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Biomedical subjects

A Shimada

Publications and source records attributed to A Shimada.

At least 127 records · Page 7Linked to original sources
PubMed1998

Aberrant expression of double-stranded RNA-dependent protein kinase in hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma.

We immunohistochemically analyzed the expression of double-stranded RNA-dependent protein kinase (PKR) using a monoclonal antibody, 71/10. Test samples included 64 human liver biopsies and 25 liver sections of rats inoculated with diethylnitrosamine. The PKR signals in human fatty livers and normal rat livers were minimum. Scoring signal intensity from 0-4, the average scores of chronic active (14 cases) and chronic persistent (6 cases) hepatitis associated with hepatitis virus C (HCV) were 2.8 and 2.0, respectively (P = 0.038). The stained cells were significantly more abundant in the periportal than centrilobular regions for both chronic active and persistent hepatitis (P < 0.001 each). The average score of liver cirrhosis associated with HCV was 1.9. Those scores of well-, moderately, and poorly differentiated hepatocellular carcinomas associated with HCV were 3.4, 2.1, and 0.3, respectively (P < 0.001 for each pair). Those scores of well- and poorly differentiated carcinomas associated with hepatitis virus B were 2.3 and 0.0, respectively (P < 0.001). The average score of rat carcinomas induced by diethylnitrosamine was 1.9. Morphologically, nuclei of the vast majority of PKR-positive cells looked not apoptotic. The ratio of PKR-positive cells to apoptotic cells by terminal transferase-mediated dUTP nick end labeling method was approximately 20 in hepatitis, and over 100 in well-differentiated carcinoma.

Animals↗
PubMed1998

Systemic delivery of interleukin 10 by intramuscular injection of expression plasmid DNA prevents autoimmune diabetes in nonobese diabetic mice.

We previously demonstrated that intramuscular plasmid injection serves as a useful method of long-term systemic delivery of cytokines. In the present study, we assess intramuscular DNA injection as a means of systemically delivering interleukin 10 (IL-10), a cytokine with immunosuppressive properties, and preventing the progression of autoimmune diabetes in the nonobese diabetic (NOD) mouse, an excellent model for human insulin-dependent diabetes mellitus (IDDM). We injected IL-10 expression plasmid (pCAGGS-IL10) or a control pCAGGS plasmid into the muscles of NOD mice twice at 3 and 5 weeks of age. IL-10 was detectable by ELISA in the sera of mice injected with pCAGGS-IL10 for more than 2 weeks after the injection. Although the severity of insulitis at 13 weeks of age was not improved by the intramuscular injection of pCAGGS-IL10, the incidence of diabetes was markedly reduced in NOD mice injected with pCAGGS-IL10 as compared with those injected with pCAGGS or as compared with nontreated NOD mice. These results show that the progression of autoimmune diseases in mice can effectively be suppressed by intramuscular DNA injection, and suggest that this method is potentially applicable to the treatment of human autoimmune diseases.

Animals↗
PubMed1998

Enzyme structure with two catalytic sites for double-sieve selection of substrate.

High-fidelity transfers of genetic information in the central dogma can be achieved by a reaction called editing. The crystal structure of an enzyme with editing activity in translation is presented here at 2.5 angstroms resolution. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly hydrolyzes only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has already been proposed. The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel domain that protrudes from the aminoacylation domain.

Adenosine Monophosphate↗
PubMed1998

Combination of genomic DNA fingerprinting into the medaka specific-locus test system for studying environmental germ-line mutagenesis.

A specific-locus test (SLT) system has been established using the medaka fish (Oryzias latipes), where recessive visible mutations (at the b, lf or gu loci) detected during early embryonic stages (TM) or after hatching (VM), and dominant lethals (DL) can be examined in the same individual F1 progeny of treated parents. It was found that approximately 90% of the F1 embryos with gamma-ray-induced specific-locus mutations were concomitantly accompanied by dominant lethals irrespective of doses and germ-cell stages at the time of exposure, suggesting that DNA alterations in such mutants might include both the marker loci and region(s) responsible for dominant lethals. In contrast, embryonic lethality of the ENU (ethylnitorosourea)-induced specific-locus mutants considerably varied among ENU concentrations as well as germ-cell stages treated. Further, synergistic effect of combined treatments with gamma-rays and ENU on induction of mutations were suggested in postmeiotic male germ cells, while in spermatogonia no synergistic effect was found. DNA alterations at the 87 arbitrarily primed polymerase chain reaction (AP-PCR) markers spread over the genome were examined for individual dominant lethal embryos from 4.75 Gy-irradiated sperm or spermatids. It was found that, 14 out of 20 dominant lethal embryos lost more than one AP-PCR markers, including multiple markers located on the identical linkage group (average genetic distances, approximately 11 cM). Also found was that frequency of loss of the AP-PCR markers in the severely malformed dominant lethal embryos was higher (approximately 4.5%) than that in the slightly malformed lethal embryos (approximately 1.6%). Here, results of these studies, including previously unpublished work, are presented to illustrate the potential usefulness of the medaka SLT system for monitoring environmental mutagens.

Animals↗
PubMed1998

Biliary cirrhosis secondary to obstruction of the common bile duct by ectopic pancreas in a cow.

A 10-year-old Japanese Black cow showed icterus with gradual emaciation for a period of 3 months. Ultrasonography demonstrated increased "echogenicity" of the entire liver, with marked dilatation of the gall-bladder. At necropsy, the common bile duct was found to be obstructed by focally thickened fibrous tissue adjacent to a flesh-like mass (9 x 4 x 4 mm) attached to the wall of the duct. The mass consisted of normal pancreatic tissue. The liver showed moderate fibrosis, with nodular regeneration of the hepatic tissue and bile duct hyperplasia. A diagnosis of biliary cirrhosis secondary to ectopic pancreas in the common bile duct was made.

Animals↗
PubMed1998

Cryopreservation and ensuing in vitro fertilization ability of boar spermatozoa from epididymides stored at 4 degrees C.

The influence of prolonged storage of boar epididymides on post-thaw sperm motility, and in vitro fertilization was evaluated. Twenty pairs of epididymides were obtained from Large White boars, and spermatozoa from one of each of the pairs were immediately collected and frozen (control group). The remaining epididymides were cooled to 4 degrees C and stored for 1, 2 or 3 d, after which spermatozoa were collected and frozen (experimental groups Day 1, 2 and 3, respectively). Sperm motility was maintained throughout the dilution procedure and then dropped (P < 0.01) after freezing and thawing. During storage the motility of nonfrozen spermatozoa decreased significantly (P < 0.01), reaching a value equal to that of frozen-thawed spermatozoa on Day 3. In vitro fertilization experiments revealed significantly (P < 0.05) lower penetration rates using Day 1, 2 and 3 stored spermatozoa (12, 13 and 2%, respectively) than that of the control group (40%). Oocyte penetration ability seemed to be reflected by acrosome integrity. However, the motility of spermatozoa with the ability to penetrate oocytes in Day 1 and Day 2 groups did not differ from that of the controls. The motility of spermatozoa lacking penetration ability, on the other hand, gradually decreased as the storage period was prolonged. This suggests that the sperm motility and penetration ability are affected by different mechanisms during the cold storage of epididymides. Finally, control and experimental groups exhibited high incidences of monospermic penetration (64 to 90%) and of male pronuclear formation (67 to 71%). These data suggest that cryopreservation of spermatozoa from boar epididymides stored at 4 degrees C for 1 to 2 d can be used for conserving male germ cells when epididymal spermatozoa can not be collected immediately and cryopreserved.

Acrosome↗
PubMed1998

Putative hyaluronan synthase mRNA are expressed in mouse skin and TGF-beta upregulates their expression in cultured human skin cells.

We examined in situ expression of putative hyaluronan synthase genes, Has1 and Has2, and effects of transforming growth factor-beta on their expression. In situ mRNA hybridization showed that mouse skin expressed both Has1 and Has2 mRNA in dermis and epidermis. In dermis, the number of cells expressing the Has1 mRNA was less than that of the Has2 mRNA, and in epidermis, some strong signals from both mRNA were seen in stratum granulosum. Northern blot analysis showed that cultured human skin fibroblasts expressed Has1 mRNA of 2.4 kb and Has2 mRNA of 3.2 and 4.8 kb, whereas human keratinocytes expressed Has1 mRNA of 4.8 but not 2.4 kb and a trace of Has2 mRNA. When the cultures were stimulated with transforming growth factor-beta, both Has1 and Has2 mRNA were upregulated in fibroblasts, and only Has1 mRNA of 2.4 but not 4.8 kb was induced in keratinocytes. The maximal amount of the upregulated Has1 mRNA in keratinocytes at 2 h after stimulation decreased time-dependently to the nonstimulated level at 18 h, although the stimulation for 18 h of fibroblasts was effective on the expression of both Has mRNA. Differences in expression pattern of Has and Has2 mRNA in mouse skin and a higher response of fibroblasts to transforming growth factor-beta suggest that Has1 and Has2 genes are regulated independently and synthesized hyaluronan may have a different function in epidermis and dermis.

Animals↗
PubMed1998

In situ expression of platelet-activating factor (PAF)-receptor gene in rat skin and effects of PAF on proliferation and differentiation of cultured human keratinocytes.

Platelet-activating factor (PAF) is a potent lipid mediator that exhibits versatile biologic activities in many diverse systems by binding to a specific cell-surface receptor (PAFR). Although the production of PAF in cultured keratinocytes and fibroblasts has been reported, physiologic roles of this mediator in skin remain unclear. In this study, we examined in situ expression of PAFR gene in rat skin and the effects of PAF on the proliferation and differentiation of cultured human keratinocytes. In rat epidermis, PAFR mRNA expression was found from the basal cells to the granular cells, and strong signals were seen in the stratum spinosum. In cultured human keratinocytes, a 3.8 kb PAFR mRNA expression was demonstrated by northern blotting, and two distinct type transcripts driven by different promoters were detected by reverse transcriptase polymerase chain reaction analysis. Addition of PAF (30-100 nM) to cultured keratinocytes during a growth phase inhibited the proliferation. This effect was receptor dependent, because the inhibition was completely blocked by a PAFR antagonist, WEB 2086 (100 nM). On the other hand, whereas PAF (30-100 nM) alone did not affect the cornified envelope formation during the process of keratinocyte differentiation, WEB 2086 (30-300 nM) accelerated it in a concentration-dependent manner. Addition of PAF (100 nM) reversed the effect of WEB 2086, suggesting that WEB 2086 induced cornification by inhibiting PAF endogeneously produced by keratinocytes in an autocrine manner. Thus, we propose that PAF is an intrinsic regulator of keratinocyte during proliferation and differentiation.

Animals↗
PubMed1998

Holmium laser resection of the prostate.

A total of 35 patients with benign prostatic hyperplasia (BPH) were treated with the Ho: YAG laser using a new technique termed holmium laser resection of the prostate or HoLRP. The laser energy was applied directly to prostatic tissue exclusively through the use of a standard 550 micron end-firing fiber. A high-powered holmium laser was used and was set at 2.4 J per pulse at 25 pulses per second for an average power of 60 W. The mean preoperative AUA Symptom Score was 24. Postoperatively, the score dropped to 10.9, 8.2, 5.2, and 4.6 at 1 week, 1 month, 3 months, and 6 months, respectively. The peak urine flow rate improved from 6.3 mL/sec preoperatively to 15.1, 15.3 and 16 mL/sec at 1 week, 1 month, 3 months, and 6 months. A foley catheter was removed within 24 hours of completion of the operation in 31 patients (89%), and voiding was improved. The HoLRP technique was bloodless, and the short-term results were satisfactory. Most importantly, the defect produced by HoLRP is identical to that of a conventional transurethral resection. These initial results demonstrate that HoLRP is a useful surgical alternative in the treatment of patients with obstructive BPH.

Diuresis↗
PubMed1998

Comparison of static mechanical properties of the passive pharynx between normal children and children with sleep-disordered breathing.

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.

Adenoids↗
PubMed1998

Localization of metallothionein-I and -II in hypertrophic astrocytes in brain lesions of dogs.

To study the neurophysiological functions of metallothioneins (MTs), localization of MT-I and -II was examined immunohistochemically in a variety of brain lesions in dogs, including infarct, laminar cortical necrosis, hemorrhage, invasive growth of tumour, inflammatory lesions in granulomatous meningoencephalitis and distemper encephalitis. MT-I and -II were demonstrated in both nucleus and cytoplasm of hypertrophic astrocytes in most brain lesions examined regardless of the type, size, localization and duration of the lesions. In addition, MT expression was stronger in a population of hypertrophic astrocytes localizing inside of the surviving brain tissue rather than those localizing at the boundary between the surviving brain tissue and necrotic area, where severe inflammatory changes were developing. These results suggest that MT-I and -II may play roles not only in protection of neurons from metals and free radicals ubiquitous in the inflammatory lesions but also in repair of injured neural tissues.

Adenocarcinoma↗
PubMed1998

Age-related changes in the cochlea and cochlear nuclei of dogs.

To study the underlying morphological changes of presbycusis, cochlea and cochlear nuclei from twenty three dogs, ranging in age from 3 days to 17 years, were examined histologically. Dogs used in this study were house dogs kept in an environment similar to that of humans. Four types of histological changes reported in human presbycusis, that is, loss of spiral ganglion cells, atrophy of the organ of Corti, atrophy of the stria vascularis, and thickening of the basilar membrane were observed in dogs. The changes were prominent at the base of the cochlea. Less intense changes were also observed in the apex of the cochlea. The degree of these changes appeared to progress as a function of age. All four types of changes with varied intensity were found in all dogs over 12 years old. In addition to the changes in the cochlea, cochlear nuclei changes including nerve cell loss, astrogliosis and ubiquitin deposition were found in dogs over 10 years old. Hearing dysfunction was accompanied by the morphological changes, though the degree of the hearing dysfunction did not always parallel to that of morphological changes. The morphological changes seen in the cochlea and cochlear nuclei of dogs were qualitatively and quantitatively similar to those reported in aged humans, indicating that otopathologic changes in the inner ear may be due to aging plus exposure to certain environmental ototoxic factors.

Aging↗
PubMed1998

Encephalitis in mice inoculated intranasally with an influenza virus strain originated from a water bird.

Five-week-old ddY mice were inoculated intranasally with a low virulent (4e) or highly virulent (24a5b) avian influenza virus strain originated from a water bird. None of mice in the 4e group showed clinical signs and brain lesions. Of the 24a5b group, two mice died and one mouse was killed at a moribund state at day 7 post-inoculation (PI). Four mice of the 24a5b group necropsied at day 5 or 7 PI had mild to severe encephalitis in the brain stem and the cerebellar white matter. Influenza virus antigen was detected in neurons, glial cells and vascular endothelium in the lesions. The distribution of the lesions seems to indicate the transneuronal invasion of the virus via cranial nerve fibers into the brain.

Animals↗
PubMed1998

Serological survey of antibody to Neospora caninum in Japanese dogs.

Prevalence of antibody to Neospora caninum (NC) in Japanese dogs were examined. The antibody was positive in 15 of 48 dogs (31.3%) reared in the dairy farms that had case of the abortions due to NC infection or had the cattle seropositive to NC, whereas the prevalence was 7.1% (14 of 198 dogs) among the dogs kept in urban areas. In one dog breeder, all 17 Shetland sheepdogs older than 7 months were seropositive, and one pup was diagnosed as neosporosis 2 months before the first serological examination. The antibody titers of the dogs kept at this breeder were almost unchanged for 1.5 years. Serological evidence of the dogs in the dairy farms and urban areas indicates the transmission of NC between dogs and cattle. Also serological results of the dogs in one breeder may suggest the potential horizontal transmission among dogs.

Abortion, Veterinary↗
PubMed1998

Malignant insulinoma with extensive liver metastases presenting as disturbance of consciousness.

A 56-year-old man was referred to our hospital for evaluation of episodic disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver metastases were found by abdominal computed tomography (CT). Based on the finding of liver biopsy, the final diagnosis was malignant insulinoma with liver metastasis. He selected conservative treatment and no hypoglycemic crisis has occurred for one year since discharge. Early diagnosis and long-term follow-up is necessary since this tumor is slow growing.

Blood Glucose↗
PubMed1998

Molecular cloning and expression of the canine metallothionein-III gene.

We have isolated and determined the complete nucleotide sequence of canine metallothionein-III (MT-III) cDNA. The predicted amino acid sequence of the canine MT-III showed a high homology (93%, 87% identity) to that of human and mouse MT-III. The canine MT-III had 2 insertions relative to known mammalian MT-I and MT-II: a threonine after the 4th amino acid and a block of 6 amino acids near the carboxyl terminus. Expression of the canine MT-III mRNA was found exclusively in the central nervous system, where neurons in the olfactory bulb, hippocampus and cerebral cortex showed predominant signals.

Amino Acid Sequence↗