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Biomedical subjects

M Ohana

Publications and source records attributed to M Ohana.

At least 37 records · Page 2Linked to original sources

The effect of halofuginone, an inhibitor of collagen type i synthesis, on urethral stricture formation: in vivo and in vitro study in a rat model.

PURPOSE: Urethral strictures are narrowing of the urethra caused by fibrosis due to excessive collagen production in response to an insult. We evaluated the effects of halofuginone, a potent inhibitor of collagen alpha1(I) gene expression, on experimentally induced urethral strictures in vivo and on rat urethral fibroblasts in vitro. MATERIALS AND METHODS: Applying coagulation current to the male rat urethra produced urethral strictures. Halofuginone was given to the animals for 7 days, starting on the day of stricture formation, either orally at 1 and 5 ppm in the diet or by injection of 0.03% halofuginone solution into the urethra. All rats were sacrificed on day 21. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, collagen content by sirius red staining and urethral morphology by urethrogram. RESULTS: Coagulation current produced reproducible strictures with a typical urethrogram appearance, which were associated with increases in collagen alpha1(I) gene expression and collagen content at the stricture site. Halofuginone injected into the urethra or orally at 5 ppm normalized the urethrogram and prevented increases in collagen alpha1(I) gene expression and collagen content. Halofuginone at a concentration of 10-8 M. inhibited the collagen secreted by fibroblasts derived from the rat male urethra, which was due to inhibition of the collagen alpha1(I) gene expression. CONCLUSIONS: Halofuginone prevented stricture formation and may become an important mode of therapy in the prevention of restenosis during urethral stricture formation.

Animals↗

Halofuginone, an inhibitor of collagen type I synthesis, prevents postoperative adhesion formation in the rat uterine horn model.

OBJECTIVE: The objective of this study was to evaluate the effects of halofuginone-a specific inhibitor of collagen type I synthesis-in preventing uterine horn adhesion formation in rats. STUDY DESIGN: Adhesions were induced by scraping the rat uterine horns until capillary bleeding occurred. Halofuginone was either injected intraperitoneally or administered orally. The number and severity of the adhesions were scored. Collagen alpha1(I) gene expression was evaluated by in situ hybridization; total collagen was estimated by sirius red staining. Collagen synthesis in response to halofuginone was evaluated in cells cultured from the adhesions. RESULTS: Regardless of the administration procedure, halofuginone reduced significantly the number and severity of the adhesions in a dose-dependent manner. Halofuginone prevented the increase in collagen alpha1(I) gene expression observed in the rats that underwent this procedure, thus affecting only the newly synthesized collagen but not the resident collagen. In cells derived from rat uterine horn adhesions, halofuginone induced dose-dependent inhibition of collagen synthesis. CONCLUSIONS: Upregulation of collagen synthesis appears to play a critical role in the pathophysiologic mechanism of adhesion formation. Halofuginone could be used as an important means of understanding the role of collagen in adhesion formation and might become a novel and promising antifibrotic agent for preventing adhesion formation after pelvic surgery.

Administration, Oral↗

Ineffective use of a detachable snare for colonoscopic polypectomy of large polyps.

BACKGROUND: Colonoscopic polypectomy of large polyps may be associated with complications such as bleeding. Use of a detachable snare may reduce the risk of bleeding. We describe several instances in which the use of such a device proved to be ineffective. METHODS: A detachable snare was used for colonoscopic polypectomy of large polyps in 18 patients (20 polyps), also applied at the residual stalk after conventional polypectomy in 5 patients (5 polyps), and evaluated retrospectively. RESULTS: Sixteen of the 20 polyps were pedunculated, and 4 were semi-pedunculated. In 3 of the 4 semi-pedunculated lesions, the loop slipped off after polypectomy because the lesions were cut close to the site of encirclement. Bleeding occurred in 4 cases because of transection by the loop of a thin stalk (4 mm) before polypectomy (1), slipping of the loop in a semi-pedunculated lesion (1), or insufficient tightening of the loop (2). After conventional polypectomy, we could not effectively snare the residual stalk because of flattening in 3 of the 5 lesions. CONCLUSIONS: Use of the detachable snare for polypectomy of thin stalked or semi-pedunculated lesions may result in technical failure of this technique. The stalk should be fully encircled with the snare before polypectomy. The detachable snare is difficult to apply at the residual stalk after conventional polypectomy.

Aged↗

Multiple pancreatic masses associated with autoimmunity.

A 59-year-old woman was detected to have a high titer of serum gamma-globulin, positive antinuclear antibody and multiple pancreatic masses. In the course of 1 yr, Sjögren's syndrome developed, and her pancreatic masses spread diffusely and compressed the main pancreatic duct. A pancreatic biopsy by an exploration of the abdomen showed that many CD4 positive T-lymphocytes had infiltrated to the ducts and acinar cells expressing HLA-DR antigens. This suggested a diagnosis of autoimmune-related pancreatitis. She was treated with oral prednisolone, and a marked improvement of the above abnormal findings followed. In this report, a case of autoimmune-related multiple pancreatic masses associated with Sjögren's syndrome is presented, and a possible mechanism is discussed.

Administration, Oral↗

Antilactoferrin antibodies in autoimmune liver diseases.

OBJECTIVE: Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases. METHODS: Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method. RESULTS: Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (p < 0.01), hepatitis C (p < 0.01), PBC (p < 0.05), and AIH (p < 0.05). CONCLUSION: Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.

Adolescent↗

Leiomyosarcoma of the mesocolon.

Retroperitoneal sarcomas are rare tumours. Although exceptional in the mesocolon, they can yet be considered as a special kind of retroperitoneal tumours. Leiomyosarcoma represents from 25 to 30% in this location. Clinical features are rarely obvious because the symptomatology depends upon displaced or compressed adjacent organs. Most authors agree on using the CT-scanner or MRI as diagnostic tools. However, the diagnosis is made after a histologic examination permitting the establishment of its grade and margins. Only a surgical treatment can offer prolonged survival and this can be improved if there is a low histological grade and total excision. The mesocolic location facilitates a radical removal and may therefore offer a better long-term prognosis.

Female↗

Focal nodular hyperplasia of the liver without central scar.

An unusual case of focal nodular hyperplasia (FNH) of the liver is presented. A 31-year-old male was admitted to our hospital for the evaluation of an hepatic mass 10 cm in diameter located in segment 4. Routine examinations including liver function tests were all normal. Hepatitis B surface antigen, hepatitis C virus antibody, alpha-fetoprotein were all negative. Imagining studies could not detect specific findings of FNH such as a central scar structure or a spoke-wheel appearance due to dilated tumor vessels coursing centrally followed by radiating peripheral coursing vessels. Extensive left lobectomy of the liver was performed. Histological examination of the specimen cut into 1-cm-thick slices revealed no central stellate scars. Preoperative diagnosis of FNH with imaging studies was difficult because of the absence of central scars.

Adult↗

Malignant lymphoma in the ileocecal region causing intussusception.

A 67-year-old female was admitted with diarrhea. Preoperatively, we diagnosed intussusception due to malignant lymphoma in the ileocecal region by image and colonoscopic examinations. We resected the right hemicolon for the tumor, which was located mainly in the cecum, causing intussusception. The stenotic terminal ileum free of the tumor was invaginated within the cecum with infiltrating tumor, thus showing the appearance of an anthill. The growth of the tumor corresponded with Wood's constrictive type, in which intussusception rarely occurs.

Aged↗

[Prognostic factors and the significance of gastrectomy in gastric lymphoma].

Fifty cases of primary gastric lymphoma treated at Tenri Hospital between 1975 and 1992 were reviewed retrospectively. Histopathologically they were classified according to the Working Formulation into three groups: low grade 3 cases, intermediate grade 42 of which 34 were diffuse large cell and high grade 5. Their clinical stages according to the Ann Arbor staging system were as follows; Stage I 15 cases, Stage II 17, Stage III 5 and Stage IV 13. Twelve variables were tested by univariate analysis for prognosis. Significant prognostic factors were clinical stage, tumor depth to the gastric wall, regional lymph node involvement, macroscopic finding of tumor shape and surgical resectability. Important variables were tested by using a multiple regression, the 5 most significant variable being curative surgical resection. The year survival after curative resection was 93.8% and 25.2% for other patients (p < 0.001). In the patients with Stage II-disease, the greater the 'N-number' of regional lymph node involvement according to the General Rules for the Gastric Cancer Study was, the lower the survival rate was due to the difficulty for curative resection (p < 0.05). The same curative resection is necessary for gastric lymphoma as for gastric cancer. In the patients with Stage III or IV disease, higher survival rate was achieved in the gastrectomy group than the others. In conclusion, an aggressive surgical intervention is warranted in the treatment of gastric lymphoma of any stage.

Adolescent↗

Low-dose heparin inhibits acute graft versus host disease in mice.

We have studied the effect of low-dose heparin on GVHD, marrow engraftment and graft-versus-leukemia (GVL) effects in an experimental murine model. Recipient (C57BL/6 x BALB/c) F1 mice were transplanted with C57BL/6 marrow and/or spleen cells and treated with daily sc injection of 5 micrograms heparin for 30 days. We have shown that heparin in low doses attenuates the severity of acute GVHD and reduces the mortality rate from 69 to 37.5% without abrogating the GVL effect induced by the allograft and without impairing marrow engraftment.

Acute Disease↗

[Evaluation of factors of female urinary incontinence and therapeutic indications].

A good understanding of the factors involved in female urinary incontinence is essential for the therapeutic management of incontinent women. Urinary stress incontinence involves three variables which participate in the pressure equilibrium during effort: mobility of the urethrovesical junction, urethral resistance and the intensity of effort. The most appropriate treatment for each patient can only be selected by investigating all three of these factors and by determining their respective roles in incontinence. Urge incontinence is also multifactorial, but, very often, no cause can be found on the aetiological assessment, leading to the diagnosis of idiopathic instability. The factors of detrusor motor instability are discussed and their aetiological treatment is proposed.

Biofeedback, Psychology↗

Continuous intravenous administration of rmGM-CSF enhances immune as well as hematopoietic reconstitution following syngeneic bone marrow transplantation in mice.

Lethally irradiated Balb/c mice injected with syngeneic bone marrow cells received recombinant murine granulocyte/macrophage colony-stimulating factor (rmGM-CSF) by continuous intravenous infusion for 4 days. When transplanted with 10(5) marrow cells, treated mice showed higher survival (62% compared with 30% in the control group, p < 0.001) and significantly enhanced hematopoietic recovery manifested by 11-fold increase in the peripheral white blood cell (WBC) count. Day 7 marrow from rmGM-CSF-treated mice resulted in 70% survival in lethally irradiated secondary recipients, while marrow harvested under identical experimental conditions from saline-treated mice had no reconstituting capacity at all. When mice were injected with 10(4) marrow cells, 20% of rmGM-CSF treated mice survived as compared with none in the controls. In vitro preincubation of 10(5) and 5 x 10(5) fresh bone marrow cells with rmGM-CSF prior to transplant significantly improved survival of lethally irradiated mice in comparison with control (12% and 37.5% respectively, p < 0.001). Proliferative responses of lymphocytes obtained from rmGM-CSF-treated mice to mitogens and allogeneic C57BL6 splenocytes as well as non-MHC restricted cytotoxicity against tumor cells were significantly higher in rmGM-CSF-treated mice as compared with controls (p < 0.01). These data suggest that a short course of continuous intravenous infusion of rmGM-CSF following BMT or in vitro culturing of bone marrow cells with rmGM-CSF improves marrow reconstituting capacity. The mechanism may be by enhancing proliferation and function of committed and perhaps even the more primitive progenitor cell.

Animals↗

[Endosonographic diagnosis of metastatic tumors in the recto-uterine or recto-vesical space by transrectal scan].

A 6-year experience of transrectal ultrasonography (TRUS) in 75 patients with advanced gastrointestinal cancers was reviewed regarding the diagnostic yield of metastatic extrarectal tumors. A diagnostic capability of TRUS (a sensitivity of 82.9%, a specificity of 97.5% and an accuracy of 90.7%) was statistically superior to that of digital rectal examination (a sensitivity of 62.9%, a specificity of 75% and an accuracy of 69.3%). However, TRUS could hardly correctly diagnose a miliary type of extrarectal tumors in contrast to nodular and thickened types. TRUS also had an advantage over conventional ultrasonography in detecting a small amount of ascites with a sensitivity of 75%, a specificity of 93% and an accuracy of 86.6%. Patients with positive signs of extrarectal tumors or ascites on TRUS survived significantly shorter than those with negative signs. TRUS renders a convenient means in the objective diagnosis of peritoneal carcinomatosis, and predicts patient's prognosis.

Adult↗

mRNA expression of cytokines and chemokines in the normal gastric surface mucous epithelial cell line GSM06 during bacterial infection with Helicobacter felis.

BACKGROUND AND AIM: A group of the proinflammatory and chemotactic cytokines (chemokines) has been considered as an important factor in the pathomechanism of different bacterial diseases, among them the common Helicobacter pylori infection. Experimental results obtained with gastric biopsy samples of H. pylori positive patients, and with H. pylori infected tumor originated gastric cell lines indicated that these cytokines have essential roles in the development and maintenance of the immune response and inflammation of the gastric mucosa during H. pylori infection. Although the mRNA expression was shown in these biopsy samples and cell lines, it is not yet proved that the normal gastric mucosal epithelial cells themselves express these cytokines. The establishment of a gastric surface mucous cell line with non-tumor origin (GSM06), and the usage of Helicobacter felis as a model of the classic H. pylori infection gave us the possibility to check this question. MATERIALS AND METHODS: in this study GSM06 cells were infected with different numbers (10(5), 10(6), 10(7), 10(8), 10(9) bacterium/ml medium) of H. felis for two different time periods (2, 4 h). Cells treated with medium only were used as control. Then the mRNA expression of the following cytokines was measured by RT-PCR method in the GSM06 cells: proinflammatory cytokine IL1-beta, and chemokine RANTES, eotaxin, MCP-1, MIP1-alpha and MIP1-beta. RESULTS: we found that neither mRNA of the investigated cytokines was expressed constitutively, however the GSM06 cells expressed the mRNA of each cytokine during H. felis infection. CONCLUSION: our results prove that normal gastric surface mucous epithelial cells express immunologically active peptides during H. felis infection. We may suppose that the epithelial cells of the gastric mucosa contribute to the immune response and inflammation by expressing proinflammatory (IL1-beta) and chemotactic (RANTES, eotaxin, MCP-1, MIP1-alpha and beta) cytokines during H. pylori infection in human.

Animals↗

Histopathological assessment of lymph node metastasis in patients with gastric cancer.

BACKGROUND/AIMS: Lymph node dissection has been carried out for two decades in Japan, resulting in improved survival of patients with gastric cancer. By analyzing dissected nodes of resected advanced gastric cancers, we intend to determine which parameter(s) are more concerned in node metastasis. PATIENTS AND METHODS: Curative gastrectomy with dissection of lymph nodes was performed for 78 of the 108 patients with advanced gastric cancer. Metastases were found in 171 of 1359 nodes (13%) dissected. In each node, the maximum and minimum diameters were measured, and the ratio of the former to the latter was calculated. RESULTS: The minimum diameter of node was closely related to node metastasis. When the minimum diameter in node metastatic criteria was "3 mm or more", a sensitivity of 81% and specificity of 54% were calculated. In false negative node, signet-ring cell carcinoma (SIG) (33%) and poorly differentiated adenocarcinoma (POR) (22%) were more frequently found as primary lesions. Half or more of these nodes were invaded by only a few carcinoma cells. When the primary lesion is histologically SIG or POR, endoscopic treatment is contraindicated for possible nodes metastasis. CONCLUSIONS: It is impossible to distinguish nodes with micrometastasis from nodes without metastasis. The minimum diameter of node is more important in node metastasis of gastric cancer than the maximum diameter of node or the ratio of both.

Adenocarcinoma↗

Clinical features of serologically non-B non-C chronic liver disease.

BACKGROUND/AIMS: To clarify the clinical features of serologically non-B non-C chronic liver disease (SNBNCLD). MATERIAL AND METHODS: Two hundred-eleven Japanese patients hospitalized for clinical manifestations associated with non-alcoholic chronic liver disease were tested by hepatitis B surface antigen (HBsAg) by reversed passive hemagglutination (RPHA) and the second generation hepatitis C antibody (HCVAb) by passive hemagglutination (PHA). RESULTS: Twenty-two patients (10.4%, 15 men and 7 women) were diagnosed as having SNBNCLD, evaluated clinically and compared with other close etiologies. Their clinical manifestations and severity of liver disease were similar to those of other etiologies. The average age was higher than hepatitis B (p < 0.001), primary biliary cirrhosis (PBC, p < 0.05), autoimmune hepatitis (AIH, p < 0.05) and hepatitis C. None of them had a history of blood transfusion before the onset. Concomitance of hepatoma was seen in 40.9%, being uncommon compared with hepatitis B (p < 0.01) and hepatitis C (p < 0.005). No significant difference of the survival rate was shown compared to other etiologies. HBsAb was more frequent (36.4%) than in hepatitis C (p < 0.05), and disappearance of HBsAg was seen in two hepatitis B patients during the follow-up period. CONCLUSION: Our data suggest that SNBNCLD is unique and important clinical entity associated with previous hepatitis B.

Aged↗