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Biomedical subjects

H Sakamoto

Publications and source records attributed to H Sakamoto.

At least 415 records · Page 23Linked to original sources

Vein of Galen aneurysmal malformation in a neonate treated by endovascular surgery--case report.

A male neonate with vein of Galen aneurysmal malformation developed fetal heart failure after a gestation period of 37 weeks. Labor was induced, but a cesarean section had to be performed because of fetal distress. His Apgar scores were 2/8 at birth. The boy required controlled ventilation due to generalized seizure and cyanosis. Neuroimaging revealed vein of Galen aneurysmal malformation with enormous arteriovenous shunt flows. Transarterial embolization was performed on days 4 and 6 to reduce the progressive high-output congestive heart failure. Three large feeders were occluded with interlocking detachable coils, markedly reducing the shunt flow. Although heart failure improved markedly, he died of pulmonary hemorrhage on day 12. Endovascular surgery can improve the prognosis of heart failure in the neonatal period less invasively than other treatment modalities, and may help to minimize ischemic brain damage and thus increase the possibility of normal brain maturation.

Arteriovenous Fistula↗

Study of hereditary cerebellar degeneration in cats.

OBJECTIVE: To elucidate the nature of ataxia observed in 3 cats spanning 2 generations. DESIGN: Experimental breeding was attempted to confirm heritability of the disease and establish the mode of inheritance; the original 3 cats and their offspring were studied. ANIMALS: Seven diseased cats spanning 3 generations and 11 neurologically normal cats. PROCEDURE: Cats were examined by use of the following methods: clinical observation, hematologic and serum biochemical examinations, neurologic examination, electrodiagnostics, magnetic resonance imaging, lysosomal enzyme activity assay, horizontal transmission test, and virologic and pathologic examinations. RESULTS: All kittens (1 male and 3 females) obtained by backcrosses developed pure cerebellar dysfunction from the age of 7 to 8 weeks onward. It became progressively worse, but not fatal, between 1 and 2.5 months. Prenatal or perinatal infection with feline panleukopenia virus, inherited lysosomal storage diseases, including gangliosidosis and mannosidosis, and feline hereditary neuroaxonal dystrophy were excluded. Magnetic resonance imaging indicated that size of the cerebellum of diseased cats was markedly reduced. Cerebellar cortical degeneration, especially with extensive destruction of Purkinje cells, was observed microscopically. CONCLUSION: The disease was concluded to be cerebellar degeneration of a new clinical form in cats having an autosomal recessive mode of inheritance. CLINICAL RELEVANCE: When cerebellar dysfunction is diagnosed in a cat, hereditary cerebellar degeneration of this type should be considered in the differential diagnosis.

Animals↗

[Separation and characterization of estrogen independent endometrial cancer cell line originated from Ishikawa strain].

An estrogen independent sub-clone of human endometrial carcinoma Ishikawa was established by culturing the mother cells in the absence of estrogen over a year. The daughter cells (designated as EIIL) possessed truncated estrogen receptors of an apparent size of 43Kd as well as normal 65Kd receptors and had lost sensitivity to estrogen or tamoxifen but remained sensitive to ICI 164,384. Analysis of the expression of the estrogen responsive element binding protein showed the presence of variant proteins which can recognize ERE. These observations indicate that long time estrogen deprivation may alter the expression of ER and this, in turn, alters cell response to estrogen as well as antiestrogens.

Endometrial Neoplasms↗

[Pseudoxanthoma elasticum with pulmonary calcification].

A woman born in 1920 had had multifocal, yellowish nodules on her skin since childhood and had been given a diagnosis of pseudoxanthoma elasticum. When she was 59-year-old, a diffuse granular shadow was seen on a chest radiograph. When she was 74-year-old, she presented with dyspnea on exertion. A thoracoscopic lung biopsy was done. Histologic examination of the lung tissue revealed small calcified nodules scattered in the alveolar septa. Pseudoxanthoma elasticum is a systemic, hereditary disorder that usually affects elastic fibers of the skin, eye, and cardiovascular system. It's incidence is quite low: 1 out of 160,000-1,000,000 population. Very few cases of pseudoxanthoma elasticum with pulmonary involvement have been reported, and we know of no previous case in Japan in which pulmonary microcalcification was confirmed histologically.

Aged↗

[A case of rheumatoid factor-positive pachymeningitis].

We report a case of rheumatoid pachymeningitis involving the posterior fossa. A 71-year-old woman presented with headache, vertigo and dizziness. MRI demonstrated hypertrophic masses in the meninges of the left cerebellar tentorium, cerebellopontine angle and the fourth ventricle. Six months of treatment with betamethasone, prednisolone and azathioprine improved the patient's neurological status. Because an inappropriate immune process and systemic immune disease may cause idiopathic pachymeningitis, the performance of immunological studies for idiopathic cases is mandatory.

Aged↗

Immunohistochemical localization of metallothionein in human prostate cancer.

PURPOSE: We investigated the expression of metallothionein in human prostate cancer. MATERIALS AND METHODS: Formalin fixed and paraffin embedded tissue specimens from 45 patients with primary prostate cancer were stained for metallothionein using a standard immunohistochemical technique. RESULTS: Metallothionein was detected in 15 of 45 prostate cancers (33.3%). Cytoplasmic and nuclear staining occurred in most cells. Additionally, metallothionein was found in basement membrane surrounding the cancer cells in 2 cases with metallothionein expression, and in secretory products of the lumen in a few cases. Statistical analysis for metallothionein expression related to tumor grade revealed a significant difference between high (7 to 10) and low (2 to 4) Gleason scores (p < 0.001), as well as between middle (5 and 6) and low scores (p < 0.05). However, no relationship was found with clinical stage. CONCLUSIONS: Our data suggest a close correlation of metallothionein expression with tumor grade and a wide range of metallothionein expression in prostate cancer.

Aged↗

[CGH (comparative genomic hybridization)].

Comparative Genomic Hybridization (CGH) is a powerful new method which allows genome-wide mapping of regions with DNA sequence copy number changes (both increases and decreases) in a single experiment without previous knowledge of the locations of the regions of abnormality. CGH is based on in situ hybridization of differentially labeled total genomic tumor DNA and normal DNA to normal human metaphase chromosomes. After hybridization copy number variations among the sequences in the tumor DNA are detected by measuring the tumor/normal fluorescence intensity ratio for each locus in the target chromosomes. Many previously unknown chromosomal regions with relative copy number changes have been detected in various tumors by CGH. Some changes have been identified as genetic markers associated with biological and clinico-pathological characteristics (i.e., histopathological grade, and clinical outcome). We review the published CGH articles and discuss briefly on current progress in CGH analysis to ovarian and uterine cervical cancer in our laboratory.

DNA, Neoplasm↗

Antibody mediated ligation of platelet/endothelial cell adhesion molecule-1 (PECAM-1) on neutrophils enhances adhesion to cultured human dermal microvascular endothelial cells.

We investigated the effects on leukocyte adhesion to cultured human dermal microvascular endothelial (DMvE) cell by antibody mediated ligation of platelet/endothelial cell adhesion molecule-1 (PECAM-1) on neutrophils. Preincubation of neutrophils with anti-PECAM-1 antibody markedly enhanced their adhesion to DMvE cells, while the adhesion-increasing action was cancelled out by anti-CR3 or anti-LFA-1 beta (CD18) antibody. These findings suggest that ligation of PECAM-1 on neutrophils increases their adhesion to cultured DMvE cells depending on the beta 2 integrin family, and PECAM-1 may have a crucial role in dermal inflammation.

Adult↗

Immunohistochemical detection of K-sam protein in stomach cancer.

The K-sam gene, originally isolated as an amplified gene from the stomach cancer cell line KATO-III, is characterized by its preferential amplification in the undifferentiated type (diffuse type) of stomach cancer and encodes one of the receptors for heparin-binding growth factors or fibroblast growth factors. The K-sam gene has been isolated by different methods and has been designated BEK, TK14, and Cek2. The receptor for keratinocyte growth factor was also found to be encoded by the same gene. To examine the expression of the K-sam protein in stomach cancer, polyclonal antibody pK1-2 was raised against the extracellular domain of the gene product. This antibody detected K-sam proteins by Western blot and flow cytometry analyses in stomach cancer cell lines KATO-III and HSC39, in which the K-sam gene is amplified and overexpressed. By immunohistochemical analysis, 20 of 38 cases of the undifferentiated type of advanced stomach cancer were K-sam positive, whereas none of 11 cases of the differentiated or intestinal type revealed K-sam staining. The K-sam product was observed predominantly in diffusely infiltrative lesions. In one autopsy case, the K-sam protein was detected only focally in the primary tumor, whereas markedly increased staining for the K-sam product was detected diffusely in the metastasized tumor in the lymph node and liver. These results suggest that K-sam overexpression is associated with the malignant phenotype of the undifferentiated type of stomach cancer, such as infiltrative growth and metastasis.

Amino Acid Sequence↗

Tumorigenicity and gene amplification potentials of cyclin D1-overexpressing NIH3T3 cells.

Cyclin D1 is a key regulator of the G1-S transition in cell cycle, and its gene is amplified and overexpressed in many cancers. To address the gene amplification potential of the cells in which the cyclin D1 gene expression is deregulated, we have established NIH3T3 clones with various levels of cyclin D1 transgene message. Those transfectants showed anchorage independent growth and tumorigenicity without in vitro morphological transformation. The degree of the transformed phenotype apparently correlated with the cyclin D1 expression level. Upon selection by N-(phosphonoacetyl)-L-aspartate (PALA), the cyclin D1-transfected NIH3T3 cells showed a higher ability to develop PALA-resistant colonies by amplifying the CAD gene, as compared to the parental NIH3T3 cells.

3T3 Cells↗

Prominent roles of secondary anchor residues in peptide binding to HLA-A24 human class I molecules.

The binding capacity of large sets of peptides corresponding to naturally occurring sequences and carrying previously defined A24-specific motifs was analyzed. It was found that only a minority (9-25%) of the motif-carrying peptides bound the relevant HLA-A molecule with good affinity (IC 50% < or = 50 nM), while the majority of them bound only weakly or not at all (IC 50% > or = 500 nM). By correlating the presence of specific residue types at each position along the peptide sequence with average binding affinity, the prominent influence of specific secondary interactions (secondary anchor residues) was revealed. Moreover, secondary interactions appeared to be size-dependent in that the specific effects detected differed in 9-mer and 10-mer peptide sets. Based on these observations, A24-specific refined motifs were also established for both 9-mer and 10-mer ligands, and their merit was verified by testing the binding capacity of independent sets of synthetic peptides. Such refined motifs should facilitate accurate prediction of potential A24-restricted peptide epitopes. It was also noted that certain crucial secondary interactions appear to be remarkably similar in the case of A24 and other HLA-A molecules previously analyzed (A*0201, A3, A11, and others). This may reflect contributions to binding affinity of relatively invariant residues located within the polymorphic pockets of the HLA binding groove.

Alleles↗

Xestoquinone activates skeletal muscle actomyosin ATPase by modification of the specific sulfhydryl group in the myosin head probably distinct from sulfhydryl groups SH1 and SH2.

Xestoquinone isolated from a sea sponge Xestospongia sapra inhibited both Ca2+ and K(+)-(EDTA) ATPase of skeletal muscle myosin. The inhibition was abolished in the presence of dithiothreitol. Xestoquinone reacted with 2-mercaptoethanol, a sulfhydryl (SH) compound. Unlike N-ethylmaleimide, a well-known SH reagent, modification of 2 mol of SH groups per myosin by xestoquinone caused a marked increase in the actomyosin ATPase activity. Kinetical analysis of stimulatory effects of xestoquinone indicates a decrease in the actin concentrations which gives half of the maximum velocity (Vmax) of actomyosin ATPase reaction without affecting the Vmax, suggesting an increase in the affinity of myosin for actin. N-Ethylmaleimide can still modify both the SH1 and SH2 groups after modification of 2 mol of SH groups by xestoquinone. Xestoquinone modified myosin SH groups which caused changes in the tryptophan fluorescence intensity and circular dichroism. These results suggest that xestoquinone modifies the specific SH groups in myosin distinct from SH1 and SH2, resulting in activation of actomyosin ATPase. It is also suggested that xestoquinone strengthens the interaction between actin and myosin through conformational change in the myosin molecule.

Actins↗

Four p53 DNA-binding domain peptides bind natural p53-response elements and bend the DNA.

Recent structural studies of the minimal core DNA-binding domain of p53 (p53DBD) complexed to a single consensus pentamer sequence and of the isolated p53 tetramerization domain have provided valuable insights into their functions, but many questions about their interacting roles and synergism remain unanswered. To better understand these relationships, we have examined the binding of the p53DBD to two biologically important full-response elements (the WAF1 and ribosomal gene cluster sites) by using DNA circularization and analytical ultracentrifugation. We show that the p53DBD binds DNA strongly and cooperatively with p53DBD to DNA binding stoichiometries of 4:1. For the WAF1 element, the mean apparent Kd is (8.3 +/- 1.4) x 10(-8) M, and no intermediate species of lower stoichiometries can be detected. We show further that complex formation induces an axial bend of at least 60 degrees in both response elements. These results, taken collectively, demonstrate that p53DBD possesses the ability to direct the formation of a tight nucleoprotein complex having the same 4:1 DNA-binding stoichiometry as wild-type p53 which is accompanied by a substantial conformational change in the response-element DNA. This suggests that the p53DBD may play a role in the tetramerization function of p53. A possible role in this regard is proposed.

Base Sequence↗

Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins.

Somatic sex determination in Drosophila depends on the expression of Sex-lethal (Sxl), whose level is determined by the relative number of X chromosomes and sets of autosomes (X:A ratio). The first step in regulation of Sxl expression is transcriptional control from its early promoter and several genes encoding transcription factors of the helix-loop-helix (HLH) family such as daughterless (da), sisterless-b (sis-b), deadpan (dpn) and extramacrochaetae (emc) have been implicated. By the use of transfection assays and in vitro binding experiments, here we show that da/sis-b heterodimers bind several sites on the Sxl early promoter with different affinities and consequently tune the level of active transcription from this promoter. Interestingly, our data indicate that repression by the dpn product of da/sis-b dependent activation results from specific binding of dpn protein to a unique site within the promoter. This contrasts with the mode of emc repression, which inhibits the formation of the da/sis-b heterodimers. These results reveal the molecular mechanisms by which Sxl gene transcription is positively or negatively regulated to control somatic sex determination.

Animals↗

Developmental expression pattern of the Caenorhabditis elegans homologue of the Drosophila suppressor of forked gene.

We cloned and sequenced the cDNA which encodes the Caenorhabditis elegans homologue (suf-1) of the Drosophila suppressor of forked (su(f)) gene product. The amino acid sequence deduced from the suf-1 cDNA shares extensive similarity with the su(f) and the human 77K subunit of the CstF, including the proline residues near the carboxy-terminus. Developmental Northern blot analysis showed that a 2.6-kb suf-1 transcript was expressed constitutively from L1 to young adult stages, suggesting it has a housekeeping function in vivo. Furthermore, this idea is consistent with the recent proposition that su(f) homologues play an essential role as a subunit of the cleavage stimulation factor (CstF) during polyadenylation of mRNA precursors.

Amino Acid Sequence↗