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Biomedical subjects

A Kobayashi

Publications and source records attributed to A Kobayashi.

At least 145 records · Page 8Linked to original sources

Effects of voluntary running exercise on blood pressure and renin-angiotensin system in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.

The effect of a voluntary running exercise on blood pressure and renin-angiotensin system (RAS) was studied in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were assigned to either voluntary running exercise or sedentary control groups at 5 wk of age. The systolic blood pressure in the exercised group for both strains of rats was significantly lower than in the sedentary control group. The plasma renin activity (PRA) and plasma renin concentration (PRC) were significantly lower in voluntary running exercised SHR than in sedentary SHR, whereas the same exercise did not result in a lower PRA and PRC in WKY. These results suggested that the blood pressure lowering effect of voluntary running exercise is related to the suppression of RAS in SHR.

Animals↗

Lack of integrative control of body temperature after capsaicin administration.

BACKGROUND: Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin, the pungent ingredient of hot peppers, facilitated heat production and heat loss simultaneously in rats. We recently found that the capsaicin-induced heat loss and heat production occur simultaneously and that the biphasic change in body temperature is a sum of transient heat loss and long-lasting heat production. Moreover, suppression of the heat loss response did not affect capsaicin-induced heat production and suppression of heat production did not affect capsaicin-induced heat loss. These observations suggest the independent peripheral mechanisms of capsaicin-induced thermal responses. Thus, the capsaicin-induced thermal responses apparently lack an integrated control. METHODS: Male Wistar rats were maintained at an ambient temperature of 24 +/- 1 degrees C on a 12 h on-off lighting schedule at least for two weeks before the experiments. They were anesthetized with urethane (1.5 g/kg, i.p.) and placed on a heating pad, which was kept between 29 and 30 degrees C. Skin temperature(Ts) was measured with a small thermistor, which was taped to the dorsal surface of the rat's tail, to assess vasoactive changes indirectly. Colonic temperature(Tc) was measured with another thermistor inserted about 60 mm into the anus. O2 consumption was measured by the open-circuit method, and values were corrected for metabolic body size (kg0.75). Capsaicin (Sigma) was dissolved in a solution comprising 80% saline, 10% Tween 80, and 10% ethanol, and injected subcutaneously at a dose of 5 mg/kg. Each rat received a single injection of capsaicin because repeated administration of capsaicin renders an animal insensitive to the subsequent administration of capsaicin. Laminectomy was performed at the level of the first and second cervical vertebrae to expose the cervical spinal cord for sectioning. The brain was transected at 4-mm rostral from the interaural line with an L-shaped knife. RESULTS: After administration of capsaicin, O2 consumption increased from 13.5 +/- 0.4 mL/min/kg0.75 at 0 min to a peak of 15.9 +/- 0.4 mL/min/kg0.75 at 71 min and gradually declined but remained higher than the basal value until the end of the 4-h observation period. Ts also immediately increased from 27.7 +/- 0.2 degrees C to 31.9 +/- 0.3 degrees C at 39 min, and it returned to the baseline level within 90 min after the capsaicin administration. Tc initially decreased from 37.1 +/- 0.1 degrees C to 36.8 +/- 0.2 degrees C at 43 min and then gradually increased over the baseline level and remained at 37.6 +/- 0.2 degrees C until the end of the experiment. In spinalized rats, the capsaicin-induced increases in O2 consumption was largely attenuated, while the basal O2 consumption was similar to that of control rats. The basal Ts of spinalized rats was 32.4 +/- 0.3 degrees C, which was higher than that of control rats. Capsaicin increased Ts by less than 1 degree C, and Tc did not change after the capsaicin administration. O2 consumption of decerebrated rats was statistically higher than that of control rats after the injection of capsaicin. However, capsaicin did not increase Ts, showing a lack of a vasodilatory response. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss but not the heat production response. CONCLUSION: These results show that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and suggest that the body temperature regulation is performed without an integrative center.

Animals↗

In-flight cerebral oxygen status: continuous monitoring by near-infrared spectroscopy.

BACKGROUND: Little is known about the in-flight cerebral oxygen status (COS) of fighter pilots. The purpose of this study was to evaluate the COS of fighter pilots during an F-15DJ flight. METHODS: Three male F-15DJ fighter pilots volunteered to serve as test subjects during aerial gunnery training (AGT) missions. During the flight, the pilots' COS was continuously monitored from the right forehead using a NIRO-300G near-infrared spectrophotometer. This new instrument is capable of measuring the concentration changes in the brain of oxygenated hemoglobin (O2Hb), reduced hemoglobin (HHb), total hemoglobin (cHb, O2Hb + HHb), and the tissue oxygenation index (TOI, O2Hb/cHb). RESULTS: Continuous changes of COS within the brain were clearly demonstrated using NIRO-300G, the changes included reductions in O2Hb, cHb, and TOI with increased +Gz, in a mirror image fashion. The maximum decreased concentration of hemoglobin during flight ranged from 12.8 to 25.6 micromol x L(-1) (of brain tissue). CONCLUSIONS: We believe this study is the first monitoring of COS during F-15 actual flight. The monitoring of COS during F-15 flight showed that the effect of +Gz was to simultaneously lower blood flow in a mirror image fashion. Our results demonstrated that near-infrared spectroscopy (NIRO-300G) provides a reliable and sensitive method for the monitoring of pilots' COS during flight.

Acceleration↗

Increased formaldehyde in jet engine exhaust with changes to JP-8, lower temperature, and lower humidity irritates eyes and respiratory tract.

BACKGROUND: Formaldehyde (FA) in exhaust from F-4 aircraft with low smoke combustor(LSC) J79 engines has been reported to be of sufficient concentration to cause irritation. It has also been noted that eye and respiratory irritation became more frequent and severe after the fuel was changed from JP-4 to JP-8. The present sturdy investigated the effect of jet fuel and power setting on formaldehyde concentrations in the exhaust. We also investigated the exposure to formaldehyde among pilots and flight line personnel. METHODS: The exhaust from LSC J79 engines using different types of fuel (JP-8 and JP-4) was sampled 50 m behind the engine at different power settings in July (summer season in Japan) and February (winter season ). It was also sampled at 75% power settings using JP-8 in July. RESULTS: At an idle power setting, the FA concentration was higher in the exhaust of engines using JP-8 (1.31 ppm in July and 2.78 ppm in February) than in engines using JP-4 (0.95 ppm in July and 1.84 ppm in February). The FA concentration increased as both ambient temperature and relative humility decreased in the sampling atmosphere. The FA concentration of JP-8 fuel at an idle power setting (65%) was higher than that at a 71.5% power setting (1.32 ppm and 0.86 ppm, respectively). CONCLUSIONS: The FA concentrations in LSCJ79 engine exhaust varies depending on the type of fuel, engine power settings, and ambient air conditions. A high FA concentration at ground level due to a change in the fuel type, low temperature, and humidity, causes frequent severe eye respiratory irritation.

Aerospace Medicine↗

Recent developments in understanding the immune response to human papilloma virus infection and cervical neoplasia.

PURPOSE/OBJECTIVES: To provide an overview of the immune system and describe the systemic and local immune response to human papilloma virus (HPV) infection in the cervix and to the development of cervical dysplasia. DATA SOURCES: Historical and current medical and nursing literature, current gynecologic oncology texts. DATA SYNTHESIS: The immune system provides protection against a wide variety of pathogens and plays a role in the response of the body to neoplastic cells. The immune system orchestrates the functions of various immune cells and proteins to fight against invading pathogens. Mucosal immunity is one of the key functions of the immune system and has unique features. Humoral and cytotoxic responses in the cervix and in the peripheral blood are seen during clearance of an HPV infection. CONCLUSIONS: The functional status of the immune system is associated closely with the development of cervical dysplasia and cancer in women with HPV infection. Clinicians must assist women in maintaining proper functioning of immune responses. IMPLICATIONS FOR NURSING PRACTICE: A better understanding of local and systemic immune responses to HPV infection may help nurses who provide care to women with cervical disease and women at high risk for cervical cancer to deliver better care and clearer information to patients.

Female↗

[Modified Jekler and Lhotka operation in minimized laparotomy for achalasia].

The rationale for surgery in achalasia is to reduce lower esophageal sphincter (LES) pressure and recontruct an antireflux mechanism. Fundopexy as an antireflux procedure after LES myotomy (modified Heller myotomy), called the Jekler and Lhotka method or the Heller and Dor operation, is commonly performed as standard surgery. In our institution, this method has been used since 1982. We have performed the modified Jekler and Lhotha method including long myotomy to confirm complete reduction of LES pressure as measured by intraoperative manometry and fundopexy plus posterior wall fixation to contract the long abdominal esophagus since 1986. Satisfactory results with this procedure have been obtained and reported. Furthermore, we have recently performed this procedure with minilaparotomy. In this review, we describe the modified Jekler and Lhotha method in minimized laparotomy and evaluate this procedure using intraoperative manometry.

Esophageal Achalasia↗

[The influence of the use of mupirocin nasal ointment on the incidence of endogenous MRSA infections in an intensive care unit].

Nasal carriage of MRSA is a significant risk-factor for the endogenous MRSA infection in immunocompromised patients. MRSA infection in ICU patients is thus mostly endogenous infection. To evaluate the impact of mupirocin use on the incidence of endogenous infection caused by MRSA in an intensive care unit, we prospectively treated all patients in the unit with mupirocin, 3 times daily for 3 days. This routine use of mupirocin led to eradication of nasal MRSA carriage in 81.8% of surveillance cultures and to a significant reduction in the total incidence of MRSA infection among MRSA carrier patients (0 episode in 11 patients) when compared to historical controls prior to the use of mupirocin (3 episodes in 7 patients). Mupirocin nasal ointment was significantly effective to prevent endogenous MRSA infection.

Administration, Intranasal↗

HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model.

PURPOSE: To investigate the function and pathogenicity of HRG4, a photoreceptor synaptic protein homologous to the Caenorhabditis elegans neuroprotein UNC119. METHODS: HRG4 was screened for mutations in patients with various retinopathies, and a transgenic mouse model was constructed and analyzed based on a mutation found. RESULTS: A heterozygous premature termination codon mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy. In some transgenic mice carrying the identical mutation, age-dependent fundus lesions developed accompanied by electroretinographic changes consistent with defects in photoreceptor synaptic transmission (depressed b-wave, normal c-wave), and retinal degeneration occurred with marked synaptic and possible transsynaptic degeneration. CONCLUSIONS: HRG4, the only synaptic protein known to be highly enriched in photoreceptor ribbon synapses, is now shown to be pathogenic when mutated.

Adaptor Proteins, Signal Transducing↗

[Three cases of liver metastasis of colon cancer responding to systemic combination chemotherapy utilizing CPT-11].

Though the first choice of treatment for liver metastasis in colon cancer is surgical resection of liver, 30-60% of such patients experience a recurrence of liver metastasis. Even if reoperation is done optimally, the surgical resection of liver metastasis may not be a definitely curative treatment. For cases of liver metastasis from colon cancer that are non-resectable due to multiple liver metastases, other organ metastases (lung, bone, brain etc.), the advanced age of the patient, or other complications (cerebrovascular disease, diabetes mellitus, heart disease etc.), hepatic arterial infusion or systemic combination chemotherapies are selected. In the present paper, we report 3 cases of effective systemic chemotherapy utilizing CPT-11 for liver metastases from colon cancers. The method was UFT + irinotecan (CPT-11), cisplatin (CDDP) + tegafur + CPT-11, UFT + CPT-11 + etoposide (ETP) + pirarubicin (THP). The result obtained was a partial response (PR) in each case. As there were few adverse effects, we could provide treatment during a short-term admission or an outpatient basis. We thus obtained good post-chemotherapeutic QOL, and these regimens may be effective forms of chemotherapies in the future.

Adenocarcinoma↗

Separate cis-acting DNA elements control cell type- and tissue-specific expression of collagen binding molecular chaperone HSP47.

HSP47 is a collagen-binding heat shock protein and is assumed to act as a molecular chaperone in the biosynthesis and secretion of procollagen. As the synthesis of HSP47 is closely correlated with that of collagen in various cell lines and tissues, we performed a promoter/reporter assay using HSP47-producing and nonproducing cells. 280 base pairs (bp(s)) of upstream promoter were shown to be necessary for the basal expression but not to be enough for the cell type-specific expression. When the first and the second introns were introduced downstream of this 280-bp region, marked up-regulation of the reporter activity was observed in HSP47-producing cells but not in nonproducing cells. This was confirmed in transgenic mice by staining the lacZ gene product under the control of the 280-bp upstream promoter and the introns. Staining was observed in skin, chondrocytes, precursor of bone, and other HSP47/collagen-producing tissues. A putative Sp1-binding site at -210 bp in the promoter, to which Sp3 and an unidentified protein bind, was shown to be responsible for this up-regulation when combined with the introns. However no difference in the binding to this probe was observed between HSP47-producing and nonproducing cells. The responsible region for cell type-specific up-regulation was found to be located in a 500-bp segment in the first intron. On electrophoresis mobility shift assay using this 500-bp probe, specific DNA-protein complexes were only observed in HSP47-producing cell extracts. These results suggest that two separate elements are necessary for the cell type-specific expression of the hsp47 gene; one is a putative Sp1-binding site at -210 bp necessary for basal expression, and the other is a 500-bp region within the first intron, required for cell type-specific expression.

3T3 Cells↗

Involvement of sympathetic activation and brown adipose tissue in calcitonin gene-related peptide-induced heat production in the rat.

We previously reported that microinjection of calcitonin gene-related peptide (CGRP; 1.6-8.0 pmol, 0.2-1.0 microliter) into the ventromedial hypothalamus (VMH) increased oxygen consumption (VO(2)), heart rate (HR), colonic temperature (T(co)), and temperature of interscapular brown adipose tissue (T(IBAT)). In the present study, we investigated whether the autonomic nervous system is involved in the CGRP-induced heat production in urethane-anesthetized rats. Intraperitoneal administration of the ganglion blocker hexamethonium (20 mg/kg) or the beta-adrenergic antagonist propranolol (5 mg/kg) suppressed the CGRP-induced increases in VO(2), HR, T(co), and T(IBAT). Pretreatment with the alpha-adrenergic antagonist phentolamine (5 mg/kg) partly attenuated the heat production response but did not affect the tachycardiac response. Bilateral sectioning of the nerves supplying the IBAT attenuated the CGRP-induced increase in T(IBAT) but not significantly that in VO(2) or T(co). In rats with adrenal demedullation, the effects of CGRP were similar to those in intact rats. These results suggest that the CGRP-induced heat production is mediated by the sympathetic nervous system and, at least in part, by the BAT through the alpha- and beta-adrenoceptors.

Adipose Tissue, Brown↗

Induction of apoptosis of monocyte-macrophage lineage cells by 5-S-GAD.

We found that 5-S-GAD, an insect-derived antibacterial peptide, inhibited murine osteoclast formation in vitro. We examined the specific time point of the inhibitory action of 5-S-GAD on osteoclast formation and found that it mainly suppressed differentiation of osteoclasts in the middle of the culture period. Using HL60 cells that are able to differentiate into multinucleated macrophage-like cells, we found that 5-S-GAD induced apoptosis of HL60 cells by producing H(2)O(2). Thus, the inhibition of osteoclast formation by 5-S-GAD could be, in part, due to apoptosis of the cells of an osteoclast lineage.

Acid Phosphatase↗

A simple assay for formate dehydrogenase activity by gas chromatography-mass spectrometry.

A new method using GC-MS was devised for the convenient measurement of formate dehydrogenase (FDH) activity in crude tissue samples. FDH activity was detected by measuring headspace 13CO2, which was enzymically converted from [13C]formic acid. This method proved to be sensitive and simple for the estimation of FDH activity without complicated pretreatment.

Formate Dehydrogenases↗

Basic transcription element-binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system. Evidence for a role in neurite outgrowth.

Thyroid hormone (3,5,3'-triiodothyronine; T(3)) is essential for normal development of the vertebrate brain, influencing diverse processes such as neuronal migration, myelin formation, axonal maturation, and dendritic outgrowth. We have identified basic transcription element-binding protein (BTEB), a small GC box-binding protein, as a T(3)-regulated gene in developing rat brain. BTEB mRNA levels in cerebral cortex exhibit developmental regulation and thyroid hormone dependence. T(3) regulation of BTEB mRNA is neural cell-specific, being up-regulated in primary cultures of embryonic neurons (E16) and in neonatal astrocytes (P2), but not in neonatal oligodendrocytes (P2). T(3) rapidly up-regulated BTEB mRNA in neuro-2a cells engineered to express thyroid hormone receptor (TR) beta1 but not in cells expressing TRalpha1, suggesting that the regulation of this gene is specific to the TRbeta1 isoform. Several lines of evidence support a transcriptional action of T(3) on BTEB gene expression. Overexpression of BTEB in Neuro-2a cells dramatically increased the number and length of neurites in a dose-dependent manner suggesting a role for this transcription factor in neuronal process formation. However, other T(3)-dependent changes were not altered; i.e. overexpression of BTEB had no effect on the rate of cell proliferation nor on the expression of acetylcholinesterase activity.

Animals↗

CGRP microinjection into the ventromedial or dorsomedial hypothalamic nucleus activates heat production.

Unilateral microinjection of calcitonin gene-related peptide (CGRP, 1.6 pmol; 0.2 microl) into the ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH) immediately increased oxygen consumption (VO2), heart rate (HR), colonic temperature (Tco), and temperature of interscapular brown adipose tissue (TIBAT) in urethane-anesthetized rats, whereas vehicle saline injection into the VMH and CGRP injection into other hypothalamic regions such as the preoptic area, lateral hypothalamic area, paraventricular nucleus, and bed nucleus of the stria terminalis had no effect. The effects of CGRP injection into the VMH were dose-dependent over the range of 0.016-1.6 pmol. CGRP administration to the lateral ventricle (LV) required 16-320 pmol to elicit similar degrees of responses that were observed after the injection into the VMH. The increase in TIBAT was always higher than that in Tco after CGRP injection. Injection of [Cys(ACM)2,7]hCGRPalpha, a selective CGRP2 receptor agonist, did not induce any thermogenic effects. Human CGRP8-37, a proposed CGRP1 receptor antagonist, by itself induced heat production responses with no signs of inhibition of CGRP-induced responses. Thus, the receptor subtype of the thermogenic effect of CGRP could not be determined by the available pharmacological tools. The present results show that centrally administrated CGRP induces heat production in the BAT specifically through the VMH or DMH.

Adipose Tissue, Brown↗

Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3.

The NF-E2-binding sites or Maf recognition elements (MARE) are essential cis-acting elements in the regulatory regions of erythroid-specific genes recognized by the erythroid transcription factor NF-E2, composed of p45 and MafK. Recently, two p45-related factors Nrf1 and Nrf2 were isolated, and they are now collectively grouped as the Cap'n' collar (CNC) family. CNC factors bind to MARE through heterodimer formation with small Maf proteins. We report here the identification and characterization of a novel CNC factor, Nrf3, encoding a predicted 73-kDa protein with a basic region-leucine zipper domain highly homologous to those of other CNC proteins. In vitro and in vivo analyses showed that Nrf3 can heterodimerize with MafK and that this complex binds to the MARE in the chicken beta-globin enhancer and can activate transcription. Nrf3 mRNA is highly expressed in human placenta and B cell and monocyte lineage. Chromosomal localization of human Nrf3 is 7p14-15, which lies near the hoxA gene locus. As the genetic loci of p45, nrf1, and nrf2 have been mapped close to those of hoxC, hoxB, and hoxD, respectively, the present study strongly argues for the idea that a single ancestral gene for the CNC family members may have been localized near the ancestral Hox cluster and have diverged to give rise to four closely related CNC factors through chromosome duplication.

Amino Acid Sequence↗

Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system.

Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory models. Although IL-12 itself activates strong anti-tumor activity, the combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL-12 has been shown to cure tumor-bearing mice more effectively than either rIL-12 or IL-2-transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL-2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL-2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12 alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL-2 cells and of rIL-12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL-2-producing glioma cells and rIL-12 may be useful in the development of treatment for patients with glioma.

Animals↗