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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 451 records · Page 25Linked to original sources
PubMed1993

Distribution of connectin (titin), nebulin and alpha-actinin at myotendinous junctions of chicken pectoralis muscles: an immunofluorescence and immunoelectron microscopic study.

The distribution of connectin (titin), nebulin and alpha-actinin in the areas of myotendinous junctions of chicken pectoralis muscles was examined by immunocytochemical methods. Staining with antibodies against connectin (4C9, SM1 and P1200) and nebulin formed 'doublets' flanking nonterminal Z-bands; near the end of muscle fibres 'singlets' were seen within the terminal sarcomere on the side adjacent to the terminal Z-bands. The apical regions of muscle processes, where no myosin filaments are present although actin filaments exist, were reactive with anti-nebulin but not with anti-connectin. Antibodies against pectoralis (skeletal muscle type) alpha-actinin stained non terminal Z-bands and that against gizzard (smooth muscle type) the sarcolemma. Terminal Z-bands were unreactive with both of these antibodies. These findings indicate that, although terminal and nonterminal Z-bands differ in their molecular composition, connectin and nebulin filaments appear to link myosin and actin filaments, respectively, to both Z-band types.

Actinin↗
PubMed1993

Effects of HMG-CoA reductase inhibitors on skeletal muscles of rabbits.

This study was undertaken to evaluate the potential of HMG-CoA reductase inhibitors, pravastatin sodium (hereafter abbreviated to pravastatin) and simvastatin, for induction of myopathy and influence on the ubiquinone content of skeletal and cardiac muscles and other tissues in the rabbit. Both drugs were administered orally to New Zealand White rabbits (n = 5) at the dose of 50 mg/kg per day for 14 days. Serum cholesterol levels in the pravastatin- and simvastatin-treated groups were reduced significantly by 47% an 58% on day 14 (P < 0.05), respectively, as compared with the control group, but the difference between the two treatment groups was not significant. In animals of the simvastatin-treated group, abnormal elevations of creatine kinase (CK) and lactate dehydrogenase (LDH) levels were observed, in association with severe lesions in skeletal muscles, but not cardiac muscle. The ubiquinone content in skeletal muscle in this treatment group was not affected, even in the muscles that had severe lesions, whereas that in liver and cardiac muscle was significantly reduced compared with the control group. The results suggest that there is no direct correlation between myopathy and the decrease of ubiquinone content in skeletal muscles. In contrast, the animals in the pravastatin-treated group did not show any changes in CK and LDH levels, ubiquinone content in liver and muscles, or in histopathological features of muscle fibers. The difference between the adverse effects seen with the two drugs could be attributed to physicochemical properties: simvastatin permeates the plasma membrane because of its hydrophobic nature, whereas pravastatin does not, because it is hydrophilic.

Administration, Oral↗
PubMed1993

Effect of halothane on intercellular adhesion molecule-1 (ICAM-1) in melanoma cells.

There have only been a few reports relating to the effect of inhalational anesthetics on the tumor cell morphology in cancer patients undergoing surgery. We hypothesized that some anesthetic agents might influence the spread of unresectable cancer cells and might additionally worsen the condition of the patient due to depressed host immune surveillance. We therefore evaluated the influence of halothane on tumor cell adhesion, which is closely linked to tumor cell metastasis. Human melanoma cells from SK-MEL-37 cell-line were exposed to 4% halothane for 3, 6, 12 or 24 hours, respectively. Furthermore, after 24 hours halothane exposure, they were incubated in a 5% CO2 atmosphere for 12 or 24 hours. The cells were then analyzed using a fluorescence flowcytometer and intercellular adhesion molecule-1 (ICAM-1) expression in SK-MEL-37 cells was quantified as the intensity of fluorescence of ICAM-1 expressed in 10,000 cells. ICAM-1 expression in cells exposed to halothane for 3, 6, 12 or 24 hours was lower than that of non-exposed cells and returned to control level after further incubation in 5% CO2 atmosphere for either 12 or 24 hours. We conclude that halothane might affect the progression of tumor cell metastasis in vitro.

Journal Article↗
PubMed1993

The effects of aging on the function of alveolar macrophages in mice.

In order to determine whether the function of alveolar macrophages (AM) is modulated by aging, we measured the TNF-alpha production, phagocytic function, and surface antigen expression of AM from young and old mice. When AM were primed by IFN-gamma (500 units/ml) and triggered by LPS (100 micrograms/ml), TNF-alpha production by AM was significantly smaller in old mice as compared with young mice (young mice: 161.7 +/- 28.2 units/ml; old mice: 89.3 +/- 13.6 units/ml, P < 0.05). The percentage of AM which phagocytosed latex particles (more than one particle) in old mice was significantly lower than in young mice (young: 78.1 +/- 2.5%; old: 62.8 +/- 3.4%, P < 0.05). Ia antigen expression of the AM was significantly higher and asialo-GM1 antigen expression was significantly lower in old mice than in young mice (Ia: young, 0.030 +/- 0.005; old, 0.092 +/- 0.024, P < 0.05; asialo-GM1: young, 0.-9 +/- 0.01; old, 0.75 +/- 0.07, P < 0.01). These results suggest that alveolar macrophage function is at least decreased in part with aging in mice.

Aging↗
PubMed1993

Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.

To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.

Adult↗
PubMed1993

Functional anatomy of the posterolateral structures of the knee.

The major supporting structures of the posterolateral knee were noted to be composed of three components: the fabellofibular ligament, the arcuate ligament, and popliteus muscle with origin from fibular head. We classified this area of the knee into seven major anatomic variants. Popliteus tendon is composed of two parts: the anterior and the posterior fibers. The anterior fibers become tight, while the posterior fibers become lax as the knee was flexed. This phenomenon is more pronounced when the tibia is rotated externally. The midpoint between the anterior and the posterior fibers insertions on the femur appeared to be the isometric point of the popliteus tendon.

Biomechanical Phenomena↗
PubMed1993

Cloning and sequencing of two chromosomal lipase genes from Geotrichum candidum.

Two chromosomal lipase genes (lip1 and lip2 encoding lipases I and II, respectively) were cloned from Geotrichum candidum by colony hybridization using lipase cDNAs as probes, and their nucleotide sequences were determined. Both genes contained 5'- and 3'-flanking regions in addition to their coding regions. The coding regions contained no intron, and there was 86% homology between their nucleotide sequences. However, no homology was observed between the flanking regions. The primer extension analysis showed that four transcription initiation sites were localized around 100-bp upstream from the ATG start codon of the lip2 gene. The putative promoter sequences of eukaryotic genes, CCAAT-----TATAAA, were found in the 5'-flanking regions of two lipase genes. These sequences might participate in the lipase induction by long-chain fatty acid. There were two inverted repeat sequences and a pyrimidine-rich sequence in the 5'-flanking region of lip2, but not in the 5'-flanking region of lip1. This specific structure of lip2 might reflect the higher transcriptional efficiency.

Amino Acid Sequence↗
PubMed1993

Stability of transpedicle screwing for the osteoporotic spine. An in vitro study of the mechanical stability.

The influence of bone mineral density on the stability of transpedicle screwing was studied in the human cadaveric lumbar vertebrae. The pull-out force correlated with bone mineral density. The tilting moment (load needed to tilt the screw 4 degrees cranially at the screw-plate junction) and the cut-up force (load needed to tip the end plate up by the screw) correlated with bone mineral density. A correlation was also found between the maximum insertion torque of the screw and bone mineral density. The maximum insertion torque correlated with the pull-out force, the tilting moment, and the cut-up force. In the cyclic tilting test (200 cycles), the mean value of the tilting moment at the 200th cycle was 67.4 +/- 6.1%, compared with the first cycle. The results suggest that preoperative measurement of BMD is necessary for transpedicle screwing in osteoporotic cases, and that the cyclic tilting motion decrease its mechanical stability. The authors have also concluded that the maximum insertion torque could predict the mechanical stability.

Aged↗
PubMed1993

Hyperthermic enhancement of cytotoxicity and increased uptake of cis-diamminedichloroplatinum(II) in cultured human esophageal cancer cells.

Thermal enhancement of cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP) has been well recognized and applied clinically to chemotherapy of various malignancies, but its fundamental mechanism remains to be elucidated. In order to obtain a clue to this mechanism, we analyzed the effect of hyperthermia on the uptake and subsequent distribution of [195mPt]CDDP in two lines of esophageal cancer cells (KYSE-150 and KYSE-170) established from clinical patients. First, we observed a significant increase in [195mPt]CDDP uptake by both types of cells at increasingly higher temperatures. The incorporated CDDP was distributed between the nucleus and the cytosol at a ratio of approximately 3:1, and the ratio remained the same at various temperatures. The CDDP was found in all four molecular fractions, i.e., DNA, RNA, protein, and TCA-soluble, with a slight preference for DNA at higher temperatures. Enhancement of cytotoxicity required simultaneous, and not sequential, treatments with CDDP and hyperthermia; hyperthermia after CDDP treatment increased the efflux of CDDP from the cells, and rather reduced the cytotoxicity of CDDP. These results suggest that thermal enhancement of the cytotoxicity of CDDP is caused mainly by acceleration of the drug entry into the cell, probably due to increased permeability, and a consequent increase in the amount of CDDP binding to DNA. This mechanism gives support for clinical trial of simultaneous treatment with CDDP and hyperthermia.

Carcinoma, Squamous Cell↗
PubMed1993

Growth factor-induced process formation of megakaryocytes derived from CFU-MK.

The extended cytoplasmic processes from megakaryocytes (MK) are believed to be structural intermediates between MK and platelets. We could observe differentiation of purified rat CFU-MK toward mature MK to form extended cytoplasmic processes. Recombinant rat interleukin-3 (IL-3), human erythropoietin (Epo), and human interleukin-6 (IL-6) each was able to stimulate process formation although they varied somewhat in their potential. Electron microscopic observations showed that these processes were very similar to those from mature MK so far reported. The combination of IL-6 with IL-3 or Epo synergistically increased the number of MK forming processes without further increase in the number of total MK formed in the presence of IL-3 or Epo alone. In addition, IL-6 significantly increased the megakaryocytic diameter and DNA content of MK induced by IL-3 or Epo and shortened the MK transit time to hasten the process formation of MK. These findings suggest that IL-6 promotes further maturity in both the cytoplasm and ploidy of MK to form extended cytoplasmic processes. The ability of these factors to generate the process formation in vitro may be related to their thrombopoietic effects in vivo.

Animals↗
PubMed1993

Favorable effects of epidural analgesia on hemodynamics, oxygenation and metabolic variables in the immediate post-anesthetic period.

Fourteen adult patients undergoing elective major abdominal surgery were divided into two groups. One group received epidural and general anesthesia (epidural group), and 20 ml of 0.125% bupivacaine and 2 mg of morphine were administered epidurally about 30 min before the end of the operation for post-anesthetic analgesia. The other group (control group) received general anesthesia alone with nitrous oxide, oxygen and enflurane. Flow-directed pulmonary arterial and radial arterial catheters were inserted preoperatively, and hemodynamic, respiratory, neuroendocrine and metabolic variables were measured serially. The data were compared during anesthesia and the immediate post-anesthetic recovery period. In the control group, the plasma epinephrine level in the post-anesthetic recovery period increased about four times over the anesthetic period. Oxygen consumption was increased and mixed venous oxygen saturation was decreased significantly. There was a close linear correlation between oxygen consumption (Y) and plasma epinephrine (X) level: Y = 285.7X + 90.5 (P < 0.01, r = 0.72). On the other hand, plasma epinephrine, oxygen consumption and mixed venous oxygen saturation did not change significantly in the epidural group in the post-anesthetic recovery period. There was also a close linear correlation between oxygen consumption (Y) and oxygen delivery (X): Y = 0.22X-32.0 (P < 0.01, r = 0.89). We conclude that the surgical stress and anesthetic reversal may seriously influence neuroendocrine responses and subsequently increase plasma epinephrine. Tissue oxygenation and metabolic imbalance may occur due to the rapid increase of epinephrine in the post-anesthetic recovery period. Epidural analgesia at this period may play a more important role and have a more favorable effect on the tissue metabolism.

Abdomen↗
PubMed1993

A phase 2 study of cisplatin in patients with hepatocellular carcinoma.

A phase 2 study of cisplatin was performed in 28 previously untreated patients with unresectable hepatocellular carcinoma. The drug was given intravenously at a dose of 80 mg/m2/day every 4 weeks. Of 26 patients evaluated, 4 (15.4%) showed partial responses lasting for > 3 months, while no patient achieved a complete response. Of 22 patients whose serum level of alpha-fetoprotein (AFP) was high (> 400 ng/ml) before treatment, 6 (27.3%) showed a > 50% reduction in serum AFP levels after treatment. The current study indicates that cisplatin is an anticancer agent worthy of further testing in patients with this disease.

Adult↗
PubMed1993

Murine granulocyte-macrophage and mast cell colony formation promoted by nerve growth factor.

The nerve growth factor (NGF) is widely distributed in the target tissues of sympathetic neurons. Hemopoietic organs such as the bone marrow (BM) and spleens are known to be innervated by noradrenergic sympathetic neurons. Some of their constitutive cells express NGF receptors (lymphocytes and stroma cells) and its biologic effects have been extensively studied in the immune system and inflammatory responses. However, the effects of NGF on hemopoiesis have been little examined. Recently, we demonstrated that NGF promoted mast cell colony formation from murine BM cells (BMC) or BMC-derived cultured mast cells and induced the phenotypic changes in standard hemopoietic assays. Besides, we demonstrated NGF-enhanced murine neutrophil survival and functional properties. In this study, in order to investigate NGF activities on neutrophil differentiation, we examined granulocyte-macrophage (GM) colony formation from murine BMC or spleen cells (SC) in the methylcellulose culture. We also assessed mast cell colony formation. GM colonies were counted on day 5 and mast cell colonies were counted on day 20 in culture. Although NGF alone (50 ng/ml) neither supported GM nor mast cell colony formation, addition of various doses of NGF to the suboptimal dose of pokeweed mitogen-stimulated SC-conditioned medium (2.5%) or interleukin 3 (50 U/ml), well-known colony-stimulating factors, increased the number of GM and mast cell colonies from both BMC and SC in a dose-dependent manner. These colony formation-enhancing effects of NGF were inhibited by the addition of neutralizing sheep anti-NGF antibodies. The results suggest that NGF may act to develop granulopoiesis including neutrophil and mast cell differentiation in cooperation with hemopoietic factor(s) during inflammatory processes.

Animals↗
PubMed1993

Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group.

PURPOSE: A phase II study was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with metastatic colorectal cancer. PATIENTS AND METHODS: From December 1989 to March 1991, 67 patients with metastatic colorectal cancer were enrolled in this study. Sixty-three patients were assessable for toxicity and response. Their median age was 57 years (range, 24 to 72). Forty-six patients (73%) had a good performance status of 0 or 1. Fifty-one patients (81%) had received prior chemotherapy. The major sites of metastasis were liver (63%) and lung (44%). CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion, or as 150 mg/m2 every 2 weeks. The dose was reduced based on the grade of leukopenia and diarrhea, if necessary. RESULTS: A partial response was obtained in 17 of 63 assessable patients (27%; 95% confidence interval, 16% to 38%). The response rate in patients with prior radiotherapy or chemotherapy was 25% (13 of 52). Liver metastases showed a 15% (six of 40) response and lung metastases showed a 39% (11 of 28) response. The median duration of partial response was 127 days (range, 49 to 353) and the median overall duration of response was 208 days (range, 99 to 381). The major toxicities (> or = grade 3) were leukopenia (16%), diarrhea (13%), nausea and vomiting (13%), and alopecia (11%). Adverse effects were generally well tolerated and reversible. Treatment could be continued on an outpatient basis for patients without severe toxicity. Hemorrhagic cystitis was not encountered in this study. CONCLUSION: CPT-11 showed promising antitumor activity against metastatic colorectal cancer that was resistant to prior therapy. Further clinical trials of combination chemotherapy using CPT-11 are justified.

Adult↗
PubMed1993

The effect of nicardipine on carotid blood flow velocity, local cerebral blood flow, and carbon dioxide reactivity during cerebral aneurysm surgery.

We studied the effects of nicardipine (initial infusion rate 0.5 micrograms.kg-1 x min-1) on blood flow velocity in the internal carotid artery, local cerebral blood flow (LCBF), and carbon dioxide reactivity in 20 patients undergoing craniotomy for cerebral aneurysm clipping under isoflurane anesthesia. The blood flow velocity in the internal carotid artery was measured at T0 and T3 by a 20-MHz pulsed ultrasound Doppler flowmeter. LCBF was measured by the thermal gradient blood flow meter. Group A consisted of 10 patients with a good neurologic status (Hunt and Kosnik Grade I); Group B consisted of 10 patients with a poor status (Grades II-IV). Nicardipine was infused until the mean arterial blood pressure decreased to about 75% of the initial value and was maintained at this level until the completion of aneurysm clipping. The measurements of hemodynamics and LCBF were performed after the exposure of the internal carotid artery (T0), and 10 and 30 min after the start of nicardipine (T1 and T2, respectively), before aneurysm clipping (T3), and 30 min after its discontinuation (T4). Carbon dioxide reactivity [% ALCBF/APaCO2 (%/mm Hg)] was evaluated at T0, T3, and T4. Mean arterial blood pressure decreased after nicardipine infusion in both groups. LCBF did not change during nicardipine infusion in either group. Blood flow velocity increased significantly in Group A after nicardipine infusion from 45.1 +/- 6.9 to 51.5 +/- 6.4 cm/s (P < 0.05), but in Group B flow velocity did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Isolation of a new species of Physarum lysophosphatidic acid, PHYLPA, and its effect on DNA polymerase activity.

A new species of lysophosphatidic acid was isolated from myxoamoebae of a true slime mold, Physarum polycephalum, and structural studies were performed. The purified substance was subjected to nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), fast atom bombardment mass spectroscopy (FAB/MS), alkaline hydrolysis and tandem mass spectroscopy (MS/MS), and the results suggested this substance to be lysophosphatidic acid composed of a cyclic phosphate and cis-11,12-methylene octadecanoic acid. The effects of the LPA on DNA polymerases were studied and compared with the effects of PHYLPA, which had been isolated as a specific inhibitor of eukaryotic DNA polymerase alpha (6). It showed a specific inhibitory activity on eukaryotic DNA polymerase alpha, but no activity on the repair-type, or mitochondrial DNA polymerases.

Animals↗