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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 253 records · Page 14Linked to original sources

Ultrasonic vocalization responses in genetically high- and low-emotional rats.

Tsukuba High Emotional (THE) and Tsukuba Low Emotional (TLE) strains of rats have been congenitally bred for use in studies of emotionality. The current study investigated THE and TLE strain differences in the footshock-induced ultrasonic vocalization responses of adult male rats. Ultrasonic vocalization response inducibility (ratio of rats emitting ultrasounds) and vocalization activity in THE rats were statistically higher than in TLE rats. We next examined the causal relation between the ultrasonic vocalizations and the activation of the pituitary-adrenocortical axis in response to footshocks in these two strains of rats. Rats were sorted into two groups, vocalizing and non-vocalizing, after being exposed to the shock regimen daily for 5 successive days. Basal plasma concentrations of ACTH and corticosterone were not different between THE and TLE rats. After receiving footshocks, significant increases in plasma concentrations of ACTH and corticosterone were induced in both strains of rats. These increases in plasma concentrations of ACTH and corticosterone were significantly higher in THE than in TLE rats. However, in vocalizing and non-vocalizing rats of both strains, no statistical differences in plasma concentrations of ACTH and corticosterone were observed after footshocks. These findings suggest that the high emotionality of the adult male rats was reflected in the emission of ultrasounds, and that the emission of ultrasonic vocalizations might not be related to the activation of the pituitary-adrenocortical axis.

Adrenocorticotropic Hormone↗

[A survey on occupational health nursing activities and evaluation in TOHOKU area].

We did a mail survey in 1998 in Tohoku district. We sent questionnaires to approximately 300 Occupational Health (OH) nurses and got 132 replies. Occupations of respondents were 66 public health nurses and 57 nurses. More than 70% did not have a managerial position. About 40% were respondents without colleagues in nursing occupations. Full time occupational physicians were in 40% of companies, and semi-full time occupational physicians were in 60%. Respondents citing good coordination in the former were 60%, and in the latter were 80%. Of all business activities occupying OH nursing employees, persons who performed more than 90% of the tasks numbered more than 30%. Persons not satisfied with present employment positions were 80%. Reasons for dissatisfaction in declining order of incidence were work duties, contract conditions for employment, and personal relations. Planning and summary of OH nursing activities were carefully done highly. For the OH nursing activity evaluation, we examined guidelines for business locations by observing them from the OH nursing aspect and the OH nursing job itself. Guidelines considered for business locales from the OH nursing vantage point show numerically, for example, rates of examinees with abnormal findings, work absenteeism, etc, and expectations as to whether or not health conditions are conspicuously reflected in productivity. Conversely, from the OH nursing vantage point for guidelines on business locales, while receiving affirmative economic evaluation of occupational health and safety measures, progress (process) should also be included in the object of evaluation. Furthermore, guidelines should be mindful of the need to have qualitative and quantitative changes in health behavior of workers and perspectives on health.

Adult↗

Correlation between the loss of the chaperone-like activity and the oxidation, isomerization and racemization of gamma-irradiated alpha-crystallin.

Alpha-crystallin possesses a molecular chaperone-like activity that prevents proteins from aggregating; however, the mechanism of this activity is not well known. Here we have taken gamma-irradiated alpha-crystallin and studied the relationship between the decrease in chaperone-like activity and the modifications such as oxidation, isomerization and racemization of amino acids in this molecule. We found that the chaperone-like activity of alpha-crystallin decreased with increasing gamma irradiation. After 4000 Gy gamma irradiation the activity of alpha-crystallin was reduced to 40% of the level of nonirradiated, native alpha-crystallin. The circular dichroism spectrum showed that the secondary structure of the irradiated alpha-crystallin had not changed. However, its tertiary structure appeared to change following more than 1000 Gy irradiation. Sodium dodecyl sulfatepolyacrylamide gel electrophoresis also indicated that cross-linking of alpha-crystallin increased with increasing radiation doses. Irradiated and nonirradiated alpha-crystallin was subjected to trypsin digestion and peptide analysis by reverse-phase high-performance liquid chromatography and mass and sequence analysis. Depending on the radiation dose, Met-1 of alpha A-crystallin was oxidized to methionine sulfoxide. In addition, Asp-151 of alpha A-crystallin was isomerized to the beta-Asp form after irradiation, and racemization of Asp-151 decreased. Thus, the loss of the chaperone-like activity of alpha-crystallin is related to changes in its isomerization, oxidation and racemization.

Animals↗

Efficacy of dentin adhesives in primary and permanent teeth.

The purpose of the present study was to investigate the efficacy of dentin adhesives and to examine acid resistance in primary and permanent teeth. The efficacy of dentin adhesives was evaluated by SEM observation and by measuring the wall-to-wall polymerization contraction gap and dentin hardness before and after conditioning. The detailed mechanism of dentin bonding was the same in both primary and permanent teeth.

Acid Etching, Dental↗

Possible risk reduction in esophageal cancer associated with MPO -463 A allele.

Myeloperoxidase (MPO), an enzyme found in lysosomes of phagocytes, causes hydroxy radicals linked to DNA damage and activation of smoking related carcinogens. A -463 G/A polymorphism in the promoter region of the MPO gene results in reduced gene expression, which would imply lower susceptibility of esophageal cancer in mutant carriers. We conducted case-control study to test this hypothesis. Cases were 91 patients with esophageal cancer and controls were 241 non-cancer outpatients. MPO genotypes were examined by PCR-RFLP. The allele frequency for MPO -463A was found to be 8.2% for cases and 10.5% for controls. The age, sex, smoking and drinking status adjusted odds ratio for all subjects for MPO -463 GG/GA as compared to the AA was 0.61 (95% CI: 0.28-1.32). The adjusted odds ratio for the GG/GA genotype was significantly low (0.15; 0.03-0.76, P=0.022) for those aged 61 years or older who had a significantly higher odds ratio for smoking than younger subjects. No difference was observed in disease risk when prevalent and incident cases were compared. Although there are limitations for interpretation of this study because of prevalent case-control study and partial statistical significance, these results suggest that MPO -463 A allele reduce the risk of esophageal cancer.

Adult↗

Smoking habit and interleukin lB C-31T polymorphism.

Recent studies suggest that smoking habit may relate to genetic traits. This study examines the association with a polymorphism (C-31T) of interleukin 1B (IL-1B), which encodes IL-1beta, a multifunctional pro-inflammatory cytokine. Since the T allele makes a TATA box, the allele is thought to be responsible for a higher potency of IL-1B expression, indicating that individuals harboring the T allele are prone to inflammation. The study subjects were two different populations; 241 non-cancer outpatients (118 males and 123 females) at a cancer hospital and 462 examinees (127 males and 335 females) of a health checkup program provided by a local government. Current smokers were 36.4% for the male outpatients, 9.8% for the female outpatients, 38.6% for the male examinees, and 5.6% for the female examinees. The sex-age-adjusted odds ratios of current smokers were calculated for the genotypes with the T allele relative to the CC genotype by an unconditional logistic model. The estimate was 0.45 (95% confidence interval, 0.21-0.97) for the outpatients, and 0.83 (0.42-1.61) for the examinees. Although not significant for the examinees, the observed associations suggest that this polymorphism may influence smoking behavior through an inflammatory response of the respiratory tract to cigarette smoke.

Adult↗

Ascorbic acid protects against peroxidative modification of low-density lipoprotein, maintaining its recognition by LDL receptors.

Peroxidatively modified low-density lipoprotein (LDL) may contribute to atherosclerotic processes; therefore, protecting LDL against peroxidation may thus reduce or retard the progression of atherosclerosis. We have evaluated the protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification. The protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification were examined by measurement of concentration of lipid hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via LDL receptor-mediated pathway. The measurement of concentration of lipid hydroperoxides in LDL showed that ascorbic acid inhibited peroxidative modification of LDL. Also, ascorbic acid preserved the ability of LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same extent as native LDL. These findings indicate that ascorbic acid may protect LDL against peroxidative modification, maintaining its ability to act as a ligand for LDL receptors in vivo.

Adult↗

A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter.

Telomerase activity has a close relationship with malignancies in many cell types and it is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). Utilizing the hTERT promoter, the authors developed a gene delivery system of Fas associated protein with death domain (FADD) (hTERT/FADD). FADD is a protein which plays an important role in the apoptotic pathway of Fas. Over-expression of FADD induces apoptosis in the cells regardless of Fas expression on the cell surface. We hypothesized that we might be able to restrict the expression of FADD in malignant glioma cells if we use the gene transfer system under the control of hTERT promoter. This study was designed to investigate whether the hTERT/FADD construct induces apoptosis effectively in malignant glioma cells while keeping normal cells intact. First, using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we confirmed that hTERT mRNA was expressed in human malignant glioma cells (U373-MG, A172 and GB-1), but not in cultured astrocytes (TEN) or fibroblasts (MRC5). After transient transfection with the hTERT/FADD construct, a significant number of FADD-positive cells and apoptotic cells were detected in hTERT-positive malignant glioma cells. In contrast, hTERT-negative astrocytes and fibroblasts remained intact. Furthermore, subcutaneously implanted U373-MG tumors treated with the hTERT/FADD construct reduced in volume significantly compared to the conrol treatment (p=0.0001). Gene transfer of FADD under the control of the hTERT promoter may be a novel and promising therapy to kill hTERT-positive malignant glioma cells while sparing normal brain cells lacking hTERT.

Animals↗

High-risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women.

To estimate the risk of human papillomavirus (HPV) infection for cervical malignancies, we conducted a case-control study in Japan. Abnormal cervical cell (366) and normal cell samples (1562) were tested for the presence of HPV DNA using a new PCR-based test (LCR-E7 PCR). When single HPV infections were considered, 26 different HPV types were identified in normal cervices and in low-grade squamous intraepithelial lesions (LSIL); whereas HPV-16, -18, -31, -33, -35, -45, -51, -52, -56, -58 and -67 were detected in high-grade squamous intraepithelial lesions (HSIL) and in squamous cell carcinoma (SCC) of the cervix, and HPV-16 and -18 were detected in cervical adenocarcinoma. HPV-6 and -11 were detected in condyloma acuminatum tissue. In HSIL and SCC, HPV-16 was the most prevalent type and HPV-51, -52, and -58 were the next most prevalent; whereas HPV-39, -59, and -68 were not detected. Analysis by odds ratio (OR) revealed that HPV-11, -39, -42, -44, -53, -59, -62, and -66 (HPV-66: OR,139; 95% confidence interval (CI) = 6.7-168) were associated with LSIL; HPV-16, -18, -31, -51, -52 and -58 (HPV-16: OR, 69; 95%CI = 36-131) were associated with SCC; and HPV-16 and -18 (OR, 94; 95% CI = 28-317) were associated with adenocarcinoma. Multiple HPV infection was associated with LSIL (OR, 24; 95%CI = 13-44), HSIL (OR, 16; 95%CI = 8.4-32), and SCC (OR, 8.3; 95%CI = 3.2-22), although the prevalence decreased with the grade of the lesions. All results suggest that HPV-6 and -11 are condyloma types, HPV-16, -18, -31, -51, -52, -58, and perhaps -33, -35, -45, -56, and -67, are the high-risk HPV types, and many other types are LSIL-associated types in Japan. HPV typing and detection of multiple HPV infections in clinical samples may be useful as surrogate markers for cervical cell abnormalities.

Adenocarcinoma↗

Pheochromocytoma of the urinary bladder: a case report.

We present a 66-year old female patient with pheochromocytoma of the urinary bladder. We performed transabdominal needle biopsy of the tumor without suspicion of pheochromocytoma because of her well-controlled blood pressure and no characteristic symptoms following administration of antihypertensive medication. Hypertensive crisis (260/130 mmHg) occurred just after the needle insertion. The diagnosis was pheochromocytoma. The norepinephrine level in the serum and her blood pressure normalized without antihypertensive medication after partial cystectomy. Pheochromocytoma should be suspected in cases of intramural bladder tumors, especially in a normotensive patients receiving antihypertensive medication.

Aged↗

[A case of small cell lung cancer with paraneoplastic cerebellar degeneration and anti-voltage-gated calcium channel antibody].

A 55-year-old man presenting with 4 weeks of progressive dysarthria, gait ataxia and vertigo was admitted to our hospital. Chest X-ray films revealed a mass shadow in the right upper lobe of the lung, and transbronchial brushing specimens showed small-cell carcinoma. Extensive examination revealed metastatic lesions in the mediastinal lymph nodes and liver, but brain MRI showed no findings suggestive of metastasis or atrophy. A diagnosis of PCD associated with SCLC was made, and the patient had a high titer of anti-P/Q-type VGCC antibody. He was treated by chemotherapy and radiation therapy, which resulted in a transient improvement in the PCD symptoms.

Autoantibodies↗

[Present situation of drug resistance and future prospects].

Antibiotic resistance has evolved over 60 years from a merely microbiological curiosity to a serious medical problem in hospitals. Resistance has been reported in almost all species of bacteria to various classes of antimicrobial agents including recently evaluated ones. Bacteria regulated resistance by different mechanisms. Inappropriate use of an antimicrobial agent selects resistant strains much more frequently. Since it is not expected that some epoch-making new antimicrobial agents will be developed in the near future, proper use of existing antimicrobial agents which is based on the mechanisms of action of antimicrobial agents and of resistance of bacteria, and of control of nosocomial infection are very important to reduce the further spread of resistant bacteria. With the search for natural sources of new antimicrobial substances now appearing frustrated, the genomic approach in the 21st century may be the only fruitful way to develop truly novel chemotherapeutic agents against bacterial diseases.

Anti-Bacterial Agents↗

Metabolism of 99mTc-ethylcysteinate dimer in infarcted brain tissue of rats.

UNLABELLED: Brain SPECT with 99mTc-ethylcysteinate dimer (99mTc-ECD) reveals a subacute cerebral infarct as a hypoactive area, even in the presence of postischemic hyperperfusion. The brain retention of 99mTc-ECD depends on hydrophilic conversion mediated by enzymes, and impaired enzymatic trapping is hypothesized to depress the retention efficiency in the infarcted region. The aim of this study was to determine whether the metabolic rate of 99mTc-ECD is actually reduced in infarcted brain tissue. METHODS: In 50 mmol/L phosphate buffer (pH 7.4), 99mTc-ECD was incubated for 30 min with homogenates of rat brain tissue with and without triphenyltetrazolium chloride (TTC) staining. The ratio of polar products was determined by thin-layer chromatography as a function of incubation time, and metabolic rates were obtained. Permanent focal ischemia was induced by occlusion of the right middle cerebral artery (MCA) in rats. The brain was removed 24 h after MCA occlusion, and the infarcted area was defined by TTC staining. The metabolic rate of 99mTc-ECD was determined in homogenates of infarcted tissue, contralateral noninfarcted tissue, and tissue sampled from sham-operated rats. The infarct volume was measured by direct and indirect methods to assess volume expansion caused by edema, and the metabolic rate in infarcted tissue was corrected for the effect of edema. RESULTS: TTC staining had no effect on the metabolic rate of 99mTc-ECD. The metabolic rates in the infarcted tissue were 0.222%/min +/- 0.054%/min and 0.285%/min +/- 0.064%/min before and after correction for edema, respectively. These rates were significantly lower than those in the contralateral noninfarcted tissue (0.426%/min +/- 0.028%/min) and the tissue sampled from the sham-operated rats (0.439%/min +/- 0.031%/min). No substantial difference in rates was observed between the contralateral tissue and the tissue from the sham-operated rats. CONCLUSION: The results of this study showed that infarction decreases the activity of enzymes that mediate the hydrophilic conversion of 99mTc-ECD in the brain and suggest that reduced metabolic activity is related to decreased accumulation of 99mTc-ECD in hyperperfused infarcts.

Animals↗

[Telomerase inhibitor].

Telomerase is a ribonucleprotein enzyme that extends telomeric repeats at the end of chromosome DNA. Telomere maintenance by telomerase leads to cellular immortality and carcinogenesis. Telomerase is activated in most malignant tumors while it is usually repressed in normal somati tissues, and telomerase activation is thought to be a critical step for cancer progression. These findings suggest that telomerase is a good target for cancer gene therapy. A variety of molecular technique have been used to inhibit telomerase activity in cancer cells. In this review, I introduce the representative methods which efficently inhibit telomerase activity and may have a potential for clinical application.

Cellular Senescence↗

Metabotropic neurosteroid/sigma-receptor involved in stimulation of nociceptor endings of mice.

In peripheral nociceptive flexor test, SA4503, (+)-pentazocine, and (+)-3-(hydroxyphenyl)-N-(1-propyl)piperidine, representative sigma-receptor agonists, elicited dose-dependent flexor responses. These responses were blocked by sigma-receptor antagonists NE-100 or BD1063, but not by pretreatments with antisense oligodeoxynucleotide for sigma1 binding protein. The sigma-agonists' nociception is attributed to the substance P (SP) release from nociceptor endings through activations of Galpha(i1) and phospholipase C (PLC). On the other hand, attomolar doses of neurosteroids such as dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate caused similar nociception, and they were blocked by progesterone (PROG). However, DHEAS nociception was not affected by pertussis toxin, but was completely inhibited by a PLC inhibitor or thapsigargin. Although the nociception by lower doses of DHEAS was abolished by diphenhydramine (DPH), H1 antagonist, there were dose-dependent responses by high doses of DHEAS in the presence of DPH. The responses by DHEAS in the presence of DPH were blocked by NE-100, and those by (+)-pentazocine were blocked by PROG. All these findings suggest that two novel types of neurosteroid receptors exist, neuronal NS1/sigma-type, which mediates activation of Galpha(i1) by neurosteroids and sigma-agonists, followed by SP release from nociceptor endings; and NS2 type, which mediates histamine release from mast cells by very low doses of neurosteroids.

Animals↗

[A preliminary report on the treatment of pleural carcinomatosis with SMANCS].

To clarify the effect of SMANCS on malignant pleural carcinomatosis, seven patients with malignant pleural effusion were treated with SMANCS administered via an intracavitary route. Five patients showed improvement after one or two injections of SMANCS into the thoracic cavity, although 2 patients needed further therapy with the immunopotentiating agent picibanil (OK-432). No serious adverse effects were observed. This simple therapeutic tactic with SMANCS may be effective in cases of malignant pleural carcinomatosis.

Aged↗

[Assessment of physical activities from functional physical fitness tests research for patients with chronic obstructive pulmonary disease].

The purpose of this study was to determine whether the level of physical activity (as measured by 12 functional physical fitness tests) differed between patients with chronic obstructive pulmonary disease (COPD) and normal subjects. Fifty male patients with COPD (70.4 +/- 7.1 yr) and 193 age-matched normal subjects (71.2 +/- 5.2 yr) participated in the study. We administered twelve functional physical fitness tests that were designed to represent muscle strength, muscular endurance, reaction, flexibility, balance, regulation and manipulation. Cardiorespiratory fitness was measured by an incremental, symptom-limited exercise test to the maximal tolerable level on a cycle ergometer, and by the 6-min walk distance. Further, we evaluated what the relationships were between cardiorespiratory fitness and physical activities. The results showed that there were significant differences between COPD and normal groups in cardiorespiratory fitness [peak oxygen uptake (15.7 +/- 4.8 ml/kg/min vs. 23.9 +/- 6.5 ml/kg/min, p < 0.05), peak load (77.9 +/- 33.7 watts vs. 110.3 +/- 37.9 watts, p < 0.05) and 6-min walk distance (466.4 +/- 106.3 m vs. 540.4 +/- 78.3 m, p < 0.05)] and muscular endurance [arm curl (22.6 +/- 5.0 rep/30 s vs. 25.2 +/- 6.0 rep/30 s, p < 0.05), Keeping a half-squat position (32.6 +/- 16.4 s vs. 42.8 +/- 17.7 s, p < 0.05)] and regulation (27.2 +/- 9.4 s vs. 23.3 +/- 5.8 s, p < 0.05) in functional physical fitness test. There were significant correlations between cardiorespiratory fitness, and muscular endurance and regulation. Furthermore, there were significant correlations between FEV1.0 and FEV1.0% pred, and regulation. Therefore, it is important that, besides exercise prescriptions based on the criteria of symptom-limited exercise tests, development of exercise programs based on the level of physical activities may be necessary for patients with COPD.

Aged↗