is simple, and appears to be of value for in situ hybridization studies on tissues containing large amounts of glycosaminoglycans.

Basal Cell Carcinoma↗

PubMed1997

A novel mutation of a leucine residue in coil 1A of keratin 9 in epidermolytic palmoplantar keratoderma.

Keratin 9 mutation was examined in a Japanese kindred of epidermolytic palmoplantar keratoderma (EPPK), which is a dominantly inherited autosomal disorder of keratinization characterized by diffuse thickening of the palms and soles and by epidermolytic hyperkeratosis histologically. We report herein a novel mutation, a C --> G transversion at nucleotide position 541 that converts a leucine residue (CTC) to a valine (GTC) at codon 159. As in all other reported cases of keratin 9 mutation in EPPK, this mutation lies within the highly conserved coil 1A of the rod domain, which is considered to play a role in the correct alignment of the coiled-coil molecules.

Amino Acid Sequence↗

PubMed1997

Clear cell acanthoma developing in epidermal nevus.

A 33-year-old Japanese woman presented with a black papule on a pigmented lesion which had been on her right thigh since her early childhood. A hematoxylin-eosin-stained section revealed a sharply demarcated, acanthotic epidermis composed of enlarged clear cells, which stained positively for epithelial membrane antigen and negatively for carcinoembryonic antigen. With antikeratin antibodies, the tumor cells stained for AE1 and AE3, but did not stain for CAM5.2. They contained abundant glycogen. Histologically, we diagnosed the case as a clear cell acanthoma which developed in the pre-existing epidermal nevus. This is the second such case in the literature.

Adult↗

PubMed1997

A case of contact dermatitis due to sodium bisulfite in an ophthalmic solution.

We report a case of contact dermatitis due to sodium bisulfite in Tathion eye drops. A 72-year-old woman was treated daily with two solutions including Tathion eye drops for senile cataract for two years and three months. She developed edema, swelling, erythema, and vesicles on her eyelids. Because contact dermatitis due to a topical medication was suspected, patch testing was performed after disappearance of her eruption. A positive reaction to sodium bisulfite in Tathion eye drops was confirmed. Therefore, we diagnosed her eruption as contact dermatitis due to sodium bisulfite. The reaction to sodium sulfite in the next patch testing was negative. To the best of our knowledge, this is the first report from Japan about contact dermatitis caused by this medication.

Aged↗

PubMed1997

Alopecia areata associated with myasthenia gravis and thymoma: a case of alopecia with marked improvement following thymectomy and high level prednisolone administration.

A 57-year-old Japanese woman who suffered from alopecia areata associated with myasthenia gravis (MG) and thymoma responded well to thymectomy and high doses of glucocorticosteroid administration. Several treatments for alopecia areata including administration of systemic prednisolone were attempted, but loss of hair on the scalp progressed. After thymectomy and high level glucocorticosteroid administration for MG, the lesions on the scalp improved within four weeks. Consequently, we suggest that this thymectomy and high level glucocorticosteroid administration assisted in improving the immune dysfunction causing the alopecic lesions in this patient.

Alopecia Areata↗

PubMed1997

Immunoadsorption for the treatment of bullous pemphigoid.

We treated 2 intractable patients with pemphigoid by absorbent plasmapheresis using dextran sulfate conjugated cellulose columns with an automated regenerating unit. During a 2 week period, this plasmapheresis was performed 4 to 6 times for Cases 1 and 2, respectively. Clinical findings including skin eruptions were remarkably improved, and the titers of antibasement membrane zone antibodies were decreased after the treatment of 1.8 to 4.2 L of plasma. These results suggest that the absorbent column is effective for intractable pemphigoid.

Aged↗

PubMed1996

Comparative pharmacokinetics of KRN8602, a new morpholino anthracycline, and adriamycin in tumor-bearing mice.

It has been reported that KRN8602 shows antitumor effects similar or superior to those of Adriamycin (ADM) against several murine and human cell lines and has been found to be effective against multidrug resistant tumor cells. We investigated the pharmacokinetics of KRN8602, a new morpholino anthracycline, in comparison with ADM in mice bearing colon26 adenocarcinoma. After intravenous administration, both drugs disappeared triexponentially from the plasma and KRN8602 was eliminated faster than ADM. The rate of elimination of KRN8602 from tissues was also faster than than of ADM. The relative order of the area under the curve (AUC) of KRN8602 was spleen > tumor > small intestine > lung > kidney > heart > liver > brain > plasma, while that of ADM was spleen > kidney > lung > liver > heart > small intestine > tumor > plasma. ADM was not detectable in the brain. The AUC of KRN8602 was higher than that of ADM in the tumor and brain, but it was lower in other tissues. The tissue-to-plasma concentration ratio (KPapp) of KRN8602 was higher than that of ADM in the tumor, spleen, small intestine and brain. KRN8602 was metabolized to several metabolites. The concentrations of M1 and M2 (glycoside-type metabolites) was relatively high in the spleen. M3 (aglycone-type metabolite) showed a very high AUC ratio in the liver (34%). In tumor, M1 and M2 concentrations were low and M3 was not detected. KRN8602 had a greater activity than ADM and M2 had a cytotoxic activity similar to KRN8602 against colon26 cells in an MTT assay. These results suggest that the strong antitumor effect of KRN8602 against colon26 is due not only to its strong cytotoxic activity but also to its marked transferability into tumors. KRN8602 shows better selective toxicity than ADM, because KRN8602 is more selective for tumors than ADM and less is transferred to normal tissues.

Adenocarcinoma↗

PubMed1996

Purification and structural analysis of extracellular matrix of a skin tumor from a patient with juvenile hyaline fibromatosis.

Juvenile hyaline fibromatosis is a rare mesenchymal dysplasia that is inherited in an autosomal recessive fashion. The histological features of the tumor-like lesions are characterized by the deposition of amorphous hyaline material in the extracellular spaces of the dermis and soft tissues. We have analyzed the hyaline substance in a specimen of a skin tumor obtained from a 4-year-old Japanese girl with juvenile hyaline fibromatosis. It was found to consist mainly of type VI collagen; a small amount of type I collagen was also present. These components were separated by DEAE-cellulose ion-exchange chromatography under reducing conditions. The ratio of the dry weights of type I and type VI collagen was 1:4. Of the three chains of type VI collagen (alpha 1(VI), alpha 2(VI) and alpha 3(VI)), alpha 3(VI) was the most abundant. Glycosaminoglycans in the tumor tissue comprised dermatan sulfate, chondroitin sulfate and hyaluronan, with dermatan sulfate predominating. In contrast, hyaluronan is the most abundant in normal skin.

Amino Acid Sequence↗

PubMed1996

Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein.

BACKGROUND: The significance of preserving the spleen has recently been shown. However, there are few reports of spleen-preserving distal pancreatectomy for lesions of the body and tail of the pancreas, and this procedure is not generally performed. The aim of this study was to clarify the technique and indications for spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for benign lesions of the distal pancreas. METHODS: Four patients (two each with an endocrine tumor and a cystic lesion) underwent the procedure. We also performed the spleen-preserving Puestow's procedure with removal of the tail of the pancreas in a 22-year-old male patient with familial chronic pancreatitis. An important technique is to remove the splenic vein from the pancreas from the body of the pancreas toward the spleen and to remove the splenic artery from the pancreas in the other direction. The splenic vein is identified behind the pancreas and within the thin connective tissue membrane, which is cut longitudinally above the splenic vein. It is important to remove the splenic vein from the pancreas from the body of the pancreas toward the spleen, because it is very difficult to remove it in the other direction. There are many branches from the splenic vein on both sides; these branches should be carefully ligated and cut. The pancreas is removed from the splenic artery from the spleen toward the head of the pancreas. This procedure is much easier than removal of the pancreas from the vein. RESULTS: The postoperative course was uneventful in four of the five patients. A pancreatic fistula remained in one patient for several weeks. The mean and standard deviation of the operative blood loss, the duration of the operation, and the postoperative hospital stay in the four uneventful cases, excluding the one in which Puestow's procedure was performed, were 600 +/- 479 ml, 290 +/- 48 minutes, and 40 +/- 21 days, respectively. No severe complications occurred in any of the five patients. CONCLUSIONS: Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein is easy and safe and should be performed for benign lesions of the distal pancreas.

Adult↗

PubMed1996

Extracellular matrix 22-kDa protein interacts with decorin core protein and is expressed in cutaneous fibrosis.

A protein with an Mr of 22,000 was purified from bovine dermis. The amino acid sequence of the protein was identical to 22-kDa protein [Neame, P.J. et al. (1989) J. Biol. Chem. 264, 5474-5479] and showed highly homologous sequences to TRAMP (tyrosine rich acidic matrix protein) [Cronshaw, A.D. et al. (1993) Matrix 13, 255-266] and dermatopontin [Superti-Furga, A. et al. (1993) Genomics 17, 463-467]. The protein was proved to associate with decorin and a modified decorin with carboxymethylated cysteinyl residues, but not to assemble to hyaluronate or dermatan sulfate chains. The pyridylethylation of cysteinyl residues in the 22-kDa protein did not affect its binding activity to decorin or modified decorin. Immunohistochemical analyses revealed positive stains in endothelial cells and the periphery of collagen fibers in normal dermis but not in the fibroblasts in tissue. Collagen fibers in sclerotic regions of progressive systemic sclerosis were stained diffusely, suggesting that the 22-kDa protein increases in parallel to the accumulation of collagen in the disease. Western blotting analyses of extracts of cultured endothelial cells revealed a lower Mr protein than that from cultured fibroblasts, suggesting the presence of a molecule related to the 22-kDa protein.

Amino Acid Sequence↗

PubMed1996

Identification of a 450-kDa human epidermal autoantigen as a new member of the plectin family.

The serum from an individual with a subepidermal blistering disease was previously shown to recognized a 450-kDa epidermal autoantigen. The molecular structure of this antigen was investigated by screening a human keratinocyte cDNA library with the patient's serum. One clone, with a 276-bp cDNA insert, that encoded an epitope recognized by the serum was isolated. Rabbit polyclonal antibodies that were prepared against the corresponding fusion protein recognized the 450-kDa epidermal antigen and stained the basal keratinocytes in human epidermis. This clone was used for further screening of the original keratinocyte and HeLa cell cDNA libraries. Two different, but closely related, 0.8- and 2.0-kb cDNAs were isolated, and their deduced amino acid sequences indicated that the encoded proteins belonged to the plectin family. Northern blot analysis of total RNA from human keratinocytes with these cDNA inserts as probes detected RNAs of approximately 12-13 kb. The 0.8-kb cDNA hybridized to polyadenylated RNA species from human skeletal muscle, heart, lung, and kidney, whereas the 2.0-kb cDNA hybridized to transcripts present only in kidney and lung. Southern blot analysis of genomic DNA from the human placenta revealed similar, but not identical, patterns of hybridization with the 0.8- and 2.0-kb cDNAs. Data suggest that the 0.8- and 2.0-kb cDNAs encode two different proteins but are derived from the same gene.

Amino Acid Sequence↗

PubMed1996

Epidemiological analysis of prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc). Scleroderma Research Committee Japan.

For the first time, we performed an epidemiological study of SSc in Japan to study the factors influencing prognosis, survival rate and cause of death of Japanese SSc patients and to compare our data with those from foreign countries. Prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc) was analyzed based on clinical data described in case cards provided by the members of the Scleroderma Research Committee of the Japanese Ministry of Health and Welfare. The essential observation period was from 5 to 20 years, at ending in 1994. Ninety patients died (males 11, females 79). The age of onset of the deceased patients was significantly higher than that of surviving patients (deceased, 45.6 yrs, surviving 41.3 yrs). Statistically significant factors for a poor prognosis were as follows: Barnett type III > type II > type I, positive for anti-Scl-70 antibody, negative for anti-centromere antibody. The survival rate at 5 years after the onset of the disease was 0.937, followed by 0.82 at 10 years, 0.567 at 20 years and 0.40 at 30 years after the onset. Sex was not a predictor for prognosis, although male patients died at an earlier stage of the disease. The most common causes of death were heart failure, pulmonary insufficiency, lung fibrosis, and renal failure. Twenty-four patients had cancer of which 13 were lung cancers. The current status of the survival rate and prognostic factors of 496 Japanese SSc patients is summarized. In future, more well-controlled studies using the same criteria should be performed for the better understanding and management of SSc.

Adult↗

PubMed1996

A case of drug eruption due to simultaneous sensitization with three different kinds of drugs.

We reported a case of drug eruption induced by combined treatment with three different kinds of drugs, amoxapine, mexiletine hydrochloride and cefaclor. A 63-year-old Japanese woman suffering from 11 years of standing reflex sympathetic dystrophy developed multiple erythematous papules on her trunk and extremities after taking 14 kinds of drugs. The provocation challenge produced positive reactions to amoxapine, mexiletine hydrochloride, and cefaclor, but was negative to the other drugs. We discussed the mechanism of simultaneous sensitization to three different kinds of drugs in our case.

Amoxapine↗

PubMed1996

Successful treatment with topical PUVA of nodular cutaneous plasmacytosis associated with alopecia of the scalp.

We obtained a successful response to PUVA therapy in a 51-year-old Japanese man who had multiple nodules of the trunk, extremities and scalp along with polyclonal hypergammaglobulinaemia; the scalp lesions were associated with extensive alopecia. Examination of skin biopsies showed a dense infiltrate of mature plasma cells in the dermis and hair follicles; no systemic disease or functional involvement of other organs was detected. The clinical and histological findings were compatible with cutaneous plasmacytosis and treatment with topical PUVA gradually reduced the size and number of the lesions.

Alopecia↗

PubMed1995

Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid receptor agonist.

Various purified lipoxygenases were incubated with [14C]arachidonylethanolamide which is an endogenous ligand for cannabinoid receptors. When radioactive products were analyzed by thin-layer chromatography, porcine leukocyte 12-lipoxygenase and rabbit reticulocyte and soybean 15-lipoxygenases produced polar compounds at about the same reaction rates as that of oxygenation of free arachidonic acid. In contrast, the reaction of human platelet 12-lipoxygenase proceeded at a much lower rate, and porcine leukocyte 5-lipoxygenase was totally inactive. The result indicated that the lipoxygenases, which had been shown previously to be capable of oxygenating esterified polyunsaturated fatty acids, were also active with the arachidonylethanolamide. High-performance liquid chromatography, ultraviolet and mass spectrometry and nuclear magnetic resonance spectroscopy identified the major product by leukocyte 12-lipoxygenase as 12-hydroperoxy-5,8,10,14-eicosatetraenoylethanolamide and that by 15-lipoxygenases as 15-hydroperoxy-5,8,11,13-eicosatetraenoylethanolamide. The 15-hydroxy derivative inhibited electrically-evoked contraction of mouse vas deferens with an IC50 of 0.63 microM as well as arachidonylethanolamide (0.17 microM), but the 12-hydroxy derivative was much less effective.

Animals↗

PubMed1995

Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum: the first case report from Japan.

We report a case of lymphocutaneous syndrome caused by Nocardia otitidiscaviarum (formerly known as N. caviae) in a 78-year-old woman who underwent long-term therapy with prednisolone for bronchial asthma. Histological examination showed granulomatous reaction with multiple polymorphonuclear leukocytes and revealed a Gram positive filament in the dermis. Gram-positive, slightly acid-fast branched filaments were also found in the smear of the purulent material. The cell wall constituents of the isolate were meso-diaminopimelic acid, arabinose, and galactose; the mycolic acid pattern of the isolate was Nocardia type. The organism decomposed xanthine and hypoxanthine, but not tyrosine or casein, which distinguished it from N. asteroides and N. brasiliensis. The skin lesions responded to minocycline and later to a combination of doxycycline and ofloxacin. This primary lymphocutaneous nocardiosis due to N. otitidiseaviarum is the first in Japan.

Aged↗