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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 199 records · Page 11Linked to original sources

Effects of electrochemotherapy on CaSki cells derived from a cervical squamous cell carcinoma.

Electrochemotherapy is a new approach to the treatment of tumors that takes advantage of the permeabilization of the cell membranes by electric pulses to facilitate the intracellular delivery of chemotherapeutic drugs into cells. Using the female genital squamous cell carcinoma cell line, CaSki, the antitumor effectiveness of electrochemotherapy was tested. In vitro studies showed that the cytotoxicity of some anticancer drugs, especially bleomycin, can be greatly enhanced by exposing cells to noncytotoxic electric pulses. This enhancement was significantly greater when the electric treatment was given after exposure to the drug than when applied preexposure. Treatment of nude mice bearing subcutaneous transplanted tumors with noneffective intraperitoneal doses of bleomycin followed by local delivery of electric pulses similar to those performed in vitro resulted in tumor reduction and complete disappearance after 12 days this electrochemotherapy. Histological changes in tumor tissue such as necrosis and degeneration were extensive even 6 hr after the electrochemotherapy. Thus the antitumor effects of bleomycin in mice can be considerably potentiated by local electric pulses, suggesting that electrochemotherapy with bleomycin may have promise for treatment of vulvar or ectocervical squamous cell carcinomas with early invasion.

Animals↗

Leiomyosarcoma of the colon presenting as acute suppurative peritonitis.

A surgical case of leiomyosarcoma arising from the ascending colon, presenting as acute suppurative peritonitis, is herein described. A 70-year-old woman complaining of lower abdominal pain presented to our clinic on October 12, 1994. She was admitted with a tentative diagnosis of peritonitis. At emergency laparatomy, purulent intraabdominal fluid was present, and a fist-sized mass was seen in the ascending colon just proximal to the hepatic flexure. A right hemicolectomy was thus performed based on a diagnosis of perforating colon cancer. The histologic findings were consistent with leiomyosarcoma with abscess formation in and around the tumor. Five mitotic figures per field were observed at 10x magnification. Immunohistochemical studies revealed immunoreactivity for alpha-smooth muscle antigen (alpha-SMA), vimentin, and desmin. After reviewing the clinicopathologic characteristics of colon leiomyosarcoma as described in 78 Japanese cases and 70 cases from the foreign literature, we thus propose that colon leiomyosarcoma frequently arises from the transverse colon. In addition, our case also represents the only reported case in Japan in which an adult patient underwent a successful operation for perforated leiomyosarcoma of the colon.

Acute Disease↗

Tensile properties of canine intrasynovial and extrasynovial flexor tendon autografts.

This study compared the biomechanical properties of intrasynovial and extrasynovial flexor tendon autografts in an adult canine model. Flexor digitorum profundus (FDP) tissue from the fifth toe of the hindpaw was harvested and transplanted as an intrasynovial graft to the second toe of the left forepaw of each animal. Peroneus longus tendon from the lateral compartment of the hind leg served as the source for the extrasynovial graft that was transplanted to the fifth toe of each dog's left forepaw. The second and fifth FDP tendons of the right forepaw constituted the respective contralateral controls. Postoperatively, each animal underwent a regimen of daily controlled passive mobilization. Three and 6 weeks after grafting, 6 animals were euthanized and their grafts evaluated for gliding function and tensile properties. Results reveal significantly greater angular rotation of the proximal interphalangeal joint in the digits that received intrasynovial grafts relative to those that received transplanted extrasynovial tendon at both 3 and 6 weeks postoperatively. The linear stiffness of the tendons receiving extrasynovial graft significantly exceeded that of the intrasynovial group. These findings correlated with histologic data that postoperative adhesions existed in the specimens with an extrasynovial graft. In addition, the extrasynovial tendon graft complex exhibited significantly higher ultimate loads than intrasynovial tendon graft complex at 6 weeks.

Animals↗

Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA.

We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance. Serum arachidonic acid (AA) level was decreased by the administration of low-dose EPA and tended to be decreased by the administration of low-dose DHA, whereas tumour AA levels were not changed. The administration of low-dose EPA and DHA may be useful for inhibiting the incidence of breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗

Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.

We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.

Amino Acid Sequence↗

Accessory cell function of a human colonic epithelial cell line HT-29 for bacterial superantigens.

The expression and up-regulation of cell adhesion molecules on a human colonic epithelial cell line HT-29, and the peripheral blood T lymphocyte proliferation responses to bacterial superantigens presented by this cell line were investigated, compared with peripheral blood monocytes. In HT-29 cells, there was constitutive expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) at a low level, but no constitutive expression of HLA-DR, LFA-1, B7-1 and B7-2 molecules. After stimulation with the supernatants of staphylococcal enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells for 48 h, there was significant up-regulation of HLA-DR and ICAM-1 molecules (both > 90% positive). However, this stimulation had no effect on the expression of LFA-1, B7-1, B7-2 and LFA-3 molecules. In the presence of all tested superantigens SEB, toxic shock syndrome toxin-1, and streptococcal pyogenic exotoxin A, stimulated HT-29 cells caused significant T cell proliferation. When monocytes were used as antigen-presenting cells (APC), the MoAbs against HLA-DR, B7-2 and LFA-3 showed a significant inhibition of SEB-induced T cell proliferation. Anti-ICAM-1 MoAb had no effect on this response. On the other hand, when stimulated HT-29 cells were used as APC, the MoAbs against HLA-DR and ICAM-1 significantly inhibited SEB-induced T cell proliferation. In contrast to monocytes, anti-B7-2 and anti-LFA-3 had no effect on this response. SEB could not induce HT-29 cells to produce IL-8 directly; however, SEB significantly induced the stimulated HT-29 cells to produce IL-8 in the presence of T cells. Thus these data demonstrate that the products of superantigen-stimulated T cell activation can increase the expression of HLA-DR and ICAM-1 molecules on HT-29 cells significantly. Stimulated HT-29 cells can serve as APC to bacterial superantigens. This response is an HLA-DR- and ICAM-1-dependent, but B7-2- and LFA-3-independent process, which was different from professional APC monocytes.

Antigen-Presenting Cells↗

Allelotype and replication error phenotype of small cell lung carcinoma.

Allelotype and replication error (RER) phenotype analyses were performed to clarify the pathogenetic significance of inactivation of tumor suppressor genes and genomic instability in the genesis and progression of small cell lung carcinoma (SCLC). We examined 37 cases of SCLC for loss of heterozygosity (LOH) and microsatellite instability at 49 loci on all 39 nonacrocentric chromosomal arms. LOH was frequently (>70%) detected on chromosomes 3p (29/32, 90.6%), 5q (15/21, 71.4%), 13q (25/26, 96.2%), 17p (22/25, 88.0%), and 22q (24/33, 72.7%). Frequent LOH (>70%) on these loci was observed even among seven cases of stage I tumors. The incidence of LOH on all 39 nonacrocentric chromosomal arms was not significantly different between primary tumors and metastases. These results suggest that inactivation of multiple tumor suppressor genes accumulates relatively early during progression of SCLC and it may be responsible for clinically and biologically aggressive phenotype of SCLC. RER was observed in 6/37 (16.2%) of SCLC, however, RER at multiple loci was observed only in two cases. Therefore, it was indicated that genomic instability is uncommon, but might play a role in the genesis of a small subset of SCLC.

Alleles↗

A case of intravascular papillary endothelial hyperplasia (Masson's tumor) arising from renal sinus.

A 55-year-old woman had a right renal tumor incidentally diagnosed by ultrasonography. CT revealed a perirenal low density mass 3 cm in diameter. Dynamic CT showed peripheral enhancement of the tumor in early phase and internal homogeneous enhancement in delayed phase. Since hemangioma was considered most likely, we performed tumor resection and spared the right kidney. The tumor was supplied by the superior ureteral artery from the right main renal artery which was considered to be derived from the renal sinus. The tumor was diagnosed as intravascular papillary endothelial hyperplasia (Masson's tumor). This is the first report of intravascular papillary endothelial hyperplasia existing in the perirenal space. Although preoperative diagnosis of intravascular papillary endothelial hyperplasia is difficult, intra-operative pathology and kidney-sparing treatment should be considered in such a case.

Diagnosis, Differential↗

Modified formalin and methanol fixation methods for molecular biological and morphological analyses.

Several simplified fixation methods were examined to determine their suitability for both molecular biological analyses and morphological study. Fixation with 10% v/v formalin alone at 4 degrees C and containing 5 mmol/L ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) at room temperature preserved significantly more high-molecular-weight DNA than 10% v/v formalin fixation at room temperature. The morphological differences between tissues fixed using these modified formalin fixation methods and conventional 10% v/v formalin fixation were negligible. Of the dehydration fixatives tested, 100% methanol did not cause regional differences due to artificial tissue shrinkage and the morphology of sections prepared by methanol fixation was preserved consistently better than that of acetone- or ethanol-fixed sections. All three dehydration fixatives preserved relatively higher-molecular-weight DNA and RNA, compared with formalin. Cold formalin, formalin containing EDTA at room temperature and 100% methanol are recommended as standard and additional fixatives routine clinicopathological laboratory use.

Breast↗

Detection of circulating tumor cells in patients with prostate cancer using prostate specific membrane-derived primers in the polymerase chain reaction.

BACKGROUND: Prostate specific membrane antigen (PSM) is a transmembrane glycoprotein that has been described as human prostate specific. It is possible that PSM could be used as a biomarker for staging prostate cancer. METHODS: Peripheral blood mononuclear cells from 2 groups of patients with prostate cancer were used for the detection of PSM messenger ribonucleic acid (mRNA) using the reverse transcriptase-polymerase chain reaction (RT PCR) method. Group 1 consisted of 29 untreated patients (13 stage B cancer, 5 stage C, and 11 stage D cancers). Group 2 consisted of 40 treated patients (23 responded well and 17 had recurrence after treatment). In addition, blood specimens from 30 patients with benign prostatic hyperplasia, 5 women, and 5 men undergoing cystoprostatectomy for invasive bladder cancer were used as controls. We then correlated patient and disease characteristics with PCR assay results. RESULTS: Samples of all 40 controls were negative for PSM-mRNA. Thirteen of 29 patients of group 1 (45%) were positive for PSM-mRNA. The PCR positive rate did not correlate with clinical stage, pathologic stage, tumor grade, or serum PSA levels. Nine of 40 patients (22%) in group 2 were positive for PSM-mRNA, and the majority (8 of 9) were derived from the group of patients with recurrent disease. CONCLUSIONS: A nested RT PCR assay for PSM mRNA can detect circulating tumor cells in the peripheral blood of patients with prostatic cancer. These results suggest that the detection of circulating tumor cells could be useful for monitoring disease progression of prostatic cancer.

Adenocarcinoma↗

Therapeutic efficacy of clenbuterol for urinary incontinence after radical prostatectomy.

BACKGROUND: Urinary incontinence is one of the most common complications occurring after radical prostatectomy. We evaluated the efficacy of clenbuterol, a selective beta 2-adrenoceptor agonist, in the treatment of incontinence occurring after radical prostatectomy, using urodynamic assessment. METHODS: Fourteen men (mean age, 68 years) with post-radical-prostatectomy incontinence were treated with 20 mg of clenbuterol twice a day for 1 month. The urodynamic assessment was performed on all patients before and after the administration of clenbuterol. A pad scoring system was used to gauge the severity of incontinence before and after treatment. RESULTS: At 1 month after administration of clenbuterol, 9 of the 14 patients (64%) had dramatic improvement in pad scores. Treatment failed in 5 patients (36%) with severe incontinence. The results of urodynamic studies showed that the mean functional urethral length of the patients with post-radical-prostatectomy incontinence increased significantly after treatment. CONCLUSION: These results suggest that clenbuterol can be used as an effective agent for treating mild-to-moderate stress incontinence after radical prostatectomy.

Aged↗

Emergence of an irreversible differentiated subclone from the poorly differentiated ovarian adenocarcinoma cell line AMOC-2 treated with sodium butyrate.

OBJECTIVE: To cast light on the capacity of an ovarian adenocarcinoma to undergo irreversible cellular differentiation, we established clonal cell lines from cultured ovarian carcinoma cells treated with sodium butyrate and examined their phenotypic changes. METHODS: The poorly differentiated ovarian carcinoma cell line AMOC-2 was exposed to 2 mM sodium butyrate for 30 days, and clonal cell lines were established by a dilution plating technique. RESULTS: Five clonal cell lines were established. One of them had a longer doubling time and lower plating efficiency than the parental clone, also demonstrating stronger expression of vimentin and 56 kD cytokeratin. This clone became columnar with pronounced polarity, formed gland-like structures when cultured in collagen gels, and exhibited no tumorigenicity, in contrast to the parental clone. CONCLUSION: Sodium butyrate treatment of AMOC-2 cells can cause phenotypic changes reminiscent of maturation in the Müllerian duct, endocervix, and/or endometrium.

Adenocarcinoma↗

[Acute toxicity studies of taltirelin tetrahydrate in mice, rats, and dogs].

The acute toxicity studies of taltirelin tetrahydrate (TA-0910), a new thyrotropin-releasing hormone (TRH) analogue, were performed in Slc:ddY mice, Slc:Wistar rats and beagle dogs of both sexes. The drug was administered to mice and rats by oral (p.o.), intravenous (i.v.) and subcutaneous (s.c.) routes, and to dogs by the p.o. and i.v. routes. LD50 values were more than 5,000 mg/kg in mice and rats of both sexes by the p.o. and s.c. routes. Some mice and rats died immediately after i.v. injection, the LD50 values were more than 2,000 mg/kg in mice of both sexes and calculated as 799 and 946 mg/kg in male and female rats, respectively. The minimum lethal doses were more than 2000 mg/kg in dogs of both sexes by the p.o. route. Though all dogs treated intravenously with 1000 mg/kg could survive during the observation period, a female dog with 500 mg/kg died on the day after administration. In general condition, hyperactivity, tremor and straub tail, that reflected central stimulatory effects of TA-0910, were observed in mice and rats, and also wet dog shaking in only rats. Vomiting and hyperactivity were seen in dogs by the p.o. route, and exaltation (during the dosing) and sedation by the i.v. route. In addition, salivation and transient tachycardia were observed in the both routes. In blood chemical examination, the transient changes of glucose, protein, lipid and/or serum enzyme were shown. In autopsy, no notable changes were seen in mice, rats and dogs.

Administration, Oral↗

Increased expression of costimulatory molecules on peripheral blood monocytes in patients with Crohn's disease.

BACKGROUND: Activation of T lymphocytes and monocytes/macrophages has been implicated in the pathogenesis of Crohn's disease (CD). Costimulatory molecules play important roles in optimal T-cell activation. METHODS: With flow cytometric analysis we have investigated the expression of the costimulatory molecules B7-1 (CD80), B7-2 (CD86), and CD18 and the intercellular adhesion molecule-1 (ICAM-1) on peripheral blood monocytes and the expression of the activation markers HLA-DR and IL-2R (CD25) on peripheral blood T lymphocytes from 31 CD patients, 17 ulcerative colitis (UC) patients, and 10 healthy controls. RESULTS: In CD patients the percentage of activated T cells (CD3+ HLA-DR+ and CD3+ IL-2R+) was significantly increased compared with those of controls and UC patients (P < 0.05). Most monocytes from all three groups expressed B7-2, CD18, and ICAM-1 molecules (all > 79%), but only a few positive cells expressed B7-1 molecules (< 5%). No significant differences were detected in the percentage positivity of all costimulatory molecules tested among CD, UC, and controls. The mean fluorescence intensity (MFI) of B7-1 in all three groups was very weak and not significantly different. However, in CD patients there was a significantly increased MFI of B7-2, CD18, and ICAM-1 molecules compared with UC and controls (P < 0.05). On the other hand, both the percentage positivity and MFI of HLA-DR molecules on monocytes of UC patients were significantly lower than those of CD patients and controls (P < 0.05). CONCLUSIONS: Expression of the costimulatory molecules B7-2, CD18, and ICAM-1 on peripheral blood monocytes of CD patients is increased. In CD patients activation of peripheral T lymphocytes may correlate with increased expression of these costimulatory molecules on peripheral blood monocytes.

Adolescent↗

T-cell lymphoma of CD3+CD4+CD56+granular lymphocytes with hemophagocytic syndrome.

A case of T-cell lymphoma of granular lymphocyte (GL) morphology and CD3+CD4+CD56+ phenotype is reported. The lymphoma originated in the subcutaneous tisse of the right thigh and subsequently infiltrated into various organs including the lymph nodes, peripheral blood, bone marrow, skin, lungs, liver, spleen, and peritoneal cavity, and the patient finally developed a hemophagocytic syndrome. The lymphoma cells were positive for CD2, CD3, CD4, and CD56, and negative for CD8, CD16, CD20, and CD57. An identical clonal rearrangement of the T-cell receptor beta chain genes was detected in cells from a lymph node, peripheral blood, and ascites fluid, indicating the monoclonal proliferation of T cells in such organs. This is a T-cell GL lymphoma, expressing the unusual phenotype of CD3+CD4+CD8-CD16-CD56+, which has not been previously reported. The development of hemophagocytic syndrome has also to our knowledge not previously been reported in T-cell GL lymphoma.

Aged↗

Expression of HuD (a paraneoplastic encephalomyelitis antigen) mRNA in lung cancer.

HuD, one of the Hu antigens (HuD and HuC), was recognized in the sera of small cell lung cancer (SCLC) patients with antibody-associated paraneoplastic encephalomyelitis/peripheral sensory neuropathy (PEM/PSN). Three forms of HuD mRNA, 197, 156, 110 nucleotides are made by alternative splicing at 868-909 residues and an additional 3'-splice site. To determine the diagnostic value of the HuD expression for small cell lung cancer, we examined 4 SCLC cell lines, 9 surgically resected SCLCs, and 12 surgically resected non-SCLCs using the reverse transcriptase-polymerase chain reaction with the HuD-specific primer pairs that spanned the putative alternative 3'-splicing site and direct DNA sequencing. None of the patients were associated with PEM/PSN. A single RNA transcript (156 nucleotides) among three forms (110, 156, 197 nucleotides) of the HuD gene was an alternatively spliced at 868-909 residues in SCLC cell lines. Expression of the HuD gene was stronger in three classic cell lines, but not in a variant cell line. Two of 9 SCLCs (22%) and 3 of 12 non-SCLCs (25%) expressed only the major RNA transcript (156 nucleotides) of the HuD gene, which was alternatively spliced in the same fashion as the cell line. These results revealed that no aberrant alternative splicing occurred in SCLC not associated with PEM/PSN and the expression of HuD gene was not specific for a particular histologic subtype of human lung cancer.

Antigens, Neoplasm↗