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Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 217 records · Page 12Linked to original sources
PubMed1996

Involvement of hydrogen peroxide production in erbstatin-induced apoptosis in human small cell lung carcinoma cells.

Tyrosine kinase inhibitor, erbstatin, induced morphological apoptosis and DNA fragmentation in human small cell lung carcinoma (SCLC) cells. Erbstatin-induced apoptosis was inhibited by antioxidants, whereas erbstatin-inhibited tyrosine phosphorylation was not affected by them. Erbstatin was shown by means of flow cytometry to induce hydrogen peroxide generation. Furthermore, hydrogen peroxide induced morphological apoptosis and DNA fragmentation in the SCLC cells. We also demonstrated that erbstatin-induced hydrogen peroxide production and DNA fragmentation were partially suppressed by inhibition of protein synthesis. Thus, erbstatin-induced apoptosis would be due to hydrogen peroxide generation via newly synthesized protein.

Antioxidants↗
PubMed1996

GABAergic and glycinergic neurons projecting to the trigeminal motor nucleus: a double labeling study in the rat.

The distribution of GABAergic and glycinergic premotor neurons projecting to the trigeminal motor nucleus (Vm) was examined in the lower brainstem of the rat by a double labeling method combining retrograde axonal tracing with immunofluorescence histochemistry. After injection of the fluorescent retrograde tracer, tetramethylrhodamine dextran amine (TRDA), into the Vm unilaterally, neurons labeled with TRDA were seen ipsilaterally in the mesencephalic trigeminal nucleus, and bilaterally in the parabrachial region, the supratrigeminal and intertrigeminal regions, the reticular formation just medial to the Vm, the principal sensory and spinal trigeminal nuclei, the pontine and medullary reticular formation, especially the parvicellular part of the medullary reticular formation, the alpha part of the gigantocellular reticular nucleus, and the medullary raphe nuclei. Some of these neurons labeled with TRDA were found to display glutamic acid decarboxylase (the enzyme involved in GABA synthesis)-like or glycine-like immunoreactivity. Such double-labeled neurons were seen mainly in the supratrigeminal region, the reticular region adjacent to the medial border of the Vm, and the dorsal part of the lateral reticular formation of the medulla oblongata; a number of them were further scattered in the intertrigeminal region, the alpha part of the gigantocellular reticular nucleus, the nucleus raphe magnus, the principal sensory trigeminal nucleus, and the interpolar subnucleus of the spinal trigeminal nucleus. These neurons were considered to be inhibitory (GABAergic or glycinergic) neurons sending their axons to motoneurons in the Vm, or to local interneurons within and around the Vm.

Animals↗
PubMed1996

Patchy distribution of substance P receptor immunoreactivity in the' developing rat striatum.

Developmental changes of the distribution pattern of substance P receptor (SPR) were investigated immunohistochemically in the rat striatum. The SPR immunoreactivity in the striatum first emerged at postnatal day 1 and transiently showed a patchy pattern of distribution until it displayed the adult pattern of homogeneous distribution by the third postnatal week. The SPR-immunoreactivity patches were most marked in the medial and dorsolateral parts of the striatum, as well as in the subcallosal streak. They matched tyrosine hydroxylase-enriched areas and, conversely, avoided calbindin-enriched zones. No neurons within the SPR-immunoreactive patches contained either choline acetyltransferase or somatostatin, which is known to be contained in intrinsic neurons in the striatum. The vast majority of SPR-immunoreactive patch neurons also contained DARPP-32, a phosphoprotein that is expressed in striatal projection neurons with D1 dopamine receptor. The results indicate that SPR-immunoreactive patches which appear transiently in the developing striatum are in register with the striatal patch compartment, and that SPR immunoreactivity within these patches may be expressed on projection neurons rather than intrinsic neurons. Such SPR immunoreactivity in projection neurons in striatal patches may fade out in adulthood.

Animals↗
PubMed1996

Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits.

E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits.

Analysis of Variance↗
PubMed1996

Monophyletic origin and unique dispersal patterns of domestic fowls.

With the aim of elucidating in greater detail the genealogical origin of the present domestic fowls of the world, we have determined mtDNA sequences of the D-loop regions for a total of 21 birds, of which 12 samples belong to red junglefowl (Gallus gallus) comprising three subspecies (six Gallus gallus gallus, three Gallus gallus spadiceus, and three Gallus gallus bankiva) and nine represent diverse domestic breeds (Gallus gallus domesticus). We also sequenced four green junglefowl (Gallus varius), two Lafayette's junglefowl (Gallus lafayettei), and one grey junglefowl (Gallus sonneratii). We then constructed a phylogenetic tree for these birds by the use of nucleotide sequences, choosing the Japanese quail (Coturnix coturnix japonica) as an outgroup. We found that a continental population of G. g. gallus was the real matriarchic origin of all the domestic poultries examined in this study. It is also of particular interest that there were no discernible differences among G. gallus subspecies; G. g. bankiva was a notable exception. This was because G. g. spadiceus and a continental population of G. g. gallus formed a single cluster in the phylogenetic tree. G. g. bankiva, on the other hand, was a distinct entity, thus deserving its subspecies status. It implies that a continental population of G. g. gallus sufficed as the monophyletic ancestor of all domestic breeds. We also discussed a possible significance of the initial dispersal pattern of the present domestic fowls, using the phylogenetic tree.

Animals↗
PubMed1996

Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area.

The subthalamic nucleus (STN) is a key structure for somatic motor control via the basal ganglia. In the present study, we demonstrate that the STN of the macaque monkey has dual sets of body part representations. Each of the two separate portions of the STN is characterized with somatotopically arranged direct cortical inputs that are derived from the primary motor cortex (MI) and the supplementary motor area (SMA). The first set of body part representations is transformed from the MI to the lateral STN, whereas the second set is transformed from the SMA to the medial STN. Intracortical microstimulation mapping was carried out to guide paired injections of anterograde tracers into somatotopically corresponding regions of the MI and the SMA. We found that direct inputs from the MI were allocated mostly within the lateral half of the STN, whereas those from the SMA were distributed predominantly within its medial half. Of particular interest was that the arrangement of somatotopical representations from the SMA to the medial STN was reversed against the ordering of those from the MI to the lateral STN; the orofacial, forelimb, and hindlimb parts were represented from medial to lateral within the medial STN, whereas these body parts were represented, in the inverse order, mediolaterally within the lateral STN. Moreover, inputs from homotopical MI and SMA regions were found to converge only partially into the STN. The present findings could account for somatotopically specific involuntary movements manifested in hemiballism that is caused by destruction of the STN.

Animals↗
PubMed1996

Presynaptic localization of a metabotropic glutamate receptor, mGluR8, in the rhinencephalic areas: a light and electron microscope study in the rat.

The present study indicated presynaptic localization of a metabotropic glutamate receptor, mGluR8, in projection neurons of the main olfactory bulb of rat. An antibody was produced by using a peptide corresponding to C-terminal 23 amino acids of mouse mGluR8. It was confirmed that the C-terminal 23 amino acids of rat mGluR8 were the same as those of mouse mGluR8 except for one, and that the antibody specifically recognized mGluR8 in the rat rhinencephalon. In layer Ia of the piriform cortex (a target area of projection fibers from the main olfactory bulb), mGluR8-like immunoreactivity (mGluR8-LI) was reduced after transection of the lateral olfactory tract, and mGluR8-LI was observed in axon terminals which were filled with round synaptic vesicles and made asymmetric synapses with dendritic spines.

Animals↗
PubMed1996

Point mutations of the topoisomerase IIalpha gene in patients with small cell lung cancer treated with etoposide.

Reverse transcription-PCR-single-strand conformation polymorphism analysis was performed to detect topoisomerase IIalpha mutations using total RNA from 19 bronchial biopsy specimens obtained from 13 patients with small cell lung cancer. An abnormally migrating single-strand conformation polymorphism band was observed in one tumor sample from a patient treated with etoposide-containing chemotherapy. DNA sequence analysis of this tumor showed two transversions at codons 486 (G to A) and 494 (A to G), resulting in two missense mutations (Arg to Lys and Glu to Gly, respectively). The codon 486 mutation was identical to that previously found in two cell lines selected for amsacrine resistance. These results demonstrate that mutations of topoisomerase IIalpha occur in patients with small cell lung cancer. The significance of these mutations in the development of resistance to etoposide needs further investigation.

Aged↗
PubMed1996

Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat.

The distribution of the neuromedin K receptor (NK3; NKR) in the central nervous system was investigated in the adult rat by using in situ hybridization and immunohistochemical techniques. The rabbit anti-NKR antibody was raised against a bacterial fusion protein containing a C-terminal portion of NKR and affinity purified with a Sepharose 4B column conjugated to the fusion protein. Immunoblot analysis was performed to test the reactivity and specificity of the antibody. Crude membrane was prepared from cDNA-transfected Chinese hamster ovary (CHO) cells expressing each of the rat NKR, substance P receptor (NK1; SPR), and substance K receptor (NK2; SKR) and from the hypothalamus, cerebral cortex, and cerebellum. Immunoreactive bands were observed specifically in the NKR-CHO cells, hypothalamus, and cerebral cortex but not in the SPR- or SKR-CHO cells, nor in the cerebellum. Molecular weights of the immunoreactive bands ranged from 73 to 89 kDa and from 59 to 83 kDa in the NKR-CHO cells and tissues, respectively. The distribution of NKR-like immunoreactivity coincided with that of NKR mRNA. The expression of NKR was indicated on neuronal cell bodies and dendrites. NKR was found to be expressed intensely or moderately in neurons in the glomerular and granule cell layers of the main olfactory bulb; glomerular and mitral cell layers of the accessory olfactory bulb; layers IV and V of the cerebral neocortex; medial septal nucleus; nucleus of the diagonal band; bed nucleus of the stria terminalis; globus pallidus; ventral pallidum; paraventricular nucleus; supraoptic nucleus; zona incerta; dorsal, lateral, and posterior hypothalamic areas; amygdaloid nuclei; medial habenular nucleus; ventral tegmental area; midbrain periaqueductal gray; interpeduncular nuclei; substantia nigra pars compacta; linear, median, dorsal, and pontine raphe nuclei; posteromedial tegmental nucleus; sphenoid nucleus; nucleus of the solitary tract; intermediate and rostroventrolateral reticular nuclei; and lamina II of the caudal spinal trigeminal nucleus and spinal dorsal horn. These findings are discussed in relation to the physiological functions associated with neuromedin K.

Animals↗
PubMed1996

Dose escalation study of carboplatin with fixed-dose etoposide plus granulocyte-colony stimulating factor in patients with small cell lung carcinoma. A study of the Lung Cancer Study Group of West Japan.

BACKGROUND: We performed a Phase I-II trial to determine the maximum tolerated dose of carboplatin (CBDCA) with a fixed dose of VP-16 and granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC) patients. METHODS: Treatment consisted of a starting dose of CBDCA, 400 mg/m2 (i.v., Day 1); VP-16, 100 mg/m2 (i.v., Days 1-3), and G-CSF, 2 micrograms/kg (s.c., Days 4-17) every 4 weeks for four cycles. The dose of CBDCA was escalated in increments of 50 mg/m2 until Grade IV toxicity on the World Health Organization scale developed in two-thirds or more of the patients. RESULTS: Seventy-five previously untreated patients with pathology confirmed SCLC were entered into the trial. Seventy-one patients were eligible and 70 patients were evaluated for response. Forty-five patients had limited disease (LD) and 26 had extensive disease (ED). The response rate of the 70 patients who could be evaluated was 81%, with 23% attaining a complete response (CR) and 58% attaining a partial response (PR). The response rate was 80% in LD patients (CR, 23%; PR, 57%) and 85% in ED patients (CR, 23%; PR, 62%). The major dose-limiting toxicity was thrombocytopenia. Nephrotoxicity, neurotoxicity, and ototoxicity were uncommon. The doses of CBDCA that resulted in unacceptable thrombocytopenia were 700 mg/m2 in patients younger than 70 years and 500 mg/m2 in patients older than 70 years. Overall median survival time (MST) was 9 months. MST of LD patients and ED patients were 11 months and 7 months, respectively. The dose-limiting toxicity of CBDCA with a fixed dose of VP-16 and using G-CSF as bone marrow rescue was age-related thrombocytopenia. The maximum tolerated dose of CBDCA was 650 mg/m2 if patients were younger than 70 years and 450 mg/m2 if they were 70 years or older. CONCLUSIONS: When we retrospectively compared our results with those using standard chemotherapy regimens, we saw no therapeutic benefit from increasing planned doses of CBDCA up to 700 mg/m2 in combination with G-CSF in patients with SCLC.

Aged↗
PubMed1996

Accuracy and precision study in vitro for peripheral quantitative computed tomography.

We evaluated the accuracy and precision of a peripheral quantitative computed tomography (pQCT) scanner, the Stratec XCT-960, using 12 human cadaveric forearms. The accuracy was determined by comparing the total bone mineral content (BMC) with the ash weight (AW). We scanned and ashed three consecutive slices (thickness 2.5 mm) at the standard position (s-position) and at 2.5 mm both proximal and distal to the s-position. The correlation coefficient between the AW and total BMC using slices at the s-position was r = 0.87 with an accuracy error (random component) of 15.5%. The correlation coefficient using all slices was r = 0.90 with an accuracy error of 14.3%. The correlation coefficient improved to r = 0.95 with an accuracy error of 9.7% after averaging the results of all three slices for each forearm. The short-term precision error expressed as the coefficient of variation (CV) of bone mineral density (BMD) and BMC was determined by measuring the forearms five times either with repositioning or without repositioning. The CVs with repositioning were 2.77 and 1.15 for total BMD and BMC, 1.85 for trabecular BMD; without repositioning they were 0.29, 0.58 and 0.69 respectively. To further evaluate the influence of positioning, additional scans were performed at 1, 2 and 5 mm proximal, and 1 and 2 mm distal to the s-position. BMD and BMC were greatly influenced by the scan location; for example, the percentage differences in trabecular BMD 1 mm distal and proximal relative to the s-position were 2.5% +/- 5.1% and 0.18% +/- 6.3%, respectively. The Stratec XCT-960 appears to be a moderately accurate and highly precise scanner with potential usefulness for evaluating BMC and BMD of ultradistal radius.

Bone Density↗
PubMed1996

Phase II study of recombinant human interleukin 3 administration following carboplatin and etoposide chemotherapy in small-cell lung cancer patients. SDZ ILE 964 (IL-3) Study.

Recombinant human interleukin 3 (rhIL-3) has been suggested to be a useful agent for the treatment of chemotherapy-induced thrombocytopenia. For evaluation of this possibility, rhIL-3 was given subcutaneously for 10 days to patients with small-cell lung cancer (SCLC). Chemotherapy consisted of carboplatin (CBDCA) given at 400 mg/m2 to previously untreated patients or at 350 mg/m2 to previously treated patients on day 1 and etoposide (VP-16) given at 100 mg/m2 on days 1-3 every 4 weeks. If the platelet count nadir was < 75,000/microliters in the control cycle of chemotherapy, patients were randomly assigned for the next cycle to rhIL-3 given at 5 or 10 micrograms/kg per day on days 4-13. A total of 41 patients (32 previously untreated patients and 9 previously treated patients) were enrolled in the study. The platelet count nadir in the cycles including rhIL-3 was significantly higher at both dose levels (P < 0.01) than in the control cycle. The duration of thrombocytopenia (< 75,000/microliters) and the mean time from the 1st day of chemotherapy to thrombocyte recovery (> 100,000/microliters) in the rhIL-3 cycle were significantly shorter than those in the control cycle (P < 0.01). The neutrophil count nadir and the duration of neutropenia (<1,000/microliters) were also significantly improved in the rhIL-3 cycle (P < 0.05). The major side effects were fever (80.5%), headache (24.3%), and fatigue (14.6%). All side effects were tolerable and of less than grade II. There was no difference in the efficacy of the two dose levels, but the 5-micrograms/kg dose appeared to be better tolerated than the 10-micrograms/ kg dose. We conclude that rhIL-3 administration following chemotherapy consisting of CBDCA and VP-16 reduces the incidence and severity of chemotherapy-induced thrombocytopenia and neutropenia with an acceptable adverse-events profile.

Adult↗
PubMed1996

Origin of thalamocortical projections to the presupplementary motor area (pre-SMA) in the macaque monkey.

The presupplementary motor area (pre-SMA) is a recently defined cortical motor area that is located immediately rostral to the supplementary motor area (SMA) and is considered to play more complex roles in motor control than the SMA. In the present study, we examined the distribution of cells of origin of thalamocortical projections to the pre-SMA in the macaque monkey. Under the guidance of intracortical microstimulation mapping, the retrograde tracer biotinylated dextran amine was injected into the pre-SMA. Retrogradely labeled neurons were distributed primarily in the parvicellular division of the ventroanterior nucleus (VApc), oral division of the ventrolateral nucleus (VLo), area X, and mediodorsal nucleus (MD). Some labeled neurons were also observed in the medial and caudal divisions of the ventrolateral nucleus. The results indicate that the pre-SMA may receive not only basal ganglia inputs via the VApc, VLo, and MD, but also a cerebellar input via the X.

Animals↗
PubMed1996

Effects of bisphosphonate (pamidronate) on bone resorption resulting from metastasis of a squamous cell carcinoma: report of an autopsy case and evaluation of bone resorbing activity in an experimental animal model.

PURPOSE: This study evaluated the ability of bisphosphonate to prevent bone resorption induced by metastatic tumor cells. MATERIALS AND METHODS: Autopsy specimens of a bone metastasis from a woman with a primary squamous cell carcinoma of the tongue who developed multiple osteolytic lesions and hypercalcemia and was treated with pamidronate were studied histologically, histochemically, and ultrastructurally. In an animal experiment, cultured tumor cells (1 x 10(5)) obtained from a metastatic submandibular lymph node in the same patient were injected in the left ventricle of nude mice, and a resulting metastatic bone lesion was studied histologically and histochemically. RESULTS: In the autopsy specimens, despite the presence of many resorption lacunae on bone surface, only a few small tartrate-resistant acid phosphatase (TRAPase)-positive cells were observed, and most of them were stained weakly and detached from the bone surface. In the animal experiment, 1 of 10 animals (10%) formed osteolytic bone metastasis, and many TRAPase-positive cells were observed histochemically. CONCLUSIONS: Biphosphonate inhibits bone resorption induced by tumor, possibly by decreasing the number of osteoclasts and inhibiting their function.

Acid Phosphatase↗
PubMed1996

Pro-gastrin-releasing peptide (31-98) as a tumour marker of small-cell lung cancer: comparative evaluation with neuron-specific enolase.

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.

Biomarkers, Tumor↗