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Biomedical subjects

I Hayashi

Publications and source records attributed to I Hayashi.

At least 73 records · Page 4Linked to original sources

Primary amebic meningoencephalitis due to Naegleria fowleri: an autopsy case in Japan.

Free-living amebas represented by Naegleria fowleri, Acanthamoeba and Balamutia have been known to cause fatal meningoencephalitis since Fowler and Carter (1965) reported the first four human cases. An autopsy case of a 25-year-old female with primary amebic meningoencephalitis (PAM) due to Naegleria fowleri is described. Headache, lethargy and coma developed in this patient, and her condition progressed to death 8 days after the onset of clinical symptoms. Cerebral spinal fluid examination confirmed clusters of amebas, which were grown in culture and identified as Naegleria fowleri. At autopsy, lesions were seen in the central nervous system (CNS) and the ethmoid sinus. The CNS had severe, suppurative meningoencephalitis with amebic trophozoites mingled with macrophages. This case is the first report of PAM due to Naegleria fowleri in Japan.

Adult↗

Pineal malignant rhabdoid tumor with chondroid formation in an adult.

A pineal tumour in a 27-year-old male is presented with the characteristic histological features of a pineal malignant rhabdoid tumor (MRT) with chondroid formation. Occasionally, tumor cells contained a single well-demarcated hyaline globular inclusion within the cytoplasm adjacent to the nucleus. The stroma of these tumors tends to be densely hyalinized and become chondroid. Immunohistochemical staining was positive for vimentin, epithelial membrane antigen, chromogranin A, synaptophysin, neuron-specific enolase, S-100 protein, and muscle actin. Despite surgery and radiochemotherapy, the tumor recurred in the pineal region and metastasized to the lower lobe of right lung. The patient died 2 years after the initial diagnosis. This is the second published case of central nervous system-MRT appearing in an adult. The clinical and pathological features of pineal MRT in this patient are presented.

Adult↗

Functional interactions of a homolog of proliferating cell nuclear antigen with DNA polymerases in Archaea.

Proliferating cell nuclear antigen (PCNA) is an essential component of the DNA replication and repair machinery in the domain Eucarya. We cloned the gene encoding a PCNA homolog (PfuPCNA) from an euryarchaeote, Pyrococcus furiosus, expressed it in Escherichia coli, and characterized the biochemical properties of the gene product. The protein PfuPCNA stimulated the in vitro primer extension abilities of polymerase (Pol) I and Pol II, which are the two DNA polymerases identified in this organism to date. An immunological experiment showed that PfuPCNA interacts with both Pol I and Pol II. Pol I is a single polypeptide with a sequence similar to that of family B (alpha-like) DNA polymerases, while Pol II is a heterodimer. PfuPCNA interacted with DP2, the catalytic subunit of the heterodimeric complex. These results strongly support the idea that the PCNA homolog works as a sliding clamp of DNA polymerases in P. furiosus, and the basic mechanism for the processive DNA synthesis is conserved in the domains Bacteria, Eucarya, and Archaea. The stimulatory effect of PfuPCNA on the DNA synthesis was observed by using a circular DNA template without the clamp loader (replication factor C [RFC]) in both Pol I and Pol II reactions in contrast to the case of eukaryotic organisms, which are known to require the RFC to open the ring structure of PCNA prior to loading onto a circular DNA. Because RFC homologs have been found in the archaeal genomes, they may permit more efficient stimulation of DNA synthesis by archaeal DNA polymerases in the presence of PCNA. This is the first stage in elucidating the archaeal DNA replication mechanism.

Amino Acid Sequence↗

Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice.

Various cytokines utilize Janus kinase (JAK) and the STAT (signal transducers and activators of transcription) family of transcription factors to carry out their biological functions. Among STATs, two highly related proteins, STAT5a and STAT5b, are activated by various cytokines, including prolactin, growth hormone, erythropoietin, interleukin 2 (IL-2), and IL-3. We have cloned a STAT5-dependent immediate-early cytokine-responsive gene, CIS1 (encoding cytokine-inducible SH2-containing protein 1). In this study, we created CIS1 transgenic mice under the control of a beta-actin promoter. The transgenic mice developed normally; however, their body weight was lower than that of the wild-type mice, suggesting a defect in growth hormone signaling. Female transgenic mice failed to lactate after parturition because of a failure in terminal differentiation of the mammary glands, suggesting a defect in prolactin signaling. The IL-2-dependent upregulation of the IL-2 receptor alpha chain and proliferation were partially suppressed in the T cells of transgenic mice. These phenotypes remarkably resembled those found in STAT5a and/or STAT5b knockout mice. Indeed, STAT5 tyrosine phosphorylation was suppressed in mammary glands and the liver. Furthermore, the IL-2-induced activation of STAT5 was markedly inhibited in T cells in transgenic mice, while leukemia inhibitory factor-induced STAT3 phosphorylation was not affected. We also found that the numbers of gamma delta T cells, as well as those of natural killer (NK) cells and NKT cells, were dramatically decreased and that Th1/Th2 differentiation was altered in transgenic mice. These data suggest that CIS1 functions as a specific negative regulator of STAT5 in vivo and plays an important regulatory role in the liver, mammary glands, and T cells.

Animals↗

Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer.

PURPOSE: The target area under the plasma-concentration-versus-time curve (AUC)-based dosing of carboplatin using Calvert's formula is expected to result in more acceptable toxicity and greater efficacy in elderly patients with small-cell lung cancer (SCLC) than the body surface area-based dosing strategy. This phase II study was designed to determine the toxicity and efficacy of carboplatin based on Calvert's formula plus the standard dose of intravenous etoposide for elderly patients with SCLC. PATIENTS AND METHODS: Carboplatin, dosed to a target AUC of 5 x (24-hour creatinine clearance + 25), was given intravenously on day 1 and etoposide 100 mg/m(2) was given intravenously on days 1, 2, and 3. Patients aged >/= 70 years old with a performance status of 0 to 2 were eligible. RESULTS: Thirty-six patients were enrolled onto the study. The patient characteristics were as follows: median age, 73 years; limited disease (LD), 16 patients; and extensive disease (ED), 20 patients. Grades 3 and 4 leukopenia occurred in 57% and 3% of patients, and grades 3 and 4 thrombocytopenia occurred in 40% and 11% of patients, respectively. There was one treatment-related death due to hemoptysis. Other toxicities were relatively mild. There were two complete responses and 25 partial responses, for a response rate of 75%. The median survival time was 10.8 months (LD, 11.6 months; ED, 10.1 months), and the 1-year survival rate was 47%. CONCLUSION: This carboplatin/etoposide combination chemotherapy is an active and relatively nontoxic regimen in elderly patients with SCLC, which suggests that the combination may be suitable for randomized controlled trials.

Aged↗

[Involvement of chymase in angiogenesis in hamster sponge granulomas].

We investigated the angiogenic effect of chymase, an alternative angiotensin II-generating enzyme, on angiogenesis using hamster sponge implant model. Exogenous administration of angiotensin II (Ang II) or angiotensin I (Ang I) directly into the sponges enhanced angiogenesis, as determined from the hemoglobin contents in the sponge granuloma tissues. Chymostatin, an inhibitor of chymase, inhibited angiogenesis induced by Ang I but not by Ang II, suggesting the presence of a chymase-like Ang II-generating activity in the sponge granuloma. TCV-116 (5 mg/kg p.o.), an antagonist of Ang II type 1 receptor, and chymostatin suppressed bFGF-induced angiogenesis, suggesting the significance of the endogenous angiotensin system. Chymase activity in the sponge granuloma increased in parallel with the rise in hemoglobin contents induced by bFGF. We also examined the effects of direct administration of human pro-chymase gene or purified hamster chymase, and demonstrated that in vivo human pro-chymase gene transfection and direct injection of purified chymase enhanced angiogenesis, which was 50% inhibited by TCV-116. Sponge granulomas treated with Ang II was supressed by vascular endothelial growth factor (VEGF) antisense. Our results suggest that chymase enhanced angiogenesis partly through the local production of Ang II, followed by up-regulation of VEGF.

Angiotensin I↗

[Subacute necrotizing lymphadenitis associated with mononeuritis multiplex. A case report].

A 20-year-old man noticed lymph node swelling in his neck in May 1997. He was admitted to our hospital on July 30 because of numbness and weakness in the right hand and bilateral lower extremities. Neurological examinations revealed that the patient had right ulnar and bilateral deep peroneal nerve palsies. Nerve conduction study showed severe axonopathy in these nerves. The sural nerve biopsy demonstrated axonal degeneration and thickening of the small arterial wall. There was no significant increase of virus titer in the serum, such as EB virus, nor human herpesvirus 6. CSF examination was normal. During the course of this disorder, he acutely developed severe pain in his right testis. Pathological finding of the testis showed necrosis with vasculitis in the small arteries. Treatment with corticosteroid was effective. Usually subacute necrotizing lymphadenitis has been thought to be a benign disease. Only a few neurological complications, such as aseptic meningitis and cerebellar ataxia have been reported. Mononeuritis multiplex associated with subacute necrotizing lymphadenitis has not been reported. We speculated that the present case initially had some viral infection, and its reaction of the host produced subacute necrotizing lymphadenitis and mononeuritis multiplex.

Adult↗

[A case of metachronous lung cancer in which tumor developed within the different ipsilateral lobe over a short period of time and completion pneumonectomy was required].

A 51-year-old man underwent a middle-lower lobectomy for squamous cell carcinoma on February 8, 1996. In July, 1997, a computed tomography revealed a mass shadow in the right upper lung field. Completion pneumonectomy was performed. Histopathological examination showed poorly differentiated adenocarcinoma. This case was the shortest time to occurrence of second tumor in our metachronous lung cancer cases. We must always give attention to exist second primary lung cancer and double primary lung cancer after resection of primary lung cancer.

Adenocarcinoma↗

[A case of superior mediastinal neurinoma resected from the supra-clavicular area].

We report a case of superior mediastinal neurinoma that was resected from the supra-clavicular area. An abnormal shadow on the chest X-ray film was pointed out in a 53-year-old male. A left supra-clavicular mass was subsequently also discovered. We underwent extirpation of the tumor through supra-clavicular approach and confirmed to be a neurinoma histologically. We consider supra-clavicular approach which allows a good view might be useful.

Humans↗

Higher-order structure and thermal instability of bovine mitochondrial tRNASerUGA investigated by proton NMR spectroscopy.

Although mammalian mitochondrial serine-specific tRNA with the anticodon UGA (tRNASerUGA) appears to possess an almost normal cloverleaf secondary structure, it exhibits an extraordinarily low melting temperature (tm). An in vitro tRNASerUGA transcript without modified nucleosides had an even lower tm and slightly less hyperchromicity, but its tertiary structure was apparently very similar to that of the native counterpart judging from its aminoacylation activity and the body of experimental evidence so far obtained for canonical tRNAs. The transcript was therefore used to investigate the higher-order structure and thermal instability of tRNASerUGA. 1H-NMR analysis of the transcript showed that it takes a nearly L-shaped tertiary structure with similar tertiary base-pairings to those found in yeast tRNAPhe, which is representative of canonical tRNAs. However, magnesium ion titration revealed that Mg2+ affected the chemical shifts of the tRNASerUGA transcript differently than those of canonical tRNAs so far studied; the former was less sensitive toward Mg2+, especially in the D-arm region. This observation was confirmed by NMR analysis with paramagnetic manganese ion titration. Hill plots derived from the CD spectral changes caused by titration with Mg2+ suggested that the tRNASerUGA transcript had fewer Mg2+ binding sites than those of yeast tRNAPhe as well as its transcript, a finding that was consistent with the NMR data. We thus surmise that the thermal instability of both the transcript and tRNASerUGA itself originated from a reduction in the number of the divalent ion binding sites within the tRNA molecule. These results suggest a new type of thermal instability for mitochondrial tRNA.

Animals↗

Purification and amino acid sequence of halystase from snake venom of Agkistrodon halys blomhoffii, a serine protease that cleaves specifically fibrinogen and kininogen.

We have isolated a serine protease, halystase, from Agkistrodon halys blomhoffii venom by chromatography on DEAE-Sepharose, heparin-Sepharose and Q-Sepharose columns, and have determined the complete amino acid sequence by Edman degradation and by mass spectral analysis of peptides generated by enzymatic and chemical cleavage. The 238-residue sequence of halystase, containing N-linked carbohydrates (about 13%) at two sites showed significant similarity to other thrombin-like snake venom serine proteases (66-72%), mammalian tissue kallikrein (42%) and thrombin (26%). Halystase contained the tentative catalytic triad of His43, Asp88 and Ser184 common to all serine proteases and Asp178 in the primary substrate-binding site. Although halystase contained an RGD sequence at residues 181-183, it did not inhibit platelet aggregation induced by ADP or collagen. It hydrolyzed most efficiently a tissue-kallikrein substrate, prolylphenylalanylarginyl-4-methyl-coumaryl-7-amide, and released bradykinin from bovine kininogen. Halystase did not coagulate human plasma, but it cleaved the fibrinogen B beta chain at the carboxyl side of Arg42 and cleaved slowly the fibrogen A alpha chain. Fibrinogen thus treated gradually became insensitive to thrombin. The proteolytic activity was inhibited with diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride or leupeptin. These results indicate that halystase is a serine protease structurally similar to coagulating thrombin-like snake venom proteases, but it specifically cleaves fibrinogen at sites different from thrombin without inducing fibrin clotting, and hydrolyzes kininogen to produce bradykinin, resulting in the reduction of blood pressure.

Agkistrodon↗

Renal ACE immunohistochemical localization in NIDDM patients with nephropathy.

A role of renal angiotensin-converting enzyme (ACE) in diabetic nephropathy has been suggested. Immunohistochemical localization of ACE was studied in 20 non-insulin-dependent diabetes mellitus patients with diabetic nephropathy and 17 healthy kidney transplant donors, with ACE gene insertion/deletion (I/D) polymorphism also examined in the latter. Immunohistochemical studies indicated that ACE staining was significantly (P < 0.01) enhanced in glomeruli and slightly decreased in proximal tubules in diabetic patients. Glomeruli positive for ACE immunostaining were observed in 23.5% of the healthy subjects and in 80% of the diabetic patients. All patients with nodular lesions had ACE-positive glomeruli and showed significantly (P < 0.01) more intense glomerular ACE immunostaining than patients without nodular lesions. Among healthy controls, subjects with the DD genotype had ACE-positive glomeruli more frequently and tended to show slightly increased intensity on proximal tubule ACE immunostaining compared with subjects with other genotypes. These observations suggest that increased ACE localization in glomeruli is likely to be one of the factors in the increased renin-angiotensin system activity in glomeruli in patients with diabetic nephropathy. There is a possibility that ACE gene I/D polymorphism may be related to renal ACE immunohistochemical localization.

Diabetes Mellitus, Type 2↗

Relationship among risk factors of atherosclerosis, leukocyte count, and soluble intercellular adhesion molecule-1.

We investigated the effects of risk factors of atherosclerosis on soluble intercellular adhesion molecule-1 (sICAM-1) concentration and leukocyte count by using multivariate statistical analysis. The subjects were 90 people who were hospitalized for a complete check-up examination. Eight risk factors were selected as candidates for predictor variables: age, body mass index (BMI), uric acid, glycohemoglobin A1c, number of cigarettes smoked daily, total cholesterol, triglyceride, and high density lipoprotein (HDL)-cholesterol. The predictor variables were selected using a stepwise method, [criterion variable - predictor variable (standardized regression coefficient)]; sICAM1 - age (0.1859), number of cigarettes (0.2558), triglyceride (0.2447); leukocytes - number of cigarettes (0.2827), triglyceride (0.2526), HDL-cholesterol (-0.2800); stab leukocytes - number of cigarettes (0.2460); segmented leukocytes - glycohemoglobin A1c (0.1495), number of cigarettes (0.2716), HDL-cholesterol (-0.3254); lymphocytes - BMI (0.2639), number of cigarettes (0.1495), triglyceride (0.3520); monocytes - glycohemoglobin A1c (0.2617). These findings indicated that the risk factors of atherosclerosis may influence sICAM1 concentration and leukocyte count.

Adult↗

Clinicopathologic study of multiple primary superficial carcinoma of the esophagus.

Endoscopic examination with iodine staining has led to the easy detection of multiple superficial esophageal carcinoma (MSEC). The purpose of this study was to better understand the characteristics of MSEC. Of 49 patients with multiple esophageal carcinomas, 19 had superficial carcinoma. Multiple esophageal carcinomas were more often found in superficial carcinomas (31.1%) than in advanced carcinomas (14.4%). Comparing the depth of invasion of multiple esophageal carcinomas, the secondary lesions represented relatively early stages. Ki-67-positive cells were seen significantly more frequently in the main lesion of MSEC than in the secondary lesions, but proliferating cell nuclear antigen positivity and p53 expression did not differ significantly. Since multiple carcinoma occurs more frequently, care should be taken to look for small secondary lesions when treating superficial esophageal carcinoma. Ki-67 immunohistochemistry suggested that tumor cells proliferate more slowly in secondary lesions than in main lesions of MSEC.

Antibodies, Monoclonal↗

Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients.

Human hepatitis B virus (HBV) and hepatitis C virus (HCV) are two major etiologic agents of chronic hepatitis, which is closely related to the development of hepatocellular carcinoma (HCC). A possible involvement of HBV co-infection was investigated in ongoing HCV-related liver diseases in HCV-infected patients. A prevalence of anti-HBc in anti-HCV-positive/HBsAg-negative chronic hepatitis patients and a low copy number of HBV DNA were found in most of the liver biopsy samples of anti-HCV-positive/HBsAg-negative patients. The present data suggest that HBV co-infects frequently with HCV and may play an important role in the development of HCC in the anti-HCV-positive/HBsAg-negative patients with chronic hepatitis.

Adult↗

Effects of a neutral endopeptidase inhibitor, BP102, on the development of deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway Katholiek rats.

The nature of all of the peptides critical to the mechanism(s) of the antihypertensive action of neutral endopeptidase (NEP) inhibitors is still unclear, but bradykinin is thought to be one such peptide. This study was designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka) rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased urine volume and urinary sodium excretion in a dose-dependent manner in anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN-Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka rats was also significantly reduced, by an 8-day administration of BP102. When BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated BN-Ka rats was markedly lowered, and their heart weights were reduced. These results suggest that kinins play no role in the antihypertensive effect of this inhibitor and that other factors may be involved in this effect.

Administration, Oral↗

Right vagal nerve stimulation during minimally invasive direct coronary artery bypass grafting in dogs. A preliminary study.

BACKGROUND: Minimal access coronary artery bypass grafting without cardiopulmonary bypass has been used with increasing frequency. However, some surgeons are still unwilling to perform MIDCAB because the anastomosis is technically demanding. The aim of this study was to assess whether autonomic activation via right vagal nerve stimulation will be an effective support technique on heart rate during MIDCAB in dogs. EXPERIMENTAL DESIGN: Preliminary study. SETTING: Cardiothoracic Surgery Unit, University Clinic. METHODS: The right cervical vagal nerve was stimulated in five dogs. In one dog, right thoracotomy was performed to isolate the vagal nerve. Bipolar hook electrodes were attached to the vagal nerve. The vagal nerve was stimulated (3-5 mA, 40 Hz) for a few seconds while suturing the coronary artery. Experiments were conducted in two groups. In Group I, two dogs received vagal stimulation via the right neck, and one dog received vagal stimulation via the right thoracic cavity approach. In Group H, all vagal stimulations were performed via the neck during intravenous infusion of diltiazem (10 mg/hrs) or verapamil (5 mg/hrs). RESULTS: In Group I, when the cervical nerve stimulation started the heart rate decreased from 190 to 45 beats/min in one dog, and from 180 to 42 beats/min in another dog. During thoracic nerve stimulation, the heart rate decreased from 205 to 70 beats/min. In Group II, vagal stimulation of one dog (10 mg/hr diltiazem) caused ventricular arrest, and in the other dogs (5 mg/hr verapamil) vagal stimulation caused marked bradycardia with atrioventricular block. After the cessation of nerve stimulation, the heart rate returned to normal sinus rhythm immediately in each dog. CONCLUSIONS: Based on our findings, this type of autonomic stimulation (especially with i.v. administration of diltiazem or verapamil) can be an effective technique in reducing heart beats, thus obtaining relatively quiet surgical field for coronary anastomosis in CABG without cardiopulmonary bypass.

Animals↗