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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 73 records · Page 4Linked to original sources

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

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

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

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

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

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

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

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

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

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

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

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

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