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Biomedical subjects

Y Noguchi

Publications and source records attributed to Y Noguchi.

At least 217 records · Page 12Linked to original sources

[Comparison of thrombolytic therapy and direct percutaneous transluminal coronary angioplasty for acute myocardial infarction: prospective multicenter trial at 16 clinical centers in Ibaraki prefecture TUGMI. Tsukuba University Group for Myocardial Infarction].

The efficacies of direct percutaneous transluminal coronary angioplasty (PTCA) and thrombolysis for the treatment of acute myocardial infarction were investigated in 80 patients treated within 12 hours of the onset of myocardial infarction by either PTCA (39 patients) or thrombolytic therapy (41 patients) followed by conservative care. The therapeutic approach was selected according to the treatment strategy at each of the 16 participating centers before the admission of the patients. The two treatment groups were closely matched in clinical characteristics except for the history of hypertension which occurred more in the thrombolysis group (22/39 vs 12/41, p = 0.026). The mean time before starting reperfusion therapy from the onset of symptoms was shorter in the thrombolysis group (2.3 +/- 1.5 vs 5.3 +/- 5.7 hours, p = 0.0001). Chest pain resolved more quickly in the PTCA group. Serial changes in the mean numbers of abnormal Q waves and mean values of the sum of elevated ST-segments on the electrocardiograms were similar in both groups. Serial changes of wall motion abnormality index on echocardiograms were similar in both groups. Coronary angiography after 4 weeks showed the thrombolysis group had greater residual luminal stenosis in the infarct-related artery. Left ventriculography after 4 weeks showed the PTCA group had better mean ejection fraction (68.1 +/- 11.2% vs 58.7 +/- 14.2%, p = 0.0263). Death (3/39 vs 1/41) and cardiac events (6/39 vs 6/41) after 4 weeks were similar in both groups. There was no significant difference in death and cardiac events between these two groups. However, the PTCA group had less severe residual luminal stenosis in the infarct-related artery and better left ventricular function after 4 weeks than the thrombolysis group.

Aged↗

[Gastrointestinal metastasis from lung cancer].

Metastasis of lung cancer to the digestive tract (excluding the esophagus) was confirmed by surgery or autopsy in 30 of the 1635 lung-cancer patients admitted to this Center during the 17-year period since 1977. The diagnosis was made before death in 7 and after death in 23. Metastasis of large cell carcinoma was the most common (3.7%), followed by adenocarcinoma (2.4%), small cell carcinoma (1.7%), and squamous cell carcinoma (0.7%). Metastasis to the stomach occurred in 0.4%, to the small intestine in 1.1% and to the colon in 0.5%. The overall percentage of metastasis to the digestive tract was 1.8%. Among the 298 cases diagnosed at autopsy, metastasis to the digestive tract occurred in 9.7%; stomach, 2.6%; small intestine, 5.7%; and colon, 3.0%. Eleven of the patients in whom the diagnosis was made at autopsy had abdominal symptoms while they were alive. In 11 cases diagnosed at autopsy, occult blood was positive in 9, but 6 of those 9 patients were asymptomatic. The occult-blood test is considered to be helpful as a supplementary diagnostic method in detecting metastasis of lung cancer to the digestive tract. Among the cases diagnosed while the patients were alive, metastasis was observed in the small intestine in 6 and in the colon in 1. The major manifestations were melena, ileus, intussusception, and perforation; 4 patients required emergency surgery. The prognosis was poor: the mean survival period from the onset of symptoms was 49 days. The direct cause of death was metastasis to the digestive tract in 5 cases. The possibility of metastasis to the digestive tract is high when progressive abdominal symptoms are observed and the stool is persistently positive on occult-blood tests.

Adenocarcinoma↗

[Preliminary screening for antiviral AIDS drugs. VII. Report for fiscal year 1994].

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 246 samples of different origin tested, six were shown to inhibit the growth of HIV in vitro. Two of the positive samples have hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.

Anti-HIV Agents↗

[Clinical studies on vancomycin in the treatment of MRSA infection].

We evaluated the effectiveness and safety of vancomycin (VCM) alone and in combination with beta-lactam antibiotics in the treatment of MRSA infections, and obtained the following results: 1. Effectiveness. (1) In cases of MRSA infections alone, the improvement rate was 71.4% (5/7 patients) with VCM alone and 77.8% (35/45) with VCM in combination with beta-lactam antibiotics. (2) In cases of polymicrobial infections, few cases were treated with VCM alone, but the improvement rate in combination use with beta-lactam antibiotics was 71.8% (28/39). 2. Bacteriological effect. (1) In cases of single infection with MRSA, the rate of bacterial eradication was 71.4% (5/7) with VCM alone and 68.2% (30/44) with VCM in combination with beta-lactam antibiotics. (2) In cases of polymicrobial infections, few cases were treated with VCM alone, but the rate of bacterial eradication in combination use with be ta-lactam antibiotics was 63.2% (24/38) against MRSA and 31.6% (12/38) against polymicrobial agents including MRSA. 3. Safety. Occurrences of adverse reactions and abnormal laboratory test values when VCM was used alone or when it is used in combination with another drug were about the same in these uses. As a whole, advance reactions were observed in 16 patients (9.5%). Main adverse reactions were whole body redness, drug eruption, and rash etc. Abnormal laboratory test values were observed mainly in hepatic functions, and renal functions. 4. VCM concentrations in blood was determined in 38 patients. Doses of 0.5 g and 1.0 g of VCM was administered by intravenous drip infusion over a period of 1 to 2 hours, and mean blood concentrations 1 to 2 hours after the completion of drip infusion were 25.4 micrograms/ml and 14.4 micrograms/ml, respectively. 5. Synergic effects between VCM and other antibiotics tested were observed in FIC index against all of the six MRSA strains isolated from six patients, and the clinical effects of improvement or better were obtained against five of them.

Adolescent↗

High-level production, chemical modification and site-directed mutagenesis of a cephalosporin C acylase from Pseudomonas strain N176.

A cephalosporin acylase from Pseudomonas strain N176 hydrolyses both 7-beta-(4-carboxybutanamido)-cephalosporanic acid (glutarylcephalosporanic acid) and cephalosporin C to 7-amino-cephalosporanic acid. However, its productivity in the original host was low and its activity against cephalosporin C was not sufficient for direct large-scale production of 7-amino-cephalosporanic acid. In order to overcome these problems, we established a high-level expression system for the acylase in Escherichia coli. Tyr270 in the acylase is reported to play an important role in the interaction with glutarylcephalosporanic acid, as determined from the reaction with an affinity-label reagent, 7 beta-(6-bromohexanoylamido) cephalosporanic acid [Ishii, Y., Saito, Y., Sasaki, H., Uchiyama, F., Hayashi, M., Nakamura, S. & Niwa, M. (1994) J. Ferment. Bioeng. 77, 598-603] and modification with tetranitromethane [Nobbs, T. J., Ishii, Y., Fujimura, T., Saito, Y. & Niwa, M. (1994) J. Ferment. Bioeng. 77, 604-609]. From carbamoylation with potassium cyanate and site-directed point mutagenesis of the cephalosporin C acylase, we have deduced that Tyr270 exists at a position where it can interact with a residue (possibly Ser239) corresponding to inactivation by carbamoylation. We mutated Met269 and Ala271 of the acylase and found that mutation of Met269 to Tyr or Phe caused a 1.6-fold and 1.7-fold increase, respectively, of specific activity against cephalosporin C as compared to that of the wild-type enzyme. Kinetic studies of these mutants revealed that their kcat values increased, although their Km values against cephalosporin C were not changed. These data indicate that the mutation of Met269 near Tyr270 induces a minor conformational change to increase the stability of the activated complex with the enzyme and cephalosporin C. In particular, a mutant in which Met269 was replaced by Tyr was 2.5-fold more efficient in converting cephalosporin C to 7-amino-cephalosporanic acid than the wild-type enzyme under conditions similar to those in a bio-reactor system.

Amino Acid Sequence↗

The induction of cell differentiation and polarity of tracheal epithelium cultured on the amniotic membrane.

We have developed a culture system of guinea pig tracheal epithelial cells using the epithelium-denuded human amnion as a source of basement membrane. Culture medium fluid over the epithelial cells was replaced by air after 7-day immersion culture and thereafter maintained for 2 weeks. Electron microscopical observations revealed that the height of epithelial cells and the ratio of ciliated epithelial cells looked like that of normal guinea pigs epithelium growth in 2 weeks after the air interface, but that no goblet cells could be found. In order to study cell polarity, we measured endothelin-1 levels in the media of apical and basal sides of the epithelial cell monolayer by means of the enzyme-linked immunosorbent assay. The endothelin-1 content of the submucosal side was over 30 times higher than that of the apical side. These findings suggest that ET-1 would be mainly released from airway epithelial cells toward the submucosal side.

Amnion↗

Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma.

BALB/c murine sarcoma Meth A is known to have three missense point mutations in p53. We previously reported that a nonamer peptide containing the codon 234 mutational product (designated 234CM) elicited 234CM-specific cytotoxic T cells and that immunization with 234CM in adjuvant before tumor challenge inhibited Meth A growth. Because interleukin 12 (IL-12) has been shown to have antitumor activity against established tumors and immuno-modulatory activities, we analyzed its effect on p53 peptide immunization and Meth A growth. Multiple injections of IL-12 alone (4 times a week for 2 weeks) caused regression of established Meth A sarcoma, and this effect was dose dependent. IL-12 treatment prior to Meth A challenge had little or no antitumor activity. To evaluate the effect of IL-12 on the generation of 234CM-specific cytotoxic T lymphocytes, spleen cells from BALB/c mice immunized with 234CM in adjuvant and injected with various doses of IL-12 were sensitized with 234CM in vitro. Multiple injections of 1 ng of IL-12 induced the highest cytotoxicity against target cells pulsed with 234CM. Higher doses of IL-12 suppressed 234CM-specific cytotoxic T-cell generation. Mice immunized with 234CM in QS-21 adjuvant and treated with 1 ng of IL-12 rejected established Meth A sarcoma. Mice comparably treated with 1 ng of IL-12 but immunized with 234CW peptide (the wild-type counterpart to 234CM) in QS-21 or with QS-21 alone showed progressive tumor growth.

Amino Acid Sequence↗

Nitric oxide inhibits LPS-induced IL-6 production in enterocytes.

In recent studies, production of interleukin-6 (IL-6) in cultured enterocytes was stimulated by lipolysaccharide (LPS). In other cell types, IL-6 production was inhibited by nitric oxide (NO). We tested the hypothesis that LPS-induced IL-6 production in the enterocyte is regulated, at least in part, by NO. IEC-6 cells (a rat intestinal epithelial cell line) were cultured for 3 days with different combinations of LPS (1-10 micrograms/ml), the NO synthase inhibitor N-omega-nitro-L-arginine (NNA, 3-300 microM), L-arginine (10 mM), the NO donor sodium nitroprusside (SNP, 0.5-1 microM), or medium alone as control. IL-6 levels in the culture medium were determined by the B9 murine hybridoma bioassay. Nitrite, a stable end product of NO metabolism, was measured by HPLC. PCR was performed to determine inducible NO synthase (iNOS) mRNA expression in the IEC-6 cells. Treatment of IEC-6 cells with LPS stimulated IL-6 production. LPS-induced IL-6 production was further increased by NNA in a dose-dependent fashion. This effect of NNA was abolished by the addition of L-arginine. SNP caused a dose-dependent decrease in IL-6 production. Nitrite production was increased in a dose-dependent fashion after LPS treatment. PCR revealed an increase in iNOS mRNA expression in IEC-6 cells after administration of 1 microgram/ml LPS. The results suggest that NO inhibits LPS-induced IL-6 production in the enterocyte. NO may be an important regulator of intestinal cytokine response during sepsis and endotoxemia.

Animals↗

Effect of eicosapentaenoic acid and docosahexaenoic acid on diabetic osteopenia.

To evaluate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are polyunsaturated fatty acids, on diabetic osteopenia, we measured the bone fragility in streptozotocin-induced diabetic rats. The fragility of femur was increased in diabetic rats, which was prevented in part by EPA or DHA. Moreover, EPA prevented osteopenia even in diabetic rats fed a low zinc feed, which was a potent accelerator of diabetic osteopenia. Plasma alkaline phosphatase activity and parathyroid hormone level showed no difference between the two groups of diabetic rats with or without EPA. Urinary excretion of calcium and phosphate was increased and plasma inorganic phosphate level was high in diabetic rats, suggesting severe mineral loss. In diabetic rats fed EPA, although urinary and plasma calcium levels did not change significantly, urinary phosphate excretion and plasma inorganic phosphate concentration were slightly lowered, which suggested that EPA may have an effect in suppressing phosphate release from bones in diabetic rats. These data suggest that EPA and DHA could be effective on diabetic osteopenia, but to elucidate the precise mechanisms, further examinations will be needed.

Alkaline Phosphatase↗

Developmental changes in P300 wave elicited during two different experimental conditions.

Age-related correlations on auditory event-related potentials were studied using a task-relevant oddball paradigm in 175 normal subjects aged 4-21 years and age-related correlations in the "ignore" condition were studied in 108 normal subjects aged 1-21 years. In the ignore condition, subjects more than 4 years of age were instructed to read a book to divert attention from the auditory stimulus. From 4 to about 17 years of age, the latencies of task-relevant P300 in event-related potentials (ERPs) gradually shortened. In the ignore condition experiment, the P300 latency shortened progressively, but stabilized at about 12 years of age. Whereas P300 in the ignore condition likely corresponds to P3a described previously (passive attention), the conventional P300 wave corresponds to P3b (active attention). The findings indicate a developmental difference between the P3a and P3b potential.

Adolescent↗

Protein synthesis in isolated enterocytes from septic or endotoxaemic rats: regulation by glutamine.

1. We studied the effect of sepsis and the regulation by glutamine of protein synthesis in enterocytes isolated from the small intestine of rats. 2. Sepsis was induced by caecal ligation and puncture; control rats were sham operated. Enterocytes were isolated from the jejunum and incubated in a medium containing [3H]phenylalanine. 3. Sixteen hours after caecal ligation and puncture, protein synthesis, measured as incorporation of radioactivity into protein, was increased by 65%, 89% and 137% respectively in enterocytes from the tips and mid-portions of the villi and from the crypts. 4. Addition of glutamine to incubated enterocytes stimulated protein synthesis in a dose-dependent manner, and this effect was most pronounced in crypt cells from septic rats. The effect of glutamine on protein synthesis was duplicated by equimolar concentrations of acetoacetate or 3-hydroxybutyrate, both of which may serve as fuel for enterocytes, and was blocked by the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine. 5. The results suggest that sepsis stimulates protein synthesis in enterocytes and that glutamine regulates protein synthesis in the same cells, probably by energy provision.

Animals↗

Differential effects of tumor and parenteral nutrition on jejunal mucosal polyamines.

Nutritional repletion of tumor-bearing (TB) organisms by means of total parenteral nutrition (TPN) has been associated with gut atrophy, immunosuppression, and increased infection rate. To assess possible molecular mechanisms of intestinal atrophy during TPN, jejunal mucosal polyamine concentrations and biosynthetic activity were assessed in non-TB (NTB) and TB rats maintained on rat chow or TPN for eight days. As expected, jejunal mucosal protein content was decreased in both groups of rats maintained on TPN. Although mucosal concentration of putrescine was decreased in TB groups and in the NTB group maintained on TPN, levels of spermidine and spermine were decreased only in the NTB-TPN group. Spermidine levels were elevated significantly in both TB groups. The concentration of spermine was also elevated in the TB-TPN group but was not changed in the TB group maintained on chow. Activity of ornithine decarboxylase was increased in the NTB-TPN group but was not altered significantly in either TB group. S-adenosylmethionine decarboxylase activity was decreased significantly in TB rats maintained on chow and was increased back to control level in the TB-TPN group. These results suggest that jejunal mucosal polyamines are decreased in NTB rats maintained on TPN. Additionally, it appears that enzyme activity is induced in NTB-TPN rats, perhaps in response to the reduction in polyamines and gut atrophy. The absence of similar changes in TB rats maintained on TPN suggests that regulatory mechanisms of polyamine biosynthesis, such as product inhibition, may be refractory. In addition, polyamine biosynthesis from other sources, such as tumor tissue, may be affecting the control of intestinal polyamine biosynthesis.

Adenosylmethionine Decarboxylase↗

Dissociated changes of frontal and parietal somatosensory evoked potentials in sleep.

We studied the changes of frontal and parietal somatosensory evoked potentials (SEPs) in the awake state versus different stages of sleep in 10 normal adult subjects. Frontal and parietal SEP components were affected differentially as sleep stages progressed. In general, the amplitudes of frontal components, notably P22, were increased in sleep, whereas the amplitudes of parietal components were decreased in sleep. A sensitive waveform change from the awake state to sleep was present in the frontal response, where a subtle notched negativity, termed "N40," was present only in the awake state and quickly dissipated in all stages of sleep, including stage 1. The amplitude changes from the awake state to stage 3/4 sleep were neither linear nor parallel among SEP components. The most discordant changes occurred in stage 3/4. The amplitudes for the frontal N18-P22-N30 complex and parietal N20-P26-N32 complex increased from stage 2 to stage 3/4, while those for frontal N30-fP40 and parietal N32-pP40 decreased. In contrast to these divergent amplitude changes, the latencies of all components except P14 and frontal N18 showed progressive prolongation from the awake state to slow-wave sleep. The SEP waveforms and latencies in REM sleep approximated those in the awake state, although amplitudes for frontal peaks still remained slightly higher and amplitudes for parietal peaks slightly lower. We postulate that interactions of excitatory and inhibitory phenomena are responsible for the component-dependent and sleep-stage-dependent amplitude enhancement or depression in sleep.

Adult↗

[Effects of stimulus rate on the ABR of acoustic tumor patients].

The effect of stimulus rate on the ABR of acoustic tumor (AT) patients was studied. We delivered 90 dB nHL click stimuli to 23 AT patients at stimulus rates of 9.5 Hz, 20 Hz, 40 Hz and 90 Hz, and recorded the ABR at each rate. Normal hearing subjects (42 ears) and sensorineural hearing loss patients (30 ears) were also studied for normative data. The following two parameters were examined: the interpeak latency difference between wave I and wave V (IPL I-V) at each stimulus rate, and the increase in IPL I-V (delta IPL I-V) when the stimulus rate was increased from 9.5 Hz. The values of both parameters were statistically larger in AT patients at all stimulus rates than in the normal and sensorineural hearing loss groups. When the upper normal limit of both parameters was defined as the mean plus 2SD of the normal hearing group, 4 of the 5 AT patients with a normal ABR at 9.5 Hz, had abnormal IPL I-V or abnormal delta IPL I-V at 90 Hz. These results suggest that recording ABR at high stimulus rates is effective in detecting acoustic tumors in patients with a normal ABR.

Acoustic Stimulation↗

[Cochlear microphonic potential (CM) recordable at non-shielded bedside--with reference to the development of a new earphone (NC-3)].

By making several improvements in current hearing aid earphones, a new earphone (NC-3) for CM measurement in electrocochleography (ECochG) has been developed. A silicone tube with a 1.5mm inside diameter, 175mm in length, was attached to the acoustic hole side of the earphone. The earphone proper was shielded with aluminum foil and one end of the foil was connected to a low noise cable. Human forearm was used as a dummy ear and the electrode HN-5 was fixed thereon, and a sound stimulus of 90dBnHL was delivered by the earphone (NC-3). No measurable artifacts, such as electromagnetic conductions and the CM-like mechanical vibrations generated by the acoustic output system, were recorded. By placing the earphone (NC-3) from a right-angle to a diagonal direction toward the electrode circuit, electromagnetic conduction contamination was prevented. With an extratympanic procedure using the electrode HN-5, ECochG-CM was recorded from normal hearing subjects in both a shielded sound-proof room and a non-shielded ordinary but quiet room. Short tone bursts at 1 and 4kHz were employed as acoustic stimuli and delivered by the earphone (NC-3). In the non-shielded quiet room, no electromagnetic conduction contamination or mechanical vibration was observed and there were no differences in CM responses between the two rooms. These results suggest that this earphone (NC-3), making CM recordings possible at the ordinary bedside without shielding, may contribute significantly to the subsequent spread of ECochG-CM measurement, by compensating for the disadvantages of a loudspeaker.

Acoustic Stimulation↗