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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 379 records · Page 21Linked to original sources
PubMed1999

Expression of vitamin D receptor in cultured human keratinocytes and fibroblasts is not altered by corticosteroids.

Topical vitamin D3 therapy is one of the mainstays of psoriasis treatment. However, the effectiveness of combination therapy with topical vitamin D3 and corticosteroids is still controversial. It has been reported that topical vitamin D3 treatment following topical corticosteroids is less effective than that without preceding corticosteroid treatment. We hypothesized that vitamin D receptor (VDR) in the skin is down-regulated by topical corticosteroids. To obtain support for this hypothesis, we determined VDR protein levels in cultured keratinocytes and fibroblasts after corticosteroid treatment. VDR levels were quantified by Western blot analysis with a Fluorolmager. Keratinocytes and fibroblasts were obtained from four psoriasis patients and four normal controls. VDR levels were altered in neither normal nor psoriatic keratinocytes by 2-day incubation with dexamethasone (1x10(-9)-1x10(-6) M) or clobetasol propionate (1x10(-9)-1x10(-6) M). Similarly, VDR levels in normal and psoriatic fibroblasts were not affected by 2-day incubation with dexamethasone (1x10(-6) M). These findings suggest that down-regulation of VDR by topical corticosteroids in keratinocytes and fibroblasts of psoriasis is unlikely.

Administration, Topical↗
PubMed1999

Growth-stimulating effects of tumor necrosis factor-alpha on simian virus 40-transformed human keratinocytes is linked to phosphorylation of retinoblastoma protein.

In this report, we show that tumor necrosis factor-alpha (TNF-alpha) has a strong growth-stimulating effect on simian virus 40 (SV40)-transformed keratinocytes, while it exerts a potent growth-inhibitory effect on normal human keratinocytes. Addition of TNF-alpha to SV40-transformed keratinocytes stimulated cell growth by 216, 246, or 248% at 25, 50, or 250 ng/ml after 4 days culture compared with untreated cells, while addition to normal human keratinocytes reduced growth to 65, 38, and 32% at the same concentrations, respectively. Cell cycle analysis by flow cytometry showed that treatment of SV40-transformed keratinocytes with 250 ng/ml TNF-alpha for 48 h increased the S-phase cells from 19.8 +/- 0.3 to 49.7 +/- 2.4%. The percentage of G1/G0 phase cells decreased from 62.6 +/- 1.6 to 32.4 +/- 3.3%. We also demonstrated by immunofluorescent staining that SV40 large T antigen was enhanced by TNF-alpha incubation. Additionally, we examined the hyper and hypo-phosphorylated state of retinoblastoma protein (pRB), the cell cycle regulatory protein. TNF-alpha induced hyperphosphorylated pRB in SV40-transformed keratinocytes. On the other hand, TNF-alpha suppressed it in normal keratinocytes. We hypothesize that the enhancement of SV40 large T antigen and hyperphosphorylated pRB is involved in the mechanism of growth stimulation of SV40-transformed keratinocytes by TNF-alpha.

Cell Division↗
PubMed1999

In vitro processing of amyloid precursor protein by cathepsin D.

The formation of beta A4 amyloid in the brains of individuals with Alzheimer's disease requires the proteolytic cleavage of amyloid precursor protein. Several lines of evidence suggest that cathepsin D, the major lysosomal/endosomal aspartic protease, may be involved in this process. In this work, we used a sensitive in vitro method of detection to investigate the role of cathepsin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of beta A4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic gamma-cleavage sites. This occurred preferentially at Thr43-Val44 and at Ala42-Thr43, generating full length beta A4 43 and beta A4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34-Met35, Thr48-Leu49 and Leu49-Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19-Phe20, Phe20-Ala21 and Phe93-Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. Digestion of C100 using different solublizing agents indicated that the cleavage of C100 by cathepsin D is greatly influenced by the structural integrity of the substrate. However, our results suggest that cathepsin D could generate the pathogenic beta A4 amyloid peptides from its precursor in vitro, which may indicate a role in the amyloidogenesis of Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

A comparison of the plasma fructose concentrations in dogs and cats and changes in the fructose concentrations in dogs following intravenous administration of fructose.

The plasma concentrations of fructose, glucose, free fatty acids (FFA) and triglycerides (TG) were measured in dogs and cats. Changes in these concentrations were investigated in dogs by an intravenous fructose tolerance test (IVFTT) at a dose of 0.1 g/kg body weight. Fructose concentrations in the plasma of dogs were significantly higher than those of cats. There was no significant difference in plasma glucose concentrations between dogs and cats. Plasma FFA concentrations decreased and TG concentrations increased after feeding in both dogs and cats. During the IVFTT, the plasma fructose concentrations in the dogs increased rapidly to a peak by 2 min and then decreased to half of the peak by 5 min after the administration of fructose. Administration of fructose resulted in an increase in the plasma TG concentrations and reduced plasma FFA concentrations in the dogs. Only 4%, of the administered fructose was detected in the urine of dogs following IVFTT. Plasma fructose was considered to be rapidly absorbed and metabolized in both dogs and cats. However, as with glucose metabolism, there appear to be some differences in fructose metabolism between dogs and cats.

Animals↗
PubMed1999

High prevalence of human papillomaviruses in the normal oral cavity of adults.

Human papillomavirus (HPV) infection in the normal oral cavity was studied by the sensitive polymerase chain reaction (PCR) using primers for the L1 region of human papillomavirus DNA and high fidelity amplification system. Cells were scraped from the oral mucosae of 7 (mean age; 42 years) and 30 (mean age; 32 years) volunteers with and without skin warts, respectively. Human papillomavirus DNA was detected in 30/37 (81.1%) specimens and their copy numbers per cell were 10(-1) to 10(-4) (mean, 10(-3)). The human papillomavirus types determined by PCR-based sequencing analysis were HPV-18 (26/30; 86.7%), -61 (18/30; 60%), -59 (7/30; 23.3%), -16 (2/30; 6.7%), -6 (1/30; 3.3%) and an unknown type (HPV-X71) (1/30; 3.3%). Multiple human papillomavirus types were present in 17/30 (56.7%) specimens. HPV-6 was detected in 2 of 7 skin warts and differed from the human papillomavirus types of the corresponding oral specimens. These data suggest that human papillomavirus infection in the oral mucosa occurs much more frequently than previously considered.

Adult↗
PubMed1999

Effects and interaction, of cariporide and preconditioning on cardiac arrhythmias and infarction in rat in vivo.

1. Although Na+-H+ exchange (NHE) inhibitors are reported to protect the myocardium against ischaemic injury, NHE activation has also been proposed as a potential mechanism of ischaemic preconditioning-induced protection. This study was performed to test any modifiable effect of cariporide, an NHE inhibitor, on cardioprotective effects of preconditioning. 2. Anaesthetized rats were subjected to 30 min of coronary artery occlusion and 150 min of reperfusion. The preconditioning (PC) was induced by 3 min of ischaemia and 10 min of reperfusion (1PC) or three episodes of 3 min ischaemia and 5 min reperfusion (3PC). Cariporide (0.3 mg kg(-1)) an NHE inhibitor, was administered 30 min (cari(30)) or 45 min (cari(45)) before coronary ligation (n=8-11 for each group). 3. Ventricular arrhythmias during 30 min ischaemia and infarct size (measured by triphenyltetrazolium (TTC) and expressed as a per cent area at risk (%AAR)) were determined. Cari(30) reduced ventricular fibrillation (VF) incidence and infarct size (from 45 to 0% and 34+/-4 to 9+/-2%; each P<0.05), whereas cari(45) did not. Likewise, 3PC reduced these variables (to 0% and 10+/-2%; P<0.05 in each case) whereas 1PC did not. Moreover, subthreshold preconditioning (1PC) and cariporide (cari(45)), when combined, reduced VF incidence and infarct size (to 0% and 15+3%; each P<0.05 ). 4. In conclusion, changes in NHE activity do not seem to be responsible for the cardioprotective action of ischaemic preconditioning. Protective effects of NHE inhibition and subthreshold preconditioning appear to act additively.

Animals↗
PubMed1999

A novel anti-diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits.

1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2. The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared with the saline control group (41.7+/-2.3%, n=10). However, it was significantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg(-1) of miglitol (25.7+/-4. 5%, n=10, and 14.6+/-2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre-reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3. Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4. Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.

1-Deoxynojirimycin↗
PubMed1999

Development of a compact computed tomographic apparatus for dental use.

OBJECTIVE: To describe a compact computed tomographic apparatus (Ortho-CT) for use in dental practice. METHODS: Ortho-CT is a cone-beam-type of CT apparatus consisting of a multifunctional maxillofacial imaging machine (Scanora, Soredex, Helsinki, Finland) in which the film is replaced with an X-ray imaging intensifier (Hamamatsu Photonics, Hamamatsu, Japan). The region of image reconstruction is a cylinder 32 mm in height and 38 mm in diameter and the voxel is a 0.136-mm cube. Scanning is at 85 kV and 10 mA with a 1 mm Cu filter. The scan time is 17 s comparable with that required for rotational panoramic radiography. A single scan collects 512 sets of projection data through 360 degrees and the image is reconstructed by a personal computer. The time required for image reconstruction is about 10 min. RESULTS: The resolution limit was about 2.0 lp mm-1 and the skin entrance dose 0.62 mGy. Excellent image quality was obtained with a tissue-equivalent skull phantom: roots, periodontal ligament space, lamina dura, and cancellous bone were clearly visualized. CONCLUSION: Ortho-CT provides three-dimensional images of excellent quality for dental use at a low entrance dose.

Humans↗
PubMed1999

Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus.

Pemphigus is an autoimmune blistering disease with two major subtypes, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating antidesmoglein (Dsg)1 and/or anti-Dsg3 IgG autoantibodies. We have previously developed enzyme-linked immunosorbent assays (ELISAs) using recombinant Dsg1 and Dsg3 expressed by baculovirus as a diagnostic tool for pemphigus. The purpose of this study was to evaluate the practical application of these ELISAs for clinical use with a large number of serum samples. We used 81 PV sera, 48 PF sera, 114 bullous pemphigoid (BP) sera, 124 collagen disease sera, nine sera of other non-pemphigus bullous diseases and 179 normal control sera. A cut-off value was determined by receiver-operating-characteristic plots. Forty-seven of 48 PF sera (97.9%) were positive in the Dsg1 ELISA and 79 of 81 PV sera (97.5%) were positive in the Dsg3 ELISA, while only two (1. 1%) and four (2.2%) of 179 normal sera were positive in Dsg1 and Dsg3 ELISAs, respectively. However, some disease control sera of BP and collagen diseases exceeded the cut-off value. Introduction of a grey zone helped to decrease the number of these false-positive sera. Furthermore, in three patients studied, the respective Dsg1 and Dsg3 ELISA scores showed parallel fluctuation with the disease activity along the time course. We conclude that Dsg1 and Dsg3 ELISAs provide a simple, sensitive and highly specific assay for the diagnosis of patients with PV and PF and that these ELISAs may be a valuable tool to monitor the disease activity. We also propose diagnostic criteria for pemphigus based on ELISA reactivity: if a serum is positive against Dsg3 it indicates a diagnosis of PV, regardless of reactivity against Dsg1; if a serum is negative for Dsg3 and positive for Dsg1, it indicates a diagnosis of PF.

Aged↗
PubMed1999

Epimorphin expression during human foetal hair follicle development.

Epimorphin is a mesenchymal protein expressed in several organs and known to have an essential role in epithelial tissue organization, including hair follicle morphogenesis, in mice. Although about 90% homology has been reported between human and mouse epimorphin exon sequences, there is no information about expression and function of epimorphin in hair follicle development in humans. In order to elucidate the expression pattern of epimorphin in human hair follicle morphogenesis and to compare it with the distribution of tenascin and neural cell adhesion molecule (NCAM), skin samples from human foetuses of a series of estimated gestational ages (EGAs) (46-168 days EGA) were studied using monoclonal anti-epimorphin antibody MC-1, anti-tenascin antibody and anti-human NCAM antibody. Epimorphin was detected in the mesenchymal cell condensation at the pregerm stage (< 75 days EGA), and there was strong expression of epimorphin in the perifollicular mesenchymal cells around the hair germ (75-84 days EGA). At the hair peg stage (85-104 days EGA), epimorphin was around the hair peg with the strongest staining in the neck portion. This sequence of staining patterns was similar to that of tenascin. In the bulbous hair peg (105-134 days EGA), the perifollicular dermal mesenchymal cells were evenly positive for epimorphin. Mesenchymal cells underneath the follicle bulb prior to formation of the dermal papilla were also positive for epimorphin. In the lanugo hair follicle (> 134 days EGA), dermal papilla cells expressed epimorphin as well as tenascin and NCAM. These results indicate that epimorphin expression is closely linked to developing hair follicles in human foetuses. This suggests that epimorphin may have an important part in induction of morphogenesis during human foetal hair follicle development.

Female↗
PubMed1999

Leptin effects on the expression of type-2 CRH receptor mRNA in the ventromedial hypothalamus in the rat.

The product of the ob gene, leptin, is thought to act in the hypothalamus to reduce food intake and body weight (b.w.) in rats and mice; however, the mechanisms of leptin action in the brain have not been fully elucidated. Corticotropin-releasing hormone (CRH) is a potent anorectic neuropeptide, and its type-2 receptor (CRHR-2) in the ventromedial hypothalamus (VMH) appears to play an important role in the expression of this anorectic effect. We explored here the impact of systemic leptin administration on CRH mRNA expression in the hypothalamic paraventricular nucleus (PVN) and CRHR-2 mRNA expression in the VMH in male rats, using in-situ hybridization histochemistry. The expression of CRH mRNA in the PVN and CRHR-2 mRNA in the VMH were increased at 2 h and 6 h, respectively, after a single intraperitoneal injection of leptin (1.0 mg/kg). Continuous subcutaneous infusion of leptin (1.2 mg/kg/day) via an osmotic minipump for 5 days increased the expression of CRHR-2 mRNA in the VMH, but not the expression of CRH mRNA in the PVN, compared with vehicle treatment. The rats that received the single or continuous administration of leptin showed reductions of food intake and b.w. compared with vehicle-treated rats. These results are consistent with our previous findings that the expression of CRHR-2 mRNA in the VMH is positively correlated with plasma leptin concentrations under various conditions, and highlight the importance of circulating leptin for the regulation of VMH CRHR-2 mRNA. The present results also raise the possibility that leptin reduces food intake and b.w. at least partially due to the enhancement of the anorectic effect of CRH via increased PVN CRH expression and/or VMH CRHR-2 expression.

Animals↗
PubMed1999

Direct and buffering effects of social support on depressive symptoms of the elderly with home help.

The purpose of the present study was to examine the prevalence of depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D) and the effect of life stressors or social support on depressive symptoms in 303 elderly people receiving social services at home. We conducted a questionnaire survey six times with a 1-month interval. In the initial wave of questionnaires, 92 (31%) scored 16 points or above on the CES-D, indicative of a risk for depression. Before life stressors, subjects with low-level support showed significantly more severe depressive symptoms than those with high-level support. Subjects with low-level support were significantly more depressive after life stressors than they had been before, whereas those with middle- and high-level support showed no such difference. The former and latter results seem to suggest the direct and buffering effects of social support on depressive symptoms, respectively.

Activities of Daily Living↗
PubMed1999

Fusion of intussusceptum and intussuscipiens in intrauterine intussusception: a rare type of intestinal atresia.

Intrauterine intussusception is well known as one of the rare causes of intestinal atresia. Although the polypoid intussusceptum is usually observed at the obstructed end on the distal side, a few cases with the polypoid lesion located apart from the blind end have been reported. To elucidate the etiology of separated polypoid intussusceptum, we reviewed 42 surgical cases of jejunal or ileal atresia over the last 12 years at Kobe Children's Hospital, Kobe, Japan. Of the 42 cases, 11 were intrauterine intussusception. Two of the 11 cases were associated with polypoid intussusceptums separated from the obstructed ends; the intestinal portion between the polypoid intussusceptum and the obstructed end showed a partial two-fold proper muscle wall and a mesenteric structure invaginated between the two walls. Another case showed linear ulcers facing each other on both the intussusceptum and intussuscipiens. Linear ulceration and subsequent fusion of the intussusceptum and intussuscipiens are suggested to be the pathogenesis of the first two cases.

Age of Onset↗
PubMed1999

Management of acute metabolic decompensation in maple syrup urine disease: a multi-center study.

BACKGROUND: Therapeutic modalities in acute metabolic decompensation in maple syrup urine disease (MSUD) are variable, and outcomes of each therapeutic measure have been known only individually. Factors that affect neurological outcome are not clear. METHODS: A questionnaire was sent throughout Japan to each pediatrician treating any of the 42 MSUD patients. RESULTS: Necessary information was available for 13 patients through the questionnaire, and through a publication for one patient. In nine of the 14 patients episodes of metabolic decompensation developed in the neonatal period. In the other five, the onset of disease was delayed until infancy or later. In the nine patients with neonatal onset, a pretreatment level of plasma leucine greater than 40 mg/100 mL or a duration of altered level of alertness longer than 10 days was associated with a poor neurological outcome. The therapeutic measures employed included intravenous infusion of glucose and electrolyte solution or hypertonic glucose and electrolyte solution, exchange transfusion, peritoneal dialysis, a large dose of thiamine and intravenous hyperalimentation. All patients had survived the episodes and were alive at the time of the survey. Five of the nine patients with neonatal onset have developed neurological sequelae to varying degrees. Episodes of metabolic decompensation in infancy or thereafter did not affect, or only minimally affected, the neurological outcome. CONCLUSION: Therapeutic goals to improve neurological outcome are to shorten the duration of the altered level of consciousness, and to minimize the peak plasma leucine level as much as possible.

Acute Disease↗
PubMed1999

3',5'-cyclic guanosine monophosphate activates mitogen-activated protein kinase in rat pinealocytes.

The role of 3',5'-cyclic guanosine monophosphate (cGMP) in the activation of mitogen-activated protein kinases (MAPKs) was investigated in rat pinealocytes. Treatment with dibutyryl cGMP (DBcGMP) dose-dependently increased the phosphorylation of both p44 and p42 isoforms of MAPK. This effect of DBcGMP was abolished by PD98059 (a MAPK kinase inhibitor), H7 (a nonspecific protein kinase inhibitor), and KT5823 [a selective cGMP-dependent protein kinase (PKG) inhibitor]. Elevation of cellular cGMP content by treatment with norepinephrine, zaprinast (a cGMP phosphodiesterase inhibitor), or nitroprusside was effective in activating MAPK. Natriuretic peptides that were effective in elevating cGMP levels in this tissue were also effective in activating MAPK. Our results indicate that, in this neuroendocrine tissue, the cGMP/PKG signaling pathway is an important mechanism used by hormones and neurotransmitters in activating MAPK.

Alkaloids↗
PubMed1999

Salivary duct carcinoma in the mandible: report of a case with immunohistochemical studies.

Salivary duct carcinoma is rare. We describe a 56-year-old man who developed salivary duct carcinoma in the mandible 10 years after removal of the right second and third molars. The tumour originated in the retromolar gland or the ectopic minor salivary gland in the mandible. The panoramic radiograph showed a radiolucent, poorly circumscribed area about 40 x 30 mm in size and distal to the lower right first molar. This tooth, together with all neoplastic tissue, was removed, and histopathological examination showed it to be a salivary duct carcinoma in the mandible. On immunohistochemical staining, keratin antibodies stained the ductal structure, 1A4 antibody stained myoepithelial cells, but S-100 protein and vimentin were not seen. The patient was well and with no sign with recurrence 6 years postoperatively.

Actins↗
PubMed1999

Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1.

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.

Adolescent↗