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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 775 records · Page 43Linked to original sources

High-performance liquid chromatography of proteins on N-methylpyridinium polymer columns.

Two types of 4-methylpyridinium polymers (4VP-DVB-Me and 4VP-EG-Me, cross-linked with divinylbenzene and ethylene glycol dimethacrylate, respectively) were employed for the analysis of proteins in ion-exchange high-performance liquid chromatography. These polymers had different physical properties in the dry state, but showed similar retentions in size-exclusion chromatography using carbohydrate standards. Generally, the 4VP-EG-Me column was superior to the 4VP-DVB-Me column with regard to separation and recovery of proteins.

Chromatography, High Pressure Liquid↗

Activity and spectroscopic properties of bacterial D-amino acid transaminase after multiple site-directed mutagenesis of a single tryptophan residue.

One of the three tryptophan residues per subunit of thermostable D-amino acid transaminase, Trp-139, is close to the active-site Lys-145 in the sequence of the protein. This tryptophan has been changed to several other types of residues by site-directed mutagenesis. The only mutant protein that was sufficiently active and stable for study had Phe substituted for Trp (W139F). The spectroscopic properties of this mutant enzyme differed from those of the wild-type transaminase. For example, denatured W139F showed the expected decrease in fluorescence emission intensity at 350 nm due to the deletion of one Trp residue, but the fluorescence emission of the wild-type and W139F enzymes in the native state did not differ in intensity. This result suggests that the fluorescence of Trp-139 in the native, wild-type enzyme is not manifested perhaps due to its proximity to the coenzyme, pyridoxal phosphate. Results of energy-transfer studies at several wavelengths could also be interpreted as due to the proximity of Trp-139 and the coenzyme. Circular dichroism studies indicated that the negative Cotton effect at 420 nm due to the coenzyme was still present in W139F. However, the 280-nm optically active band present in the wild-type enzyme was greatly diminished in W139F. The mutant protein with Asp at position 139 (W139D) could not be isolated presumably because it was degraded. The other mutant enzymes, W139P, W139A, and W139H, were isolated with partial activities (15-35%) that were slowly lost upon storage at 4 degrees C. Overall, these results indicate the importance of Trp-139 in the thermostable D-amino acid transaminase.

Bacillus↗

Identification of puberty-accelerating pheromones in male mouse urine.

Gas chromatography-mass spectrometry was employed to identify the two volatile amines in male mouse urine. These amines were much less concentrated in urine of castrated males. The identified amines, isobutylamine and isoamylamine, were assayed for the potential of puberty acceleration in postweaning female mice. A total of 105 young female mice were exposed to one of the following five odors: distilled water (control), 0.1 M isobutylamine, 0.1 M isoamylamine, a mixture of 0.05 M isobutylamine and 0.05 M isoamylamine, or fresh male mouse urine. The mixture of these amines accelerated the vaginal opening of young females. Except for the control, all experimental odors accelerated the first vaginal estrus in ICR strain mice.

Amines↗

Scirrhous carcinoma of the stomach: a clinical and pathological study of 106 surgical cases.

Clinical and pathological characteristics of scirrhous carcinoma of the stomach were studied in 106 cases treated by gastrectomy between 1973 and 1983. The male to female ratio was 0.58. The percentage of scirrhous carcinomas to all gastric carcinomas resected in the same period was three times higher in females than males. The age distribution of the patients suggested that there were two peaks in the forties and sixties in the male, and in the thirties and fifties in the female. The incidence of scirrhous carcinoma in all types of gastric carcinoma was significantly higher in the twenties, thirties and forties compared to the lowest incidence in the seventies. In the female group the primary lesion had a tendency to be adjacent to the fundic gland area and to avoid intestinal metaplasia. In the male the opposite was recognized. Cancer nests with single cells or only several cells were common in this type of carcinoma. These findings suggest that there might be two biologically different scirrhous carcinomas both in the male and the female, the appearance of single carcinoma cells might be favored by female sex hormones and young ages, and not only the original gastric mucosa but also mucosa with intestinal metaplasia could be precursors of single carcinoma cells.

Adenocarcinoma, Scirrhous↗

Separation and determination of theophylline from paraxanthine in human serum by reversed-phase high-performance liquid chromatography.

A sensitive and highly specific method for the determination of theophylline in serum by high-performance liquid chromatography (HPLC) has been developed. Theophylline was completely separated from paraxanthine, a major metabolite of caffeine which has been known to interfere with most isocratic reversed-phase HPLC methods, with a mixture of acetonitrile/tetrahydrofuran/acetate buffer (10 mM, pH 5.0; 5:1:94, v/v %) as the mobile phase using a C18 bonded reversed-phase column. Neither the other xanthine and uric acid derivatives nor numerous drugs tested were found to interfere. The proposed method was applied to therapeutic monitoring utilizing its excellent precision, reproducibility and high specificity for theophylline.

Aged↗

Total replacement of the suprarenal inferior vena cava with an expanded polytetrafluoroethylene tube graft in 2 patients with tumor thrombi from renal cell carcinoma.

Total replacement of the suprarenal inferior vena cava using an expanded polytetrafluoroethylene vascular graft was successful in 2 renal cell carcinoma patients with extended tumor thrombi densely adherent to the vena caval wall. Right radical nephrectomy in 1 patient and enucleation of the tumor in the solitary right kidney were performed concomitantly. Both patients are well without tumor recurrence and with good vena caval patency 14 and 6 months postoperatively. This procedure could be a safer mode of operation in cases of extended vena caval involvement by malignant tumors. Total reconstruction of the inferior vena cava enables more radical resection of the tumor.

Blood Vessel Prosthesis↗

Immunoadjuvant effects of periodontitis-associated bacteria.

Sonic extract (SE) from periodontopathic bacteria were studied for their effects on the immune response and adjuvanticity. The preparations of SE from A. actinomycetemcomitans, B. intermedius and B. gingivalis were found to have strong immunomodulating activity against the antigen itself and also sheep erythrocytes (SRBC) in in vivo experiments using C3H/HeN mice. All the SE enhanced the immune response to antigen and SRBC at low concentration. A strong immuno suppressive effect, however, was found at high concentrations of A. actinomycetemcomitans and B. intermedius but not of B. gingivalis. Moreover, these immunosuppressive effects were enhanced by the 3-day-prior injection to SRBC even at low concentrations, including that of B. gingivalis. The suppressive effect of SE from A. actinomycetemcomitans was dependent on the protein fraction in the SE tested, because suppressed anti-SRBC immune response was restored by pronase treatment or heating. Failure to recover immune response, found in a similar experiment using Bacteroides intermedius, indicated that its suppressive effect was due to a heat-stable and pronase-resistant substance. These findings, along with the data presented in this paper, support the hypothesis that patients who harbor these bacteria could suffer systemic immune suppression not only from the initial periodontopathic bacteria but also from secondary infecting bacteria. These suppressive effects may also enhance the pathogenicity of other opportunistic organisms in the gingival crevice.

Actinomyces↗

[Effect of antibiotics and anti-cancer drugs on gastrointestinal infections and dissemination by C. albicans in mice inoculated orally with C. albicans].

The authors studied the effect of antibiotics, hydrocortisone and anti-cancer drugs on gastrointestinal infections and dissemination by C. albicans in mice inoculated orally with C. albicans. The mice were given orally, vancomycin, amikacin and polymyxin B, and they also were injected with ampicillin and gentamicin. Hydrocortisone, cyclophosphamide (CPA) which causes leukopenia and neutropenia, and methotrexate (MTX) which injures the mucous membrane of the gastrointestinal tract were injected to the mice. In the mice treated with antibiotics and anti-cancer drugs, and inoculated orally with C. albicans, the colony forming units of the feces conspicuously increased. Gastrointestinal candidiasis was frequently observed, particularly at the cardia and the cardio-antrum line of the stomach of these mice. In addition to these sites, gastrointestinal candidiasis was observed at the antrum and the small intestine of the mice injected with MTX. C. albicans was frequently recovered from the livers and lungs of the mice treated with antibiotics and MTX + CPA which cause leukopenia, neutropenia and the damage of mucous membrane of the gastrointestinal tract. It is suggested that the threshold gut population of C. albicans is a determinant for gastrointestinal candidiasis, and that leukopenia, neutropenia and the damage of mucous membrane of the gastrointestinal tract are important factors for dissemination by C. albicans from the primary gastrointestinal lesions.

Administration, Oral↗

Cranial bone marrow in children: assessment of normal development with MR imaging.

Magnetic resonance images of cranial bone marrow in 238 patients (246 examinations) less than 25 years old were reviewed to establish normal age-related standards. Bone marrow in the clivus and calvaria had uniformly low signal intensity (grade 1) on T1-weighted images in most infants less than 1 year old. The number of patients with grade 1 marrow decreased rapidly in early childhood, while the number of patients with marrow of low and high signal intensity (grade 2) and uniformly high signal intensity (grade 3) gradually increased with age. A grade 1 marrow was no longer observed in either the clivus or calvaria after age 7. Most patients had a grade 3 marrow by age 15. Because bone marrow in certain pathologic conditions has decreased signal on T1-weighted images and therefore resembles grade 1 or 2 appearances of normal marrow in children, these results may be useful for differentiating normal and abnormal bone marrow signal intensities in infants and children.

Adult↗

Carcinoma of the cervix: staging with MR imaging.

Demonstration and staging of carcinoma of the cervix with magnetic resonance (MR) imaging was evaluated prospectively in 67 patients with histologically proven lesions. Findings were correlated with surgical/pathologic results obtained within 2 weeks. MR imaging had an accuracy of 95% in demonstrating invasive disease (stage IB or higher). It was capable of depicting the location and extent of tumor invasion of cervical stroma and helped detect tumor beneath relatively normal epithelium or within the endocervical canal that had not been detected by means of colposcopic biopsy. The overall accuracy of MR imaging in staging carcinoma of the cervix was 76%, and in demonstrating parametrial status, the overall accuracy was 89%. In 39 patients with proven invasive disease, the accuracy in demonstrating parametrial status was 82%. In 13 of these 39 patients the low-signal-intensity stromal ring of the cervix on MR images was completely preserved and there were no false-positive results. MR imaging is a highly promising method for directly demonstrating and staging carcinoma of the cervix and seems to be capable of providing answers to crucial questions regarding mode of therapy.

Adult↗

Enlarged uterus: differentiation between adenomyosis and leiomyoma with MR imaging.

The potential of magnetic resonance (MR) imaging in differentiation of adenomyosis from leiomyoma was evaluated in 93 patients who had a palpable enlarged uterus that was suspect for leiomyoma or adenomyosis. In all cases, MR images were correlated with surgical/pathologic findings. Pathologic findings showed that 71 enlarged uteri were due to leiomyoma, including one leiomyosarcoma, and 16 were due to adenomyosis. The other six patients were shown to have an enlarged uterus attributable to simultaneous involvement of both lesions. On T2-weighted images, adenomyosis appeared as an ill-defined, relatively homogeneous low-signal-intensity area embedded with sparse high-intensity spots. In contrast, leiomyomas were well-circumscribed masses with a spectrum of signal intensity. The cause of uterine enlargement was correctly diagnosed with MR images in 92 of the 93 cases. It is concluded that MR imaging is highly accurate in helping to distinguish between adenomyosis and leiomyoma in cases of enlarged uterus.

Adult↗

Neurofibromatosis types 1 and 2: cranial MR findings.

Neurofibromatosis 1 (NF-1) (von Rekhlinghausen disease) and neurofibromatosis 2 (NF-2) (bilateral acoustic neurofibromatosis) have been recently recognized to be distinct disorders through genetic linkages. The authors compared the cranial magnetic resonance (MR) images of 53 patients with NF-1 and 11 with NF-2. In the NF-1 group, MR imaging revealed 19 patients with optic gliomas and eight with parenchymal gliomas. In 32 patients, foci of prolonged T2, similar to those reported previously as hamartomas, were identified in the cerebellar peduncles, globus pallidus, midbrain, and other locations. The frequency of these foci was related to both age and the presence of optic gliomas. In the NF-2 group, MR imaging revealed eight patients with cranial nerve schwannomas and six with meningiomas (in addition to acoustic schwannomas in all 11). These findings demonstrate that NF-1 and NF-2 are different diseases requiring different imaging protocols. NF-1 seems to be associated with tumors of astrocytes and neurons and NF-2 with tumors of meninges and Schwann cells.

Adolescent↗

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T.

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.

Adolescent↗

Gamna-Gandy bodies of the spleen: evaluation with MR imaging.

The authors retrospectively evaluated magnetic resonance (MR) images obtained in 64 patients with portal hypertension. Multiple low-intensity nodules were noted within the spleen in eight patients. In all eight cases, these nodules were most apparent on images obtained with the GRASS (gradient-recalled acquisition in the steady state) technique, which is known to be more sensitive to heterogeneity of the magnetic susceptibility, usually caused by hemosiderin deposition. In one of these cases, ultrasonography demonstrated diffuse hyperechoic spots that had been reported to represent Gamna-Gandy bodies of the spleen (ie, organized hemorrhage caused by portal hypertension). Although there was no pathologic proof in their series, the authors believe these low-intensity nodules seen on MR images may represent the hemosiderin deposits of Gamna-Gandy bodies.

Adult↗

Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.

To elucidate the expression of the atrial natriuretic polypeptide (ANP) gene in the ventricle of the human failing heart, we have measured ANP and ANP messenger RNA (ANPmRNA) levels in left ventricular aneurysm obtained at operation, biopsy specimens of left ventricles from dilated cardiomyopathy (DCM) and autopsy samples of old myocardial infarction (OMI) and DCM hearts, and compared the levels with those in the normal ventricle. The ANP level (mean +/- SE) was 17.5 +/- 6.9 ng/g in the normal ventricle, and increased to 660.3 +/- 122.2 ng/g in the left ventricular aneurysm tissues and to 3,138.6 +/- 1,642.1 ng/g in the biopsy specimens of the DCM ventricle. These levels were approximately 40 and 200 times higher than in the normal ventricle. The increase of ANP levels was observed in both infarcted and noninfarcted regions of the OMI heart, and in the entire ventricle of the DCM heart. A significant positive correlation was found between the ANP level in aneurysm tissues and pulmonary capillary wedge pressure (r = 0.85). The ANPmRNA level in the left ventricular aneurysm showed about a 10-fold increase compared with that in the normal heart and reached 23% of that in the atrium of the same heart. A similar increase in the ANPmRNA level was observed in the entire ventricle of DCM. These data clearly indicate that the expression of the ANP gene in the ventricle is augmented in the failing heart in accordance with the severity of heart failure. In the atrium of the failing heart, ANP and ANPmRNA levels were only two times higher than those in the normal atrium. Thus, the augmentation in the expression of the ANP gene was more prominent in the ventricle than in the atrium. Taking tissue weight into account, the total content of ANPmRNA in the ventricle of the failing heart is much the same as that in the normal atrium. The ratio of the ANP level to the ANPmRNA level in the ventricle is much smaller than that in the atrium. These results suggest more rapid secretion of ANP after synthesis in the ventricle. These findings demonstrate that the expression of the ANP gene is augmented in the human ventricle of the failing heart and suggest that the ventricle becomes a substantial source of circulating ANP in congestive heart failure.

Aged↗

Angiotensin-converting enzyme inhibitors: synthesis and structure-activity relationships of potent N-benzyloxycarbonyl tripeptide inhibitors.

A new series of gamma-D-Glu-containing N-benzyloxycarbonyl (Z) tripeptide inhibitors of angiotensin-converting enzyme (ACE) was synthesized. The effect of varying the antepenultimate amino acid residue in this series on the biological activity was studied. Introduction of Lys and Orn residues at the P1 position provided the most potent inhibitors, 25a and 25b (IC50: 3.5 and 4.9 x 10(-9) M, respectively), which exhibited an oral antihypertensive activity. This result suggests that basic amino acid residues at the P1 position play an important role in binding with the S1 subsite of ACE in this series. Oral antihypertensive activity of selected compounds was evaluated.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of coronary artery bypass surgery on regions showing persistent defects in thallium myocardial images.

The indications for revascularization surgery and its effects on myocardial regions showing persistent defects in thallium myocardial images are controversial. The effects of aortocoronary bypass surgery on myocardial perfusion and wall motion in the regions with persistent defects were evaluated in 47 patients with thallium-201 single photon emission computed tomography and left ventriculography. In areas showing persistent thallium defects preoperatively the rate of improvement of perfusion was only 24% by postoperative thallium imaging, and 57% by wall motion analysis. These results were significantly inferior to those of regions with transient defects, which were 84% and 82%, respectively. A persistent defect may not be a definitive marker of a non-viable scar, but the results of surgery on such regions were unsatisfactory. It is concluded, therefore, that revascuralization surgery in regions with persistent defects is not always recommended and that the indications for surgery should be individually determined with operative risk balanced against benefits.

Adult↗