Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 145 records · Page 8Linked to original sources

PubMed1998

Increased sensitivity to long-term 5-fluorouracil exposure of human colon cancer HT-29 cells resistant to short-term exposure.

A 5-fluorouracil (5-FU)-resistant subline of human colon cancer HT-29 cells was developed by repeated 1-h exposure in vitro to 5-FU. This subline (HT-29/5-FU/S) had 8-fold resistance to 5-FU in a 1-h exposure assay. However, it had rather increased sensitivity to 5-FU when assayed after a continuous 96-h exposure to it. Significantly less 5-fluorouridine-5'-triphosphate was produced in the resistant cells, leading to a lower level of 5-FU incorporation into the cellular RNA. The reduced activity of orotate phosphoribosyltransferase might explain these results. In contrast, the HT-29/5-FU/S cells were more sensitive to the inhibition of in situ thymidylate synthase (TS) by 5-FU than were the parent cells. The lower in situ TS activity may have made HT-29/5-FU/S cells more sensitive to TS inhibition by 5-FU as compared with the parent cells. The fact that HT-29/5-FU/S was more resistant to short-term 5-FU exposure but more sensitive to long-term exposure than the parent line confirmed the existence of different modes of action of 5-FU, depending on the exposure time.

Colonic Neoplasms↗

PubMed1998

An autopsy case of fetal Gaucher disease.

BACKGROUND: A case of fetal form of Gaucher disease in a Japanese fetus is presented. RESULTS: A macerated baby showing hydrops fetalis was dissected at 29 weeks of gestation. The fetus was heavier in the body, liver and spleen than a normal fetus at the same gestation period. It also suffered from pericardial effusion and ascites. The diagnosis of Gaucher disease was made by histological and biochemical findings. In microscopical examinations 'Gaucher cells', which were periodic acid-Shiff (PAS)-positive, alcian blue-positive and CD68-positive, existed in the lungs, liver, spleen, thymus, adrenal glands, bone marrow and brain. In thin layer chromatography, a large quantity of glucocerebroside was seen to have accumulated in the patient's organs.

Adult↗

PubMed1998

Mechanisms for 5-fluorouracil resistance in human colon cancer DLD-1 cells.

A 5-fluorouracil (5-FU)-resistant subline, DLD-1/5-FU, was established by repeated 5-d exposures of human colon cancer DLD-1 cells to 5-FU. DLD-1/5-FU cells were 41- and more than 75-fold resistant to 96-h and 1-h exposures to 5-FU, respectively. When exposed to 5-FU, DLD-1/5-FU cells exhibited marked resistance to in situ thymidylate synthase (TS) inhibition by 5-FU as compared to DLD-1 cells, and incorporation of 5-FU into cellular RNA in DLD-1/5-FU cells decreased to 25% of that in DLD-1 cells. As causes of resistance to DNA and RNA-directed actions of 5-FU, remarkable reduction of intracellular levels of both 5-fluorouridine 5'-triphosphate (FUTP) and 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) in DLD-1/5-FU cells was confirmed. It was found that activities of uridine kinase, orotate phosphoribosyltransferase and thymidine kinase of DLD-1/5-FU cells were significantly lower than those of the parent cells. Intracellular levels of TS were similar between the two cell lines. These results indicated that the mechanism of resistance to 5-FU in DLD-1/5-FU cells involves reduced enzymatic activation of 5-FU.

Antimetabolites, Antineoplastic↗

PubMed1998

Proline, leucine, and alanine transport in placental microvillous membrane vesicles prepared from late gestational rats.

To characterize the active transport of amino acids across the placenta, uptakes of proline, leucine, and alanine were kinetically examined in placental microvillous membrane vesicles (PMV) prepared from rats in the late gestational period. Uptake rates of these amino acids in PMV showed saturable hyperbolic curves that obeyed Michaelis-Menten kinetics. Proline, leucine, and alanine transport were demonstrated to be carrier mediated systems with sodium-dependent, -independent, and both manner, respectively. In addition, sodium-dependent L-alanine transport showed two different systems, and new sodium-independent alanine transport system (K(m) of 1.12 mM) was observed in rat placenta. From these results, rat placenta has carrier mediated amino acid transport systems, and possesses at least three different transport systems for alanine.

Alanine↗

PubMed1998

Temporal and spatial distribution of alkaline phosphatase activity in male hypogonadic rat (hgn/hgn) testis during postnatal development.

In male hypogonadic mutant rat (hgn/hgn), gonocytes degenerate and peritubular cells form multiple layers around seminiferous tubules during early postnatal testicular development. Alkaline phosphatase (AP) activity has been used as not only a tracer for the primordial germ cells (PGCs) but also a histochemical marker for the peritubular myoid cells. In the present study, we examined the localization of AP activity during the postnatal testicular development in the hgn/hgn and phenotypically normal (+/+ or +/hgn) rat. In the normal testis, high AP activity was located in the surface of the PGCs on 3 days of age. As the PGCs differentiated into spermatogonia, the AP activity drastically decreased in intensity on 7 days and was completely lost by 12 days. In the hgn/hgn, the PGCs showing high AP activity occupied the inside of dilated seminiferous tubules on 3 and 7 days of age. The luminal AP activity declined gradually by 18 days and disappeared on 21 days, when the germ cells completely degenerated in the hgn/hgn testis. In the normal, high AP activity emerged in a layer of the peritubular cells surrounding the tubules on 7 days and afterwards, indicating that the peritubular cells were differentiating into myoid cells. In the hgn/hgn, the peritubular cells formed multiple layers around the tubules and showed weak AP activity on 3 to 18 days of age. On 21 days of age, high AP activity emerged in a single layer of the peritubular cells directly attached to the basement membrane in the hgn/hgn. These results indicate that the PGCs showing AP activity kept remained at later stage in the hgn/ hgn and that the single layer of mature myoid cells showing high AP activity appeared much later in the hgn/hgn testis than in normal.

Aging↗

PubMed1998

Stiffness indexes beta of the common carotid and femoral arteries are associated with insulin resistance in NIDDM.

OBJECTIVE: To investigate the association between arterial wall stiffness indexes beta of the common carotid artery (CCA) and the femoral artery (FA) and insulin resistance in NIDDM subjects in a cross-sectional study. RESEARCH DESIGN AND METHODS: We evaluated the arterial stiffness indexes beta of CCA and FA using an ultrasonic phase-locked echo-tracking system in 60 NIDDM subjects attending the diabetes center in Osaka City University Hospital, compared with 120 age- and sex-matched control subjects. Insulin sensitivity indexes were evaluated using a euglycemic-hyperinsulinemic clamp. RESULTS: Stiffness indexes beta of both CCA and FA were significantly higher in NIDDM subjects than in control subjects (CCA 18.1 +/- 0.9 vs. 11.7 +/- 0.3, respectively, P < 0.001; FA 35.7 +/- 2.3 vs. 23.7 +/- 0.8, respectively, P < 0.001). The mean insulin sensitivity index in NIDDM subjects was 4.69 +/- 0.29 mg.kg-1.min-1.mU-1.l. The stiffness indexes beta of both CCA and FA were inversely correlated with insulin sensitivity indexes (CCA r = -0.393, P = 0.002; FA r = -0.329, P = 0.010), as well as with age, duration of diabetes, and mean blood pressure. In stepwise multiple regression analyses, insulin sensitivity index and duration of diabetes were identified as significant independent variables for stiffness indexes beta in both CCA and FA (CCA R2 = 0.249, P = 0.0003; FA R2 = 0.336, P < 0.001). CONCLUSIONS: Arterial stiffness indexes beta of CCA and FA were associated with insulin resistance in NIDDM subjects.

Adult↗

PubMed1998

Sympathetic function test of vasoconstrictor changes in foot arteries in diabetic patients.

OBJECTIVE: We studied the relationship between vasoconstrictor changes in foot arteries (pedal, metatarsal, and digital arteries) and autonomic neuropathy in diabetic patients to estimate the degrees of sympathetic dysfunction. RESEARCH DESIGN AND METHODS: Sixty-two patients and nineteen age-matched control subjects were studied. The resistance index (RI) and pulsatility index (PI) were measured as vascular hemodynamic parameters using Doppler sonography, and the increases in these hemodynamic parameters (%RI and %PI) from rest to a deep breath were measured as indexes of the degrees of sympathetic vasoconstrictor function. Cardiovascular autonomic function tests (AFTs) were performed and the score was compared to %RI and %PI values obtained. RESULTS: Of the 62 diabetic patients, 51 had various degrees of autonomic neuropathy. Both %RI and %PI in the diabetic patients were significantly less than those in the control subjects for all foot arteries tested (all P < 0.001). There were strongly inverse correlations between the %RI and %PI of foot arteries and the AFT score (r = -0.556 to -0.846, P < 0.0001). The %RI of the digital artery was the most strongly correlated with AFT score (r = -0.846, P < 0.0001) among foot arteries tested. The abnormality of sympathetic vasoconstriction was detectable in the majority of the diabetic patients with the early phase of autonomic neuropathy (%RI: 89.5%; %PI: 94.5%). CONCLUSIONS: We conclude that the %RI of the digital artery is a useful and reliable sympathetic function test of early phase in diabetic patients.

Adult↗

PubMed1998

Effect of the vasodilatory beta-blocker, nipradilol, and Ca-antagonist, barnidipine, on insulin sensitivity in patients with essential hypertension.

OBJECTIVES: To assess the effects of a vasodilatory beta-adrenoceptor blocker, nipradilol, and a long-acting Ca channel blocker, barnidipine, on insulin sensitivity. DESIGN: Insulin sensitivity was determined using a euglycemic hyperinsulinemic clamp technique before and after a 12-week treatment period in eighteen patients with essential hypertension. RESULTS: Both drugs decreased blood pressure without affecting any serum parameters of glucose and lipid metabolism. Nipradilol significantly augmented glucose infusion rate (GIR) from 3.11+/-0.28 to 4.69+/-0.57mg/kg/min (p=0.027). Barnidipine also increased GIR from 3.91+/-0.43 to 5.29+/-0.43 mg/kg/min (p=0.028). Plasma norepinephrine concentrations significantly increased with barnidipine treatment, while nipradilol had no effect on plasma norepinephrine levels. No adverse events were reported during the study. CONCLUSIONS: These results suggest that vasodilatory beta-blockers such as nipradilol and long-acting Ca channel blockers such as barnidipine may be useful in the treatment of insulin resistant hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed1998

[Secondary osteoporosis and its treatment--diabetes mellitus].

Japanese epidemiological study showed higher frequency of osteopenia/osteoporosis in diabetic patients as compared with sex- and age-matched control. The mechanism by which bone loss occurs in diabetic patients could be explained by a reduction of insulin/insulin-like growth factor-I action, sustained hyperglycemic state, a generation of advanced glycosylation end-products, and diabetic complication such as neuropathy, nephropathy and myopathy. Osteoblast deficit is hypothesized to play a major role in the occurrence of diabetic osteopenia. Besides the deficiency of insulin and insulin-like growth factor-I, we demonstrated that sustained hyperglycemia alone causes suppression of osteoblast proliferation and its response to parathyroid hormone and 1 alpha, 25-dihydroxyvitamin D, Hyporesponse of osteoblast to 1 alpha, 25-dihydroxyvitamin D, was also confirmed in diabetic patients as reflected by a reduction in an incremental response of serum osteocalcin during 1 alpha, 25-dihydroxyvitamin D administration. The regimens having stimulatory effect on bone turnover, such as intermittent PTH therapy and vitamin D, are recommended to treat diabetic osteopenia, besides improvement of diabetic control state.

Diabetes Complications↗

PubMed1998

[A case of pheochromocytoma with a large pseudocyst].

We report a case of pheochromocytoma with a markedly large pseudocyst. A 51-year-old man with the complaint of headache and palpitation was referred to our hospital. Ultrasonography (US) revealed a right adrenal cystic mass. Computerized tomography (CT) and magnetic resonance imaging (MRI) confirmed an adrenal cyst. MRI showed a high intensity mass in both T1 and T2-weighted-images, suggesting an adrenal hemorrhagic cyst. 131I-meta-iodo-benzylguanidine (MIBG) scintigraphy showed a prominent accumulation at the right adrenal lesion. Considering the abnormal elevation of cathecholamines in blood and urine samples, we performed right adrenolectomy with the clinical diagnosis of pheochromocytoma. 131I-MIBG scintigraphy was the most important diagnostic tool in the diagnosis of pheochromocytoma.

3-Iodobenzylguanidine↗

PubMed1998

[Multilocular chronic intracerebral hematoma due to metastatic brain tumor: a case report].

Chronic intracerebral hematoma is a fairly rare clinical entity. We report a case of a 76-year-old man who presented with left hemiparesis on admission. CT scan revealed a hematoma in the right basal ganglia. Under observation, the hyperdense lesion on CT scan changed to isodense 2 weeks after admission and then changed to low density 4 weeks after the first scan. These findings suggested hypertensive intracerebral hemorrhage but, 3 months after admission, hemiparesis grew worse and the appearance of the lesion changed from low density to isodensity again. When the patient presented disturbance of consciousness, CT scan revealed a new hemorrhage from the capsule of the hematoma and the new hematoma markedly expanded 2 weeks later. The contents of the hematoma was old uncoagulated hematoma resembling chronic subdural hematoma and drainage was carried out under local anesthesia. The patient died because of respiratory failure and autopsy was performed. Histopathologically cancer cells were shown in the hematoma cavity and the capsule of the hematoma was composed of two layers: a collagenous layer on the inside and a granulation layer with neovascular system on the outside. As the neovascular system existed on the outside of the capsule, the rebleeding occurred outside the capsule and the second hematoma appeared beside the initial one. We suspected that the initial bleeding occurred in the tumor tissue and the rebleeding occurred in the granulation layer of the capsule.

Adenocarcinoma↗

PubMed1998

[Effects of the aldose reductase inhibitor on diabetic polyneuropathy--the efficacy of F wave measurement].

The effects of the aldose reductase inhibitor epalrestat (150 mg/day) on electrophysiological function were examined in 22 NIDDM patients with diabetic polyneuropathy for 6 months. Although no significant differences were observed in sensory (the sural nerve) or motor (the posterior tibial nerve) conduction velocities and amplitude, only F wave conduction velocities were significantly improved at 3 and 6 months after the treatment. There were no significant changes in CV-RR, vibration threshold and laboratory data. No serious side effects were observed during the therapeutic trial. This study suggests F wave is appropriate for the assessment of diabetic neuropathy and for therapeutic trials.

Aldehyde Reductase↗

PubMed1998

[FLAIR images of mild head trauma with transient amnesia].

A newly advanced MRI pulse sequence, the FLAIR (fluid-attenuated inversion recovery) imaging, in which a long TE spin echo sequence is used with suppression of the CSF with an inversion pulse, displays the CSF space as a no signal intensity area. We examined 45 cases of mild head trauma with posttraumatic amnesia by FLAIR images and could detect some findings which could not be detected by CT scan and conventional MR images. These findings could be detected in many patients with long post-traumatic amnesia (over 2 hours), but they could not be detected in patients with short posttraumatic amnesia (within 30 mins). These findings existed surrounding lateral ventricles and we classified them into 3 types: type 1 is anterior horn of lateral ventricle, type 2 is the base of frontal lobe, type 3 is cerebral deep white matter. Some of them were examined again by FLAIR images a month later, and these findings had disappeared. We suspect that these lesions were brain edema or mild contusion without hemorrhage.

Adolescent↗

PubMed1997

High levels of a major histocompatibility complex II-self peptide complex on dendritic cells from the T cell areas of lymph nodes.

T lymphocytes recirculate continually through the T cell areas of peripheral lymph nodes. During each passage, the T cells survey the surface of large dendritic cells (DCs), also known as interdigitating cells. However, these DCs have been difficult to release from the lymph node. By emphasizing the use of calcium-free media, as shown by Vremec et al. (Vremec, D., M. Zorbas, R. Scollay, D.J. Saunders, C.F. Ardavin, L. Wu, and K. Shortman. 1992. J. Exp. Med. 176:47-58.), we have been able to release and enrich DCs from the T cell areas. The DCs express the CD11c leukocyte integrin, the DEC-205 multilectin receptor for antigen presentation, the intracellular granule antigens which are recognized by monoclonal antibodies M342, 2A1, and MIDC-8, very high levels of MHC I and MHC II, and abundant accessory molecules such as CD40, CD54, and CD86. When examined with the Y-Ae monoclonal which recognizes complexes formed between I-Ab and a peptide derived from I-Ealpha, the T cell area DCs expressed the highest levels. The enriched DCs also stimulated a T-T hybridoma specific for this MHC II-peptide complex, and the hybridoma underwent apoptosis. Therefore DCs within the T cell areas can be isolated. Because they present very high levels of self peptides, these DCs should be considered in the regulation of self reactivity in the periphery.

Animals↗

PubMed1997

Inhibition by 1alpha,25-dihydroxyvitamin D3 of activin A-induced differentiation of murine erythroleukemic F5-5 cells.

1alpha,25-Dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and other vitamin D3 (VD3) analogs enhanced the inhibitory effect of Activin A on murine erythroleukemia (MEL) cell proliferation and differentiation in a dose-dependent manner. 1alpha,25-(OH)2D3 inhibited differentiation more potently than proliferation by one order of magnitude. The VD3 analog study demonstrated either effect of VD3 on MEL cells via vitamin D receptor (VDR), as evidenced from the close relationship with the reported affinities for VDR. The effects of 1alpha,25-(OH)2D3 were preceded by the suppression of ornithine decarboxylase (ODC) activity, a rate-limiting enzyme in polyamine metabolism. Difluoromethylornithine (DFMO), an inhibitor of ODC, inhibited MEL cell proliferation, which was reversed by the simultaneous addition of putrescine, a product of ODC, but did not affect differentiation. 1alpha,25-(OH)2D3 inhibited cell differentiation during the phenotype-expression stage as reflected by the inhibition of beta-globin gene expression, while it inhibited proliferation in the commitment stage. Furthermore, it seems unlikely that the different effects of VD3 on proliferation and differentiation may be a result of upregulation of VDR or nongenomic action. In summary, it was suggested that 1alpha,25-(OH)2D3 inhibited Activin A-induced MEL cell proliferation and differentiation by distinct mechanisms and inhibited the proliferation by inhibiting ODC activity. We demonstrated the presence of 1alpha,25-(OH)2D3 action on leukemic cells at physiological concentration, which was distinct from the pharmacological effect of VD3 reported thus far.

Acetyltransferases↗

PubMed1997

Presence of B cell progenitors in the thymus.

We characterize B cell progenitors in the thymus. Although mature thymic B cells are surface Ig+, B220(high), but CD43-, B cell progenitors in the thymus were found to be slg-, B220(med), and CD43+. Most progenitors showed rearranged Ig D-J and V-D-J patterns when DNA from sorted B cell progenitors was amplified by PCR, blotted, and probed. When B cell progenitors were purified from the thymus and injected intrathymically into Ig heavy chain (Igh) allotype-disparate recipients, B cells bearing donor-type Igh6 were detected in the thymus but not in the periphery. Thymic B cells generated from these progenitors were CD5+ cells, although there was a broad range of expression of CD5 molecules. Furthermore, B cells purified from thymus that had been inoculated with B cell progenitors were able to differentiate into Ab-forming cells under the influence of CD40 ligand plus IL-10, and secreted IgM with donor Igh6 allotype. We thus clarified the existence of B cell progenitors in the thymus and also characterized the surface markers and their developmental functions.

Animals↗

PubMed1997

Osteopontin gene expression and protein synthesis in cultured rat mesangial cells.

It is controversial whether osteopontin (OP) is expressed in glomeruli and involved in glomerular diseases. We examined whether the OP expression is present at gene and protein levels in cultured rat mesangial cells (MCs). Northern blotting revealed a 1.7 kb OP-mRNA expression in MCs. Fetal calf serum (FCS) and TNF-alpha increased OP gene expression in serum-starved MCs by 2.7- and 1.8-fold over 24- and 12-hour periods, respectively. PDGF, IL-1beta, and TGF-beta had little effect on OP gene expression. Western blotting detected the OP protein expression (69 kDa). FCS and TNF-alpha increased OP protein expression in serum-starved MCs over 48- and 24-hour periods, respectively. The present study clearly demonstrated the expression of OP gene and protein in cultured rat MCs. Increased OP production under serum or TNF-alpha stimulation suggests that intraglomerular OP may contribute to the development of glomerular diseases.

Animals↗

PubMed1997

Pluripotent hemopoietic stem cells are c-kit<low.

Pluripotent hemopoietic stem cells (P-HSCs) were thought to be c-kit+, but recent reports indicate that they are c-kit(low). In the present report, we provide evidence using Ly5 congenic mice that P-HSCs are c-kit(<low). Lineage-negative (Lin-)/CD71- cells among bone marrow cells (BMCs) from C57BL/6 Ly5.1 mice were separated into major histocompatibility complex class I(high) (class I(high))/c-kit(low) and class I(high)/ c-kit(<low) populations. Each population (500 cells) was transplanted into lethally (9.0 Gy) irradiated C57BL/6 Ly5.2 congenic mice along with Ly5.2 (2 x 10(5)) compromised cells. Donor-derived Ly5.1+ cells were detected 6 months after transplantation in primary recipients reconstituted with either class I(high)/c-kit(low) or class I(high)/c-kit(<low) cells. BMCs (1 x 10(6)) from the primary recipients were further transplanted into secondary recipients (Ly5.2 mice) to assess their long term repopulating activity. Six months after bone marrow transplantation, Ly5.1+ cells in all lineages were detected only in secondary recipients that had been given BMCs from the primary recipients reconstituted with class I(high)/c-kit(<low) cells but not in cells that were class I(high)/c-kit(low). When the BMCs (1 x 10(6)) of these secondary recipients were further transplanted into tertiary recipients, all tertiary recipients that had been given BMCs from the secondary recipients originally reconstituted with Lin-/CD71-/class I(high)/c-kit(low) cells died within 10 days whereas all six tertiary recipients originally reconstituted with Lin-/CD71-/class I(high)/c-kit(<low) cells showed donor (Ly5.1+)-derived cells in their peripheral blood. In the single tertiary recipient that was killed, donor-derived T cells, B cells, macrophages, and granulocytes also were detected in several major hematolymphoid organs. The remaining five mice continue to survive more than 6 months after the tertiary bone marrow transplantation.

Animals↗