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Biomedical subjects

K Nakashima

Publications and source records attributed to K Nakashima.

At least 307 records · Page 17Linked to original sources

Overlapping and distinct signals through leptin receptor (OB-R) and a closely related cytokine signal transducer, gp130.

The structure of leptin receptor (OB-R) is highly homologous to that of gp130, the common signal transducing receptor component for the interleukin-6 family of cytokines. Based on this structural similarity, we examined signaling processes initiated by OB-R in comparison with those by gp130. Stimulation of either a long form of OB-R or gp130 led to tyrosine phosphorylation of STAT3, whereas stimulation of the truncated form of OB-R that is predominantly expressed in dbldb mice failed to do so. Stimulation of the long form OB-R did not induce tyrosine phosphorylation of a Src homology domain 2 containing protein tyrosine phosphatase, SHP-2, while stimulation of gp130 did. In contrast, activation of p42ERK2 is mediated by either the long form OB-R or gp130. Two closely related molecules, OB-R and gp130, thus appear to mediate overlapping but distinct signaling procedures.

Antigens, CD↗

Instability of expressed Cu/Zn superoxide dismutase with 2 bp deletion found in familial amyotrophic lateral sclerosis.

The mutant Cu/Zn superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (FALS) with a 2 bp deletion was produced in two protein expression systems. The mutant SOD1, expressed as a fusion protein in E. coli, had immunoreactivity to an anti-human SOD1 antibody but no SOD activity. It was more susceptible to proteolysis and its immunoreactivity decreased more rapidly than the wild type. The mutant SOD1, expressed in Cos1 cells, was not detected by either SOD activity staining or Western blot analysis, although expression of its mRNA was confirmed. These results suggest that the mutant SOD1 is seriously unstable in mammalian cells.

ATP-Binding Cassette Transporters↗

Nerve expansion in nerve regeneration: effect of time on induction of ornithine decarboxylase and Schwann cell proliferation.

We studied the effect of initiation time of nerve expansion after nerve transection on the induction of ODC activity and Schwann cell proliferation in nerve tissue under Wallerian degeneration. The levels of ODC activity and Schwann cell proliferation decreased as the initiation time of nerve expansion was delayed after nerve transection, and peak levels of ODC activity following nerve expansion preceded peak levels of Schwann cell proliferation.

Animals↗

P300-like potential disappears in rabbits with lesions in the nucleus basalis of Meynert.

The nucleus basalis of Meynert (nbM, substantia innominata) in the basal forebrain provides a single major source of cholinergic innervation for the entire cerebral cortex. We tested the effects of nbM lesions on rabbit P300-like potentials. The P300-like event-related potential (ERP) was recorded in 14 female adult white rabbits using a conventional auditory oddball paradigm. The probability of occurrence for the 2-kHz and 1-kHz stimulus tones was 90% (frequent) and 10% (rare), respectively. The nbM was destroyed bilaterally in seven rabbits referred to as the nbM (+) group. In the other seven rabbits [nbM (-) group], putamen nuclei (n=6) or amygdaloid nuclei (n=1) were destroyed bilaterally. The evoked responses were recorded before and 1 week after the destruction. In the nbM (+) group, P300 amplitude to rare stimuli significantly decreased after the lesion. In the nbM (-) group, no component of ERPs showed changes after the lesions. These results indicate that the nbM might be involved in the generation of the rabbit P300.

Acoustic Stimulation↗

Evaluation of brain oxygenation during selective cerebral perfusion by near-infrared spectroscopy.

BACKGROUND: Although selective cerebral perfusion (SCP) has been used for cerebral protection in aortic arch operations, the appropriate perfusion conditions of SCP are unclear. METHODS: We used near-infrared spectroscopy, which evaluates brain ischemia noninvasively and continuously, to determine whether perfusion with SCP (core temperature, 20 degrees C; flow rate, 10 mL.kg-1.min-1) was acceptable in terms of oxyhemoglobin and deoxyhemoglobin in patients having SCP for aortic arch operations (SCP group, n = 6) versus patients having cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CPB group, n = 6). RESULTS: There were no significant differences in age (65 +/- 10 versus 63 +/- 12 years), CPB time (199 +/- 67 versus 199 +/- 52 minutes), changes in hematocrit (-12.9% +/- 3.7% versus -12.5% +/- 6.0%), lowest blood pressure (43 +/- 7 versus 45 +/- 10 mm Hg), or highest central venous pressure (8 +/- 2 versus 9 +/- 4 mm Hg) between the SCP and CPB groups. In the SCP group, the maximum decrease in oxyhemoglobin level and the maximum increase in deoxyhemoglobin level were -5.0 to -11.4 mumol/L and -0.1 to 3.9 mumol/L, respectively; in the CPB group, the respective changes were -3.2 to -14.2 mumol/L and -0.4 to 3.6 mumol/L. Changes of oxyhemoglobin and deoxyhemoglobin levels in the SCP group were almost within the range of those in the CPB group. There were no brain complications in either group. CONCLUSIONS: As described here, SCP is acceptable and safe for brain protection in aortic arch procedures.

Adult↗

Odorant evoked magnetic fields in humans.

We investigated the olfactory evoked magnetic fields (OEFs) in 14 normal subjects. Pulses of odorant air containing amyl acetate or phenethyl alcohol, and odorless air were administered to the subject through a nasal tube. A clear and consistent OEF component, 1M, was identified in all subjects, and a second component, 2M, was detected in seven subjects, but no consistent component was identified in response to the odorless air. The peak latencies of the 1M and 2M components were approximately 320 and 630 ms, respectively. The waveforms produced by the odorless air were subtracted from the waveforms produced by the odorant air to obtain the 'subtraction' waveform, which indicated the 1M and 2M component more clearly. Their equivalent current dipoles (ECDs) were estimated in the regions around the Sylvian fissure symmetrically in both hemispheres. Therefore, these areas are proposed to be involved in olfactory perception in humans.

Adult↗

Instrumentation of a handy microscopic probe for concurrent observation and measurement of active sweat secretion, and its applications.

Instrumentation for the concurrent, dynamic monitoring of active sweat glands and perspiration volume is described. A device for the measurement of the rate of sweat secretion was installed on the head part of a microscope. The combined apparatus (microscopic probe) is handy for use and its weight is very light (ca. 300 g). The microscopic probe is easily attached to the surface of human skin. The dynamic activities of the sweat glands on the forehead and nose and under the nose were observed and measurement when thermal, mental and physical stimuli were applied. The activities of individuals sweat glands were asynchronous when observed in units of a few seconds or less; however, they worked synchronously in a unit period of several seconds. The latter were recorded as fine peaks by a strip chart recorder. The proposed system may be useful for the study of the sympathetic nervous system, the skin sympathetic reflex and the working of sudomotor nerves.

Adult↗

Chemiluminescence determination of tiopronin by flow injection analysis based on cerium(IV) oxidation sensitized by quinine.

A flow injection analysis method is proposed for the determination of tiopronin based upon the oxidation by cerium(IV) in dilute sulfuric acid medium and sensitized by quinine. With the peak height as a quantitative parameter applying optimum working conditions, tiopronin is determined over the 1-400 microM range (150 microliters per injection, n = 10, r = 0.9994) with a detection limit of 0.34 microM and an RSD (n = 10) less than 2% at 20 and 50 microM. The proposed method, combining the advantages of speed and sensitivity, was applied to the routine determination of tiopronin in a pharmaceutical preparation.

Cerium↗

Effect of continuous pressure on histopathological changes in denture-supporting tissues.

The histopathological changes in denture-supporting tissues were studied in relation to continuous pressure exerted through an experimental denture base. The experimental dentures were designed to load continuous pressures (1.5, 3.4 or 4.9 kPa) to the palate of molar region of rat. Histopathological changes caused by the continuous pressure were observed, and the intensity of the pressure was also estimated. A high correlation was observed between the histopathological changes under the denture base and the intensity of the continuous pressure. In groups exposed to 4.9 and 3.4 kPa, the continuous mechanical pressure caused bone resorption; in 1.5 kPa group, no evidence of bone resorption was observed. The epithelium and lamina propria mucosa under the denture base, which were compressed by the continuous pressure, recovered histopathologically depending on the decrease of the pressure caused by bone resorption; no quantitative recovery of the absorbed bone tissue was observed. No inflammatory change was induced by the continuous pressure. From the histopathological results observed in this study, the possibility of the existence of a threshold for bone resorption induced by continuous pressure was suggested.

Acrylic Resins↗

A nuclear gene, erd1, encoding a chloroplast-targeted Clp protease regulatory subunit homolog is not only induced by water stress but also developmentally up-regulated during senescence in Arabidopsis thaliana.

A cDNA, ERD1, isolated from one-hour-dehydrated plants of Arabidopsis thaliana L. encodes a putative protein that is similar to the regulatory ATPase subunit (ClpA) of the Clp protease and contains a putative chloroplast-targeting transit-peptide at the N-terminus. A chimeric gene with the putative plastid-targeting sequence of the erd1 gene fused to the synthetic green-fluorescent protein (sGFP) gene was constructed and introduced into Arabidopsis protoplasts. The N-terminal region of the ERD1 protein directed the sGFP protein into the plastids of the protoplasts, and functioned as a transit peptide. Northern blot analysis indicated that expression of the erd1 gene was induced not only by water stress, such as dehydration and high salinity, but also by natural senescence and dark-induced etiolation. The erd1 gene was not strongly induced by exogenous abscisic acid. A chimeric gene with the 0.9 kb promoter region of the erd1 gene fused to the beta-glucuronidase (GUS) reporter gene was constructed, and tobacco plants transformed with the construct. The GUS reporter gene driven by the erd1 promoter was induced by dehydration and high salt stress at significant levels in the transgenic plants. The GUS gene was strongly expressed in older leaves without dehydration, and was induced by dark-induced etiolation. Furthermore, GUS activity was reduced by cytokinin treatment during dark-induced etiolation. These results indicate that expression of the erd1 gene is developmentally up-regulated by senescence as well as by water stress.

Adenosine Triphosphatases↗

Growth inhibition of Helicobacter pylori by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone).

The anti-proliferative effect of methylglyoxal bis(cyclopentylamidino-hydrazone) (MGBCP), a multi-enzyme inhibitor of polyamine biosynthesis, on the growth of Helicobacter pylori was investigated. MGBCP inhibited the cell growth of H. pylori in a dose-dependent manner. The inhibition was partially reversed by the addition of spermidine. Synthesis of macromolecules, DNA, RNA and protein, was inhibited in the spermidine-depleted H. pylori cells. These findings suggest that MGBCP exhibits an anti-proliferative effect on H. pylori by suppression of macromolecule synthesis.

Anti-Bacterial Agents↗

Platelet ionized magnesium, cyclic AMP, and cyclic GMP levels in migraine and tension-type headache.

Decreased serum and intracellular levels of magnesium have been reported in patients with migraine. It has been suggested that magnesium may play an important role in the attacks and pathogenesis of headaches. We measured ionized magnesium, cyclic AMP (adenosine monophosphate), and cyclic GMP (guanosine monophosphate) in platelets of patients with migraine, in patients with tension-type headache, and in healthy controls. The platelet level of ionized magnesium from patients with tension-type headache was significantly lower than the levels from the other two groups. The platelet level of cyclic AMP from patients with migraine was higher than those from the other groups. We found no significant differences in the platelet cyclic GMP levels among the three groups. It is suggested that reduced platelet ionized magnesium in patients with tension-type headache is related to abnormal platelet function, and that increased platelet cyclic AMP in patients with migraine is related to alteration of neurotransmitters in the platelet.

Adolescent↗

Acrophase amplitude of ambulatory blood pressure decreases in migraineurs.

Ambulatory blood pressure was recorded and analyzed in 13 migraineurs during headache-free periods and in 11 healthy subjects. Systolic blood pressure, mean blood pressure, diastolic blood pressure, pulse pressure, and pulse rate were recorded for 48 hours (three times every hour from 6 AM to mid-night, once an hour at night). Circadian variation of blood pressure was analyzed using single cosinor analysis and group mean cosinor analysis methods. Single cosinor analysis identified significant circadian rhythm of systolic blood pressure in 10 of 11 control subjects (90.9%) and 5 of 13 migraineurs (38.5%, P < 0.02 versus controls, Fisher's exact test). Incidences of significant circadian rhythm of mean blood pressure and diastolic blood pressure were 100% and 100% in controls, 46.2% and 53.8% in the migraineurs (P < 0.01, P < 0.02 versus controls). Incidences of significant rhythm of pulse pressure were 36.3% in controls and 38.5% in the migraine group (difference was not significant). Group mean cosinor analysis identified significant circadian rhythm in both the migraine group and the controls. The MESOR (midline estimating statistic of rhythm) values of systolic, mean, and diastolic blood pressures showed no significant differences between the migraine group and the controls. Acrophase amplitudes of systolic, mean, and diastolic blood pressure were 4.2, 5.2, and 5.9 mm Hg in the migraine group, respectively; and 7.2, 7.3, and 7.5 mm Hg in the controls, respectively. These amplitudes of systolic, mean, and diastolic blood pressures in the migraine group were significantly smaller than those in the controls. These data suggest that some migraineurs lose or alter their circadian blood pressure rhythm. Evaluating migraineurs as a group, significant circadian rhythm of blood pressure can be identified and oscillation amplitudes of blood pressures are decreased. The present results suggest that migraineurs may be subject to dysfunction of the circadian rhythm generator and the autonomic nervous system. Possible involvement of serotonergic projections from the raphe to the suprachiasmatic nuclei of the hypothalamus in migraine is discussed.

Adult↗

Cloning and functional analysis of rat cyclin D2 promoter: multiple prolactin-responsive elements.

Structure and function of the promoter region of rat cyclin D2 gene were investigated by cloning, sequence analysis and DNA mobility shift assay using nuclear extracts of prolactin-stimulated Nb2 cells. The results show that the expression of rat cyclin D2 gene is not dependent on the TATA-box but is stimulated by multiple transcription factors induced by prolactin at an immediate-early stage of the cell cycle.

Amino Acid Sequence↗

A clinical and bacteriologic investigation of invasive streptococcal infections in Japan on the basis of serotypes, toxin production, and genomic DNA fingerprints.

In a survey of invasive streptococcal infections in Japan, we analyzed isolates of Streptococcus pyogenes collected between 1992 and 1994. Genomic DNA fingerprints produced by pulsed-field gel electrophoresis (PFGE) were compared by computer-assisted analysis. Conventional serologic M types were subdivided into PFGE types showing close genetic similarity. Among the 42 isolates from patients with invasive diseases, 16 PFGE types were identified and genetic diversity was clearly demonstrated. Identical fingerprints were observed in both invasive and noninvasive isolates. Only 43% of invasive isolates produced streptococcal pyrogenic exotoxin A (SPE A), and 31% did not contain the speA gene. These findings suggest that the dissemination of a specific clone is not sufficient to explain all cases of these diseases in Japan and pose a question as to the role of SPE A as a major virulent factor. Bacterial factors other than SPE A and host factors should be considered in evaluation of the pathogenesis of the diseases.

Antibodies, Bacterial↗

Transmission of Streptococcus pyogenes causing toxic shock-like syndrome among family members and confirmation by DNA macrorestriction analysis.

Streptococcus pyogenes can cause severe infections, such as toxic shock-like syndrome (TSLS). The transmission and pathogenesis of TSLS are poorly understood, and information is needed to develop prevention strategies. Four cases were identified in which the organism was transmitted among patients with TSLS and their family members. DNA macrorestriction endonuclease analysis using pulsed-field gel electrophoresis demonstrated the spread of S. pyogenes clones that caused TSLS among the family members. Although 14 persons related to the case-patients experienced only colonization or self-limited disease, 3 developed invasive infections (pneumonia, severe pharyngitis requiring hospitalization, and puerperal sepsis). These findings indicate that antimicrobial prophylaxis for close contacts of patients with TSLS should be considered and reinforce the need for further studies on epidemic control of TSLS.

Adult↗

Regulation of levels of proline as an osmolyte in plants under water stress.

Compatible osmolytes are potent osmoprotectants that play a role in counteracting the effects of osmotic stress. Proline (Pro) is one of the most common compatible osmolytes in water-stressed plants. The accumulation of Pro in dehydrated plants is caused both by activation of the biosynthesis of Pro and by inactivation of the degradation of Pro. In plants, L-Pro is synthesized from L-glutamic acid (L-Glu) via delta(1)-pyrroline-5-carboxylate (P5C) by two enzymes, P5C synthetase (P5CS) and P5C reductase (P5CR). L-Pro is metabolized to L-Glu via P5C by two enzymes, proline dehydrogenase (oxidase) (ProDH; EC 1.5.99.8) and P5C dehydrogenase (P5CDH; EC 1.5.1.12). Such metabolism of Pro is inhibited when Pro accumulates during dehydration and it is activated when rehydration occurs. Under dehydration conditions, when expression of the gene for P5CS is strongly induced, expression of the gene for ProDH is inhibited. By contrast, under rehydration conditions, when the expression of the gene for ProDH is strongly induced, the expression of the gene for P5CS is inhibited. Thus, P5CS, which acts during the biosynthesis of Pro, and ProDH, which acts during the metabolism of Pro, appear to be the rate-limiting factors under water stress. Therefore, it is suggested that levels of Pro are regulated at the level of transcriptional the genes of these two enzymes during dehydration and rehydration. Moreover, it has been demonstrated that Pro acts as an osmoprotectant and that overproduction of Pro results in increased tolerance to osmotic stress of transgenic tobacco plants. Genetically engineered crop plants that overproduce Pro might, thus, acquire osmotolerance, namely, the ability to tolerate environmental stresses such as drought and high salinity.

1-Pyrroline-5-Carboxylate Dehydrogenase↗

Effect of zinc administration on pancreatic regeneration after 80% pancreatectomy.

We studied the effect of oral zinc administration on functional and morphological regeneration of the remnant pancreas after 80% pancreatectomy in dogs. After 80% pancreatectomy, both endo- and exocrine function (assessed by the sum of plasma immunoreactive insulin on the intravenous glucose tolerance test and amylase output on the cerulein-secretin test) markedly deteriorated, the pancreatic regeneration rate (change in weight of the remnant pancreas between the time of surgery and autopsy) was very poor, and the zinc concentration in pancreatic tissue decreased in dogs fed the standard diet. In dogs fed the high-zinc diet, pancreatic function and regeneration rate were significantly improved, and the zinc concentration in pancreatic tissue was maintained. Early cell proliferation (assessed by ornithine decarboxylase activity. DNA synthesis, and proliferating cell nuclear antigen labeling index in the remnant pancreas) after pancreatectomy was significantly enhanced in the high-zinc diet group compared to the standard diet group. Correlation analyses between parameters of early cell proliferation and zinc concentration in pancreatic tissue yielded significant positive correlations, and the zinc concentration in pancreatic tissue was significantly correlated with both endo- and exocrine function and the pancreatic regeneration rate. These results suggest that a high-zinc diet after major pancreatectomy is effective in maintaining the zinc concentration in pancreatic tissue, which not only enhance early cell proliferation in the remnant pancreas but improves pancreatic endo- and exocrine function in the late period, promoting pancreatic regeneration.

Animals↗