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Biomedical subjects

S Takai

Publications and source records attributed to S Takai.

At least 181 records · Page 10Linked to original sources

Enhanced CD34 expression of sinusoid-like vascular endothelial cells in hepatocellular carcinoma.

The immunohistochemical expression of CD34 (human hematopoietic stem cell and endothelial cell marker) and laminin were studied in chronic liver diseases and hepatocellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non-cancerous sinusoids and sinusoid-like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and laminin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and perinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid-like tumor vessels. However, early-stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid-like vessels. Laminin was strongly expressed in advanced HCC but not in early-stage HCC. The results indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothelial cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.

Antigens, CD34↗

Identification of intermediately virulent Rhodococcus equi isolates from pigs.

We recently reported the existence of Rhodococcus equi isolates with at least three virulence levels, isolated from AIDS patients: virulent R. equi having 15- to 17-kDa antigens that kills mice with 10(6) cells, intermediately virulent R. equi having a 20-kDa antigen that kills mice with 10(7) cells, and avirulent R. equi that does not kill mice with 10(8) cells or more (S. Takai, Y. Imai, N. Fukunaga, Y. Uchida, K. Kamisawa, Y. Sasaki, S. Tsubaki, and T. Sekizaki, J. Infect. Dis. 172:1306-1311, 1995). Virulent R. equi having the 15- to 17-kDa antigens has been isolated frequently from horses and their environment, but the source of intermediately virulent R. equi having the 20-kDa antigen is poorly understood. There are many reports of the isolation of R. equi from the lymph nodes of pigs with and without lesions resembling those of tuberculosis. Therefore, we analyzed antigens of R. equi isolates from the submaxillary lymph nodes of pigs by immunoblotting with monoclonal antibodies against these virulence-associated antigens. Immunoblots of whole-cell antigen preparations of R. equi pig isolates revealed the presence of the 20-kDa antigen in almost all the pig isolates studied, and these isolates were intermediately virulent for mice. We also demonstrated that the expression of the 20-kDa antigen and its pathogenicity in mice were associated strongly with the presence of five large, distinct plasmids of 70 to 95 kb; two of the five plasmids from pig isolates were the same sizes as those from human isolates. These results suggest that R. equi having the 20-kDa antigen exists in the submaxillary lymph nodes of pigs and that the source of infection in some human cases might be associated with pigs and their environment.

AIDS-Related Opportunistic Infections↗

Irradiation effects on the metabolism of metastatic brain tumors: analysis by positron emission tomography and 1H-magnetic resonance spectroscopy.

To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The tumor origins were lung cancer in three patients and breast cancer in two. Treatment volume was 0.4-10.1 cm3 (mean: 5.5 cm3). The marginal dose to the tumor was 24-30 Gy (mean: 26.2 Gy). The follow-up period was 5-19 months (mean: 13.4 months). No patients had conventional whole-brain radiation therapy. 18F-fluoroboronophenylalanine (18FBPA) or 18F-fluorodeoxyglucose (18FDG) were used as tracers for the PET study. Using 1H-MRS, several metabolites were simultaneously measured in metastatic brain tumor and adjacent brain. In the PET study of the representative case, the uptake rate of 18FBPA that is actively transported to the tumor decreased markedly 15 days after radiosurgery and continued to decrease thereafter. In the 1H-MRS study, choline, which is characteristically high in metastatic brain tumors, also decreased over time. In two cases with suspected radiation injury, the enhanced region, which was decreased in size in early follow-up, enlarged progressively and was accompanied by edema. However, 18FBPA and 18FDG were not transported to the enhanced region. The peak of free lipid, which might show destruction of the cell membrane, was recognized in the enhanced region and adjacent brain in these cases. This study revealed that radiation effects on the metabolism of metastatic brain tumors occur at an early stage after radiosurgery and continue over several months. In particular, in the case of radiation injury, PET and 1H-MRS studies made it possible to distinguish between regrowth of the tumor and radiation injury.

Aged↗

Polyethylene glycol-modified pokeweed mitogen (PWM) as a potential non-immunogenic stimulator of lymphokine-activated killer cells.

Among the various plant lectins, pokeweed mitoge (PWM) is most effective in enhancing the cytotoxicity of human lymphokine-activated killer (LAK) cells. However, the use of PWM in adoptive immunotherapy has been limited due to the strong immune response against the protein of plant origin. Amino groups in PWM was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chioro-s-triazine, activated PEG2, to form PEG-PWM conjugates. Its immunoreactivity towards anti-PWM antibodies was reduced by increasing the degree of modification of amino groups in PWM. PEG-PWM, in which 54% of amino groups in PWM was modified with activated PEG2, had a nearly complete reduction of immunoreactivity. Intraperitoneal administration of PEG-PWM to mice did not produce substantial levels of anti-PWM antibodies. Nevertheless, PEG-PWM retained the ability to induce the maximum levels of cytotoxicity of human LAK cells in vitro.

Animals↗

Immunohistochemical detection of virulence-associated antigens of Rhodococcus equi in pulmonary lesions of foals.

Rhodococcus equi was isolated from the lungs of six foals with bronchopneumonia. All isolates expressed 15-17-kd antigens by immunoblot analysis and contained a virulence-associated plasmid of 85 or 90 kb. Immunohistochemically, R. equi from all pulmonary lesions showed the expression of 15-17-kd antigens mainly in the phagocytic cells. The specific monoclonal antibody to 15-17-kd antigens of R. equi (MAb 10G5) may be an aid in the diagnosis of R. equi-induced pneumonia.

Actinomycetales Infections↗

Isolation of virulent and intermediately virulent Rhodococcus equi from soil and sand on parks and yards in Japan.

Rhodococcus equi is an emerging opportunistic pathogen of human immunodeficiency virus-infected patients. However, little is known about the distribution of virulent and intermediately virulent R. equi in human environment. In the present study, R. equi was isolated from 173 of 234 (73.9%) samples collected from soil and sand on 115 parks and 49 yards in Japan. The numbers of R. equi from soil and sand ranged from 2.5 x 10(1) to 1.2 x 10(5) per gram of sample. None of 1,294 isolates from those samples showed virulence-associated 15- to 17-kDa antigens and a 20-kDa antigen. These results suggest that avirulent R. equi is widespread in parks and yards, but the human environment has not been contaminated with virulent and intermediately virulent R. equi strains yet.

Antigens, Bacterial↗

[Somatostatin analogue treatment for malignant hypercalcemia associated with advanced breast cancer].

We describe the successful treatment with octreotide, a somatostatin analogue, of a patient with malignant hypercalcemia associated with advanced breast cancer. A 70-year-old female with advanced breast cancer was admitted to our department for treatment of hypercalcemia. The administration of pamidronate disodium was effective to decrease serum calcium from 6.2 mEq/l to 4.0 mEq/l for the first time, but her hypercalcemia later responded less to pamidronate, and her serum calcium remained raised in spite of the administration of pamidronate and elcatonin. Then, her condition deteriorated with hypercalcemic symptoms, such as nausea vomiting and drowsiness. After octreotide treatment (100 microg/body/day, s.c.) with a combination of prednisolone, her serum calcium level improved from 6.7 mEq/l to 5.0-5.5 mEq/l, Leading to a dramatic improvement in her symptoms. During these treatments, anti-cancer therapy, hydration and the administration of diuretics have been continued. We think octreotide is very useful for the treatment of malignant hypercalcemia associated with advanced breast cancer.

Aged↗

[Selective thermocoagulation of unresectable malignant tumors using radiofrequency].

Based on our experimental findings on porcine liver, we have been conducting a clinical trial of selective hyperthermia by radiofrequency (RF) capacitive heating with laparotomy for patients with unresectable malignant tumors. In 10 patients with malignant tumors (8 carcinoma of the pancreas, 2 carcinoma of the gallbladder), laparotomy and RF heating were performed after informed consent. The local heat coagulation was produced by heating equipment using 13.56 MHz radiofrequency produced by Omron Corporation, Japan. Four 2-cm electrode needles were placed in the tumor in a square array at intervals of 2.0 cm. Hyperthermia was given for 30 min with a controlled temperature of 50 degrees C in the RF field (2 x 2 x 2 cm3). That of the surrounding area was maintained at less than 40 degrees C. The calculated volume treated by RF ranged between (2 x 2 x 2 cm3) x 1 and (2 x 2 x 2 cm3) x 6. We followed all patients by computed tomographic (CT) scan 2 weeks after coagulation. Tumor markers in the blood were assayed before and 14 days after heating. Follow-up CT scans demonstrated that after the tumor mass had been heterogeneously enhanced, it changed to a homogeneous low-density area in 6 of 10 patients. The levels of tumor markers decreased to lower than the pre-treatment values in 9 of 10 patients. In all patients, the changes in CT scans and/or decrease in the markers were confirmed. Complications such as bleeding or abscess formation were not observed. It was suggested that the selective hyperthermia was safely produced by this equipment. The encouraging results in these patients justify further clinical trials.

Biomarkers, Tumor↗

Sequence of the Rhodococcus equi gene encoding the virulence-associated 15-17-kDa antigens.

The nucleotide sequence of the Rhodococcus equi gene encoding the virulence-associated 15-17-kDa antigens, located on plasmid pREAT701, has been determined. The gene encodes a 19-kDa protein of 189 amino acids, with an Ala-rich leader signal sequence (SS). At least five SS peptidase cleavage sites were found in this region. The molecular diversity of 15-17-kDa antigens might be attributed to the multiple SS peptidase cleavage sites.

Amino Acid Sequence↗

Frequent loss of heterozygosity at telomeric loci on 22q in sporadic colorectal cancers.

To date, several tumor-suppressor genes responsible for the tumorigenesis of colorectal cancer have been identified. However, studies of loss of heterozygosity (LOH) have suggested several chromosomal regions which may contain additional tumor-suppressor genes for colorectal cancer. To determine the extent and variation of allelic loss on 22q, on which LOH has been frequently observed, a total of 68 sporadic colorectal cancers was examined for LOH on the chromosome arm by means of 16 polymorphic DNA markers. LOH was observed in 28 tumors (41%), of which 9 showed LOH at all informative loci. The remaining 19 tumors showed variable patterns of partial loss on 22q, delimiting the smallest region of overlap (SRO) between D22S90 and D22S94. Moreover, LOH within the SRO correlated with a progression in terms of Dukes' stages. These results suggest that an additional tumor-suppressor gene for colorectal cancer may exist on 22q distally to the NF2 locus and that inactivation of the gene may possibly play a role in the progression or metastasis of colorectal cancers.

Chromosome Deletion↗

Deletion mapping of the long arm of chromosome 22 in human meningiomas.

Cytogenetic and molecular genetic analyses have shown that a tumor-suppressor gene for human meningioma is located on the long arm of chromosome 22. Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas. However, tumorigenesis of certain cases of meningioma cannot be fully explained by inactivation of the NF2 gene alone. Thus, to obtain some indication as to the existence of another tumor-suppressor gene, it seemed important to re-examine the loss of heterozygosity (LOH) on 22q in sporadic meningioma. A total of 46 sporadic meningiomas was examined for LOH at 20 loci on 22q. LOH was observed in 29 tumors (63%), of which 13 (28%) showed different patterns of a partial loss of 22q. However, the NF2 locus was retained in one tumor that lost a more distal part of 22q. Moreover, 27 of the 28 tumors which showed LOH at the NF2 locus also lost alleles at more telomeric loci. These results raise the possibility that another tumor-suppressor gene for meningioma may exist on 22q and that its localization may be distal to the D22S102 locus.

Chromosome Deletion↗

Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms.

Developmentally regulated mouse gene Nedd2 encodes a protein similar to the product of the nematode Caenorhabditis elegans cell death gene ced-3 and the mammalian interleukin-1 beta-converting enzyme. Overexpression of Nedd2 in cultured mammalian cells induces apoptosis that can be blocked by proto-oncogene BCL2. We have isolated cDNA clones for the human homologue of the mouse gene and, by using these as probes, mapped the human NEDD2 gene to 7q34-35 by fluorescence in situ hybridisation. The potential tumour suppressor function of NEDD2 is discussed.

Apoptosis↗

Assignment of the developmentally regulated gene NEDD1 to human chromosome 12q22 by fluorescence in situ hybridization.

The developmentally regulated mouse gene Nedd 1 encodes a protein showing similarities with the beta-subunit of heterotrimeric GTP-binding proteins and has growth suppressing activity when overexpressed in various cultured cell types. We have mapped the human homolog (NEDD1) of the mouse gene to chromosome 12q22 by fluorescence in situ hybridization using R-banded human (pro)metaphase chromosomes.

Animals↗

The human interleukin-10 receptor gene maps to chromosome 11q23.3.

The human interleukin-10 receptor (IL-10R) gene has previously been mapped to chromosome 11. Here, we have determined the precise location of the human IL-10R gene by the fluorescence in situ hybridization method, and have found that the IL-10R gene maps to chromosome 11q23.3.

Chromosome Mapping↗