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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 361 records · Page 20Linked to original sources

Dilatation and constriction of rat gastric mucosal microvessels through prostaglandin EP2 and EP3 receptors.

BACKGROUND: Prostaglandin (PG)E2 has both a vasodilating action and a protective function in the gastric mucosa. There are four subtypes of PGE2-sensitive, or EP, receptors. AIM: To identify the subtype of EP receptors in the microvessels of the rat gastric mucosa using EP2 and EP3 receptor agonists. METHODS: The posterior wall of the anaesthetized rat stomach was secured in a chamber and superfused with Tyrode's solution, and the gastric microcirculation of the mucosal base was observed through a window with transillumination. PGE2 and its derivatives (20 microL) were applied topically in the window. RESULTS: PGE2 (0.001-10 micromol/L), misoprostol (EP2/EP3 receptor agonist; 0.01-100 micromol/L) and butaprost (EP2 receptor agonist; 1-1000 micromol/L) dilated the arterioles dose-dependently, but M&B 28 767 (EP3 receptor agonist; 0.001-10 micromol/L) did not alter their diameters. M&B 28 767 constricted the venules and collecting venules dose-dependently whereas butaprost dilated them. PGE2 and misoprostol had bell-shaped dose-response curves: constriction by low doses of PGE2 and misoprostol (0.001-0.1 micromol/L and 0.01-1 micromol/L) and dilation by high doses of PGE2 and misoprostol (0.1-100 micromol/L and 1-100 micromol/L). CONCLUSIONS: These results suggest that PGE2 dilated both arterioles and venules in the rat gastric mucosa through the EP2 receptors and constricted the venules through the EP3 receptors.

Alprostadil↗

Antibody-independent classical complement pathway activation and homologous C3 deposition in xeroderma pigmentosum cell lines.

Of human malignantly transformed cell lines, xeroderma pigmentosum (XP) cell lines were found to be highly susceptible to homologous complement (C): cells were opsonized by C3 fragments on incubation with diluted normal human serum. C3 fragment deposition on XP cells was Ca2+-dependent and occurred on live cells but not UV-irradiated apoptotic cells. (Ca2+ is required for activation of the classical C pathway via C1q and the lactin pathway via mannose binding lectin (MBL), and the surface of apoptotic cells usually activates the alternative C pathway.) In this study we tested which of the pathways participates in XP cell C3 deposition. In seven cell lines that allowed C3 deposition (i), Clq was shown to be essential but MBL played no role in C activation, (ii) Cls but not MASP bound XP cells for activation, (iii) no antibodies recognizing XP cells were required for homologous C3 deposition, and (iv) the alternative pathway barely participated in C3 deposition. Furthermore, the levels of C-regulatory proteins for host cell protection against C, decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), were found to be relatively low in almost all XP cell lines compared with normal cells. These results indicate that XP cells activate the classical C pathway in an antibody-independent manner through the expression of a molecule which directly attracts C1q in a C-activating form, and that relatively low levels of DAF and MCP on XP cells facilitate effective C3 deposition. The possible relationship between the pathogenesis of XP and our findings is discussed.

Antibodies↗

Association of CTLA-4 polymorphism with positive anti-GAD antibody in Japanese subjects with type 1 diabetes mellitus.

OBJECTIVE: CTLA-4, expressed on activated T cells, is thought to be a negative regulator of T cell function. Its gene (2q33) may confer genetic susceptibility to type 1 diabetes mellitus (IDDM12). The present study was undertaken to clarify the role of CTLA-4 gene polymorphism in Japanese subjects with type 1 diabetes and its effect on their clinical features. SUBJECTS AND METHODS: In 117 Japanese subjects with type 1 diabetes, the CTLA-4 exon 1 polymorphism (49 A/G) was defined by PCR-RFLP analysis. Anti-GAD antibodies (GAD-Ab) and fasting serum C-peptide were also determined. 141 healthy age- and sex-matched subjects served as controls. RESULTS: The frequency of each polymorphism was not different between the type 1 diabetic subjects and the controls; AA 21, AG 42 and GG 54 for the diabetic subjects, and AA 22, AG 47 and GG 72 for the controls. The frequency of the GG genotype was higher in the diabetic subjects with positive GAD-Ab (greater than 8 U/ml) (67%) than in the GAD-Ab negative subjects (39%) (P < 0.05). The prevalence of positive GAD-Ab declined with the duration of diabetes. In the diabetic subjects with disease duration of less than 5 years (n = 40), the frequency of the GG genotype was also higher in the GAD-Ab positive subjects (71%) (P < 0.05). In the analysis of all the diabetic subjects, there was a strong association between positive GAD-Ab and beta cell function (P < 0.0001). CONCLUSIONS: There was no evidence that the CTLA-4 exon 1 polymorphism (49 A/G) confers genetic susceptibility to type 1 diabetes mellitus in our case-control study in Japanese subjects. However, the frequency of positive GAD-Ab was higher in the GG subjects. CTLA-4 polymorphism might contribute to the clinical heterogeneity of type 1 diabetes mellitus in Japanese subjects.

Abatacept↗

Purification and characterization of thyroid-hormone-binding protein from masu salmon serum. A homolog of higher-vertebrate transthyretin.

We purified a thyroid-hormone-binding protein (THBP) from serum of masu salmon at the stage of smoltification when the concentrations of endogenous thyroid hormones in plasma reach the highest levels. All steps of sequential column chromatography suggest that this THBP is responsible for most L-3,5,3'-triiodothyronine-binding activity in serum at this stage. The molecular mass of this protein was estimated to be 60 kDa by gel filtration but only 15 kDa by SDS/PAGE, which suggests that it is comprised of four identical subunits. The amino acid sequence of its N-terminal portion was highly similar to those of vertebrate transthyretins. These molecular features indicate that masu salmon THBP is a homolog of transthyretins from tetrapods. However, in contrast with mammalian transthyretins, the affinity of masu salmon transthyretin for L-3,5,3'-triiodothyronine was three times greater than for L-thyroxine. This rank order affinity is similar to that of avian and frog transthyretins. Scatchard analysis revealed that masu salmon transthyretin possesses a single class of binding site for L-3,5,3'-triiodothyronine, with a Kd of 13.8 nM at 0 degrees C. Taken together with the data reported by Chang et al. [Eur. J. Biochem. (1999) 259, 534-542], these results suggest that transthyretin has changed from a L-3,5, 3'-triiodothyronine-carrier protein to a L-thyroxine-carrier protein during mammalian evolution.

Amino Acid Sequence↗

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients.

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.

Antibodies, Viral↗

Estrogen receptor mRNA in uteri of normal estrous cycling and ovariectomized rats by in situ hybridization.

Biological effects of estrogen are mediated via its binding to the estrogen receptor (ER), the contents of its protein and mRNA varying during the estrous cycle. In the present study, the ERalpha mRNA expression in different cell components of the uterus was investigated in normal estrous cycling rats using nonisotopic in situ hybridization. Additionally, ovariectomized (OVX) rats treated with 17beta-estradiol (E2: 5 microg/kg, sc injection daily) were also investigated to clarify the effects of exogenous E2. At proestrus and diestrus, and especially the former, the luminal and glandular epithelial (LE and GE) cells were strongly positive, along with stromal cells beneath the luminal epithelium. At estrus, the expression was slightly diminished in LE cells, but almost completely lacking in GE cells. At metestrus, positive signals appeared again in GE cells. In the myometrium, ER mRNA was demonstrated to be constantly positive in all estrous cycle stages. OVX rat uteri underwent marked atrophy, but ER mRNA still remained in all cell types. After 2 consecutive days of E2 treatment, markedly increased intensity was observed, especially in LE and GE cells. The uteri of OVX rats treated with E2 for 14 days, however, showed slightly diminished expression, whereas the serum concentration of E2 was comparable to that in rats after 2 days. These results provide evidence that cell-type specific patterns of ER mRNA expression characterize the uteri of both normal estrous cycling rats and OVX rats after estrogen treatment.

Animals↗

The fourth-compartment syndrome: its anatomical basis and clinical cases.

We propose a new term, the "fourth-compartment syndrome" to describe chronic dorsal wrist pain of the fourth compartment. Five main causes responsible for this syndrome are thought to be as follows: 1. Ganglion involvement, including an occult ganglion; 2. Extensor digitorum brevis manus muscle; 3. Abnormal extensor indicis muscle; 4. Tenosynovialitis; 5. Anomaly or deformity of carpal bones. Should the above mentioned conditions occur in the fourth compartment, pressure within the fourth compartment increases, ultimately compressing the posterior interosseous nerve directly or indirectly. Anatomical studies of the fourth compartment of the wrist and the posterior interosseous nerve are presented and the fourth-compartment syndrome is summarized with twelve clinical cases (six cases of occult ganglions, two cases of extensor digitorum brevis manus, two cases of tenosynovialitis, one case of abnormal extensor indicis muscle, and one case of carpal bossing).

Adolescent↗

Prothiofos metabolites in human poisoning.

CASE REPORT: A 63-year-old woman was admitted to a local hospital after the ingestion of 40% prothiofos preparation (Tokuthion) 370 mL. Gastric lavage was performed and cathartics, active charcoal, diuretics, atropine sulfate, and pralidoxime were administered. Serum cholinesterase activity was 1.3 IU/L (normal 200-460 IU/L). The patient's consciousness was gradually restored after 4 hours of charcoal hemoperfusion and she was discharged 5 days after admission with no sequelae. METHOD: Plasma and urine prothiofos and metabolites were detected by gas chromatography-flame photometry and gas chromatography-mass spectrometry. Two despropyl metabolites were synthesized for identification and estimation. RESULTS: The main metabolites were identified with authentic prothiofos and methyl esters of synthesized des-S-propyl prothiofos oxon (O-2,4-dichlorophenyl O-ethyl phosphate), despropyl prothiofos oxon (O-2,4-dichlorophenyl O-ethyl phospholothiolate), and des-S-propyl prothiofos (O-2,4-dichlorophenyl O-ethyl phosphorothioate). Despropyl prothiofos (O-2,4-dichlorophenyl O-ethyl phosphorodithioate) was also identified in plasma. Large amounts of the hydrolyzed product, 2,4-dichlorophenol and its conjugate were also found. The metabolic pattern of prothiofos in humans appears to be different from that in rats.

Charcoal↗

Atypical adenomatous hyperplasia of the lung. Implications for the pathogenesis of peripheral lung adenocarcinoma.

Bronchioloalveolar lung carcinoma (BAC) exhibits many features that distinguish it from bronchogenic carcinomas. For early detection, therapy, and prevention of BAC, it is essential to understand its pathogenesis. Development of BAC appears to be stepwise, and the earliest lesion to be recognized is atypical adenomatous hyperplasia (AAH), the proliferative lesion of atypical epithelial cells along the alveolar septa. Our review of the studies of AAH revealed that certain populations of AAH cells exhibit active proliferation, aneuploidy, 3p and 9p deletions, K-ras codon 12 mutation, and disruption of the cell cycle control, but p53 gene aberrations are rare and telomerase activation is absent. We emphasize that AAH is an alveolar intraepithelial neoplasia. This allows more precise analyses of the process and mechanism of the development of BAC. Furthermore, AAH could serve as a surrogate end-point biomarker in future chemoprevention trials. The criteria for the diagnosis of AAH and related lesions should be established as early as possible.

Adenocarcinoma↗

Codon 72 polymorphism of p53 as a risk factor for patients with human papillomavirus-associated squamous intraepithelial lesions and invasive cancer of the uterine cervix.

Squamous intraepithelial lesions (SIL) and invasive cancer of the uterine cervix are thought to be a series of lesions derived from normal cervical squamous tissue. Infection by high risk human papillomavirus (HPV) and integration of viral DNA may initially lead normal cervical cells to become pre-malignant cells in SIL and result in cervical malignancies later on. High risk HPVs, including types 16 and 18, produce a viral protein, E6, which is required for viral replication in host cells. The E6 protein is able to bind to host p53 causing inactivation of its function through the mechanism of ubiquitin-dependent degradation. It has recently been reported that the extent of p53 dysfunction caused by HPVs depends on the status of a polymorphism at codon 72 of p53, Pro or Arg. In that study, it was demonstrated that a patient homozygous for the Arg allele had about a seven times higher risk of developing cervical cancer than a patient homozygous for Pro. In an attempt to confirm this result and elucidate whether this allelic deviation of the Arg genotype seen in invasive cervical cancer occurs in the pre-malignant lesion SIL, we analyzed 219 SIL and 101 invasive cancer samples from Japanese patients using a PCR-based assay. Samples from 88 SIL and 76 invasive cancers were identified as HPV-infected samples and used for further analyses. In these, the frequencies of Arg homozygotes were 31.8, 33.0 and 36.8% in controls, SIL and invasive cancer, respectively. The distributions of the different alleles of codon 72 (Pro/Pro, Pro/Arg and Arg/Arg) did not show significant differences between either control and SIL groups or control and invasive cancer groups. Also, no difference in the frequency of Arg/Arg genotype was detected even between the control and HSIL groups or control and invasive cancer infected with high risk HPVs groups. In conclusion, there was no obvious relationship between the Arg genotype at codon 72 of p53 and predisposition to HPV-associated cervical neoplasia.

Amino Acid Sequence↗

Antidepressant treatment of patients with diffuse esophageal spasm: a psychosomatic approach.

The cause of diffuse esophageal spasm (DES) has not been clearly established, and effective treatment is lacking. To determine whether a psychosomatic approach can be effective in treating DES patients, nine patients and 26 healthy volunteers were studied. Esophageal manometry and psychological testing were performed in both groups. The psychological background of the DES patients was investigated. Psychiatric diagnoses were made according to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. The authors started psychosomatic treatment with isosorbide dinitrate for 1 month, then prescribed serotonin reuptake inhibitor antidepressants for an additional month. Anxiety and depression scores were substantially higher for the DES group than for the control group. Five of the nine DES patients (56%) were diagnosed as having major psychiatric disorders. Only one patient showed improvement with isosorbide dinitrate, and eight patients improved with antidepressants. These initial observations suggest that psychosomatic treatment with antidepressants may be effective in the treatment of DES.

Adult↗

Macrocystic schwannoma in the seventh cervical nerve.

We have recently treated a case of asymptomatic macrocystic schwannoma discovered between the left neck and the supraclavicular fossa. The tumor, originating from the left seventh cervical nerve, was extirpated. Nearly 70 percent of the tumor area showed macrocyst with transparent fluid collection. The tumor was diagnosed as macrocystic schwannoma histopathologically. Schwannoma is often associated with small cysts but rarely with macrocysts. Because schwannoma is a benign tumor, partial resection against an attempt at total removal resulting in progressive neurologic deficits is recommended. In general, schwannoma does not present any apparent symptoms at an early stage, because it occurs and progresses very slowly. Schwannoma originating at the spinal nerve root has been called a dumbbell-shaped tumor because of its characteristic shape on MRI and cystogram images. We recently have treated a case of dumbbell-shaped tumor that was an asymptomatic macrocystic schwannoma in the seventh cervical nerve.

Adult↗

The hsp operons are repressed by the hrc37 of the hsp70 operon in Staphylococcus aureus.

The heat-shock proteins are coded for the polycistronic operons hsp70 and hsp60 in Staphylococcus aureus. The hsp70 operon is comprised of five genes, hrc37, hsp20, hsp70, hsp40 and orf35, and the hsp60 is comprised of two genes, hsp10 and hsp60. The hsp70 operon transcribed five different sizes of mRNA from three promoters: P1, the most active promoter, transcribed 6.0 and 3.6 kb mRNAs; P2 transcribed a single 1.8 kb mRNA; and P3 transcribed 4.2 and 2.4 kb mRNAs. The hsp60 operon transcribed a single 2.1 kb transcript from only one promoter, P1. Both operons had a common structure of inverted repeat element (CIRCE, Controlling Inverted Repeat of Chaperon Expression) at the promoter region. All of the transcripts were heat (46 C) inducible. One of the unidentified genes, hrc37, was characterized. The disruptant of the hrc37 in the hsp70 operon enhanced the transcription of both operons at 37 C (derepression). Complementation of the disruptant with the cloned hrc37 plasmid recovered the repression of the transcription of both operons at 37 C. The product of hrc37, Hrc37, was found to bind to the CIRCE element. These findings indicated that Hrc37 from the hsp70 operon repressed the transcription of both the hsp70 and hsp60 operons by binding to the CIRCE element located at the promoter region.

Base Sequence↗

Chromosome-determined zinc-responsible operon czr in Staphylococcus aureus strain 912.

A novel operon, czrAB (zinc-responsible genes), was identified in the chromosome of Staphylococcus aureus. The operon consists of two genes, czrA and czrB. The czrA gene, coding for an 11.5 kDa protein, was homologous to cadC, arsR of S. aureus plasmid pI258 and smtB of Synechococcus PCC7942. The czrB, coding for a 36 kDa membrane spanning protein, was homologous to the czcD gene, cobalt, zinc and the cadmium-resistant factor of Bacillus subtilis and Alcaligenes eutrophus. In the presence of zinc (0.1-10 mM), the transcription of czrAB was enhanced in a concentration-dependent manner. Other heavy metals, such as cobalt, copper, manganese and nickel showed no effect on czrAB expression. The disruptant of the czrB gene became sensitive to zinc ion (MIC, 2 mM; MBC, 10 mM), and the complementation with the plasmid recovered the resistance to zinc at the same concentration as a parental strain (MIC, 5 mM; MBC, 20 mM). The disruptant accumulated intracellular zinc up to 0.4 mg per g dry weight of the organism, while that of the parental strain was 0.25 mg per g dry weight. The findings indicated that the novel operon czrAB should play a role in the transportation of zinc across the cell membrane to maintain the proper intracellular concentration.

Amino Acid Sequence↗

Wakame seaweed suppresses the proliferation of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in rats.

We examined the anti-tumor proliferation effects of wakame seaweed on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced rat mammary tumor. DMBA was administered to 8-week-old female Sprague-Dawley rats, and rats which developed mammary tumors were assigned randomly to three groups. Commercial rat feed was used in a control group (group I-A), and two feed mixtures were prepared, which contained commercial rat feed blended with wakame at 1.0% (group I-B) and 5.0% (group I-C) by weight. The respective feeds were given to each group for 8 weeks, and changes in mammary tumor size were compared. At the end of the experiment, mammary tumors and thyroid glands were resected to compare their weights. Serum total iodine and thyroxin (T4) levels were measured. Immunohistochemical studies for bromodeoxyuridine (BrdU) labeling, transforming growth factor (TGF)-beta, and apoptosis were carried out in the resected tumor. Significant suppression of tumor growth was observed in groups I-B and I-C compared with I-A. In groups I-B and I-C, the weights of resected mammary tumors were significantly lower and serum total iodine concentration was significantly higher than in I-A. BrdU indices were significantly lower in groups I-B and I-C, compared with I-A. TGF-beta and apoptotic index were inversely related to BrdU. These results suggest that iodine is transported from the serum into mammary tissues and induces apoptosis through the expression of TGF-beta. In conclusion, wakame suppressed the proliferation of DMBA-induced mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗

ST segment elevation in the right precordial leads induced with class IC antiarrhythmic drugs: insight into the mechanism of Brugada syndrome.

We evaluated two patients without previous episodes of syncope who showed characteristic ECG changes similar to Brugada syndrome following administration of Class IC drugs, flecainide and pilsicainide, but not following Class IA drugs. Patient 1 had frequent episodes of paroxysmal atrial fibrillation resistant to Class IA drugs. After treatment with flecainide, the ECG showed a marked ST elevation in leads V2 and V3, and the coved-type configuration of ST segment in lead V2. A signal-averaged ECG showed late potentials that became more prominent after flecainide. Pilsicainide, a Class IC drug, induced the same ST segment elevation as flecainide, but procainamide did not. Patient 2 also had frequent episodes of paroxysmal atrial fibrillation. Pilsicainide changed atrial fibrillation to atrial flutter with 2:1 ventricular response, and the ECG showed right bundle branch block and a marked coved-type ST elevation in leads V1 and V2. After termination of atrial flutter, ST segment elevation in leads V1 and V2 continued. In this patient, procainamide and quinidine did not induce this type of ECG change. In conclusion, strong Na channel blocking drugs induce ST segment elevation similar to Brugada syndrome even in patients without any history of syncope or ventricular fibrillation.

Anti-Arrhythmia Agents↗