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H Mochizuki

Publications and source records attributed to H Mochizuki.

At least 163 records · Page 9Linked to original sources

Expression of cyclooxygenase-2 protein in gastric adenocarcinoma.

BACKGROUND AND OBJECTIVES: Epidemiological studies have suggested that the regular use of nonsteroidal antiinflammatory drugs, which inhibit cyclooxygenase (COX), reduces the risk of colon cancer. The inducible COX-2 isoform has been reported to be upregulated in colorectal carcinomas and may play a role in colorectal carcinogenesis. The purpose of this study was to investigate the expression of COX-2 protein in human gastric adenocarcinomas. METHODS: COX-2 protein expression was examined in 23 patients with gastric adenocarcinoma by immunoblotting and immunohistochemistry. RESULTS: There was an increase in COX-2 protein levels in 19 of the 23 carcinomas (83%) compared with the paired normal gastric mucosa by an immunoblot analysis. There was no correlation between tumor histology and COX-2 protein expression. An immunohistochemical study in the 19 cases showed diffuse COX-2 staining in the cytoplasm of cancer cells. Mononuclear cells or fibroblasts of the cancer stroma were not stained with COX-2. Sporadic staining for COX-2 was observed in the normal fundic or metaplastic glandular cells in all cases. CONCLUSIONS: COX-2 protein expression was elevated in most human gastric adenocarcinomas in comparison to the normal mucosa. COX-2 may therefore play an important role in gastric carcinogenesis.

Adenocarcinoma↗

Transcutaneous oxygen tension measurements during methacholine challenge of prematurity in infants with chronic lung disease.

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine inhalation challenge. Twelve infants with CLD and 22 age-matched children without respiratory diseases were enrolled in this study (ages--5 to 36 months; mean age--16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO2 had been reached (Dmin-PO2) was considered to represent the dose at which reactivity to methacholine (RO2meth) had occurred. In the CLD group, Dmin-PO2 (3.50 +/- 0.1 log x milli-units) was significantly lower than in the preterm control infant group (4.31 +/- 0.2 log x milli-units) and the term infant group (4.21 +/- 0.1 log x milli-units) (P = 0.004, P < 0.001). Dmin-PO2 in the preterm control infant group was not significantly different than in the term infant group (P > 0.5). These results suggest that infants who require additional therapeutic oxygen and mechanical ventilation during the early months of life are at risk of developing early-onset, long-lasting respiratory disease that is related to an acquired BHR.

Bronchial Hyperreactivity↗

Inhibitory effect of protease inhibitor on endothelial cell activation.

BACKGROUND: Endothelial cells (EC) are important for regulating the hemostatic balance of prothrombotic and antithrombotic activities. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha) play an important role in the regulation of EC and also regulate the production of plasminogen activator inhibitor type 1 (PAI-1), which is an EC-producing factor with the inhibitory activity of fibrinolysis, and the expression of intercellular adhesion molecule-1 (ICAM-1), which is an adhesion molecule that plays an important role in inflammation. Protease inhibitors such as gabexate mesilate (GM) and ulinastatin (UTI) have been shown to improve the microcirculatory environment and reduce tissue damage, but the mechanism for this has yet to be fully elucidated. We investigated the effect of GM or UTI on EC regarding PAI-1 synthesis and ICAM-1 expression. METHODS: Human umbilical vein endothelial cells (HUVECs) were obtained and stimulated with TNFalpha. GM or UTI was added to HUVECs just before TNFalpha stimulation. The PAI-1 activity in the culture medium of HUVECs was measured by using an enzymatic assay kit. The PAI-1 mRNA expression was assayed by a semiquantitative reverse transcriptase polymerase chain reaction assay. The ICAM-1 expression on HUVECs was assayed by a flow cytometric analysis. RESULTS: GM inhibited the PAI-1 synthesis of HUVECs stimulated with TNFalpha in a dose-dependent manner as shown by the mRNA expression. However, UTI was not able to inhibit PAI-1 synthesis. In contrast, both GM and UTI significantly inhibited the ICAM-1 expression on HUVECs stimulated with TNFalpha. CONCLUSIONS: These data suggest that GM may thus provide a beneficial effect which improves the microcirculatory environment and prevents tissue damage by inhibiting the activation of the vascular EC themselves.

Base Sequence↗

Prognostic significance of extranodal microscopic foci discontinuous with primary lesion in rectal cancer.

PURPOSE: The most common recurrence after curative resection of rectal carcinoma originates from tiny, undetectable residual foci within the pelvic cavity. The significance and methods used to predict the presence of extramural and extranodal microscopic cancer foci discontinuous with the main lesion of rectal cancers were investigated. METHODS: Four hundred twenty-seven patients who underwent resection of rectal carcinoma were studied. All resected specimens were examined for histologic evidence of extramural cancer separate from the main lesion. RESULTS: Extramural cancers not in continuity with the main rectal lesion were classified as follows: 1) extranodal microscopic cancers; 2) large tumor nodules; 3) lymph node metastases. Each classification was found to influence long-term prognosis. Among them, microscopic cancer was thought to be especially relevant because, by virtue of its microscopic nature, it may be left in the pelvic cavity, causing local recurrence. The existence of large tumor nodules and metastatic lymph nodes correlated closely with the presence of microscopic cancer. Because large tumor nodules and lymph node metastases are possibly detectable during the operation by palpation and may be analyzed by microscopic frozen sections, they might be useful predictors of the presence of microscopic cancers. CONCLUSIONS: In cases with extensive local rectal cancer spread, the nerve-sparing rectal resection that omits lateral dissection may be insufficient for local control because of incomplete removal of occult microscopic cancer, resulting in local recurrence. Presence of microscopic cancer correlates closely with large tumor nodules and metastatic lymph nodes. Intraoperative frozen section investigations may, thus, help in deciding on extent of location resection.

Adenocarcinoma↗

Intraperitoneal exfoliated cancer cells in patients with colorectal cancer.

PURPOSE: The aims of this study were to evaluate potential predictors of exfoliated free cancer cells in the peritoneal cavity and to assess intraoperative peritoneal lavage cytology as a prognostic indicator in patients with colorectal cancer. METHODS: From 1985 to 1987, intraoperative peritoneal lavage cytology was performed in 140 patients with colorectal cancer. Among them, 88 patients underwent curative resection and 52 patients had noncurative surgery. Cytology was examined twice, i.e., immediately after opening the peritoneal cavity (precytology) and just before closing the abdomen (postcytology). One hundred milliliters of saline was poured into the peritoneal cavity and it was retrieved by suction after irrigation. Cytologic examination was performed after staining with Papanicolaou, Giemsa, periodic acid-Schiff, and Alcian blue stains. RESULTS: Among the 140 patients examined, the incidence of positive cytology in the prelavage was 15 percent, and that in the postlavage was 9 percent, although it was 16 percent in either lavage. Among patients with curative resection, 10 percent had positive cytology. Seven characteristics were identified as features of tumors which are prone to exfoliate cells into the peritoneal cavity: 1) macroscopic peritoneal dissemination, 2) liver metastasis, 3) more than 20 ml of ascites, 4) ulcerated tumors without definite borders, 5) invasion of the serosal surface or beyond, 6) semiannular or annular shape, and 7) moderate or marked lymphatic invasion. In patients undergoing curative surgery, among these features, circumferential involvement was the only one correlated closely with positive cytology (P < 0.02). Positive cytology was associated with a worse outcome. In patients who were resected curatively, the postcytology had a stronger influence on local recurrence than the precytology; the local recurrence rate in patients with positive postcytology was higher than in those with negative postcytology, regardless of the precytology. All patients with cancer cells in the peritoneal cavity at the end of surgery had recurrence. CONCLUSIONS: Seven characteristics were identified as risk factors for exfoliation of cancer cells into the peritoneal cavity in patients with colorectal cancer. These findings may be helpful for the choice of laparoscopic surgery in this era of increasing port-site metastases after laparoscopic procedure. The results of peritoneal lavage cytology at the end of surgery were correlated with the long-term postoperative outcome of colorectal cancer. Thus, meticulous follow-up and possibly adjuvant chemotherapy may be beneficial for patients with free cancer cells in lavage fluid, even after curative surgery.

Adult↗

Carbonic anhydrase I and II as a differentiation marker of human and rat colonic enterocytes.

Carbonic anhydrase (CA) is an enzyme that is expressed in the intestine and catalyzes the reversible hydration of CO2 in the following reaction: CO2 + H2O<==>H2CO3<==>H(+)+HCO3-. To elucidate the association of CA expression with the differentiation of colonic enterocytes, we investigated the expression and localization of CA using a Northern blotting analysis, Western blotting analysis, and immunohistochemical staining. A Northern blotting analysis revealed an abundant expression of CA I and II mRNA in the colonic epithelial cells. However, the expression of CA III mRNA was not detected. According to the results of immunohistochemical staining of the human colonic mucosa using antisera against CA I and II, both CA I and II were localized on the cytoplasm of non-goblet columnar cells in the upper half of the crypts where more differentiated cells are located. According to the results of immunohistochemical staining of the rat colonic mucosa, neither CA I and II were detected at the new-born stage. The expression of CAs in the upper half of the crypts began to rise from 1 week after birth, and thereafter increased according to the growth of the rats. At 3 weeks after birth, the expression of CAs was almost the same as that of the adult rats. The amount of CA proteins evaluated by a Western blotting analysis revealed that the expression of CAs increased gradually until reaching a maximum level at 6 or 8 weeks. These results therefore suggest that CA I and II appear to be good markers for the differentiation of enterocytes in the colonic mucosa.

Animals↗

Relationship between nodal stage and the number of dissected perigastric nodes in gastric cancer.

To evaluate the rationality of the current nodal staging system in gastric cancer, we retrospectively analyzed 152 patients with perigastric node involvement localized to a single station, in whom the route of metastasis to distant nodes was limited. No significant differences in pathology or survival were observed between patients with stage n1 and those with stage n2-3 nodal involvement, but the mean (standard deviation) number of perigastric nodes dissected was 22.6 (12.6) in those with stage nl involvement and 18.5 (9.5) in those with stage n2-3 involvement (P = 0.04). When perigastric node involvement was localized to station 3, the mean number of dissected station 3 nodes was 7.7 (4.2) in nl patients and 5.3 (2.8) in n2-3 patients (P = 0.04). This tendency was also observed in patients with perigastric node involvement limited to either station 1 (P = 0.08) or station 6 (P = 0.11). Thus, patients with fewer perigastric nodes may have more lymphatics that bypass perigastric nodes and empty directly into distant nodes, increasing the likelihood of skip metastases. The number of positive nodes, affected to a lesser degree by lymphatic distribution than the location of positive nodes, should be incorporated into the staging criteria.

Adult↗

Cortico-cortical inhibition of the motor cortical area projecting to sternocleidomastoid muscle in normals and patients with spasmodic torticollis or essential tremor.

OBJECTIVES: To investigate whether the cortico-cortical inhibition originally reported for the human hand motor area is present in the motor cortex for sternocleidomastoid muscle (SCM) and to evaluate the amount of inhibition in spasmodic torticollis and essential tremor. METHODS: Subjects were 14 normal healthy volunteers, 10 patients with spasmodic torticollis and 5 with essential tremor involving neck muscles. A paired-pulse magnetic stimulation was performed for the SCMs and first dorsal interosseous muscles (FDIs). RESULTS: In normal subjects, a subthreshold magnetic conditioning stimulus suppressed responses to a suprathreshold magnetic test stimulus when their interval was 1-5 ms in SCM. This indicates that the similar cortico-cortical inhibitory mechanism is present in the motor cortex for SCM as in the hand motor area. In the patients with spasmodic torticollis, the cortico-cortical inhibitory effect was reduced or absent in SCM, but normal in the FDI. In contrast, in patients with essential tremor, normal cortico-cortical inhibition was seen in both the SCM and FDI. CONCLUSIONS: The cortico-cortical inhibitory mechanisms of the motor cortex for SCM can be studied by a paired-pulse magnetic stimulation method. Our result of reduced cortico-cortical inhibition in torticollis patients suggests abnormal excitability (hyperexcitable or disinhibited) of the motor cortex for SCM in spasmodic torticollis.

Adult↗

Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation.

BACKGROUND: Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation. OBJECTIVE: We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation. METHODS: Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways. RESULTS: A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control animals and those sensitized and challenged for 3 weeks at all airway levels. CONCLUSION: Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.

Administration, Inhalation↗

Fluorophotometric measurement of the buffering action of human tears in vivo.

PURPOSE: The buffering action of human tears is thought to be important to keep its pH constant. We measured the change in pH in the precorneal tear film in vivo when the acidic solution is challenged, using a fluorophotometric technique. METHODS: Twelve eyes from 6 healthy subjects were entered in this study. Each subject was pretreated with either one drop of 0.4% oxybuprocaine for once (light anesthesia), three times (deep anesthesia), or none (controls). The measurement was initiated by instilling 20 microl of 0.067 M phosphate buffer at pH 5.5 containing 2 mM bis-carboxyethyl-carboxyfluorescein free acid, a pH sensitive dye, into the subject's eye. The pH was determined by the ratio of fluorescent intensities at two excitation wavelengths (490 and 430 nm). pH recovery time (PHRT) as defined by the time required for pH to reach 95% of pH at equilibrium was used for the marker of tear buffering action. Tear turnover rate was also determined using the fluorescent decay curve at 430 nm, which was independent of pH, but dependent on dye concentration. RESULTS: Immediately after the instillation, the pH value in the tear film was around 6.0-6.5 in all cases. The tear film rapidly became more alkaline, reaching its normal value in 2.3 +/- 0.5 min in untreated eyes. The pretreatment with 0.4% oxybuprocaine retarded the neutralization process. A single regression analysis revealed that the PHRT had a significant negative correlation with the tear turnover rate (r = -0.78). CONCLUSIONS: Our results suggest that the neutralization process of tears largely depends on the tear turnover rate. The buffering action of tears in vivo consists of the tear turnover as well as its chemical buffering capacity.

Acid-Base Equilibrium↗

Role of liver NK cells and peritoneal macrophages in gamma interferon and interleukin-10 production in experimental bacterial peritonitis in mice.

Gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-10 (IL-10) production by liver, spleen, lung, peripheral blood mononuclear cells (MNC), and peritoneal exudate cells (PEC) in experimental bacterial peritonitis was examined by cecum ligation and puncture (CLP) (with an 18-gauge needle) of BALB/c mice. MNC of organs were cultured for 18 h, and cytokine levels in supernatants were examined. Cytokines contained in peritoneal lavage fluid were regarded as those produced by PEC. Only liver MNC and PEC produced substantial amounts of IFN-gamma, and PEC were the main source of IL-10, especially 12 h after CLP. As reflected by the cytokine production by liver MNC and PEC, serum IFN-gamma and IL-10 levels were elevated after CLP. C57BL/6 (B6) mice and BALB/c nude mice showed a similar pattern of cytokine production. TNF-alpha levels in culture supernatants, peritoneal lavage fluid, and sera were not significantly elevated compared to those of sham-operated mice. In vivo depletion of NK cells of B6 mice with anti-asialo GM1 or anti-NK1.1 antibody greatly decreased IFN-gamma levels in liver MNC culture supernatants and sera, suggesting that liver NK cells are IFN-gamma producers. On the other hand, plastic-adherent PEC macrophages are the major IL-10 producers. Mice subjected to a cecum ligation and cut procedure (which have a more severe peritonitis) showed much higher IFN-gamma and IL-10 levels than those subjected to CLP, while mice subjected to CLP with a smaller (22-gauge) needle showed low levels of these cytokines. These findings show that liver NK cells and PEC macrophages are important for the production of proinflammatory and anti-inflammatory cytokines in bacterial peritonitis.

Animals↗

High-titer human immunodeficiency virus type 1-based vector systems for gene delivery into nondividing cells.

Previously we designed novel pseudotyped high-titer replication defective human immunodeficiency virus type 1 (HIV-1) vectors to deliver genes into nondividing cells (J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, S. Karlsson, and M. Schubert, Proc. Natl. Acad. Sci. USA 93:15266-15271, 1996). Since then we have made several improvements with respect to the safety, flexibility, and efficiency of the vector system. A three-plasmid expression system is used to generate pseudotyped HIV-1 particles by transient transfection of human embryonic kidney 293T cells with a defective packaging construct, a plasmid coding for a heterologous envelope (Env) protein, and a vector construct harboring a reporter gene such as neo, ShlacZ (encoding a phleomycin resistance/beta-galactosidase fusion protein), HSA (encoding mouse heat-stable antigen), or EGFP (encoding enhanced green fluorescent protein). The packaging constructs lack functional Vif, Vpr, and Vpu proteins and/or a large portion of the Env coding region as well as the 5' and 3' long terminal repeats, the Nef function, and the presumed packaging signal. Using G418 selection, we routinely obtained vector particles pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) with titers of up to 8 x 10(7) CFU/microgram of p24, provided that a functional Tat coding region was present in the vector. Vector constructs lacking a functional Tat protein yielded titers of around 4 x 10(6) to 8 x 10(6) CFU/microgram of p24. Packaging constructs with a mutation within the integrase (IN) core domain profoundly affected colony formation and expression of the reporter genes, indicating that a functional IN protein is required for efficient transduction. We explored the abilities of other Env proteins to allow formation of pseudotyped HIV-1 particles. The rabies virus and Mokola virus G proteins yielded high-titer infectious pseudotypes, while the human foamy virus Env protein did not. Using the improved vector system, we successfully transduced contact-inhibited primary human skin fibroblasts and postmitotic rat cerebellar neurons and cardiac myocytes, a process not affected by the lack of the accessory proteins.

Animals↗

Quantitative analysis of lipid deposits from Schnyder's corneal dystrophy.

AIM: To report the quantitation of the lipid composition of a corneal button from a Japanese woman in her 60s with clinically and histopathologically proved Schnyder's corneal dystrophy. METHODS: Total lipids extracted from the corneal button of the patient were analysed by the method of thin layer chromatography flame ionisation detection. Two different solvent systems were used for neutral lipid analysis and phospholipid analysis. Results were compared with three age matched corneal buttons obtained from cadaveric eyes. RESULTS: The lipids that accumulated in the cornea in Schnyder's dystrophy consisted mainly of unesterified cholesterol and phospholipids. The analysis of phospholipids showed sphingomyelin to be the predominant phospholipid in the patient's cornea. CONCLUSION: Findings suggest that this disorder involves a disturbance of the metabolism of cholesterol and/or sphingomyelin metabolism that is limited to the cornea.

Cholesterol↗

Increasing effect of dietary taurine on the serum HDL-cholesterol concentration in rats.

Taurine, 2-amino ethanesulfonic acid, is the major free intracellular amino acid present in many tissues and plays an important role in lipid metabolism such as that of bile acid conjugation for fat absorption. The effect of taurine on the serum cholesterol level in normal rats was investigated. Taurine enhanced the serum HDL-cholesterol concentration in a dose-dependent manner without any change in total cholesterol.

Animals↗

Autosomal dominant familial hypoparathyroidism and sensorineural deafness without renal dysplasia.

OBJECTIVE: A family is described which has a unique combination of autosomal dominant hypoparathyroidism and sensorineural deafness without renal dysplasia. CASE REPORT: The proband was a male infant aged 1 month with episodes of seizures for 20 days. He was born at 35 weeks' gestation without asphyxia, weighing 2040 g. His initial calcium, phosphorus and percentage of tubular reabsorption of phosphorus were 6.8 mg/dl (normal range 8.5-10.5 mg/dl), 8.9 mg/dl (normal range 5.5-7.4 mg/dl) and 96.8% (normal range 85-95%) respectively. He had normal values for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D. No abnormalities were found by renal imaging and a routine renal function study. He showed a brisk plasma cAMP increase in response to human PTH-(1-34) infusion. He had normal karyotype 46, XY, without a microdeletion in chromosome 22q11.2 by an in situ hybridization method. Five family members were affected with hypoparathyroidism with sensorineural deafness with autosomal dominant transmission. The study of calcium-sensing receptor and preproPTH gene showed a normal DNA sequence. CONCLUSION: The combination of familial hypoparathyroidism with sensorineural deafness without renal dysplasia is novel and the cause may be distinct from previously reported familial hypoparathyroidism with sensorineural deafness and renal dysplasia.

Adult↗