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Biomedical subjects

T Nishi

Publications and source records attributed to T Nishi.

At least 199 records · Page 11Linked to original sources

Tumor-derived monocyte chemoattractant protein-1 induces intratumoral infiltration of monocyte-derived macrophage subpopulation in transplanted rat tumors.

By immunohistochemistry using anti-rat macrophage monoclonal antibodies RM-1, ED1, ED2, ED3, TRPM-3, and Ki-M2R, we studied transplanted rat tumors of 9L (rat gliosarcoma), Ad-2 (rat mammary carcinoma), and MT-P (rat malignant fibrous histiocytoma) cell lines to examine the distribution pattern of macrophages within and around the tumors. Most tumor-associated macrophages expressed RM-1, ED1, and Ia antigens, indicating activated macrophages. Based on differences in their immunophenotypical expression, these macrophages were distinguished into two major subpopulations. One expressed TRPM-3 and/or ED3, and the other was positive for ED2 and Ki-M2R. The former was considered to be monocyte-derived macrophages, whereas the latter showed the immunophenotype of tissue-fixed, resident macrophages. Infiltration and distribution patterns in the two macrophage subpopulations differed in the three different tumors. Monocyte-derived, activated macrophages infiltrated into 9L- and Ad-2-transplanted tumors, which markedly produced monocyte chemoattractant protein-1 (MCP-1). Additionally, numerous ED2- and Ki-M2R-positive macrophages were observed within the Ad-2-transplanted tumors, and some of them expressed TRPM-3. However, there were few macrophages in the MT-P-transplanted tumors that showed no MCP-1 production. In transplanted tumors of four MT-P/MCP-1 cell lines established by transfecting a rat MCP-1 gene expression vector (pCEP4/MCP-1) into the MT-P cell line, different levels of MCP-1 production were detected, which correlated well with the numbers of intratumorally infiltrated TRPM-3-positive macrophages. In contrast, ED2- and Ki-M2R-positive macrophages were not detected in any MT-P/MCP-1-transplanted tumors. MT-P/MCP-1-transplanted tumors exhibited lower growth rate than parental MT-P-transplanted tumors. These results indicate that tumor-derived MCP-1 induces intratumoral infiltration of monocyte-derived macrophages, but not macrophages with the immunophenotype of tissue-fixed, resident type. The former population of macrophages seems to have a suppressive effect on the growth of tumors.

Animals↗

[A case of gastric cancer with Borrmann type 4 responding to 5-FU-MMC combined chemotherapy].

A 70-year-old man with advanced Borrmann type 4 was preoperatively treated with 5-FU-MMC combined chemotherapy. The primary tumor including a palpable mass in the abdomen was diminished, and eventually the patient underwent curative resection. This preoperative regimen for advanced Borrmann type 4 gastric cancer might be recommended from the standpoint of less adverse effects of chemotherapy. The patient died suddenly of cardiac infarction in 9 months without recurrent signs.

Adenocarcinoma↗

Gonadal mixed germ cell tumor combined with a large hemangiomatous lesion in a patient with Turner's syndrome and 45,X/46,X, +mar karyotype.

In this report, we describe bilateral gonadal tumors with characteristic histopathological findings in a patient with Turner's syndrome who had 45,X/46,X, +mar mosaicism. The left gonad contained a gonadoblastoma and a remnant of streak gonad. The right gonad was entirely replaced by a 15x11x7-cm solid and cystic tumor, which was revealed to be a combination of a mixed germ cell tumor and a cavernous hemangiomatous lesion. The latter occupied approximately half of the entire tumor volume, and there was an incomplete boundary between it and the mixed germ cell tumor lesion. To our knowledge, this is the first reported case of Turner's syndrome with a combination of a mixed germ cell tumor and a hemangiomatous lesion in the gonad.

Adolescent↗

[A case of infrarenal left inferior vena cava with macrohematuria after contusion in the lumber region].

A 33-year-old woman was admitted with macrohematuria after contusion in the left lumber region. The excretory urogram showed no abnormal findings, but color doppler and RI-angiography revealed infrarenal left-sided inferior vena cava (left IVC). The pressure in the dilated left renal vein was higher than that in the right one. Renal contusion in addition to the congestion of the left renal vein due to left IVC was thought to be the cause of hematuria in this case. Hematuria disappeared after retrograde instillation of 0.2% AgNO3 water solution into the left renal pelvis. Left IVC rarely presents clinical symptoms, and is usually found by chance on CT scan or ultrasonography during examinations for upper abdominal organs. Our case is the 69th one of left IVC in Japan, and belongs to Type 2' according to our classification of left IVC.

Adult↗

[1,25-Dihydroxyvitamin D3 effects on human cultured osteoclast-like multinucleated cells].

This enzyme- and immuno-histochemical study investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the derivation of multinucleated cells from mononuclear cells of human bone marrow. The mononuclear cells differentiated into multinucleated cells after 3 weeks of culturing in the presence of the 1,25(OH)2D3. The tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells having more than three nuclei were counted and analyzed statistically. The findings were investigated to determine the effects of 1,25(OH)2D3, cellular density of mononuclear marrow cells, and of the age of the bone marrow donor. The main findings were; 1) the phenotypic expression of the cultured multinucleated cells coincided with that of the osteoclast, 2) the multinucleated cells increased in number significantly (p < 0.05) when cultured in the presence of 1,25(OH)2D3, and at a higher density of mononuclear marrow cells per dish, and 3) the multinucleated cells were very difficult to observe in the culture of marrow cells from old-aged donors. In conclusion, the osteoclasts were successfully cultured from the mononuclear cells of human bone marrow. The factors which correlated with increased development and differentiation of the multinucleated osteoclasts included a higher initial density of mononuclear cells, and a young age of bone marrow donor, in addition to the presence of the 1,25(OH)2D3 in the culture medium.

Acid Phosphatase↗

[A case of intracranial arteriovenous malformation presenting with intracranial hypertension].

A case of unruptured arteriovenous malformations (AVMs) presenting benign intracranial hypertension is reported. A 14-year-old male suffered from headache and papilledema. Intracranial pressure was 260 mmH2O. Unenhanced CT demonstrated no evidence of hemorrhage or hydrocephalus. Angiogram demonstrated a large AVM in the left temporal lobe supplied by the left posterior cerebral artery and left middle cerebral artery. It drained into the transverse sinus. Surgical excision of the AVM eliminated the headache and papilledema. AVM causes hemorrhage in 50% of cases, seizure in 30%, and other focal neurological deficits in 20%. Benign intracranial hypertension is an uncommon effect of unruptured AVMs. Only 13 cases have been reported in the literature. Benign intracranial hypertension associated with unruptured AVMs occurs in young patients with high flow AVMs that drain into the major sinus. The mechanism of intracranial hypertension associated with unruptured AVM is unknown. However, there are several possible mechanisms of intracranial hypertension associated with unruptured AVMs. The arterial blood shunting into a major sinus impedes venous return from the surrounding brain. That causes the increase of cerebral blood volume and the elevation of sinus pressure. This mechanism would reduce CSF absorption and would increase intracranial pressure. Pharmacological therapy is ineffective in controlling intracranial hypertension. Surgical excision of AVM effectively reduced intracranial hypertension. Thus, surgical excision of AVMs, if it can be done with low risk, is the treatment of choice to decrease intracranial hypertension in patients with unruptured cerebral AVMs.

Adolescent↗

Expression cloning of a novel Gal beta (1-3/1-4) GlcNAc alpha 2,3-sialyltransferase using lectin resistance selection.

This report describes the isolation of a cDNA encoding a novel human Gal beta (1-3/1-4)GlcNac alpha 2,3-sialyl-transferase involved in the biosynthesis of the sialyl Lewis x determinant (NeuAc alpha 2-3 Gal beta 1-4(Fuc alpha 1-3)GlcNAc). A cDNA library of the human melanoma cell line WM266-4 was constructed in an Epstein-Barr virus-based cloning vector. Selection of the B-cell line Namalwa expressing transfected cDNAs in the presence of the cytotoxic lectin Ricinus communis agglutinin 120 gave a cDNA encoding a protein with type II transmembrane topology, as found for mammalian glycosyltransferases. The use of this lectin, which is specific to galactose residues (especially the Gal beta 1-4GlcNAc structure), originates from our prediction that the modification of the Gal beta 1-4GlcNAc structure (a backbone of the sialyl Lewis x structure) by glycosyltransferases may increase the levels of resistance to this lectin. Comparison of this cDNA sequence with those of three other cloned sialyltransferases revealed two conserved regions shared by all four enzymes. Expression of the COOH-terminal catalytic domain of this protein showed alpha 2,3-sialyltransferase activity with substrate specificity different from that of CMP-N-acetylneuraminate:N-acetyllactosaminide alpha-2,3-sialyltransferase (Gal-beta 1-3(4)GlcNAc alpha 2,3-sialyltransferase, EC 2.4.99.6). Furthermore, expression of this cDNA in Namalwa cells increased the level of sialyl Lewis x antigens. The cloning approach based on lectin resistance may be useful for the isolation of cDNAs encoding other mammalian glycosyltransferases.

Amino Acid Sequence↗

Bacterial expression of an active tyrosine kinase from a protein A/truncated c-src fusion protein.

The carboxy-terminal half of the c-src protein fused to the protein A moiety was expressed in bacteria. The protein A/truncated c-src fusion protein, which does not have SH2 and SH3 domains, is found in the periplasmic space allowing for a simple one-step purification and demonstrated high efficiency in autophosphorylation and exogeneous substrate phosphorylation. The missense mutation at codon 294 (Ile-->Thr), which is located in the ATP-binding domain of the c-src, resulted in dramatic reduction of tyrosine kinase activity of the fusion protein. Using the fusion protein, we also revealed that staurosporin, a well-known kinase inhibitor, directly affects autophosphorylation of the C-terminal half of the c-src protein. This truncated c-src expression system provides a good source of enzyme for diverse experiments and is an ideal model for understanding the implication of structural alterations in the catalytic activity of the c-src kinase by site-directed mutagenesis experiments.

Alkaloids↗

Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase.

CD44 is a cell-surface glycoprotein postulated to play a role in a variety of biological processes, including lymphocyte homing and tumor-cell metastasis. Several isoforms of CD44 have been identified in human cells, and the genesis of some of these isoforms has been attributed to alternative splicing. In the study presented here we amplified three novel transcript variants of CD44 from human cell lines using a reverse transcriptase-polymerase chain reaction strategy. Two of the novel isoforms differed from previously described CD44 isoforms as a result of alternative splicing that occurred at previously reported splice junctions. The third novel CD44 isoform was generated from a previously unreported alternative splice junction near the 5' end of the open reading frame. Southern blot analysis of genomic DNA revealed that these novel isoforms and all of the previously described CD44 isoforms arose from alternative splicing. The capability of cells to modify their CD44 alternative splicing pattern was demonstrated in MCF-7 cells, which altered their CD44-isoform expression pattern in response to treatment with hyaluronidase. A better understanding of mechanisms regulating CD44 alternative splicing may provide insights into diverse processes, including tumor-cell metastasis and lymphocyte homing.

Alternative Splicing↗

Detection of p53 alterations in human astrocytomas using frozen tissue sections for the polymerase chain reaction.

The polymorphism of amino acid residue 72 on the human p53 tumor-suppressor gene is a useful marker for detecting intragenic loss of heterozygosity (LOH). We examined the LOH of the p53 gene in human malignant astrocytomas by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from frozen tissue sections under histologic examination. Eleven of 16 informative cases (69%) of the malignant astrocytomas were found to have LOH in the p53 gene. Sequential frozen sections were analyzed by immunohistochemistry using anti-p53 antibody PAb1801 to detect overexpression of the p53 protein, which is presumably altered if it is detectable. Ten of the 11 cases that had LOH of the p53 gene overexpressed the p53 protein. Moreover, 4 of the 11 patients with LOH of the p53 gene developed a second neoplasm in addition to an astrocytoma, possibly indicating genetic instability in these patients. These data suggest that alterations of the p53 gene may play an important role in the genesis of malignant astrocytoma. The combination of the PCR-RFLP method and immunohistochemical analysis using frozen tissue sections is a practical diagnostic tool for examination of human malignancies, including astrocytomas. astrocytomas.

Astrocytoma↗

Prenatal diagnosis and treatment strategy for congenital mesoblastic nephroma.

By means of the recent sophisticated technology regarding prenatal diagnosis, congenital mesoblastic nephroma (CMN) has become detectable before birth, or at a younger age than previously. Recently we treated an infant with a huge CMN in whom fetal asphyxia and tumor rupture occurred during the perinatal observation period after prenatal detection. Emergency surgery was required, and the postoperative course was complicated. The treatment strategy of the perinatal care team should focus on (1) reliable maternal transportation (2) continuous monitoring of fetal condition including cardiovascular status, (3) control of polyhydramnios to avoid premature labor, and (4) elective surgery at a stable or stabilized condition. Emergency surgery should be performed when circulatory disturbance, respiratory distress, and/or impending rupture are suspected.

Adult↗

Studies of HIV-1 protease inhibitors. II. Incorporation of four types of hydroxyethylene dipeptide isosteres at the scissile site of substrate sequences.

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors containing four types of hydroxyethylene dipeptide isosteres were designed and synthesized. These inhibitors consist of eight stereoisomers of phenylalanylproline (Phe-psi[H.E.]-Pro), four stereoisomers of phenylalanylalanine [Phe-psi[H.E.]-Ala), and one stereoisomer each of phenylalanylglycine (Phe-psi[H.E.]-Gly) and cyclohexylalanylalanine (Cha-psi[H.E.]-Ala) hydroxyethylene dipeptide isosteres. For the synthesis of the latter two isosteres, a newly developed synthetic method for gamma-lactone was applied. The inhibitory activities of these peptides were evaluated by cleavage assay of partially purified gag proteins or purified synthetic peptide. Of the inhibitors examined, compounds 2c (Z-Asn-(2S,3R,4S,5S)-Phe-psi[H.E.]-Pro-NHB(un); Bu(n) = n-butyl, Ki = 0.50 microM), 21a (Z-Asn-(2R,4S,5S)-Phe-psi[H.E.]-Ala- NHBu(n), Ki = 0.34 microM) and 23 (Z-Asn-(2R,4S,5S)-Cha-psi[H.E.]-Ala- NHBu(n), Ki = 0.46 microM) were moderately potent inhibitors. The results revealed that the alkyl substituent at C2 is essential, and the stereochemistry of the hydroxyethylene dipeptide isosteres greatly affected their inhibitory activities.

Amino Acid Sequence↗

Synthesis and antibacterial activity of new 2-substituted penems. I.

A new type of penem derivative (3-6) having a cyclic amidine moiety or a quaternary heterocycle moiety at the C-2 position was prepared. The susceptibility to renal dehydropeptidase-1 (DHP-1) and the antimicrobial activity of these compounds were determined. Some of these compounds (5,6) showed a broad spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma.

BACKGROUND: The aim of this study was to characterize patients with pulmonary metastasis of parathyroid carcinoma and to evaluate the long-term effect of surgical and medical therapy. METHODS: Seven patients with pulmonary metastasis of parathyroid carcinoma were treated between 1980 and 1992. Six patients underwent resection of pulmonary metastases, and one patient has had long-term bisphosphonate therapy alone. Bisphosphonate was also given before or after operation to three patients. RESULTS: Two patients underwent a unilateral thoracotomy for a single pulmonary lesion, and four other patients with multiple lesions underwent staged bilateral thoracotomies. The postoperative serum calcium level returned to normal after each thoracotomy in three patients who were alive and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted in the other three patients. In two of the patients, bisphosphonate therapy was also unable to control hypercalcemia. In one patient the serum calcium level has been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone for 3 years. CONCLUSIONS: The aggressive surgical approach to pulmonary metastasis of parathyroid carcinoma was shown to be effective for palliation in selected patients. Bisphosphonate therapy is an alternative to resection but has only a temporary calcium-lowering effect.

Adolescent↗

[A case of bronchogenic cyst in the posterior mediastinum with high level of serum SCC antigen].

A 78-year-old man was picked up by chest X-ray findings. His CT scan film showed a posterior mediasinal tumor shadow. Serum level of SCC antigen was high and thoracotomy revealed bronchogenic cyst with high production of SCC antigen. After resection of the cyst, his serum level of SCC was within normal range. It is proposed that the elevated serum level of SCC is due to chronic inflammation or structural feature of the cystic wall.

Aged↗