Biomedical subjects

Y Yano

Publications and source records attributed to Y Yano.

446 records · Page 25Linked to original sources

PubMedDate not supplied

delta-aminolevulinic acid dehydratase in low level lead exposure.

No statistically significant correlation was observed between log delta-aminolevulinic acid dehydratase (ALAD) activity and blood lead levels (Pb-B) in rural or urban habitants (p greater than .5 and P greater than .1, respectively) in whom no occupational source of lead was known. However, when the values the the two groups were pooled, there was a fairly good negative correlation (r = 0.509, P less than .01). Stepwise correlation coefficient analysis indicated the existance of a threshold value of Pb-B (around 15 mug/100 ml) below which ALAD activity had nor orderly relationship with the Pb-B. In contrast with married couples, parents and their children showed a remarkably high interrelationship in values of ALAD. It is concluded that in low level lead exposure primarily genetic factors influence the activity of ALAD and, thus ALAD is useful for the evaluation of lead exposure only when the lead level is higher than the threshold.

Absorption↗

PubMedDate not supplied

Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus.

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.

Adolescent↗

PubMedDate not supplied

Dose-dependent amplification by L-ascorbic acid of NaHCO3 promotion of rat urinary bladder carcinogenesis.

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which received basal diet (Oriental MF) containing AsA at 0, 1, 2, 3.5, or 5% plus 1.5% NaHCO3 for 32 wk. Relative urinary bladder weights in the 5% AsA group were significantly increased as compared to the 0 or 1% group values due to the development of tumors. Both the incidence and number of microscopic urinary bladder lesions (tumors and preneoplastic lesions) showed dose-dependent increases. Furthermore, the sizes of the urinary bladder tumors (carcinomas and papillomas) were significantly increased with the highest dose, 5-bromo-2'-deoxyuridine labeling indices showed slightly increased proliferation in preneoplastic lesions of the urinary bladder epithelium with 5% AsA treatment. In a separate experiment, scanning electron microscopic observation revealed that administration of 5% AsA plus 1.5% NaHCO3 for 8 wk, without BBN, altered the urinary bladder surface. Elevation of urinary bladder epithelium AsA content, as well as urinary AsA, was also noted. Ornithine decarboxylase (ODC) activity and ODC messenger RNA levels in urinary bladder epithelium of rats treated with 1.5% NaHCO3 plus 5% AsA for 8 wk showed no statistically significant differences as compared to the control group. The results indicate that AsA amplifies the rat urinary bladder carcinogenesis promotion activity of NaHCO3 and that its intensity of action depends on the dose, particularly at high dose.

Animals↗

PubMedDate not supplied

Effect of the calcium channel blocker nilvadipine on urinary albumin excretion in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus.

A 24-week study was conducted to evaluate the effects of the dihydropyridine calcium channel blocker nilvadipine on urinary albumin excretion in eight microalbuminuric hypertensive patients with non-insulin-dependent (type II) diabetes mellitus. Blood pressure and urinary albumin excretion measurements before the administration of nilvadipine (8 mg) were compared with those after 4, 8, 12 and 24 weeks of treatment. No significant changes were observed in the mean values of haemoglobin A1C. Systolic blood pressure was significantly reduced from 174 +/- 23 mmHg before treatment to 144 +/- 13 mmHg after 24 weeks of treatment (P < 0.02). Diastolic blood pressure was significantly reduced from 93 +/- 11 mmHg at baseline to 79 +/- 8 mmHg after 24 weeks of treatment (P < 0.05). Urinary albumin excretion was significantly reduced from 65.4 +/- 37.4 mg/g creatinine at baseline to 51.6 +/- 41.1 mg/g creatinine (P < 0.05) after 4 weeks, and to 39.1 +/- 26.9 mg/g creatinine (P < 0.02) after 24 weeks of treatment. These data suggest that in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus, treatment of hypertension with the calcium blocker nilvadipine may slow the progression of diabetic nephropathy.

Aged↗

PubMedDate not supplied

Elevation in putrescine level and spermidine/spermine N1-acetyltransferase activity coincide with tumor development in 1, 2-dimethylhydrazine-induced rat colon.

Spermidine/spermine N1-acetyltransferase (SSAT), rate-limiting enzyme of polyamine interconversion, has been demonstrated to play an important role in malignant transformation of cells. We examined the involvement of altered polyamine metabolism in the colonic carcinogenesis, using 1,2-dimethylhydrazine (DMH)-induced rat colon tumor model. Following findings were obtained: i) Ornithine decarboxylase demonstrated high activity from the early phase in colon mucosa, and increased significantly in tumors. ii) Spermidine and spermine levels gradually elevated in DMH-treated mucosa, while putrescine increased significantly in tumor tissues. iii) SSAT activity increased gradually in DMH-treated colon mucosa, which preceded elevation of tissue putrescine level, and coincided with tumor development. In conclusion, elevation of putrescine level and induction of SSAT activity are suggested to have a close association in colonic carcinogenesis.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

A case of undifferentiated carcinoma of the gallbladder with anomalous arrangement of the pancreaticobiliary ductal system.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is a congenital anomaly associated with gallbladder carcinoma. Especially patients with noncystic dilatation and without dilatation of the biliary tract are at risk of gallbladder carcinoma. A 56-year-old woman with advanced gallbladder cancer associated with AJPBD but without dilatation of the biliary tract was treated at our hospital. Although histologically cancer cells remained in the layer of the proprial mucosa, extensive metastases to lymph nodes including the paraaorta and peripancreas were detected. According to the TNM classification this case was of Stage IVB. The cancer consisted of medullary round cells, and was diagnosed as undifferentiated carcinoma. After surgery poor prognosis was expected, but three years have elapsed with no recurrence. The case is of interest because of two points of discrepancy: the primary cancer did not show deep invasion but demonstrated extensive lymph node metastases; the cancer was histologically malignant but prognosis was relatively good.

Bile Ducts↗

PubMedDate not supplied

[Slowly progressive dressing and constructional apraxia: symptomatological study, especially for dressing apraxia].

In 1982, Mesulam drew attention to a clinical picture characterized by slowly progressive aphasia without dementia, and since then, there have been many such reports. Recently, there have been 30 reports of slowly progressive apraxia. However, the nature of this apraxia is not uniform. We now report a patient with slowly progressive dressing and constructional apraxia. The patient is a 60-year-old right-handed woman with a 2-year history of a slowly progressive praxic disturbance. On admission, she was alert and aware of this difficulty. A neurological examination disclosed mild rigidity and myoclonus in her left hand. A neuropsychological assessment disclosed severe dressing apraxia, which was unlikely to be caused by dementia and moderate constructional apraxia. Her dressing apraxia was manifested in upper limbs, neck, trunk and lower limbs. However, she could express verbally the action of dressing. She also showed mild limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was present. Aphasia and agnosia were also absent. On an MRI, the bilateral cerebral hemispheres were atrophic (right > left). A 99m-Tc ECD SPECT revealed decreased uptake in the right cerebral hemisphere and left frontal lobe, and an EEG showed slow waves over the right cerebral hemisphere. There have been 30 reports of slowly progressive apraxia. Most of these cases presented with slowly progressive clumsiness in one or both hands as an initial symptom, followed by constructional, ideomotor or dressing apraxia. Our patient differed from these cases in that dressing and constructional apraxia progressed slowly without any other apraxia except only mild limb-kinetic apraxia. There was a similarity between dressing apraxia of our patient and that of Marie's and Brain's original cases.

Activities of Daily Living↗

PubMedDate not supplied

Relationship between ornithine decarboxylase gene abnormalities and human hepatocarcinogenesis.

BACKGROUND/AIMS: Ornithine decarboxylase is essential for cell growth. Its activity was high in human hepatocellular carcinoma tissues and was highest in poorly differentiated tumors. METHODOLOGY: To find if there are tumor-specific ornithine decarboxylases, we examined the ornithine decarboxylase cDNA sequences of 91 clones prepared from hepatoma tissue and non-cancerous tissue of resected liver specimens from 15 patients with hepatocellular carcinoma. RESULTS: Ornithine decarboxylase gene mutations were more frequently detected in the hepatoma tissue. The incidence of mutation in hepatoma tissue was related to dedifferentiation. Mutation in regions rich in proline, glutamic acid, serine, and threonine were detected in moderately and poorly differentiated hepatocellular carcinoma only. CONCLUSIONS: Our findings suggested that the sequence of ornithine decarboxylase in hepatocellular carcinoma often is different from that in normal liver and that mutation of its gene is related to the progression of hepatocellular carcinoma.

Adult↗

PubMedDate not supplied

Induction of apoptosis in CTLL-2 cells by protocatechualdehyde.

The purpose of this study was to investigate the possible molecular mechanisms of the antiproliferative effect induced by protocatechualdehyde (PA, a dihydroxybenzene derivative). The viability of cytotoxic T cells (CfLL-2) stimulated by IL2 was significantly inhibited at 0.12 mM PA. This inhibitory effect was associated with the induction of apoptosis detected by DNA fragmentation assay. DNA ladder appeared at 0.12 mM PA and the intensity of DNA ladder was visible at 0.3 mM PA. PA inhibited the Ib2-dependent tyrosine phosphorylation of 91, 80 and 55 KDa proteins, but did not affect IL2-dependent serine/threonine phosphorylation of proteins. The levels of bcl-2 protein and mRNA were suppressed by PA. An alteration in bax protein expression on the apoptosis process in CTLL-2 cells was not observed. However, caspase-3 activity was increased by PA. Our results demonstrate that PA inhibited cell proliferation and induced apoptosis in CTLL-2 cells. It is concluded that PA is a potent anti-proliferative agent and is expected to be a promising candidate for novel therapeutics.

Apoptosis↗

PubMedDate not supplied

Effect of perfusion rate on the local disposition of cefixime in liver perfusion system based on two-compartment dispersion model.

The effect of perfusion flow rate upon the estimated parameters in the two-compartment (non-equilibrium) dispersion model, such as dispersion coefficient, volume of the blood space, partition ratio, and irreversible transfer (or elimination) rate constant, was evaluated in the rat liver perfusion system, using cefixime as a test drug. The rats were divided into five groups and the perfusion experiments were performed at various perfusion rates (Q = 6.4, 11.3, 14.1, 16.3, and 19.6 ml/min/liver). The two-compartment dispersion model was fitted to the outflow cefixime concentration profiles after bolus input into the portal vein using the nonlinear least squares program MULTI(FILT). Results of curve fitting suggested that the corrected dispersion coefficient (DC) and the volume of blood space (VB) increased with increase in flow rate. In contrast, the partition ratio (k'), which is a measure of the extent of drug partition between the blood and the hepatic tissues, decreased when flow rate increased. The single-pass extraction ratio of cefixime is small, and the irreversible transfer rate constant (ke) was independent of flow rate. These parameters were correlated to the moment characteristics such as the recovery ratio (FH), the mean hepatic transit time (tH), and the relative variance of the transit time (sigma 2/tH2). FH and sigma 2/tH2 were independent of the flow rate, whereas tH decreased and the apparent distribution volume (VH) increased with increase in perfusion rate.

Animals↗

PubMedDate not supplied

Neuronal intranuclear hyaline inclusion disease: report of a case and review of the literature.

A case of neuronal intranuclear hyaline inclusion disease (NIHID) is described. The patient was a 26-year-old man who died of a progressive neurologic disorder, the onset of which occurred at the age of 11 years. Clinically, the disease presented as juvenile parkinsonism, and pathologically it was characterized by multiple-system degeneration in conjunction with the ubiquitous presence of intranuclear hyaline inclusions in neurons of the central and peripheral nervous system including the autonomic ganglia. Smaller and less eosinophilic intranuclear inclusions were also present in a small number of glial cells. The neuronal inclusions emitted a strong yellow-green autofluorescence under ultraviolet light and were composed of filaments 10-15 nm in diameter. The glial inclusions also consisted of similar filaments but their autofluorescence could not be determined with certainty because of their small size and background autofluorescence. A review of the literature revealed 19 similar autopsy cases up to 1987. Since the clinical presentation and distribution of neuronal loss as well as the characteristics of the inclusions showed some differences among the cases, some authors speculated that NIHID represented more than one variant of a multiple-system degenerative disease. However, about half of the reported cases had favorable sites of neurodegeneration, such as the pallidum, substantia nigra, motor nuclei of the brain stem, anterior horn cells, Clarke's column and spinal ganglion as well as similarities among the inclusions. Thus, there seems to be a discrete group among cases of NIHID.

Adult↗

PubMedDate not supplied

Disseminated necrotizing leukoencephalopathy following irradiation and methotrexate therapy for central nervous system infiltration of leukemia and lymphoma.

The authors report four adult patients with disseminated necrotizing leukoencephalopathy (DNL) following therapy for central nervous system (CNS) involvements of leukemia and lymphoma. Five to fourteen months after starting therapy with 30.6-62.5 Gy of whole brain irradiation and 120-500 mg of intrathecal methotrexate (MTX), DNL developed. Brain CT scans demonstrated a characteristic symmetrical white matter low density area. Furthermore, the brain CT scans disclosed tumorous lesions with contrast enhancement in three cases. In two of the three cases autopsy proved the tumorous lesions to be necrotic foci but not leukemic tumors. Post-mortem neuropathological studies of three patients disclosed characteristic features of DNL: multiple coagulative necrosis in the white matter with myelin degeneration, swollen axons, prominent calcification, and enlarged reactive astrocytes. Three of the four patients obviously received greater doses of whole brain irradiation and intrathecal MTX than patients who remained free from DNL after treatment with whole brain irradiation and/or MTX. Analysis of the etiological factors in this series underscores the prevailing danger of treatment for neoplastic CNS involvement with excessive doses of whole brain irradiation combined with intrathecal MTX.

Adolescent↗

PubMedDate not supplied

Inhibition of farnesyl protein transferase by monoterpene, curcumin derivatives and gallotannin.

Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to extend their biological activity. Previous studies have indicate an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group, and that using inhibitors of the mevalonate pathway could block the transforming properties of ras oncogene. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we partially purified farnesyl protein transferase (FPTase) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro from porcine kidney epithelial-like LLC-PK 1 cells, human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells. This FPTase activity requires a divalent cation, such as Mg2+ or Zn2+ ions, sulfhydryl protecting agent, DTT, as well as certain pH which is linear with time and with enzyme concentration, and is present in many mammalian normal cell and tumor cell lines. Sequentially, we observed the effects of the monoterpene compound, d-limonene; curcumin derivatives, CD-I and CD-II; polyphenol compound, gallotannin; Salvia miltiorrhiza derivative, SMD; and retinoid acid derivative, RAD on FPTase activity. We found that curcumin derivatives and gallotannin had a strong inhibition on FPTase besides d-limonene, while gallotannin was the strongest among synthetic and natural compounds tested. Salivia miltiorrhiza and retinoid acid derivatives had no influence on FPTase activity. Our results suggest that compounds containing polyphenol hydroxyl may be a new source of FPTase inhibitors. The experiment also showed that availability of an in vitro farnesyl protein transferase assay could be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.

Alkyl and Aryl Transferases↗

PubMedDate not supplied

The antiproliferative effect of HGF on hepatoma cells involves induction of apoptosis with increase in intracellular polyamine concentration levels.

Hepatocyte growth factor (HGF) induced apoptosis and decreased the DNA synthesis in Hep G2 cells. In the HGF group interleukin-1 converting enzyme, ornithine decarboxylase (ODC) activity and intracellular polyamine concentrations were increased compared to those of the control group. Administration of the ODC inhibitor decreased polyamine concentration, and inhibited apoptotic changes in the cells. These changes were reversed by exogenous addition of polyamine. These findings suggest that one of the mechanisms by which HGF exerts its antiproliferative effect is induction of apoptosis and that increase in intracellular polyamine concentration may be one of the triggers of cell death.

Apoptosis↗