Interleukin-1 receptors: cloning studies and role in central nervous system disorders.
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Animals↗
Biomedical subjects
K Hashimoto
Publications and source records attributed to K Hashimoto.
Linear focal elastosis: Keloidal repair of striae distensae.
Linear focal elastosis and striae distensae coexisted in a 32-year-old black man in their typical distribution on the lower back. Many striae appeared when he lost 50 lb in 1991. Only some of them became hypertrophic and others remained atrophic; striae distensae of the shoulders and buttocks remained atrophic, whereas most in the lumbosacral region became indurated and cordlike. Histologically, the former lacked elastic fibers and the latter showed a marked increase in thick elastic fibers. Linear focal elastosis in some patients may represent hyperplasia of elastic fibers in response to their damage. This "elastic fiber keloid" seems to be equivalent to collagen keloid, i.e., ordinary keloid, in the lumbosacral region.
Adult↗
Insertion/deletion polymorphism in intron 16 of the ACE gene and left ventricular hypertrophy in patients with end-stage renal disease.
We studied the relationship between polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene and left ventricular (LV) hypertrophy in uremic patients treated with hemodialysis therapy. The LV parameters were not different for age-, hematocrit-, and blood pressure-matched patients in DD, ID, and II genotype groups. The most important factor for LV hypertrophy was systolic blood pressure, which correlated with the posterior wall thickness (r=0.35; P=0.001) and LV mass index (LVMI; r=0.23; P=0.032). Among nonhypertensive patients, the frequency of interventricular septum (IVS) hypertrophy (>12 mm) and hypertrophy in LVMI (>145 g/m2) was significantly greater in patients with the DD genotype than in I allele-positive (+) patients. The odds rate for IVS hypertrophy was 5.04 (95% confidence interval, 1.15 to 24.8). These data suggest that the DD genotype of the ACE gene polymorphism is a contributory factor for the development of LV hypertrophy in patients with end-stage renal disease (ESRD).
Age Factors↗
Congenital teratoid cyst with a median fistula in the submental region: case report and ultrastructural findings.
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Child↗
Inhibition of flagellar motility of demembranated fowl spermatozoa by protease substrates.
We investigated the effects of various protease substrates on the motility of demembranated fowl spermatozoa. In the presence of ATP, the motility of demembranated spermatozoa was vigorous at 30 degrees C, but decreased markedly following the addition of protease substrates, such as N alpha-carbobenzoxy-L-lys-thiobenzyl ester (BLT), N-benzoyl-phe-val-arg p-nitroanilide or N alpha-benzoyl-D,L-arg p-nitroanilide (BAPNA) in a dose-dependent manner, within the range 0-1 mM. The subsequent addition of 100 ng/ml trypsin released the inhibitory effect of protease substrates within 10 s. Phosphorylation or dephosphorylation of several proteins of demembranated spermatozoa was observed following the addition of protease substrates, however, no consistent patterns of protein phosphorylation or dephosphorylation were associated with the inhibition of motility. These results suggest that endogenous protease activity is instrumental in the maintenance of fowl sperm motility and that the site of action of this protease is in the axoneme and/or accessory cytoskeletal components. This enzyme may not act directly on the phosphorylation of sperm proteins involved in the regulation of motility.
Animals↗
Psychosomatic aspects of patients complaining of dizziness or vertigo with orthostatic dysregulation.
Eighty-five patients (26 males and 59 females) with orthostatic dysregulation who visited our clinic complaining of dizziness or vertigo between December, 1990 and August, 1996 were analyzed using the Japanese Edition Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford Personality Test. The condition of OD was most commonly noted in 29 patients (34.1%) with dizziness or vertigo of indeterminate etiology, followed by in 14 (16.5%) with Meniere's disease, in ten (11.8%) with hypotension and CNS disorder each, and in 22 (25.9%) with other disorders. The percentage classed as Type III (possible neurotic) or Type IV (probable neurotic), was 46.1% in males and 47.4% in females. The percentage classed as Type B or Type E, suggestive of emotional or psychological disturbance, was 38.5% in males and 37.3% in females. There was good correlation between the Japanese Edition Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford Personality Test results as to psychosomatic aspects. We conclude that, in the treatment of patients with orthostatic dysregulation, it is necessary to consider both physical and psychological aspects of the condition.
Adult↗
Three siblings of fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microcephaly.
We report three male siblings born with fatal encephalopathy comprising microcephaly, myoclonus and muscle hypertonia. All three patients died during infancy. Postmortem examination on the brain revealed that all infants had neuronal loss in the cerebellar cortex, inferior olivary and pontine nuclei, which were more pronounced in the older subject than the younger ones. In addition, they were associated with polymicrogyria in the cerebral cortex of the insula, olivary and dentate nuclear dysplasia, and a hypoplastic corticospinal tract. The clinical and neuropathological findings in our cases were identical to those in fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microencephaly [Albrecht et al., Acta Neuropathol 1993;85:394-399], but an association of malformations suggests a new genetic factor in pathogenesis of olivopontocerebellar hypoplasia.
Abnormalities, Multiple↗
Growth inhibition of human keratinocytes by a new vitamin D3 analogue in vitro.
SM-10193 (26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3; F6-1,23(S),25-(OH)3D3) is one of the active vitamin D3 analogues, which is under exploration as a new therapeutic agent for psoriasis. In this paper, we present that SM-10193 induces the growth inhibition and differentiation of cultured normal human keratinocytes more effectively than 1,25(OH)2D3. The growth of keratinocytes was inhibited in the presence of 10(-11), 10(-10), 10(-9), 10(-8), 10(-7) and 10(-6) M of SM-10193 by 36.8, 42.1, 48.5, 47.6, 66.0 and 85.9% respectively. SM-10193 increased the number of involucrin positive cells (the marker for keratinocyte differentiation) from 4.9 +/- 0.1 to 12.5 +/- 0.8, 20.1 +/- 1.6 and 42.8 +/- 1.0% (P < 0.01) at 10(-8), 10(-7) and 10(-6) M, respectively. To elucidate the mechanism of SM-10193-induced growth inhibition, we analyzed cell cycle related distribution and the alteration of hyperphosphorylated and hypophosphorylated state of retinoblastoma protein (pRB). SM-10193 induces growth arrest in G1/G0 and G2 + M phases and an increase of the hypophosphorylated form of pRB more remarkably than 1,25(OH)2D3 does.
Calcitriol↗
Synchronization of normal human keratinocyte in culture: its application to the analysis of 1,25-dihydroxyvitamin D3 effects on cell cycle.
In this report, we applied the isoleucine-deprivation method to normal human keratinocytes in cultivation with serum-free MCDB153 medium. The growing cells were synchronized by transfer to MCDB153 medium prepared without isoleucine, and the degree of synchronization was analyzed by the cell cycle distribution and phosphorylation of retinoblastoma protein (pRB), one of the tumor suppressor gene products. 1,25-dihidroxyvitamin D3 (1,25(OH)2D3), a biologically active form of vitamin D3, is supposed to induce the differentiation and growth inhibition of human keratinocytes caused by cell cycle arrest. We examined its effect on cell cycle kinetics, especially progression from G1/G0 to S-phase, by using this synchronized system. We showed that 10(-6) M 1,25(OH)2D3 inhibited the progression from G1/G0 to S-phase strikingly in synchronized normal human keratinocytes.
Blotting, Northern↗
Familial gastrointestinal stromal tumours with germline mutation of the KIT gene.
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Animals↗
MS-551 and KCB-328, two class III drugs aggravated adrenaline-induced arrhythmias.
We investigated the proarrhythmic effects of MS-551 and KCB-328, class III antiarrhythmic drugs using adrenaline-induced arrhythmia models in halothane anaesthetized, closed-chest dogs. In the control period, adrenaline, starting from a low dose of 0.25 to up to 1.0 microg/kg/50 s i.v., was injected to determine the arrhythmia inducing dose and the non-inducing dose. After MS-551 or KCB-328 administration, the adrenaline injection was repeated and the interval between the injection and the occurrence of arrhythmia (latent interval), the changes in arrhythmic ratio (as calculated by dividing the number of ventricular premature contraction by the number of the total heart rate) and the severity of arrhythmia were observed. MS-551 infusion, 1 mg/kg/30 min, decreased the heart rate (HR) by 16% (P<0.01) and prolonged the QTc interval by 20% (P<0.01). During the 30 min of MS-551 infusion, arrhythmias occurred in three out of seven dogs (torsades de pointes (TdP) type VT in one dog). After these arrhythmias disappeared, MS-551 decreased the latent interval of the adrenaline arrhythmias produced by the inducing dose (30+/-2 s compared with 43+/-3 s of the control interval, P < 0.05), increased the arrhythmic ratio (P<0.05) and induced arrhythmias by non-inducing adrenaline doses (P<0.05). Effect of a new class III drug KCB-328 infusion, 0.3 mg/kg/30 min, was compared witih MS-551 using the same model. KCB-328 decreased the HR by 21% (P<0.01) and prolonged the QTc interval by 25% (P<0.01). During the 30 min of infusion, arrhythmias occurred in five out of seven dogs (TdP in two dogs). KCB-328 also decreased the latent interval of the adrenaline arrhythmias produced by the inducing doses (31+/-3 s compared with 49+/-7 s of the control period, P<0.05), but did not significantly alter the arrhythmic ratio. Adrenaline induced TdP only after MS-551 or KCB-328 was administered, i.e. after MS-551, 1 mg/kg/30 min, 3/7 versus 0/7 in the control; KCB, 0.3 mg/kg/30 min, 3/7 versus 0/7 in the control. To examine the direct arrhythmogenic effect of MS-551 and whether an adrenergic mechanism plays some role on this arrhythmogenesis, a bolus injection of MS-551, 3 mg/kg, was injected either without pre-treatment or after pre-treatment with propranolol 0.3 mg/kg. MS-551 induced arrhythmias in five out of seven dogs (TdP in one dog). Also in the propranolol pre-treated dogs, MS-551 induced arrhythmias in five out of seven dogs (TdP in 1 dog). In conclusion, these observations indicate that MS-551 and KCB-328 induced arrhythmias and intensified proarrhythmic effects of adrenaline, MS-551 being stronger than KCB-328 at the same QTc prolonging doses. The direct arrhythmogenic effect of MS-551 was not influenced by beta-blocker treatment.
Adrenergic alpha-Agonists↗
Food-dependent exercise-induced anaphylaxis: a case related to the amount of food allergen ingested.
A 24-year-old Japanese woman had suffered for 2 years from attacks of urticaria, dyspnoea and syncope associated with exercise after the ingestion of wheat. Specific IgE measurements revealed RAST class 2 for wheat and gluten (a major wheat protein), and class 3 for rye. Skin prick tests with wheat, bread, gluten and udon (a Japanese noodle made of wheat) were all positive. Food-dependent exercise-induced anaphylaxis (FDEIA) caused by wheat was suspected. Challenge tests with bread were performed. Exercise following ingestion of 64 g, but not 45 g, of bread induced generalized urticaria. Challenge tests with udon also triggered allergic reaction in a dose-dependent manner: 200 g, but not 100 g or 150 g, of udon elicited wealing and erythema with exercise. Ingestion of bread or udon alone failed to elicit any allergic reaction. This is the first case of FDEIA in which the dependence of the triggering allergic reaction on the amount of allergen ingested was clearly confirmed.
Adult↗
A novel immunosuppressant, FTY720, increases the efficiency of a superantigen-induced peripheral T-cell deletion whilst inhibiting negative selection in the thymus.
A novel immunosuppressant, FTY720, was generated by chemical modification of ISP-I, an immunosuppressive compound purified from culture filtrates of Isaria sinclairii. FTY720 directly induces apoptotic cell death in lymphocytes, which is believed to be the mechanism by which this drug exerts its immunosuppressive effect. We examined the effect of FTY720 treatment on antigen-induced apoptotic cell death in peripheral T cells and thymocytes. A superantigen, staphylococcus enterotoxin B (SEB), induces T-cell antigen receptor (TCR) Vbeta-specific apoptotic cell death in mature T cells in vivo. In this well-documented experimental system, FTY720 administration significantly enhanced the efficiency of superantigen-induced T-cell deletion. We also determined that apoptotic cell death with DNA fragmentation induced in T-hybridoma cells after stimulation in vitro with anti-TCR antibodies was enhanced in the presence of non-cytolytic doses of FTY720. In sharp contrast, negative selection of T cells in the thymus, another example of antigen-induced apoptosis, was found to be inhibited by FTY720 treatment. A rescue effect was observed on clonal deletion in the H-Y-specific TCRalpha beta transgenic male thymus. In a chicken egg albumin (OVA)-specific TCRalphabeta transgenic system, OVA-induced apoptotic cell death of CD4+CD8+ thymocytes was also inhibited by FTY720 injection. Thus, FTY720 increased the susceptibility of mature T cells to TCR-mediated apoptosis but decreased that of immature thymocytes. The results in this report suggest that the potent immunosuppressive effect of FTY720 is, in part, a result of the augmentation of effects on antigen-induced apoptosis in mature T cells, and that two distinct apoptotic cell death pathways are operating in mature and immature T cells.
Animals↗
A clinical and radiographic study of 25 autotransplanted third molars.
This paper is a report on 25 autotransplantations of third molars with complete root formations. The study consists of 23 patients in whom 25 third molars were transplanted. The mean age was 29.6 years (range 20-54). In nine cases third molars were directly transplanted into the new socket. In 11 cases the sockets were widened and made deeper with a bur. In five cases the recipient beds were made by splitting osteotomy of the alveolar region. The transplanted third molars were stabilized with silk sutures, resin, wire splint or circumferential wiring for 1-6 weeks. Two-three weeks after transplantation, the root canals were treated and filled. After operation, the marginal and the periapical conditions were examined clinically and radiographically. The transplanted teeth clinically appeared to become firmer with the passage of time. Progressive root resorption was not found and good results were obtained. This study shows that autotransplantation of third molars with complete root formation produces an acceptable result using the procedures outlined.
Adult↗
A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response.
The composition of high-density lipoprotein (HDL) changes during inflammation; however, potential changes of HDL function during inflammation and the effects of acute phase proteins that are either on the HDL particles or in the serum have not been clarified. The concentrations of C-reactive protein (CRP), serum amyloid A protein (apoSAA) isoforms, lipids and apolipoproteins, and the activities of lecithin-cholesterol acyltransferase (LCAT) and paraoxonase (PON) were measured before and after laparoscopic cholecystectomy, in 12 patients with cholecystolithiasis to clarify the function of acute-phase HDL and the relationship between acute-phase proteins and HDL functions. Both acute-phase apoSAA (A-apoSAA) and CRP increased, reached their maximum levels 3-6 days after the operation, and then returned to preoperative levels after 2 weeks. In contrast, apolipoproteins and LCAT decreased reciprocally, reached their minimum levels 3-6 days after the operation, and returned to preoperative levels after 2 weeks. However, PON decreased 3-6 days after the operation, and remained low even after 2 weeks. At the nadir the mean activities of LCAT and PON were 56 and 76% of the preoperative levels, respectively. HDL-cholesterol or constitutive apoSAA did not change significantly. LCAT has been reported to be involved in reverse-cholesterol transport and PON to be preventive for lipid peroxidation of low-density lipoprotein in vitro. Thus, during the acute phase of inflammation, HDL may be altered to an atherogenic state due to a decrease in LCAT and PON activities. Therefore, this longitudinal analysis was carried out to determine whether HDL function is modified in a single episode of inflammation and thus may contribute to the occurrence of atherosclerotic disease in patients with chronic or recurrent acute inflammation.
Acute-Phase Reaction↗
Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice.
To study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST-deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.
ATP-Binding Cassette Transporters↗
Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1.
Oral mucosal lesions are seen in most cases of pemphigus vulgaris, whereas they are only rarely seen in pemphigus foliaceus; however, both pemphigus vulgaris and pemphigus foliaceus sera show positive immunofluorescence staining on oral mucosa. To explain this apparent paradox, we examined the expression level of desmoglein (Dsg)3, pemphigus vulgaris antigen, and Dsg1, pemphigus foliaceus antigen, in human squamous mucosal epithelia and epidermis by immunofluorescence staining and immunoblotting. For immunofluorescence staining, Dsg isotype-specific antibodies were produced by immunoadsorbing pemphigus vulgaris sera with either recombinant Dsg1 or Dsg3 baculoprotein. In oral mucosa and esophagus both Dsg were immunoreactive on cell surfaces throughout the entire epithelia, but staining intensity was weaker for Dsg1 than for Dsg3. Immunoblotting was performed to compare Dsg1 and Dsg3 expression levels in extracts from epidermis and oral mucosa. The total amount of desmosomal proteins applied was adjusted to give the same degree of staining intensity for desmoplakin, a cytoplasmic plaque protein of desmosomes. In the mucosal extract, the Dsg1 band was much weaker than Dsg3, whereas in the epidermal extract the Dsg1 band was stronger than Dsg3. These data suggest that although Dsg1 and Dsg3 are expressed in a similar distribution throughout squamous mucosal epithelia, Dsg1 is expressed at a much lower level than Dsg3. This finding provides a good explanation for the paradox: even though anti-Dsg1 autoantibodies block the function of Dsg1 in the mucosal epithelia, Dsg3 may be sufficient for cell-cell adhesion, with consequently no apparent oral involvement in pemphigus foliaceus patients.
Autoantigens↗
Endogenous EGF-family growth factors are necessary for the progression from the G1 to S phase in human keratinocytes.
Recently several endogenous epidermal growth factor (EGF)-family growth factors (transforming growth factor-alpha, amphiregulin, and heparin-binding EGF-like growth factor) have been identified in human keratinocytes. These factors are known to play an important role in the regulation of cell proliferation. Here we show that the interaction between these factors and EGF receptor are key factors in the progression from the G1 phase to the S phase (the G1/S progression) in human keratinocytes. In this study, human keratinocytes were cultured in serum-free MCDB153 medium and then partially synchronized by isoleucine deprivation. After synchronization, the number of S phase cells increased and reached a maximum after 18-24 h. The immediate addition of anti-EGF receptor blocking antibody (1 microg per ml) to synchronized cells decreased S phase cells by 42.5% compared with untreated keratinocytes at 18 h. By contrast, the addition of anti-EGF receptor antibodies at 12 h or later did not alter the percentage of S phase cells. Northern blot analysis of synchronized cells demonstrated that mRNA expression of transforming growth factor-alpha, amphiregulin, heparin-binding EGF-like growth factor, and EGF receptor reached a maximum within 0.5-3 h after synchronization, when many cells initiated progression from the G1 to the S phase. The results show that anti-EGF receptor antibodies block the G1/S progression and the rapid increase of mRNA expression of endogenous EGF-family growth factors and EGF receptor during G1/S progression. These findings indicate that growth factor binding and EGF receptor activation are involved in the G1/S cell cycle progression of human keratinocytes.
Amphiregulin↗