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Biomedical subjects

Y Nozaki

Publications and source records attributed to Y Nozaki.

At least 19 recordsLinked to original sources
PubMed1995

Expression of tumor necrosis factor receptors in human lung cancer cells and normal lung tissues.

The purpose of this study was to investigate the expression of tumor necrosis factor (TNF) receptors for the control of the biologic action of TNF-alpha in lung cancer cells and normal lung tissues. Lung cancer specimens and normal lung tissues were freshly obtained in pairs from 15 patients who underwent surgery for lung cancer. Thirteen lung cancer specimens expressed the 55 kDa TNF receptor messenger RNA (mRNA), whereas only six lung cancer specimens expressed the 75 kDa TNF receptor mRNA by Northern blot analysis. The 55 kDa and 75 kDa TNF receptors mRNA were detected in all and 11 normal lung tissues, respectively. All four lung carcinoma cell lines examined expressed the 55 kDa TNF receptor mRNA, but only RERF-LC-MS (MS) expressed both the 55 kDa and 75 kDa TNF receptors mRNA. Immunohistochemical examination revealed that lung cancer cells expressed the 55 kDa TNF receptor, but not the 75 kDa TNF receptor at the protein level. In normal lung tissues, the 55 kDa TNF receptor was detected in alveolar macrophages, bronchioles, and some small vessels. The 75 kDa TNF receptor was detected in alveolar macrophages. All four lung carcinoma cell lines examined exhibited the only 55 kDa TNF receptor. TNF-mediated tumor cell lysis was observed in all lung carcinoma cell lines that exhibited the 55 kDa TNF receptor except A549, which is a TNF-insensitive cell line. In surface binding assays, specific surface binding of TNF-alpha to TNF-insensitive cell line A549 was observed to be about half that of TNF-sensitive cell lines. We demonstrated the expression of two distinct TNF receptors in human lung cancer and normal lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1995

TAN-1323 C and D, new concanamycin-group antibiotics; detection of the angiostatic activity with a wide range of macrolide antibiotics.

We detected potent angiostatic activity in a MeOH extract from the mycelia of microbial strain S-45628 in the chick chorioallantoic membrane (CAM) assay. The producer was taxonomically characterized as Streptomyces purpurascens. Active principles designated TAN-1323 A-D were isolated and determined to be 18-membered macrolide antibiotics; components C and D are new members of this group, while components A and B are identical to concanamycins C and A, respectively. When tested in the CAM assay, components B and D gave huge avascular zones at the extremely low doses of 10-100 ng/disk, although components A and C showed far weaker activity due to their preferential tissue-damaging effect on the CAM. The discovery that these 18-membered macrolide antibiotics are angiostatic substances prompted us to examine other types of macrolide antibiotics, leading to the discovery that 16-membered macrolide antibiotics such as bafilomycin C1, tylosin and leucomycin also show angiostatic activity on the CAM. Thus, angiostatic potential is widely distributed among macrolide antibiotics. The mechanism of action of these macrolide antibiotics is also discussed.

3T3 Cells↗
PubMed1995

[Hemichorea-hemiballism associated with nonketotic hyperglycemia and presenting with unilateral hyperintensity of the putamen on MRI T1-weighted images--a case report].

A 74-year-old man was admitted to our hospital with abrupt onset of hemichorea-hemiballism in the left arm and leg. On admission, the blood glucose level was 296 mg/dl, glycosylated hemoglobin Alc was 17.0%, and the serum osmolality was 296 mOsm/l. Urinalysis was negative for ketone bodies, but was strongly positive for glucose. After normalization of the blood glucose level, ballistic movement disappeared, but choreiform movement of the left arm and leg continued for 10 months. Brain CT showed a slight high density of the right putamen, which disappeared on 37th day after the onset. MRI showed high intensity on T1-weighted images and low intensity on T2-weighted images in the right putamen, which disappeared 10 months after the onset. SPECT on the 21th day after the onset showed hyperperfusion in the right putamen. 4 months later, the blood flow slightly reduced in the right putamen. The abnormality in the right putamen was considered to be the cause of his involuntary movements. High intensity in the putamen on T1-weighted MR images in the present case are presumed to have developed following mild ischemia and the reversible deposition of calcium or other material which occurred in association with nonketotic hyperglycemia.

Aged↗
PubMed1994

[Establishment of hyperbilirubinuria rat mutant--a new animal model for jaundice].

A new animal model for jaundice, a hyperbilirubinemic rat mutant (EHBR, Eizai hyperbilirubinuria rat), was established from Sprague-Dawley rats. Hyperbilirubinemia was inherited as an autosomal recessive trait. The gene manifesting jaundice was named "hyb". Homozygotes developed jaundice immediately after birth, and a high bilirubin concentration was detected in plasma and urine. The plasma bilirubin levels were high in the neonatal period, but they decreased from 6 to 10 weeks old. In male homozygotes, plasma bilirubin levels increased rapidly until about 40 weeks, and decreased thereafter. Female homozygotes showed slightly high plasma bilirubin levels until 56 weeks, then increased rapidly thereafter. At 72 weeks, the plasma bilirubin level of females was comparable to that of males. About 80 percent of the plasma bilirubin was conjugated. Plasma biochemistry demonstrated the increase of total cholesterol and total bile acid in the homozygotes. Histopathologically, the homozygote was characterized by brown pigment in the hepatocytes, and glomerular lesions with mesangial expansion. From these findings it was considered that EHBR might be a useful animal model for studying constitutional conjugated hyperbilirubinemia and bilirubin metabolism.

Animals↗
PubMed1994

A case of a primary hepatic tumor causing segmental changes on imaging and its relation to Zahn's infarct.

A 69-year-old female was admitted to our hospital for further examination of an intrahepatic mass which had been found while undergoing a complete physical examination. The mass measured 4 cm in size and was located in the medial segment (S4) of the liver. On computed tomography (CT), S4 was observed to be 'atrophied' and was well enhanced segmentally. A celiac angiogram showed segmental staining, and a transarterial portogram demonstrated portal stoppage of S4 from the left branch. However, no segmental intensity difference was seen on magnetic resonance imaging (MRI). An aspiration biopsy showed adenocarcinoma and thus an operation was performed under a tentative diagnosis of intrahepatic cholangiocarcinoma. The postoperative diagnosis of the tumor was combined hepatocellular and cholangiocellular carcinoma. However, no histological abnormality was seen in S4, contrary to the expectation of Zahn's infarct. In this study, we discuss the mechanism and imaging findings of Zahn's infarct, the possible reasons as to why no pathological change was seen in S4, as well as stress the rarity of reports on Zahn's infarct in cases of portal thrombus due to hepatocellular carcinoma.

Aged↗
PubMed1993

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes.

We correlated monoamine concentrations in the cerebrospinal fluid from de novo (untreated) patients with Parkinson's disease with their clinical symptoms and therapeutic outcome after two years of L-dopa with/without other anti-parkinson medication. A significant correlation was found between the severity of some parkinsonian symptoms and the reduction in particular monoamines: Hoehn and Yahr's stage with dopamine, norepinephrine, and homovanillic acid: rigidity with dopamine; akinesia with dopamine and norepinephrine; freezing of gait with norepinephrine; and dementia with dopamine and homovanillic acid. Tremor had no correlations with the concentrations of the monoamines measured. Patients with dementia had a significantly increased level of epinephrine concentrations. Insufficient therapeutic responses of individual symptoms were associated with significantly decreased concentrations of particular monoamines before treatment: Hoehn and Yahr's stage with norepinephrine and epinephrine; akinesia with homovanillic acid and 5-hydroxyindoleacetic acid; and freezing of gait with dopamine, norepinephrine, homovanillic acid, and 5-hydroxyindoleacetic acid. These results suggest a significant correlation between the reduction in particular monoamines and the severity of some parkinsonian symptoms and their subsequent responses to L-dopa.

Aged↗
PubMed1993

TAN-1120, a new anthracycline with potent angiostatic activity.

A potent angiogenesis-inhibitory compound TAN-1120 was found to be produced by a Streptomyces species isolated from a soil sample. The producing organism was characterized as a new subspecies of S. triangulatus and named S. triangulatus subsp. angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silica gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analyses to be a new baumycin-group anthracycline. Reduction of TAN-1120 gave two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed remarkably potent angiostatic activity in two conventional angiogenesis assay systems in vivo, while doxorubicin and daunomycin had far weaker activity. It strongly inhibited proliferation of vascular endothelial cells did not prevent capillary cord formation in vitro by the endothelial cells on extracellular matrix-coated plates. TAN-1120 is one of the most potent angiostatic agents reported.

3T3 Cells↗
PubMed1993

[Adult case of aortopulmonary window with aortic regurgitation: a case report].

A 45-year-old woman was admitted to our hospital because of the evaluation of heart murmur. Her height was 152 cm and body weight was 46 kg. The physical examination showed a grade 4 continuous murmur widely audible on the anterior chest wall. The chest X-ray film was normal. The electrocardiogram showed premature ventricular contractions and left ventricular (LV) hypertrophy. The two dimensional echocardiogram demonstrated the presence of moderate aortic regurgitation (AR), however, aortopulmonary window could not be detected. The aortic valve showed neither atherosclerotic nor rheumatic changes. At cardiac catheterization, pulmonary artery (PA) pressure was 20/11 mmHg and aortic pressure was 133/60 mmHg, and a step-up of O2 saturation between right ventricule and pulmonary artery (PA) was demonstrated. The aortography revealed an aortopulmonary window between the proximal ascending aorta and the main PA, and grade 2 AR. The pulmonary to systemic flow ratio averaged 1.5:1. The coronary artery and the LV wall motion was normal. Aortopulmonary window is a very rare anomaly and often requires operation in childhood because of its large left-to-right shunt in most cases. Neither an asymptomatic adult case with this anomaly nor a case with AR has not been reported so far.

Aortic Valve Insufficiency↗
PubMed1992

[The effect of the thyrotropin releasing hormone (TRH) on the motor speech disorder in spinocerebellar degeneration].

A prospective study regarding the effect of TRH on the motor speech disorder of three patients with spinocerebellar degeneration (SCD), the first with hereditary cortical cerebellar atrophy, the second and third with sporadic olivo-ponto-cerebellar atrophy, was performed. The effect was analyzed by using speech evaluation, such as the auditory impression, the questionnaire of the consciousness for verbal communication, the phonetic evaluation and the acoustic analysis. The results of the analysis and the mechanism of the improvement of the motor speech disorder are discussed. Only the first patient showed a remarkable improvement subjectively. In addition, the improvement of phonation and articulation was demonstrated quantitatively in the evaluation of the first patient. On the other hand, by phonation analysis using VISI-PITCH, it was seen that there were a decrease in the perturbation of the voice pitch and an increase in voice range in all three patients. Therefore, it was concluded that the improvement of phonation plays a major role in the improvement of the motor speech disorder. Such improvement of the phonation seems to have resulted from the improvement of coordination, mainly due to the normalization of the muscle tone of the larynx by TRH administration. Although a remarkable beneficial effect of TRH may be obtained in exceptional patients of SCD, the mechanism of such an effect of TRH should be more extensively studied using the quantitative clinical evaluation of phonation and articulation.

Articulation Disorders↗
PubMed1992

Prolyl endopeptidase purified from granulomatous inflammation in mice.

Activity of prolyl endopeptidase (EC 3.4.21.26) which hydrolyses the Pro7-Phe8 bond in angiotensin II has been found to elevate in experimentally produced granulomatous inflammation in liver and skin. We purified the enzyme 1,536-fold by 6 steps from murine hepatic granulomas. The purified enzyme has a molecular weight of 79 kDa and physicochemical properties equivalent to those previously reported for prolyl endopeptidase purified from other sources. By HPLC analysis, the cleavage of Phe8-Leu10 and Phe8 from angiotensin I and II, respectively, was detected and quantified. Monospecific IgG was prepared from serum of rabbits injected with purified enzyme. Concentration of the enzyme was immunohistochemically detected in cells which form granulomatous organization, but not in inflammatory cells surrounding the foci. The antibody, however, cross reacted with the enzyme in adjacent liver cells and weakly stained their cytoplasm. The findings indicate that this enzyme, in addition to angiotensin converting enzyme, may serve as a useful biochemical marker for granulomatous tissue reactions.

Angiotensin I↗
PubMed1992

Concentrations of monoamines and their metabolites in the cerebrospinal fluid from patients with senile dementia of the Alzheimer type and vascular dementia of the Binswanger type.

We measured the concentrations of total (conjugated and unconjugated) monoamines (dopamine, DA; norepinephrine, NE) and monoamine metabolites (homovanillic acid, HVA; 3-methoxy-4-hydroxyphenyleneglycol, MHPG; 5-hydroxyindoleacetic acid, 5-HIAA) in the cerebrospinal fluid (CSF), using HPLC-ECD in 11 patients with Alzheimer's disease (AD) or senile dementia of the Alzheimer type (SDAT), 17 patients with vascular dementia of the Binswanger type (VDBT), and 15 controls. In AD/SDAT, there was a significant decrease in the DA concentration and a significant increase in the MHPG concentration. The average NE concentration was not altered, but significantly increased with the progression of intellectual disability. There were no significant changes in HVA and 5-HIAA concentrations. Patients with VDBT showed a significant increase in the DA concentration and a significant decrease in HVA and 5-HIAA concentrations. The DA concentrations increased significantly with the progression of dementia and ventricular enlargement. These results indicate that the noradrenergic and dopaminergic system in particular are altered in AD/SDAT, while the dopaminergic and serotonergic systems are mainly involved in VDBT.

Aged↗
PubMed1992

Mutations within the S gene of hepatitis B virus transmitted from mothers to babies immunized with hepatitis B immune globulin and vaccine.

A variant of hepatitis B virus (HBV) having a specific mutation within the S gene has been found to infect vaccinees. To know whether similar variants were involved in Japan, we analyzed two cases of maternal transmission of HBV in infants immunized with hepatitis B immune globulin and hepatitis B vaccine. DNA clones of HBV S genes were propagated from patients and family members and sequenced. In one family, the DNA clones from the baby patient had a Gly-to-Arg mutation at the 145th codon of the S gene, whereas those from her mother had no such mutations. In the other family, all the DNA clones obtained from the two infected children had the 145th codon intact, but they had a missense mutation at the 126th codon of the S gene, causing an amino acid substitution of Asn for Thr or Ile. This same mutation was observed in 12 of 17 clones of DNA obtained from their mother. In comparison with the wild type HBV-derived hepatitis B surface antigen, the two types of S gene mutations, either at the 145th or the 126th codon, were associated with a significant decrease in the antigenicity of some determinants on the hepatitis B surface antigen, measured by MAb. Amino acid substitution at these sites, therefore, would have induced the escape from conventional vaccines that were S gene products of wild type HBV and also from hepatitis B immune globulin, whose main components were probably also antibodies against the S gene products expressed by wild type HBV.

Adult↗
PubMed1992

Sperabillins, new antibacterial antibiotics with potent in vivo activity. Taxonomy, fermentation, isolation and biological activity.

A Gram-negative bacterium was found to produce new antibacterial antibiotics, sperabillins A, B, C and D, and the producing bacterium was characterized and identified as Pseudomonas fluorescens YK-437. Sperabillins were isolated by column chromatographies using cation-exchange resins, activated carbon and cation-exchange Sephadex, and preparative reverse-phase HPLC. Sperabillins showed antibacterial activity against Gram-negative and Gram-positive bacteria including antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Sperabillin A inhibited DNA, RNA, protein, and cell wall biosynthesis in Escherichia coli. Sperabillins showed good protective effects in experimentally infected mice.

Amidines↗
PubMed1992

A new rat mutant with chronic conjugated hyperbilirubinemia and renal glomerular lesions.

A new mutant strain of inbred Sprague Dawley rats with autosomal recessive hyperbilirubinuria, were studied by biochemical, histologic, and ultrastructural methods. The plasma bilirubin concentration in the homozygote was significantly higher than that of the heterozygote, and about 80% of the bilirubin was conjugated. Plasma BSP and ICG clearance were both severely delayed in the homozygote. Plasma BSP elimination kinetics suggested that the pathophysiologic defect was not hepatic uptake or storage but rather in secretion into bile. Histopathology of the liver demonstrated brown pigment in the hepatocytes that appeared to be lipofuscin. The electron microscopic features of the hepatic pigment resembled those of the Dubin-Johnson syndrome. Homozygote histopathology also revealed glomerular lesions with mesangial expansion and proliferation in the kidneys. Immunohistologic studies disclosed mesangial granular deposition of IgG, IgA, and to a lesser degree, IgM and C3. These renal changes resembled those of IgA nephropathy. The spontaneous hyperbilirubinuric rat (EHBR) may be a useful animal model for studying constitutive conjugated hyperbilirubinemia, bilirubin metabolism, cholestasis, and glomerulonephropathy subsequent to hepatic dysfunction.

Animals↗
PubMed1991

The significance of 3-O-methyldopa concentrations in the cerebrospinal fluid in the pathogenesis of wearing-off phenomenon in Parkinson's disease.

We determined concentrations of 3-O-methyldopa (3-OMD), L-3,4-dihydroxyphenylalanine (L-dopa), dopamine (DA) and other related substances in the cerebrospinal fluid in patients with Parkinson's disease (PD) 15 h after L-dopa/carbidopa medication, and compared patients with and without the wearing-off phenomenon. Concentrations of 3-OMD significantly increased, and the ratio of DA to 3-OMD was significantly shifted in favor of 3-OMD in patients with the wearing-off compared with patients without the wearing-off. However, concentrations of L-dopa, DA, and homovanillic acid (HVA) were not different between the groups. These results suggest that even if 3-OMD is related to the pathogenesis of the wearing-off, it is not through competition with L-dopa for uptake into the brain, but through other unknown mechanisms within the brain.

Biogenic Monoamines↗
PubMed1991

Concentrations of tyrosine, L-dihydroxyphenylalanine, dopamine, and 3-O-methyldopa in the cerebrospinal fluid of Parkinson's disease.

We determined the concentrations of tyrosine, L-3,4-dihydroxyphenylalanine (DOPA), dopamine (DA), and 3-O-methyldopa (3-OMD) in the cerebrospinal fluid (CSF) of parkinsonian patients and elevated potential interactions between the substances. We found a significant increase in tyrosine, and a significant decrease in DOPA, DA, and 3-OMD. We also found that for a given concentration of DOPA, DA and 3-OMD were proportional. In addition, the ratio of DA to 3-OMD was significantly shifted in favor of DA in parkinsonian patients.

Aged↗