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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 541 records · Page 30Linked to original sources
PubMed1998

Gene expression of mouse S100A3, a cysteine-rich calcium-binding protein, in developing hair follicle.

We have previously identified a cysteine-rich calcium binding protein S100A3 present in the cuticle of human hair fiber. In this study, we cloned a cDNA for mouse S100A3, identified its gene location, and elucidated the expression profile throughout hair follicle development. The mouse S100A3 gene was clustered with other S100 family members on chromosome 3, and specifically expressed in dorsal skin containing hair follicles. The level of S100A3 mRNA was elevated during the anagen phase of the hair growth cycle, and sharply declined from the regression phase on. In situ hybridization revealed that the S100A3 gene was prominently expressed in cuticular cells of the hair follicle, and mRNA levels were highest in the keratogenous zone over the entire cuticular layer. Expression was also observed to a lesser extent in differentiated cortical cells; however, expression was not observed in any other component of the hair follicle or dorsal tissues. Immunohistochemical analysis showed that the S100A3 protein accumulated in cuticular and cortical cells undergoing terminal differentiation. These results indicate that the S100A3 gene is exclusively expressed, and the translation product retained, in follicular cells differentiating into major components of the hair shaft. It seems likely that S100A3 plays an important role in calcium-dependent processes leading to hair shaft formation.

Amino Acid Sequence↗
PubMed1998

A case of congenital mumps infection complicated with persistent pulmonary hypertension.

A low-birth-weight female baby was admitted with respiratory distress after birth. Her mother had been diagnosed with mumps 4 weeks and 5 days prior to delivery. Mumps IgM antibody was elevated in the neonate and mumps virus ribonucleic acid was detected in the umbilical cord blood by reverse transcription-polymerase chain reaction. The perinatal virus infection was complicated with persistent pulmonary hypertension of the newborn and pulmonary hemorrhage. Successful treatment included the use of high frequency oscillation ventilation together with the administration of artificial surfactant.

Antibodies, Viral↗
PubMed1998

Changes in tissue oxygen tension caused by contrast media injected into the femoral artery of the dog.

PURPOSE: To document changes in tissue oxygen tension as measured directly in an area perfused with contrast medium. MATERIAL AND METHODS: Changes in tissue oxygen tension in response to the injection of ionic and non-ionic contrast media into the femoral arteries were measured in the femoral adductor (proximal) and gastrocnemius (distal) muscles of 8 dogs. Amidotrizoic-acid and iopamidol were injected in two different iodine concentrations (370 mg I/ml and 185 mg I/ml respectively) and tissue oxygen tension in the proximal and distal muscles was monitored continuously using polarographic needle electrodes. RESULTS AND CONCLUSION: A transient decrease and subsequent increase of muscle tissue oxygen tension were observed after the injection. The extent of these changes depended on the concentration and osmolality of the medium. To minimize changes in peripheral tissue oxygen tension, contrast media with low osmolality and low concentration are recommended for femoral angiography.

Angiography↗
PubMed1998

Requirement for p56(lck) tyrosine kinase activation in Th subset differentiation.

The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented with regard to its role in regulating T cell activation and thymocyte development through delivery of signals via the mature alphabeta TCR as well as the pre-TCR. Little is known, however, about the role of Lck in Th cell subset differentiation in the periphery. Here, we assess the requirement for tyrosine kinase activation of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck (DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that directs high expression in mature T cells, in which splenic CD4 T cells developed normally. This Tg mouse provides a good experimental model system to investigate the roles of Lck in mature T cell function in vivo. We show that the catalytically inactive Lck protein at about twice-normal concentrations inhibits Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of the other T cell subset, Th1, intact. These data indicate a requirement for Lck activity in Th2 cell differentiation, and a differential dependence for Lck activity between Th2 and Th1 cell differentiation.

Amino Acid Sequence↗
PubMed1998

Secretory leukocyte protease inhibitor (SLP) concentrations in seminal plasma: SLPI restores sperm motility reduced by elastase.

In this study, we quantified secretory leukocyte protease inhibitor (SLPI) and elastase in ejaculates from normal donors and infertile patients with or without leukospermia and investigated the effect of SLPI on sperm motility reduced by elastase. Western blot analysis revealed that SLPI protein was detected in the seminal plasma. The SLPI titre in the seminal plasma with leukospermia was lower than that in the seminal plasma without leukospermia and in the seminal plasma of fertile donors. The elastase concentration in the seminal plasma with leukospermia was significantly higher than that in the seminal plasma without leukospermia. A significant correlation between SLPI and elastase concentrations in the seminal plasma (r = 0.36, P< 0.01) was observed. There was a positive correlation between SLPI titre in the seminal plasma and sperm motility (r = 0.51, P < 0.001). SLPI recovered the sperm motility reduced by elastase in a dose-dependent manner. Our results suggest that SLPI is a potential substance to treat infertile patients with leukospermia.

Adult↗
PubMed1998

Time course of a new ultrashort-acting beta-adrenoceptor-blocking drug, ONO-1101: comparison with those of esmolol and propranolol by using the canine isolated, blood-perfused heart preparations.

Time courses of beta-adrenoceptor-blocking actions of ONO-1101, a new cardioselective beta-blocker, were compared with those of esmolol and propranolol by using the isolated, blood-perfused sinoatrial node (SAN) and papillary muscle (PM) preparations of dogs. ONO-1101 per se given intraarterially (i.a.) in each nutrient artery did not affect basal sinoatrial rates (SARs; 99 +/- 2 beats/min, n = 7) in the SAN and developed tension (DT; 3.2 +/- 0.7 g, n = 7) of the PM preparations. Norepinephrine (NE) injected i.a. into the each artery induced increases in SAR (42 +/- 6 beats/min at 0.051 +/- 0.014 microg) and PMDT (2.9 +/- 0.4 g at 0.048 +/- 0.011 microg). The i.a. injections of NE were repeated every 3 min after i.v. bolus injections of ONO- 1101 into the support dog. NE-induced increases in SAR and PMDT were maximally inhibited 3 to 6 min after the i.v. injections of ONO-1101. Maximal percentage inhibitions by ONO-1101 of NE-induced increases in SAR were 54 +/- 6, 78 +/- 3, and 96 +/- 2% at 0.01, 0.1, and 1 mg/kg of the drug, respectively. Similarly, maximal percentage inhibitions by ONO-1101 of NE-induced increases in PMDT were 50 +/- 12, 93 +/- 2, and 100% +/- 0, respectively. The inhibition was quickly recovered; times required for 50% recovery (RT1/2) were 12 +/- 3. 17 +/- 3, and 32 +/- 10 min in the SAN preparation, and 13 +/- 3, 16 +/- 2, and 39 +/- 11 min in the PM preparations, after i.v. injections of 0.01, 0.1, and 1 mg/kg of ONO-1101, respectively. In comparison, maximal percentage inhibitions by esmolol of NE-induced increases in SAR were 45 +/- 5, 79 +/- 6, and 96 +/- 2%, and those in PMDT were 34 +/- 4, 75 +/- 5, and 97 +/- 1%, whereas the RT1/2 values were 11 +/- 2, 15 +/- 4, and 40 +/- 12 min in the SAN preparation, and 10 +/- 2, 16 +/- 7, and 27 +/- 6 min in the PM preparations, after i.v. injections of 0.01, 0.1, and 1 mg/kg of esmolol, respectively. In contrast, the maximal percentage inhibitions by an i.v. bolus injection of 0.1 mg/kg of propranolol of NE-induced increases in SAR and PMDT were 77 +/- 18% and 87 +/- 13% (n = 4). respectively. The maximal inhibitions were obtained 6-15 min after injections of propranolol and then slowly recovered only by 21% in the SAN and 8% in the PM preparations, even after 60 min. These results clearly demonstrate that ONO-1101 is an ultrashort-acting beta-blocker, but the recovery time is dose dependent, and that the beta-blocking action of ONO-1101 is almost similar to or slightly more potent (or both) than esmolol.

Adrenergic beta-Antagonists↗
PubMed1998

Antiarrhythmic effects of a novel class III drug, KCB-328, on canine ventricular arrhythmia models.

KCB-328 is a newly synthesized class III drug. To determine whether this drug has antiarrhythmic or proarrhythmic effects, we used canine ventricular arrhythmia models induced by coronary ligation and reperfusion, programmed electrical stimulation (PES), two-stage coronary ligation, digitalis, or epinephrine. KCB-328, in an intravenous infusion of 0.5 mg/kg/30 min, prolonged the QTc interval only 11%, but had antiarrhythmic effects on the reentry arrhythmias induced by PES (12 of 12 dogs with old myocardial infarction; p < 0.05). KCB-328, in an infusion of 1 mg/kg/h, suppressed the occurrence of fatal ventricular fibrillation (VF) induced by coronary ligation and reperfusion under either halothane anesthesia (p < 0.05) or pentobarbital anesthesia (p < 0.05). Under the halothane anesthesia, KCB-328 alone showed proarrhythmic effects [i.e., induction of ventricular premature contractions (VPCs)], but it did not induce a more severe effect such as torsades de pointes-type ventricular tachycardia (VT). In addition, KCB-328 had weak antiarrhythmic effects on the automaticity arrhythmias induced by 24-h coronary ligation but was effective neither on 48-h coronary ligation arrhythmias nor on the digitalis- and epinephrine-induced arrhythmias. Our results indicate that KCB-328 has powerful antiarrhythmic effects with fewer proarrhythmic potencies.

Animals↗
PubMed1998

Spiny keratoderma: a common under-reported dermatosis.

Spiny keratoderma is a dermatosis consisting of multiple projections located on the palms and soles, with a distinct histology characteristic of a parakeratotic column above a hypogranular epidermis. We report six cases discovered within a year and review the present literature on spiny keratoderma. The average age of the patients was 57 years. Fifty-seven percent of the patients were male and forty-three percent were female. The duration of lesions ranged from 4 months to 40 years. Symptoms were variable, however, lesions were often unnoticed by the patient. The location of the lesions involved the palms and soles or the palms alone. Past medical history was significant for hypertension and hyperlipidemia treated with HMG-CoA reductase inhibitors. Lesions often occurred in patients involved in manual labor. Spiny keratoderma is a relatively common under-reported dermatosis found most often in older patients with history of manual labor and is possibly related to treatment with HMG-CoA reductase inhibitors.

Adult↗
PubMed1998

Staining of eccrine and apocrine neoplasms and metastatic adenocarcinoma with IKH-4, a monoclonal antibody specific for the eccrine gland.

The histogenesis of apocrine and eccrine neoplasms has always interested dermatopathologists. In addition, the histologic differential diagnosis of eccrine carcinoma from metastatic adenocarcinoma is of practical importance. We describe a novel monoclonal antibody IKH-4 which stains the eccrine secretory coil, but not the apocrine secretory segment. Positive staining was observed in eccrine hidradenoma, eccrine poroma, eccrine spiradenoma, papillary eccrine adenoma, eccrine hidrocystoma, syringoma, eccrine carcinoma, and in 1 case of syringocystadenoma papilliferum. Negative staining was observed in apocrine adenocarcinoma, hidradenoma papilliferum, erosive adenomatosis of the nipple, and primary and metastatic adenocarcinomas. IKH-4 antibody was useful in differentiating eccrine from apocrine neoplasms and in differentiating eccrine carcinoma from metastatic adenocarcinomas.

Adenocarcinoma↗
PubMed1998

Ultrastructural localization of cell junctional components (desmoglein, plakoglobin, E-cadherin, and beta-catenin) in Hailey-Hailey disease, Darier's disease, and pemphigus vulgaris.

The distribution of desmoglein, plakoglobin, E-cadherin, and beta-catenin in the peri-lesional and lesional skin of Hailey-Hailey disease, Darier's disease, and pemphigus vulgaris was examined by immunoelectron microscopy. In the peri-lesional skin, the immunolabeling of these desmosomal components was localized to desmosomes. Adherens junction-associated E-cadherin and beta-catenin were at the cell periphery, excluding desmosomes. The labeling pattern was similar among these diseases, but the labeling intensity particularly that of plakoglobin in Hailey-Hailey disease and Darier's disease, was less than that of normal controls, suggesting that these glycoproteins are quantitatively less concentrated in the normal epidermis of these inherited diseases. In the acantholytic cells of Hailey-Hailey disease and Darier's disease the immunolabeling of the components of desmosomes was diffusely distributed in the cytoplasms, whereas that of adherensjunction was mostly at the cell periphery and partly diffusely in the cytoplasm. In contrast, desmosomes of detaching keratinocytes in pemphigus vulgaris still showed the labeling of desmoglein and plakoglobin. These findings suggest that the inherited acantholytic diseases, i.e., Hailey-Hailey disease and Darier's disease have a different pathogenesis from that of autoimmune acantholysis in pemphigus vulgaris: The intracellular components of desmosomes may primarily be disrupted in the genetic acantholytic diseases in the initial stages of acantholysis. Several unsolved questions in the previous light microscopic immunofluorescence studies using the same antibodies are now answered: 1) the diffusion of desmosomal proteins is not due to the internalization of desmosomes, 2) intracellular components of adherens junction are also finally dissolved, 3) diffuse cytoplasmic immunofluorescence patterns of desmosomal components could be explained by immunoelectron microscopy as those attached to cell membrane and trapped in tonofilament aggregates.

Cadherins↗
PubMed1998

Collodion baby and lamellar ichthyosis.

It is important to differentiate the collodion baby from harlequin ichthyosis as the latter rarely survives past the first few days of life. Occasionally, babies share features of both disorders and defy a clinical diagnosis. We recently encountered such a baby who initially presented with harlequin-like features, but evolved into lamellar ichthyosis once the keratin cast was shed. Since the routine histology of all these ichthyoses is similar, we used electron microscopy to study serial biopsy specimens from the affected infant on days 7, 14, and 150, and compared them to our own other cases of harlequin ichthyosis and lamellar ichthyosis. Electron microscopic studies of our case revealed that the marginal band of cornified cells of the stratum corneum was absent when the baby exhibited collodion/harlequin ichthyosis features. Another biopsy taken when the clinical picture evolved into lamellar-like ichthyosis, showed a well-formed marginal band in the cornified cells. In harlequin ichthyosis, the marginal band is present at birth. It is suggested that electron microscopy can differentiate severe collodion baby from harlequin ichthyosis at birth using the absence of the marginal band. Previously reported features of harlequin ichthyosis, such as the presence of giant mitochondria and an abnormal formation of the marginal band in luminal villi of acrosyringeal eccrine duct, were absent in our case.

Abnormalities, Multiple↗
PubMed1998

Pagetoid Merkel cell carcinoma: epidermal origin of the tumor.

We report a case of intraepidermal Merkel cell carcinoma which occurred on the face of a 76-year-old white male. This slow-growing tumor was mostly confined in the epidermis and pilosebaceous apparatus where tumor cells spread in a pagetoid fashion forming tumor cell nests. Histologically it resembled a superficial spreading melanoma. A heavy lymphocytic infiltration was seen beneath the epidermal lesion as is often seen in pagetoid melanomas. Histochemical and ultrastructural features such as the presence of cytokeratin 20, synaptophysin, neuron specific enolase, desmosomes, and dense cored granules confirmed the diagnosis of Merkel cell carcinoma. Occasional mitotic cells and many apoptotic cells were found in the tumor. Dylon positive, amyloid depositions were seen in the lower epidermis and papillary dermis; they were probably derived from apoptotic tumor cells. It was thought that apoptosis limited the speed of growth of this tumor. We believe that this is probably the most convincing case of intraepidermal Merkel cell carcinoma originating from epidermal Merkel cells or its precursors (stem cells).

Aged↗
PubMed1998

The innermost cells of the outer root sheath in human anagen hair follicles undergo specialized keratinization mediated by apoptosis.

The innermost cell layer of the outer root sheath (IORS) is a special single cell layer located just outside Henle's layer. In situ end-labeling immunohistochemistry for apoptosis showed that labeled cells were most consistently located in the IORS from the suprabulbar portion to the infundibulum of anagen terminal hair follicles of the human scalp. Labeled cells were also sparsely scattered in the middle portion, including the bulge area of the outer root sheath of anagen hair, the regressing lower portion of catagen hair and the bulb of telogen hair. Ultrastructurally, the cells of the innermost layer underwent cellular degeneration through cytoplasmic vacuolization and nuclear pyknosis without keratohyalin production. These were compatible with the morphology of apoptotic cells. These findings confirmed that the innermost cell layer is different from other layers of the outer root sheath, not only by previously demonstrated criteria such as Ki67 immunostainability and characteristic ultrastructure but also by the mode of cell death.

Adult↗
PubMed1998

Functional involvement of urokinase-type plasminogen activator receptor in pemphigus acantholysis.

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cultures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis.

Acantholysis↗
PubMed1998

Involvement of prolonged ras activation in thrombopoietin-induced megakaryocytic differentiation of a human factor-dependent hematopoietic cell line.

Thrombopoietin (TPO) is a hematopoietic growth factor that plays fundamental roles is both megakaryopoiesis and thrombopoiesis through binding to its receptor, c-mpl. Although TPO has been shown to activate various types of intracellular signaling molecules, such as the Janus family of protein tyrosine kinases, signal transducers and activators of transcription (STATs), and ras, the precise mechanisms underlying TPO-induced proliferation and differentiation remain unknown. In an effort to clarify the mechanisms of TPO-induced proliferation and differentiation, c-mpl was introduced into F-36P, a human interleukin-3 (IL-3)-dependent erythroleukemia cell line, and the effects of TPO on the c-mpl-transfected F-36P (F-36P-mpl) cells were investigated. F-36P-mpl cells were found to proliferate and differentiate at a high rate into mature megakaryocytes in response to TPO. Dominant-negative (dn) forms of STAT1, STAT3, STAT5, and ras were inducibly expressed in F-36P-mpl cells, and their effects on TPO-induced proliferation and megakaryocytic differentiation were analyzed. Among these dn molecules, both dn ras and dn STAT5 reduced TPO- or IL-3-induced proliferation of F-36P-mpl cells by approximately 30%, and only dn ras could inhibit TPO-induced megakaryocytic differentiation. In accord with this result, overexpression of activated ras (H-rasG12V) for 5 days led to megakaryocytic differentiation of F-36P-mpl cells. In a time course analysis on H-rasG12V-induced differentiation, activation of the ras pathway for 24 to 28 h was required and sufficient to induce megakaryocytic differentiation. Consistent with this result, the treatment of F-36P-mpl cells with TPO was able to induce prolonged activation of ras for more than 24 h, whereas IL-3 had only a transient effect. These results suggest that prolonged ras activation may be involved in TPO-induced megakaryocytic differentiation.

Cell Differentiation↗
PubMed1998

Down regulation by iron of prostaglandin E2 production by human synovial fibroblasts.

OBJECTIVE: To examine the effect of iron on the prostaglandin (PG) E2 production by human synovial fibroblasts in vitro. METHODS: Human synovial fibroblasts were isolated from synovial tissue of rheumatoid arthritis (RA) and osteoarthritis (OA) patients and cultured in medium. Synovial fibroblasts were stimulated by human recombinant interleukin (IL) 1 beta (0.1-10 ng/ml) with or without ferric citrate (Fe-citrate, 0.01-1 mM). The amount of PGE2 in the culture medium was measured by an enzyme linked immunosorbent assay. RESULTS: The production of PGE2 by the synovial fibroblasts was increased by stimulation with IL1 beta at all concentrations tested. Fe-citrate but not sodium citrate (Na-citrate) down regulated the production of PGE2 by the synovial fibroblasts, both with and without stimulation by IL1 beta. Fe-citrate inhibited the spontaneous PGE2 production by the cells in a dose dependent manner, and a maximum inhibition by Fe-citrate was observed at the concentration of 0.1 mM with IL1 beta stimulation. The down regulation by iron was reversed by the co-addition of desferrioxamine (100 micrograms/ml), an iron chelator. CONCLUSION: Iron down regulates the PGE2 production by synovial fibroblasts in vitro.

Aged↗
PubMed1998

Altered expression of type 2 CRH receptor mRNA in the VMH by glucocorticoids and starvation.

In the rat, high-dose corticosterone (Cort) administration, the hypercortisolism of starvation, and adrenalectomy are all associated with decreased food intake and weight loss. We report here a study of the effects of high-dose Cort administration, starvation, and adrenalectomy on two peripheral hormones known to influence food intake and energy use, insulin and leptin. We also studied the impact of these interventions on the levels of type 2 corticotropin-releasing hormone receptor (CRHR-2) mRNA in the hypothalamic paraventricular nucleus (PVN) and ventromedial hypothalamus (VMH). The VMH is classically referred to as the satiety center because electrical stimulation of the VMH leads to inhibition of food intake, whereas CRHR-2 are thought to transduce the profound anorexogenic effects of CRH or its related peptide urocortin. Starvation and adrenalectomy each lowered plasma insulin and leptin levels and were associated with decrements in CRHR-2 mRNA levels in the VMH. Cort administration increased plasma leptin levels profoundly, as well as plasma insulin levels and the levels of VMH CRHR-2 mRNA. Under all experimental conditions, a positive correlation was seen between plasma leptin levels and VMH CRHR-2 mRNA. These data suggest that decreased food intake and weight loss after high-dose Cort administration at least partially depend on the profound impact of Cort on plasma leptin secretion in the rat; they suggest, moreover, an additional mechanism for the satiety-inducing effects of leptin, namely increasing CRHR-2 in the VMH. The concordance of a fall in plasma insulin and leptin levels with the fall in VMH CRHR-2 mRNA levels further supports the idea that compensatory responses during starvation and adrenalectomy include not only the disinhibiting effects of reduced insulin and leptin levels on appetite through already-described mechanisms but also via an effect of leptin on VMH CRHR-2. Neither Cort administration, starvation, nor adrenalectomy influenced the levels of CRHR-2 mRNA in the PVN, suggesting that these receptors are differentially regulated in different hypothalamic regions.

Adrenalectomy↗