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Biomedical subjects

S Shimizu

Publications and source records attributed to S Shimizu.

At least 685 records · Page 38Linked to original sources

Extramammary Paget's disease arising in mature cystic teratoma of the ovary.

We report a case of extramammary Paget's disease in ovarian mature cystic teratoma. The patient was a 70-year-old Japanese woman who complained of lower abdominal pain. Examination showed elevation of carcinoembryonic antigen and CA 19-9. Ultrasonography and computer tomography revealed a cystic tumor of the left ovary. The gross appearance of the resected ovary was typical for mature cystic teratoma. Microscopic observation revealed a lesion of Paget's disease within the squamous epithelium. The tumor cells had intracytoplasmic mucin and positive immunoreactivity for carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin; but they were negative for S-100 protein and vimentin. On multiple and serial sections, underlying adenocarcinomas were not found either in the ovary or other primary sites. From these pathological findings, we concluded that the disease was an intraepithelial adenocarcinoma, possibly derived from multipotential cells in squamous epithelium of ovarian mature cystic teratoma. This is the first reported case, to our knowledge, of extramammary Paget's disease arising in mature cystic teratoma of the ovary.

Adenocarcinoma↗

Establishment and characterization of a new spontaneous metastasis model of human gastric carcinoma in nude mice.

A poorly differentiated medullary carcinoma of human stomach, designated HY-1, was successfully transplanted to nude mice by either the subcutaneous or intramuscular route for five generations. The transplanted tumor showed spontaneous lung metastases in nearly 100% of KSN and Balb/c female nude mice. There were over 20 visible lung metastatic nodules in KSN and Balb/c nude mice bearing tumors for over 80 days. Immunostaining of type IV collagen and electron microscopy revealed that tumor cells were often in direct contact with basement membrane (BM) of tumor blood vessels in the primary tumor tissue. At the site of contact between tumor cells and vascular BM, focal disappearance of the BM, disruption of endothelial cells and entry of tumor cell clusters into vascular lumen were observed. Immunostaining of 72 kDa gelatinase/type IV collagenase demonstrated that tumor cells expressed this enzyme in their cytoplasm. These results suggest that spontaneous metastasis of this tumor may be partly due to a marked tendency to vascular invasion involving the following sequential events: tumor cell contact with vascular BM, BM degradation possibly by 72 kDa gelatinases and endothelial disruption. This model could be a useful tool for understanding the mechanism of hematogenous metastasis of human gastric cancer.

Aged↗

Mixed invasive aspergillosis and candidiasis in a fatal case of leukemia.

A fatal case of leukemia complicated by mixed invasive aspergillosis and candidiasis is presented. Mixed fungal infections may occur in any immunocompromised patients. We should be careful to look for different morphologies of fungi in diagnostic examinations of lesions in these patients.

Adolescent↗

[A case of agranulocytosis and jaundice due to cellulitis caused by insect bite].

A 58-year-old female was introduced to our hospital for admission on April 22, 1988, because of high grade fever and agranulocytosis. She had eschers on her left zygomatic region and medial region of the right thigh. The latter lesion was accompanied by cellulitis. Laboratory tests showed her WBC was 600/mm3 and T-Bil was 6.51 mg/dl. By using minocyclin, piperacillin and other drugs, her general condition and laboratory data became better in a few days. Although her skin lesions resembled "Tsutsugamushi disease", serological tests showed no evidence for Rickettia infection. So we could not rule out that another kind of insect bite may also develop such a severe clinical course. Furthermore, Staphylococcus aureus or Clostridium spp., which were detected in her pus, might have the toxic effects of inducing agranulocytosis, which might mainly be the result from the local WBC emigration, and jaundice, just like the effects of the endotoxin of Gram negative bacteria.

Agranulocytosis↗

In vitro and in vivo evaluation of Ro 09-1428, a new parenteral cephalosporin with high antipseudomonal activity.

Ro 09-1428, a new parenteral cephalosporin with a catechol moiety attached at position 7 of the cephalosporin ring, showed high in vitro activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Streptococcus pyogenes, with MICs for 90% of strains tested (MIC90s) of less than or equal to 0.39 micrograms/ml. Morganella morganii, Providencia rettgeri, Citrobacter freundii, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were inhibited with MIC90s of less than or equal to 3.13 micrograms/ml. Serratia marcescens was less susceptible to Ro 09-1428, with a MIC90 of 25 micrograms/ml. The most distinctive feature of Ro 09-1428 was its potent activity against Pseudomonas aeruginosa and Acinetobacter calcoaceticus, with MIC90s of 0.39 and 6.25 micrograms/ml, respectively. Most of the ceftazidime-resistant strains of P. aeruginosa, E. cloacae, and C. freundii were inhibited by Ro 09-1428, while those of S. marcescens were resistant at a concentration of 12.5 micrograms/ml. Ro 09-1428 was more active than ceftazidime against staphylococci. PBP 3 was the most sensitive target in E. coli and P. aeruginosa. The response to ferric iron in growth medium suggests that Ro 09-1428 may be taken up by transport mechanisms similar to those of other catechol cephalosporins. In accordance with its in vitro activity, Ro 09-1428 activity was equal to or greater than ceftazidime activity in efficacy against experimental septicemias in mice. The results indicate that Ro 09-1428 is a broad-spectrum cephalosporin with advantages over ceftazidime in its activity against P. aeruginosa, staphylococci, and ceftazidime-resistant strains of C. freundii and E. cloacae.

Animals↗

Transformation of a Methylotrophic Bacterium, Methylobacterium extorquens, with a Broad-Host-Range Plasmid by Electroporation.

An efficient method for the transformation of the methylotrophic bacterium Methylobacterium extorquens NR-2 with a broad-host-range plasmid, pLA2917, by electroporation was examined. Transformants of M. extorquens NR-2 expressing resistance to kanamycin were obtained after electric pulse. These transformants were found to harbor a single plasmid which was electrophoretically identical and homologous to pLA2917 obtained from Escherichia coli. Several factors which determined the transformation efficiency were optimized, resulting in a transformation efficiency of up to 8 x 10 transformants per mug of plasmid DNA by 10 pulses at a field strength of 10 kV/cm and a pulse duration of 300 mus.

Journal Article↗

Modification of the properties of a Ruminococcus albus endo-1,4-beta-glucanase by gene truncation.

An endo-1,4-beta-glucanase (EgI) gene isolated from Ruminococcus albus was deleted at the 5'-flanking region by gene truncation or at the 3'-flanking region by insertion of an omega (omega) fragment with a universal stop codon at the EcoRI or BamHI site. These modified genes were integrated into pUC vectors to construct chimera plasmids for Escherichia coli. The truncated EgIs were produced from transformants (E. coli) harboring the chimera plasmids. An EgI with a 15-amino-acid N-terminal deletion exibited higher activity at lower pH and temperature compared with the activity of the original EgI. The EgIs with 59- and 75-amino-acid deletions from the N and C terminals, respectively, had no activity, indicating that both terminal moieties are essential for enzyme activity.

Amino Acid Sequence↗

Relationship between chromosomal breakpoint and molecular rearrangement of T-cell antigen receptors in adult T-cell leukaemia.

The relationship between chromosome breakpoints associated with T-cell antigen receptor (TCR) genes and TCR-alpha/beta/tau/delta rearrangements of peripheral leukaemic cells in 8 Japanese patients with the acute type of adult T-cell leukaemia (ATL) was examined. Break of the 14q11 region with the assigned locus of TCR-alpha/delta was revealed in 6 patients, interstitial deletion of the 7q32-36 region with assigned locus of TCR-beta in 1 patient, and break of the 7p15 region with assigned locus of TCR-tau in 2 patients. Molecular analysis revealed TCR-alpha rearrangement in 7 patients, TCR-beta rearrangement in all patients, and TCR-tau rearrangement in 5 patients. TCR-delta was deleted in all patients. These findings indicate a close relationship between 14q11 anomaly and TCR-alpha rearrangement, which may play an important role in the leukaemogenesis of ATL.

Aged↗

Oxygen consumption in resting dog gracilis muscle perfused at varying oxygen delivery.

The different response of O2 uptake (VO2) of resting skeletal muscle to the changes in blood flow has been thought to reflect a species difference. To scrutinize this notion, we investigated the relation between O2 delivery (arterial O2 content multiplied by blood flow) and VO2 in isolated dog gracilis muscle perfused solely with normal hematocrit (Ht) blood (n = 9), or alternately with normal and low Ht blood (n = 6), or alternately with normal and high Ht blood (n = 3) at varying perfusion rates. Eleven out of the 18 preparations showed an autoregulation of blood flow, and the others did not. But, in all preparations, the VO2 was delivery-independent above a critical O2 delivery (0.45 ml/(min.100 g muscle)) and showed the constant VO2 of 0.30 ml/(min.100 g), while below the critical level it turned out to be delivery-dependent. The maximal extraction ratio was 0.67. The same relationship was found with the low and high Ht perfusion. The pattern observed in dog gracilis muscle was essentially the same as that in rat gracilis muscle (KOLAR and JANSKY, 1984).

Animals↗

Differences in response between SHRSP and WKY vascular smooth muscle cells to inhibition of cell proliferation by sodium nitroprusside.

The effects of sodium nitroprusside on the proliferation of cultured vascular smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were examined. Sodium-nitroprusside (SNP, 1mM) inhibited DNA synthesis by SMC from SHRSP and WKY by 90% and 95%, respectively. SNP also decreased cell proliferation. However, SNP was inactive when SMC were pretreated 6 and 12 hrs before growth stimulation by FCS. On the other hand, the inhibitory action of SNP decreased with time (posttreatment) in SHRSP SMC (42% inhibition at 12 hr post addition). However, in WKY SMC, the decrease of inhibitory action was very slight and SNP still inhibited 73% of DNA synthesis at 12 hr post treatment. SNP inhibited RNA synthesis for 3-6 hr and 6-9 hr after FCS stimulation, however no difference was noted between SHRSP and WKY. Protein synthesis was inhibited more strongly by SNP (9-12 hr after FCS stimulation) in WKY SMC than SHRSP SMC. It is probable that the specific protein(S) whose synthesis is inhibited by SNP is/are responsible for the differences in cell proliferation rate between SHRSP and WKY SMC.

Animals↗

Morphine analgesia mediated by activation of the acupuncture-analgesia-producing system.

Analgesia caused by intraperitoneal 0.5 mg/kg morphine (MA) in rats is equivalent to acupuncture analgesia (AA) caused by low frequency stimulation of the tibial muscle (Tsusanli acupuncture point). Analgesia equivalent to both AA and MA was produced by intrathecal application of 0.05 microgram morphine. This analgesia exhibits individual variation in effectiveness which is parallel to those of both AA and MA, and disappears after 250 mg/kg intraperitoneal D-phenylalanine. Analgesia that persisted after termination of acupuncture stimulation was not affected, maximally developed MA and AA were both partially antagonized, and the initial development of AA and MA were completely antagonized by intrathecal application of 0.2 microgram naloxone. Analgesia caused by intrathecal 0.05 microgram morphine was abolished by bilateral lesion of the anterolateral tract (ALT) of the spinal cord and that caused by acupuncture stimulation was abolished by contra-lateral lesion. Analgesia caused by larger doses (0.1-0.2 microgram) of intrathecal morphine was not abolished, but persisted after ALT lesion, unilateral lesion of the dorsal periaqueductal central gray (D-PAG), or hypophysectomy. Potentials were evoked by acupuncture stimulation in the bilateral D-PAG. Analgesia produced by D-PAG stimulation was not affected by ALT lesion nor by intrathecal naloxone, but was abolished by lesion of the dorsolateral funiculus. These results imply two types of morphine action in the spinal cord to produce analgesia: activation of the ascending AA pathway; and direct inhibition of pain message in the spinal cord. They also show that the AA producing pathway ascends contralaterally in the ALT and then bilaterally in the D-PAG.

Acupuncture Analgesia↗

[A case of metastatic renal tumor originating from a malignant mixed tumor of the submandibular gland].

A rare case of metastatic renal tumor originating from a malignant mixed tumor of the submandibular gland is reported. The patient was a 45-year-old woman with hard masses palpated in the right upper arm and the right upper gluteal region. She had a history of surgical resection of a right submandibular tumor followed by radiotherapy in 1977. Biopsy findings of the gluteal mass suggested a malignant clear cell tumor. A chest X-ray, excretory urogram, CT scan, MRI and renal angiogram were highly suggestive of a right renal cell carcinoma with metastases to the right lung (S1 & S10), the left 4th and 5th ribs, the right upper arm muscle and the right upper gluteal muscle. Right nephrectomy and resection of the right upper arm and right upper gluteal tumors were performed. Microscopic examination showed that all tumors were malignant mixed tumors. When compared to the previous surgical specimen, the tumors were believed to be identical. The tumors of the lung and ribs subsequently resected were malignant mixed tumors. The patient is well with no objective or subjective evidence of recurrent neoplastic disease 7 months post-operatively. To our knowledge only one report of metastatic renal tumor originating from a malignant mixed tumor of the salivary gland has been published in Japan. But metastatic renal tumor originating from the same tumor of the submandibular gland has not been reported previously in Japan.

Female↗

Thymic atrophy in type 2 reovirus infected mice: immunosuppression and effects of thymic hormone. Thymic atrophy caused by reo-2.

Suckling mice infected with reovirus type 2 showed a thymic atrophy followed by a marked suppression of the antibody, production to SRBC (a T cell dependent antigen) and bacterial LPS, when measured by the splenic PFC assay. The PFCs produced were sometimes less than 1% of uninfected control animals. Histologically the thymus was usually smaller than normal, and atrophy of the cortex and increased number of Hassal's bodies were observed. Number of nucleated cells in the thymus of infected mice showed 90% decrease as compared to uninfected mice. The spleen, although larger in size, showed depletion of lymphocytes from the thymus-dependent and follicular areas. No viral replication was detected in lymphatic organs using virological methods. Virus-infected mice transferred with the splenocytes or thymocytes from age-matched uninfected mice restored the antibody production against SRBC to normal levels. Thymocytes were more efficient than splenocytes in enhancing the antibody production in virus-infected mice. Injection of several different kinds of immunopotentiating agents enhanced the antibody production to SRBC, although LPS exacerbated the unresponsiveness. Thymic hormones such as FTS and TP5 enhanced antibody production to SRBC and LPS more efficiently than MDP. Flow cytometric analysis showed that percentage of CD4+ single positive cells was slightly increased in virus-infected mice treated with FTS, while there was no difference in the phenotypic distributions of thymocyte subpopulations among virus-infected mice, FTS-untreated and FTS-treated normal mice.

Age Factors↗

[Pharmacokinetic and clinical evaluations of flomoxef in neonates].

To evaluate pharmacokinetics and clinical efficacy of flomoxef (6315-S, FMOX) in neonates, FMOX was administered to 21 neonates. With 20 mg/kg and 40 mg/kg of intravenous drip-infusion of FMOX 60 minutes, half lives (T 1/2's) was 64.9 minutes and 130.3 minutes, respectively, and when 20 mg/kg of FMOX was infused intravenously to 2 cases, half lives were 70.8 minutes and 110.1 minutes, respectively. When 45-100 mg/kg of FMOX was administered to 17 neonates with infections (pneumonia 8, sepsis 1, sepsis suspected 2, intrauterine infection 2, urinary tract infection 2, omphalitis 2), the efficacy rate was 88.2% (15 of 17). No adverse reactions were observed clinically in the 21 neonates. Transient elevation of eosinophilia was observed in 1 case and transient elevation of S-GOT and S-GPT 1 in another. These results suggest that FMOX is an effective and safe antibiotic to use in neonates.

Alanine Transaminase↗

Purification and characterization of hepatocyte growth factor from injured liver of carbon tetrachloride-treated rats.

A hepatocyte growth factor (HGF)-like substance that strongly stimulated DNA synthesis of adult rat hepatocytes in primary culture was found to increase markedly in liver of rats treated with carbon tetrachloride (CCl4). This increase of HGF-like activity was time- and dose-dependent, and 36 h after a dose of CCl4 of 0.2 ml per 100 g body weight the activity was about 20-times the normal level. The extent of induction of HGF-like factor correlated well with the extent of liver damage. The HGF-like factor was purified to homogeneity from the liver of CCl4-treated rats by a four-step procedure. The purified HGF-like factor had a molecular weight of 82-85 kDa, as estimated by SDS-PAGE, and was a heterodimer composed of a large subunit of about 69 kDa and a small subunit of 34 kDa linked by disulfide bridges. This factor had similar biological and chemical properties to HGF purified from rat platelets. Moreover, the N-terminal amino acid sequence of its 34-kDa subunit was identical to that of the small subunit of rat HGF. These findings indicate that the HGF-like factor in damaged liver of CCl4-treated rats is HGF and that liver itself can produce HGF when injured.

Amino Acid Sequence↗