Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 433 records · Page 24Linked to original sources

PubMed1994

[Bone marrow transplantation for a patient with ALL from her 75-year-old mother using cryopreserved bone marrow cells].

We report a 42-year-old woman with acute lymphoblastic leukemia who received allogeneic bone marrow transplantation (BMT) in the first remission from her 75-year-old, HLA-identical, MLC-non-reactive mother. Considering the difficulty to obtain a sufficient number of bone marrow cells from such an old donor, we harvested the cells (2.31 x 10(8)/kg) on day -37 and cryopreserved them until use. BMT was performed on June 3rd, 1993 after conditioning regimen with total body irradiation, high-dose AraC and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxisis was attempted by cyclosporin A and short-term methtrexate. Her hematopoietic recovery was favorable with no signs and symptoms of GVHD as far as day 218.

Adult↗

PubMed1994

[Present strategy for new drug development in the USA].

Development of new anticancer drugs is essential to improve the response and survival of cancer patients. Nationally supported organizations have a key role in conducting very experimental expensive and ethical clinical trials. In the U.S., the NCI-US has designated six cancer centers as "phase I institutes for new drug evaluation," supported by NCI funding. CTRC and JHOC are active centers for phase I trials. They have evaluated more than 10 new drugs a year. Their team consists of younger physicians, research nurses, data managers, pharmacologists, technicians and the primary investigator under strong leadership. Recently, international harmonization of the U. S., -Europe and Japan is postulated politically, However, we have to recognize that this interrelationship has another meaning, that of "international competition and comparison" with each other in the field of new drug development.

Antineoplastic Agents↗

PubMed1994

Cost containment: the Pacific. Japan.

The Japanese healthcare system is structured to provide universal healthcare access to the entire Japanese population via a constitutional guarantee. Increasing costs within the Japanese healthcare system are largely attributable to the country's rapidly aging population. Intensive care services are provided primarily in large tertiary care hospitals by a relatively small cadre of dedicated critical care physicians. Triage pressure is high in many Japanese hospitals due to a relatively small proportion of ICU beds. As a result, few patients are admitted to the ICU at low risk of adverse outcome or monitoring. Costs associated with providing critical care are poorly understood because of current hospital cost accounting systems. Critical care costs have only recently become an area of concern. Nevertheless, critical care physicians are taking steps to more fully understand severity of illness, clinical outcome, and utilization of resources in order to effectively guide healthcare policy and resource allocation decisions impacting Japanese critical care.

Accounting↗

PubMed1994

[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group].

A multi-institutional collaborative late phase II study of irinotecan hydrochloride (CPT-11) was performed on patients with advanced gastric cancer. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion or as 150 mg/m2 fortnightly. Of 81 registered patients, 77 cases were eligible and 60 cases were evaluable for response. The overall response rate for evaluable cases was 23.3% (14/60), and the response rate was 16.1% (9/45) for the patients who had received prior chemotherapy. The primary tumor showed a 4.5% response, while metastatic lesions in the lymph-nodes, lungs, and liver showed response rates of 36.4%, 33.3%, and 17.4%, respectively. The major toxicities (> or = Grade 3) were leukopenia (41.2%), anemia (28.9%), diarrhea (22.4%) and anorexia (19.7%). These toxicities were generally reversible. CPT-11 showed activity against advanced gastric cancer, suggesting that further clinical studies of CPT-11 combined with other active chemotherapy agents are warranted.

Adenocarcinoma↗

PubMed1994

[A late phase II study of CPT-11, irinotecan hydrochloride, in patients with advanced pancreatic cancer. CPT-11 Study Group on Gastrointestinal Cancer].

A late phase II study of CPT-11 was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with advanced pancreatic cancer as a cooperative study of 19 institutions. From February 1990 to June 1992, 61 patients with advanced pancreatic cancer were enrolled in this study. Fifty-seven patients were evaluable for toxicity and 35 for response. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion (regimen A) or as a 150 mg/m2 every two weeks (regimen B). The response rate was 11.4% (4/35). The primary tumor showed a 10.3% (3/29) response and the liver metastases showed a 10.5% (2/19) response. The major toxicities were myelosuppression and gastrointestinal symptoms. The incidences (> or = Grade 2) of leukopenia, anemia, anorexia, nausea/vomiting, alopecia and diarrhea were 61.4% (35/57), 56.1% (32/57), 70.2% (40/57), 56.1% (32/57), 40.4% (23/57) and 36.8% (21/57), respectively. The incidence of diarrhea was higher with regimen A than with regimen B, but the antitumor activity was no different between the two regimens. These results suggested that CPT-11 has some antitumor activity against advanced pancreatic cancer.

Adult↗

PubMed1994

Age and radiation sensitivity of rat mammary clonogenic cells.

The relative risk of breast cancer is very high among women who were exposed to ionizing radiation during or before puberty. In the current studies, the surviving fractions of clonogenic mammary cells of groups of virgin rats were estimated after single exposures to 137Cs gamma rays at intervals from 1 to 12 weeks after birth. The radiosensitivity of clonogens from prepubertal rats was high and changed with the onset of puberty at between 4 and 6 weeks of age. By this time, the increase in the size of the clonogenic cell subpopulation was slowing and differentiation of terminal mammary end buds and alveolar structures was occurring. Analysis of the relationship of clonogen survival and radiation dose according to the alpha/beta model showed that the exponential alpha D term predominated at the second and fourth weeks of age. By the eighth week of age, the beta D2 term had come to predominate and the survival curve had a pronounced initial convex shoulder. Further experiments are required to determine whether there is an association between the high sensitivity of the prepubertal and pubertal mammary clonogens to radiation killing and a high susceptibility to radiogenic initiation of cancer.

Aging↗

PubMed1993

Different mode of action of endothelin-1 in parietal and visceral veins.

The mode of contractile effect of endothelin-1 in venous smooth muscles was evaluated using three isolated veins, the jugular vein, the portal vein and the inferior caval vein of dogs. The contractile responses to endothelin-1 were attenuated by atropine and augmented by neostigmine in the inferior caval and portal veins, but were not affected by either agent in the jugular vein. We conclude that the contractile responses of visceral veins to endothelin-1 are partly mediated via endogenously released acetylcholine.

Animals↗

PubMed1993

Cloning and sequence analysis of an esterase gene from Pseudomonas sp. KWI-56.

The gene encoding an esterase from Pseudomonas sp. KWI-56 was cloned and sequenced. The nucleotide sequence contained an open reading frame encoding a polypeptide comprising 262 amino acids, whose molecular weight agreed well with the value obtained by SDS-PAGE. Comparison of the amino acid sequence with those of the other homologous enzymes suggested that Ser-92 and His-24l might be included in the catalytic triad.

Amino Acid Sequence↗

PubMed1993

Relation of epidermal growth factor receptor concentration to growth of human esophageal cancer cell lines.

The relation between the concentration of epidermal growth factor (EGF) receptor and the effects of EGF on cell proliferation were studied using 16 newly established human esophageal cancer cell lines. According to 125I-EGF binding assay, the amount of EGF receptor was found to vary from 6 x 10(4) to 1.2 x 10(7) (sites/cell). Changes in EGF-stimulated tyrosine-specific protein kinase activity almost paralleled changes in the number of EGF receptors per cell. Amplification of EGF receptor gene was detected in only one cell line. Under monolayer culture conditions, we found three types of growth responses of esophageal cell lines to EGF; growth in 5 cell lines was inhibited and that in 4 cell lines was stimulated while that in the other 7 cell lines remained unaffected. Relation was observed between the number of EGF receptors per cell and the growth response to EGF. On the other hand, cell lines whose growth was inhibited by EGF in monolayer culture were stimulated by EGF in soft agar culture, though the opposite was not necessarily true.

Cell Division↗

PubMed1993

[Results of electron beam irradiation for tongue cancer].

One hundred and eighty three patients with squamous-cell carcinoma of the tongue were treated with electron beam irradiation at the Dept. of Radiology, Nihon University School of Medicine, from 1967 to 1988. We analyzed the therapeutic results of the investigation to find out indications of squamous-cell carcinoma of the tongue to see if it could be treated by intra-oral cone irradiation with electron beam (IOC). The patients were restaged, as follows: stage I, 38 cases: stage II, 64 cases: stage III, 58 cases: stage IV, 23 cases. There were 113 males and 70 females, ranging in age from 18 to 87 years old. IOC was applied for T 1 or smaller T 2 cases. External neck irradiation and IOC were combined for larger T 2, T 3 or T 4 cases. The two-year local-control rates for primary lesions with the present method were 85% for T 1, 73% for T 2, and 58% for T 3. There were no two-year local-control cases for T 4. Clinical feature of the tumor were classified into tumourous type, small ulcerating type, and large ulcerating type. The two-year local-control rates were as follows: 80% for tumorous types, 68% for small ulcerating types and 53% for large ulcerating types. Uneven fractionated irradiation was performed on 144 cases and even fractionated irradiation was performed on 39 cases. The two-year local-control rates were as follows: 68% for uneven fractionated irradiation cases, 61% for even fractionated irradiation. In T 2 and T 3 cases, the two-year local-control rates were as follows: 77%, 63% for uneven fractionated irradiation cases, 56%, 40% for even fractionated irradiation cases. The two-year local-control rates were increased by uneven fractionated irradiation for T 2, T 3 cases (P < 0.05). We analyzed the therapeutic results in details for T 3 cases. T 3 patients were classified into two categories according to tumor size (category 1: long axis X short axis > 1000mm2: category 2: long axis X short axis < or = 1000mm2). The two-year local-control rates were 48% for category 1, and 72% for category 2. T 3 patients were classified into two categories according to clinical feature of the tumor (tumors with ulcers and tumors without ulcers). The two-year local-control rates were 43% with ulcers, and 74% without ulcers. The actuarial five-year survival rates were 92% for stage I, 72% for stage II, 67% for stage III, and 12% for stage IV.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1993

Intermediate voltage electron microscopy of transverse tubules at myotendinous junctions.

The 3-dimensional distribution of transverse (T) tubules at myotendinous junctions (MTJs) was studied by intermediate voltage (400 kV) electron microscopy of thick sections of rat vastus intermedius and chicken pectoralis muscles stained with lanthanum nitrate. Transversely oriented T tubules were seen to run at the level of A-I junctions (the rat vastus intermedius) and Z bands (the chicken pectoralis), but were absent from such levels adjacent to the end of MTJ processes. These tubules opened to the lateral wall of sarcolemmal infoldings of MTJs and to the lateral cell surface. Longitudinally running T tubules were seen to connect with the transverse T tubules and to open at the bottom of junctional folds. The lack of T tubules at the final sarcomeric regions seems to indicate that the terminal sarcomeric half in close proximity to MTJs may be activated from the sarcoplasmic reticulum which forms couplings with the MTJ sarcolemma and/or longitudinal tubules in the MTJ processes.

Animals↗

PubMed1993

Fine structure of transverse tubules and the sarcoplasmic reticulum at the myotendinous junction of stretched muscle fibers of the rat.

The transverse (T) tubules and the sarcoplasmic reticulum (SR) at the myotendinous junction of stretched rat skeletal muscle were examined by conventional and intermediate voltage electron microscopy. Stretching induced a large cytoplasmic space devoid of myofibrils at the ends of lengthening fibers. In this space, irregularly running tubular elements were seen. They were connected both with subsarcolemmal caveolae and with T tubules traversing to the A-I junctional level of the preexisting myofibrils. The SR was arranged at regular intervals which were narrower than those of the adult sarcomere. This orderly spacing of the SR seems to indicate that they may play some role(s) in myofibril assembly and/or T tubule arrangement.

Animals↗

PubMed1993

Erythropoietin-specific cell cycle progression in erythroid subclones of the interleukin-3-dependent cell line 32D.

Recently, a variety of growth factor-dependent subclones of the murine interleukin-3 (IL-3)-dependent cell line 32D have been isolated. These subclones include those dependent for growth on erythropoietin (Epo) (32D Epo), granulocyte-macrophage colony-stimulating factor (GM-CSF) (32D GM), or granulocyte colony-stimulating factor (G-CSF) (32D G). 32D Epo1.1 is a revertant of 32D Epo and is capable of growing in IL-3. These cell lines express the differentiation program appropriate to the specific growth factor and depend on the growth factors not only for proliferation but also for survival. To determine how the signal for proliferation is triggered by various growth factors, we examined the DNA histograms and the expression of cell cycle-specific genes in the different cell lines. The cell cycle-specific genes analyzed were myc (early G1), myb (late G1), and the structural genes for the calcium-binding protein 2A9 (middle G1) and histone H3 (G1-S boundary). The DNA histogram analysis of cells in the logarithmic phase of growth showed that approximately 40% of 32D, 32D GM, 32D G, and 32D Epo1.1 (growing in IL-3) were cells with a 2N DNA content (and therefore in G0/G1), and another 40% have a DNA content intermediate between 2N and 4N (in S phase). In contrast, 32D Epo and 32D Epo1.1 (growing in Epo) had fewer cells in the G0/G1 phase of the cell cycle compared with the number of cells that were in the S phase (19% to 31% v 69% to 78%, respectively). Because all the cell lines have comparable doubling times (15 to 18 hours), the cell distribution among the phases of the cell cycle is proportional to the length of the phase. Therefore, cells growing in IL-3 (32D and 32D Epo1.1), GM-CSF (32D GM), or G-CSF (32D G) progress along the cycle in a manner typical of previously reported nontransformed cell lines. In contrast, cells growing in Epo (32D Epo or 32D Epo1.1) spend relatively less time in G0/G1 and correspondingly more time in S. These data were confirmed by the analysis of the tritiated thymidine (3H-TdR) suicide rate and of the expression of cell cycle-specific genes. The 32D and 32D Epo1.1 cells growing in IL-3 had a suicide rate of congruent to 50%, whereas the suicide rate of 32D Epo and 32D Epo1.1 growing in Epo was higher than 75%.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas.

We analyzed mutations of the p53 gene by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing through all coding exons and exon-intron junctions in 32 cases with esophageal squamous cell carcinoma. Mutations were detected in 15 of 32 (47%) tumor samples, in which G:C to T:A transversions were rather frequent (33%). Previously, we reported deletion of chromosome 17p where the p53 gene is located in 45% of Japanese esophageal squamous cell carcinoma, and here the relationship between mutation of the p53 gene and loss of 17p was analyzed. Mutations were observed in 12 of 16 patients with loss of 17p, whereas only 2 of 11 without loss were positive for mutations, suggesting that mutations of the p53 gene were closely associated with a 17p deletion. Furthermore, we immunohistochemically analyzed the expression of p53 protein in esophageal squamous cell carcinoma tumor tissues using a monoclonal antibody. Five of 6 tumors with missense mutations of the p53 gene were positively stained, while in tumors with nonsense mutations or without mutations of the p53 gene staining was very weak or negative. These results suggest a good correlation between mutations and abnormal expression of the p53 gene.

Aged↗

PubMed1993

Dynamics of actin and assembly of connectin (titin) during myofibrillogenesis in embryonic chick cardiac muscle cells in vitro.

Immunogold electron microscopy of cardiac myocytes microinjected with biotin-labeled actin showed that gold labeling was first found around the A band level of myofibrils at their proximal parts. This observation suggests that polymerization of actin and/or the addition of newly formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. At the distal portions of developing myofibrils, their terminal ends were initially labeled, suggesting that continued reorganization and/or de novo formation of myofibrils occurs at these locations. Soon, gold particles were seen along the termini of growing myofibrils. This appears to indicate that actin subunits are added at the membrane-associated ends of preexisting actin filaments to increase the length of myofibrils. Adhesion plaque proteins, e.g., vinculin, do not appear to play any role in assembling actin monomers at these sites on the inner surface of the sarcolemma. Immunofluorescence and immunoelectron microscopy of cardiomyocytes double-stained with antibodies against two distant domains of connectin (titin) filaments and other sarcomeric proteins showed that these domains of connectin filaments and myosin were synthesized almost simultaneously on large polyribosomes and/or associated immediately after the synthesis of these molecules. Connectin and myosin bands were formed after alpha-actinin striations (Z bands) were seen on preformed I-Z-I-like structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinin↗

PubMed1993

Prognostic significance of cell culture in carcinoma of the oesophagus.

The prognostic significance of the potential of cells to grow in tissue culture was studied in 50 patients with oesophageal cancer. The ability of cell lines to grow from resected oesophageal specimens was determined; from 50 patients, 21 cell lines were established (42 per cent). The patients were divided into two groups on this basis: group 1, from whom cancer cells could be grown as continuous cell lines and group 2, from whom cell lines could not be established. The cumulative survival rate of patients in group 1 was significantly lower than that of those in group 2 (P < 0.05). There was also a significantly higher incidence of lymph node metastases in group 1 (P < 0.05). These results suggest that the potential of cancer cells for growth is a useful long-term prognostic indicator for patients with oesophageal carcinoma.

Aged↗

PubMed1993

Incorporation of microinjected biotin-labelled actin into nascent myofibrils of cardiac myocytes: an immunoelectron microscopic study.

Incorporation of microinjected biotin-labelled actin into nascent myofibrils of cultured cardiac muscle cells was investigated by immunogold electron microscopy. At the proximal parts of myofibrils, gold labelling was first found (at about 4 min after injection) around the A-band level. This observation suggests that polymerization of actin or the addition of newly-formed actin filaments occurs preferentially in association with myosin filaments to increase the myofibrillar girth. The distal terminals of developing myofibrils were also labelled at about 4 min after injection. This rapid incorporation of actin subunits at the myofibrillar ends suggests the continued reorganization and/or de novo formation of myofibrils at these positions. Along the extending direction of the myofibrillar terminals, gold particles were arranged in rows on the inner surface of the sarcolemma. These rows of particles continued to become longer with incubation. It appears that actin subunits are added at the membrane-associated ends of pre-existing actin filaments to increase the length of myofibrils.

Actins↗

PubMed1993

Characterization of Geotrichum candidum lipase III with some preference for the inside ester bond of triglyceride.

A new form of Geotrichum candidum lipase with a unique positional specificity was found to exist in the culture broth as a minor component together with the well-documented major form. Unlike the major form, which cleaves both the inside and outside ester bonds of triglyceride indiscriminately, the newly isolated form showed some preference for the inside (2-position) ester bond. The new enzyme was also characterized by its own fatty acid specificity, i.e., an outstandingly high activity towards triolein and methyl oleate among the simple triglycerides and fatty acid methyl esters tested. Moreover, the enzyme possessed a specific activity three times as high as the major form. Notable difference in circular dichroism spectra were observed between the two forms, indicating distinct conformational differences. Edman degradation revealed that the N-terminal sequence of the new form differed from that of the major form, thus demonstrating the existence of a novel lipase gene on the chromosome.

Amino Acid Sequence↗