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Biomedical subjects

H Ishikawa

Publications and source records attributed to H Ishikawa.

At least 37 records · Page 2Linked to original sources

Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma.

BACKGROUND AND AIM: Recent studies indicated that hepatic stem cells in the bone marrow could differentiate into mature hepatocytes, suggesting that bone marrow cells could be used for replacement of damaged hepatocytes in a variety of liver diseases. Hepatocellular carcinoma (HCC) is thought to arise from hepatic stem cells. In this study, we investigated the malignant potential of hepatic stem cells derived from the bone marrow in a mouse model of chemical hepatocarcinogenesis. METHODS: Bone marrow cells were obtained from the male beta-galactosidase (beta-gal) transgenic mouse and transplanted into female recipient mice. Hepatocarcinogenesis was induced by a year of treatment with diethylnitrosamine and phenobarbital (NDEA/PB). One year later, the liver was removed from each treated mouse and evaluated by x-gal staining, immunohistochemistry, and fluorescence in situ hybridisation (FISH). RESULTS: Forty per cent of recipient mice survived and developed multiple HCC. Clusters of beta-gal positive mature hepatocytes were detected sporadically in the entire liver of NDEA/PB treated mice who underwent bone marrow transplantation (BMT) with while no such hepatocytes were identified in the liver of BMT mice that were not treated with NDEA/PB. The Y chromosome was detected with the same frequency as the donor male liver in clusters of beta-gal positive mature hepatocytes by FISH. However, no HCC was positive for beta-gal or the Y chromosome. Immunohistochemically, beta-gal positive mature hepatocytes did not express CD34 or alpha-fetoprotein. CONCLUSIONS: Our results suggest that hepatic stem cells derived from the bone marrow have low malignant potential, at least in our model.

Animals↗

Role of intestinal bacterial flora in oral tolerance induction.

In healthy individuals, the immune responses against foods cannot be induced. This phenomenon is known as oral tolerance. We observed that the oral tolerance was impaired in germfree mice, and that Th2-dependent antibodies such as IgE could be thus induced by an orally given antigen. As a result, the germfree mouse was considered to be a good animal model for allergic disorder. When germfree mice were mono-associated with such bacteria as E.coli and B. infantis, then oral tolerance was restored in these gnotobiotes to a level similar to that observed in SPF mice. Thus, these bacterias seemed to be important in oral tolerance induction. In addition, the probiotics using these bacteria may be a useful material for the treatment of allergic disorders.

Administration, Oral↗

Outcome of 51 nonmalignant nodules in the liver: usefulness of aspiration cytology for diagnosis of dysplastic nodules.

Pathologic diagnostic criteria for intrahepatic nonmalignant nodules using needle biopsy are controversial. To evaluate the cytodiagnostic criteria for dysplastic nodules using aspiration biopsy, a follow-up study of nonmalignant nodules was performed. Fifty-one intrahepatic nodules diagnosed histologically and cytologically as nonmalignant using an aspiration biopsy in 39 patients were followed up without treatment. The outcomes of the nodules were investigated using the Kaplan-Meier method and Cox's multivariate analysis. The cumulative rates of development to HCC at the 2nd year were 0%, 18%, and 53% in the non-dysplastic nodules, the low-grade dysplastic nodules, and the high-grade dysplastic nodules, respectively; and significant differences were seen among them (P= 0.0001). Multivariate analysis showed that cytologic grade was a significant risk factor for development to HCC (P=0.020). In conclusion, aspiration cytology was useful for diagnosis of the dysplastic nodules to predict risks of development to HCC.

Adult↗

Gasless, video endoscopic transanal excision for carcinoid and laterally spreading tumors of the rectum.

BACKGROUND: The aim of this study is to determine whether gasless, video endoscopic transanal-rectal tumor excision (gasless VTEM) is a valid treatment for rectal carcinoid and laterally spreading tumors (LST). METHODS: Eighty-four patients with an adenoma, adenocarcinoma (Tis/T1), or carcinoid tumor of the rectum were divided into three groups: (i) LST ( n = 17 patients), (ii) carcinoid ( n = 11), and (iii) control with other types of tumors ( n = 56). RESULTS: The LST group had a longer median operating time than in the control group, whereas the carcinoid group had a shorter operating time. Two patients (11.7%) in LST group developed peritoneal entry during the operation, while 2 patients (3.6%) in the control group experienced postoperative complications. During a median follow-up length of 55.2 months, one patient in the LST group developed a recurrence. CONCLUSIONS: Gasless VTEM is a simple, minimally invasive procedure used to treat LST and carcinoid tumors of the rectum. However, resection for the LST group had a high risk of peritoneal entry during operation.

Adenocarcinoma↗

HnRNP A2/B1 proteins in nontumorous alveolar cells.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1, had been reported to detect preclinical lung cancer for early detection. In order to examine whether the expression of the protein is specific for lung cancer, we investigated the expression of the protein in human nonmalignant alveolar cells. Human airway cells obtained by bronchoalveolar lavage (BAL) were analyzed by immunostaining and Western blotting using monoclonal antibodies 4G8 (specifically reacts to A2) and 2B2 (specific to B1). In alveolar cells obtained by BAL, hnRNP A2/B1 proteins were localized primarily in the nucleus, excluding the nucleolus, although the expression of A2 protein was weaker than that of B1 protein. Staining pattern of these cells was similar to those observed in cancer cells. Western blotting with 4G8 and 2B2 demonstrated expression of A2 and B1 proteins in the airway cells. HnRNP A2/B1 proteins were apparently expressed in nonmalignant alveolar cells as well as cancer cells, although the expression in alveolar cells was weaker than that of cancer cells. More quantitative determination of A2/B1 is required to elucidate their significance in early lung cancer detection.

Adult↗

Significantly lower rate of smoking in female compared to male patients with lung adenocarcinoma.

To examine the relationship between smoking and lung adenocarcinoma in female patients, we performed a retrospective chart review for 470 patients with lung adenocarcinoma at our hospital. The proportions of non-smokers were higher in female patients than those of male patients. A significant difference in smoking history was found between female and male patients. Not only active smoking but also passive smoking may influence the development of female lung adenocarcinoma, which reinforces the need for effective programmes aimed refraining from smoking and cessation among men as well as women.

Adenocarcinoma↗

Evaluation of root-end cavity preparation using ultrasonic retrotips.

AIM: To evaluate and compare the efficiency of root-end preparations using ultrasonic retrotips coated with diamond and zirconium nitride. METHODOLOGY: Eighty-five extracted single-rooted teeth were root filled, and then resected 3 mm from their apices. Root-end cavities were prepared with KiS (zirconium nitride-coated retrotip), CT-5 (stainless steel tip) or diamond-coated (DC) ultrasonic retrotips, and 10 teeth served as controls. Thirty teeth were used for evaluation of the time required to prepare the root-end cavity, the number of microcracks produced on the resected surface and the number of dentinal tubule openings on the root-canal wall using scanning electron microscope (SEM) images. A further 55 teeth were used for evaluation of dye penetration following filling of the root-end cavities with Super EBA. The degree of dye penetration in millimetres was measured under the microscope after 7 days of immersion in India ink. Statistical analyses were performed using the one-way ANOVA and Scheffe's F-test as the post hoc test. RESULTS: There was no significant difference in the number of microcracks and dentinal tubule openings present in the root apices prepared by the three retrotips. The time required for root-end cavity preparation using the DC retrotip was significantly less than that using the other groups (P<0.01). Positive controls showed dye penetration throughout the length of the root-end cavity, and negative controls showed no dye penetration. There was no significant difference between the three experimental groups in dye penetration. CONCLUSIONS: In this laboratory study, the time required to prepare root-end cavities using KiS retrotips was the same as that using CT-5 retrotips, and longer than that using DC retrotips. There was no significant difference in the number of microcracks or dye penetration between the three kinds of retrotips.

Analysis of Variance↗

The role of cryptopatch-derived intraepithelial lymphocytes in the development of chronic ileocecitis.

Lympho-haemopoietic progenitors residing in murine gut cryptopatches (CPs) have been shown to generate intestinal extrathymic intraepithelial lymphocytes (IELs). However, the role of CPs in the development of intestinal inflammation remains unclear. To investigate the role of CPs in the development of intestinal inflammation, we examined SAMP1/Yit mice, which spontaneously develop a chronic intestinal inflammation localized to the terminal ileum and cecum. Here, we showed the sharp correlation between the disease onset and the decreased number of CPs, resulting in decreased number of both thymus-independent IELs including T-cell receptor gammadelta+ (TCRgammadelta+) and CD8alphaalpha+TCRalphabeta+ cells but not thymus-dependent CD8alphabeta+TCRalphabeta+ and CD4+TCRalphabeta+ cells in SAMP1/Yit mice. These data provide the first suggestion that thymus-independent IELs derived from CP might play protective role against the onset and the development of intestinal inflammation.

Animals↗

Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice.

MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut-associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/- and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed. However, PPs in 2-week-old MyD88-/- mice were significantly smaller than those in MyD88+/- mice. Also, in 2-week-old TLR4-/-, but not TLR2-/- mice, PPs did not develop rapidly. The development of PPs in MyD88-/- and TLR4-/- mice was completely recovered in 10 weeks. PP cells from MyD88-/- mice showed significant decrease in proliferation when stimulated with lipopolysaccharide. The development of CP and IEL was also normal in 10-week-old MyD88-/- mice. These results suggest that the TLRs/MyD88 pathway might be involved in the development of PPs only at early postnatal stage, and TLRs/MyD88-independent signalling is critically involved in the development of GALT in adult mice.

Adaptor Proteins, Signal Transducing↗

Bone metastasis as the first manifestation of lung cancer.

Bone metastasis usually occurs late in the course of the disease, but in some patients it is the first manifestation of lung cancer. To evaluate the characteristics of patients with bone metastasis as a first manifestation of lung cancer, the medical records of 1063 patients with lung cancer between 1976 and 2001 were reviewed retrospectively. Twenty-four (2.3%) lung cancer patients presented symptoms of bone metastasis as a first manifestation; 11 patients had bone metastasis as the only site of spread in lung cancer; 16 had adenocarcinoma; five had a primary lesion <30 mm, and nine had N0-1 disease. Patients with sole bone metastasis did not have a more favourable survival rate than patients with bone and other systemic metastases (p=0.2938). Whether metastasis is the first manifestation of lung cancer or not, the occurrence of bone metastasis generally means a poor prognosis.

Adenocarcinoma↗

Development of a high-efficiency phosphorus recovery method using a fluidized-bed crystallized phosphorus removal system.

The authors have been engaged in the research and development concerning the recovery of MAP (Magnesium Ammonium Phosphate) using a fluidized-bed crystallized phosphorus removal system. In the reactor of the fluidized-bed crystallized phosphorus removal system, seed crystals (of MAP) are fluidized previously and new MAP crystals are produced on the seed crystal surfaces. Conventionally, the reactor consisted of one reaction tank only, but this practice had the problem that as the crystallization progresses, the seed crystal is grown excessively and as a result, the effective reaction surface areas are decreased and the fluidization effect is degraded, causing the recovery ratio to be decreased. Recently, the authors have devised a two-tank type reactor by adding a sub reaction tank to the reactor (now the main reaction tank) so that the MAP particle size in the main reaction tank may be kept constant making the recovery ratio stable. They conducted a demonstration test with a pilot experimental system of the 2-tank type reactor. For raw water T-P 111 to 507 mg/L, the main reaction tank treated water T-P 14.0 to 79.5 mg/L and phosphorus recovery ratios 84 to 92% were obtained. Because the mean MAP particle size in the main reaction tank could be kept constant, the phosphorus recovery ratio could always be above 80%, realizing stable treatment.

Bioreactors↗

Ullrich disease: collagen VI deficiency: EM suggests a new basis for muscular weakness.

Ullrich disease is a form of congenital muscular dystrophy characterized clinically by generalized muscle weakness, contractures of the proximal joints, and hyperflexibility of the distal joints from birth or early infancy. Recently, mutations of the collagen VI gene have been associated with Ullrich disease. The authors report on a boy with Ullrich disease who has complete deficiency of collagen VI and harbors compound heterozygous mutations in the collagen VI alpha 2 gene. Absence of microfibrils on EM, together with normal collagen fibrils and basal lamina, suggests that loss of a link between interstitium and basal lamina may be a new molecular pathomechanism of muscular dystrophy.

Child, Preschool↗

Effects of human recombinant calcitonin on a rat osteopenia model induced by TPTX and arotinoid.

Recombinant human calcitonin (rh-CT) has been developed as an agent for patients with excessive bone resorption to replace calcitonins from animal species, which are associated with tolerance problems. In this study, inhibitory effects of rh-CT against bone resorption were examined in thyroparathyroidectomized (TPTX) rats, the animal model of accelerated bone resorption induced by administering a synthetic retinoid (arotinoid). The arotinoid-treated TPTX rats exhibited signs of stimulated bone resorption, such as hypercalcemia, reduced bone mineral density, and inferior bone strength. Significant improvements were seen in all of these changes after a daily treatment with rh-CT (30, 300 U/kg s.c.) for 1 week. A histomorphometrical analysis showed that the treatment with rh-CT markedly suppressed the reduction of trabecular bone volume and that of cortical thickness in the femur of arotinoid-treated TPTX rats. These results suggest that rh-CT may prevent osteopenia caused by accelerated bone resorption.

Animals↗

Expression of ABH/Lewis-related antigens as prognostic factors in patients with breast cancer.

PURPOSE: The prognostic value of altered blood group factor and Lewis-related carbohydrate antigen expression in breast cancers has not been fully determined. METHODS: To this end, breast carcinoma samples from 87 radical mastectomy patients with primary cancer were analyzed by immunohistochemistry for the ABH factors, Le(a), sialyl Le(a), Le(x), and sialyl Le(x). RESULTS: It was found that ABH, Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens were expressed in 25 (21.8%), 26 (22.6%), 26 (22.6%), 36 (31.3%), and 37 specimens (32.2%), respectively. Tumors with lymph node metastasis expressed Le(x) or sialyl Le(x) antigens more frequently than those without lymph node metastasis ( P=0.0020 or P=0.039, respectively). The survival time of patient s after surgery was significantly shorter for those whose tumors expressed Le(x) or sialyl Le(x) than for those without Le(x)- or sialyl Le(x)-positive tumors ( P=0.0028 and P=0.0029, respectively). Cox's multiple regression analysis revealed that sialyl Le(x) expression was an independent prognostic factor for patient survival regardless of primary tumor (T factor) and lymph node (N factor) status (hazards ratio, 3.80). CONCLUSIONS: Thus, expression of sialyl Le(x) antigen in tumor cells is associated with poor prognosis in patients with breast cancer and must be considered in the design of future therapeutic trials.

ABO Blood-Group System↗

Comparison of gastroduodenal, renal and abdominal fat biopsies for diagnosing amyloidosis in rheumatoid arthritis.

The aim of the study was to determine the frequency of amyloidosis detected by gastroduodenal biopsy in rheumatoid arthritis (RA) patients, and to investigate correlations between the results of gastroduodenal biopsy and abdominal fat and renal biopsies. A total of consecutive 1006 RA patients underwent gastroduodenal biopsy. The 71 patients who tested positive for gastrointestinal (GI) amyloidosis were asked to undergo renal and abdominal fat biopsies, and 21 did so. Renal biopsies were also performed on 12 patients with no amyloidosis but indicators of drug-induced renal damage, and abdominal fat biopsies were performed on 50 RA patients with no indication of amyloidosis. The prevalence of GI amyloidosis was 7.1%. Urinary abnormalities and GI symptoms were common in GI amyloidisis, and inflammatory markers were elevated. Sixty-one (86%) had either depressed creatinine clearance or urinary symptoms. Nineteen of the 21 patients (91%) with GI amyloidosis who underwent renal biopsies also had renal amyloid deposits. Eleven of the 21 (52%) had amyloidosis on abdominal fat biopsy. None of the 12 patients without GI amyloidosis had renal amyloidosis on renal biopsy, and none of the 50 patients without GI amyloidosis had amyloidosis on abdominal fat biopsy. Gastroduodenal biopsy reveals a high prevalence of amyloidosis in RA patients. Amyloidosis is often associated with signs of renal impairment. Results of GI biopsy are highly correlated with those of renal biopsy, but the results of fat biopsy are not. We recommend GI biopsy for RA patients for the screening of systemic amyloidosis.

Abdominal Wall↗

Interleukin-2 levels are elevated in the bone marrow serum of patients with mutilans-type rheumatoid arthritis.

In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients and cytokine levels measured. The serum levels of five cytokines (IL-1beta, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly higher in all RA patients than in those with OA. Mean (+/-SD) IL-2 levels were significantly higher in patients with mutilans-type RA (309.8+/-686.3 pg/ml) than in patients with other types of RA (66.5+/-173.1 pg/ml; P<0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of RA (P < 0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables were no different between mutilans RA and other types of RA. No correlations were observed between IL-1beta, IL-2, IL-3, IL-6 and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related to systemic inflammation, as there was no correlation with other inflammatory factors.

Aged↗

Surgical technique and outcome of gasless video endoscopic transanal rectal tumour excision.

BACKGROUND: Transanal endoscopic microsurgery (TEM) is unpopular because of its high cost and most surgeons' unfamiliarity with microscopic surgery. This report describes an experience with a modification of TEM, gasless video endoscopic transanal rectal tumour excision (gasless VTEM), which incorporates a standard laparoscopic video camera and requires no carbon dioxide insufflation system. METHODS: One hundred and one patients with 105 rectal tumours underwent gasless VTEM between 1993 and 2000. RESULTS: Histological examination revealed 18 adenomas, 75 carcinomas (Tis, 47; T1, 23; T2, five), 11 carcinoid tumours and one lymphoma. The median height above the dentate line and maximum tumour diameter was 5.0 (range 2-14) cm and 2.0 (range 0.4-8.0) cm respectively. The peritoneal cavity was opened intraoperatively in two patients. The median operating time was 53 (range 15-202) min. Bleeding, suture dehiscence and transient incontinence developed after operation in four patients. There was no operative death. Median hospital stay was 5 (range 1-21) days. Eleven patients with T1/T2 staging underwent subsequent radical resection. The median duration of follow-up was 52.3 months. One patient with a carcinoma developed a recurrence. CONCLUSION: Gasless VTEM is a feasible, safe and minimally invasive procedure for the treatment of selected rectal adenomas and early carcinomas. The suggested modifications may make the procedure more widely available.

Adenocarcinoma↗