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Biomedical subjects

H Mochizuki

Publications and source records attributed to H Mochizuki.

At least 109 records · Page 6Linked to original sources

Clinical significance of telomerase activity in biopsy specimens of gastric cancer.

Telomerase has been reported to be activated in most immortal cells and human cancers. The purpose of this study was to assess the clinical significance of telomerase activity in biopsy specimens of gastric cancer. Telomerase activity in endoscopic biopsy specimens obtained preoperatively from 31 patients with gastric cancer was determined semiquantitatively using the telomeric repeat amplification protocol assay, a polymerase chain reaction-based assay. Cancer tissues had significantly higher telomerase activity than adjacent normal tissues (13.9 +/-2.0% vs. 7.0 +/- 0.8%; p < 0.05). The ratio of the telomerase activity in cancer tissues to that in normal tissues (telomerase index) was significantly higher in tumors invading the proper muscle layer or deeper or in tumors with moderate or marked lymphatic invasion than in tumors without these invasive factors (4.7 +/- 1.4 vs. 1.1 +/- 0.1 for depth of invasion and 4.4 +/- 1.3 vs. 1.2 +/- 0.2 for lymphatic invasion; p < 0.05 for both). These results suggest that the analysis of telomerase activity in biopsy specimens might contribute to preoperative assessment of the invasive activity or stage of gastric cancer.

Adult↗

Neutrophils mediate acute lung injury in rabbits: role of neutrophil elastase.

We investigated the roles of neutrophil and neutrophil elastase in acute lung injury (ALI) to elucidate the mechanism of ALI. We designed two protocols. Protocol I: Experimental ALI was induced by endotoxin (0.02 mg/kg) and platelet-activating factor (8 microg/kg/4 h) in untreated rabbits (control group I), in neutropenic rabbits pretreated with nitrogen-N-oxide hydrochloride, and in untreated rabbits infused with a neutrophil elastase inhibitor (ONO-5046; 20 mg/kg/4 h). Protocol II: ALI was induced by smaller doses of endotoxin (0.015 mg/kg) and platelet-activating factor (7 microg/kg/4 h) than those used in protocol I in untreated rabbits (control group II), in neutrophilic rabbits pretreated with human recombinant granulocyte colony-stimulating factor, and in neutrophilic rabbits infused with ONO-5046 (as in protocol I). The severity of ALI was assessed by the protein concentration, the elastase activity in the bronchoalveolar lavage fluid, and the histologic pulmonary edema ratio. The degree of pulmonary neutrophil accumulation was assessed by pulmonary myeloperoxidase activity and histological findings. Both ALI and pulmonary neutrophil accumulation were suppressed by neutropenia (protocol I), while they were exacerbated by neutrophilia (protocol II). The neutrophil elastase inhibitor could suppress ALI, but it could not suppress pulmonary neutrophil accumulation in both untreated and neutrophilic rabbits (protocols I and II). These findings indicate that neutrophils play an important role in the pathogenesis of ALI via neutrophil elastase.

Acute Disease↗

Amplifying effect of dietary taurine on the induction of cytochrome P-450 and on the urinary excretion of ascorbic acid in rats fed on phenobarbital-containing diets.

Dietary taurine amplified the induction of cytochrome P-450 and the urinary excretion of ascorbic acid in rats fed on phenobarbital (PB)-containing diets. These facts suggest that taurine could influence the hepatic metabolism of xenobiotics via the induction of drug-metabolizing enzymes (DME) and the ascorbic acid metabolism. Taurine might improve the function of DME exposed by some xenobiotics.

Animals↗

Bronchial hyperresponsiveness before and after the diagnosis of bronchial asthma in children.

OBJECTIVE: To assess at what age bronchial hyperresponsiveness (BHR) is acquired in children with asthma. BACKGROUND: A relationship between BHR and infantile wheezing diseases has been reported. Infants with a genetic predisposition to atopy are more likely to wheeze with respiratory viral infection or bronchiolitis, and it is suspected that the continued BHR after the first attack of asthma may be induced or triggered by some viral infections. Also, recent studies have reported the existence of atopic and BHR-related genes. However, whether BHR is congenital or acquired after asthma attacks, and when BHR in children with asthma is established or acquired remain unclear. METHODS: We performed methacholine inhalation challenge using a transcutaneous oxygen pressure (tcPO(2)) monitoring system in 205 children without asthma from 6 months to 6 years of age. During follow-up, 18 of these participants were diagnosed with asthma (group N-A). This group and 15 age-matched children without asthma (group N-N) were tested twice using methacholine inhalation challenge. For comparison, 39 age-matched atopic-type asthmatic children (group A-A) were also given the inhalation challenge twice. Methacholine inhalation challenge using a tcPO(2) monitoring system was performed while the participants were asleep in the supine position. Sequential doses of inhaled methacholine delivered by oxygen mask were doubled until a 10% decrease in tcPO(2) from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO(2) (minimal dose of methacholine [Dmin]-PO(2)) was considered to represent BHR. RESULTS: In groups N-N and A-A, there was no difference in Dmin-PO(2) between the first and second challenge. However, the Dmin-PO(2) in group N-A significantly decreased from the first challenge to the second challenge. There was no significant difference between the Dmin-PO(2) in group N-N and the first Dmin-PO(2) in group N-A; or between the Dmin-PO(2) in group A-A and the second Dmin-PO(2) in group N-A. CONCLUSIONS: These data suggest that BHR in many infants with asthma is acquired after several asthma attacks.bronchial hyperresponsiveness, childhood asthma, methacholine inhalation challenge, transcutaneous oxygen pressure.

Asthma↗

Persistence of hepatitis B surface antibody levels after vaccination with a recombinant hepatitis B vaccine: a 3-year follow-up study.

We conducted a 3-year follow-up study of 2,008 individuals for the persistence of antibody levels after vaccination with a recombinant hepatitis B vaccine. At 1 month after vaccination had been completed 96.3% of subjects had acquired protective HB surface (HBs) antibody titers on passive hemagglutination assay (PHA) of 2, and 3 years after completion of the vaccination 63.1% had acquired similar titers. The titer decreased below this level after 3 years in 34.5% of subjects who had initially acquired protective antibody titers. The mean acquired HBs antibody titer on PHA was 2 at 1 month and 2 at 3 years after completion of the vaccination. The regression line for these changes was expressed as logY = 1.800-0.24X by the least squares method. The antibody level was estimated to decrease to 2 at 37 months and to seronegativity at 75 months. On the basis of the relationship between PHA antibody titers and the period of their persistence, the persistence of antibody levels after vaccination with a recombinant vaccine can be estimated from the acquired antibody titer determined 1 month after completion of the vaccination, as with plasma-derived vaccines.

Adult↗

Urokinase type plasminogen activator and its receptor regulate the invasive potential of gastric cancer cell lines.

To assess the role of urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) on the invasive potential of cancer cells, in vitro experiments were performed using two human gastric cancer cell lines, NUGC-3 and MKN-28. NUGC-3 cells secreted a higher level of uPA than MKN-28 cells, while the uPAR expression of NUGC-3 cells was lower than that of MKN-28 cells. Both cancer cell lines expressed Met protein and did not express hepatocyte growth factor (HGF). In Matrigel invasion assay, MKN-28 cells demonstrated significantly lower invasion index than NUGC-3 cells. The addition of exogenous uPA significantly increased the invasive activity of MKN-28 cells. The uPA expression in NUGC-3 cells was enhanced by adding conditioned media of fibroblast cells or HGF. These results suggest that uPA promotes the invasive capacity of the uPAR-positive cancer cells, and that stromal cells may play an important role in cancer cell invasion by supplying uPA and/or promoting uPA production.

Adenocarcinoma↗

Atherosclerotic plaques composed of a large core of foam cells covered with thin fibrous caps in twice-injured carotid arterial specimens obtained from high cholesterol diet-fed rabbits.

We attempted to find atherosclerotic plaques including a large lipid core and thin fibrous cap in twice-injured arterial specimens obtained from high cholesterol diet (HCD) fed rabbits. Rabbits fed a HCD were subjected to carotid artery injury using a balloon catheter. After 2 or 4 weeks of cholesterol feeding, a second mild injury was induced in the same region as the first injury. The rabbits were given a standard diet for 2 weeks after the second injury. Typical atherosclerotic plaques with a fibrous cap formed by smooth muscle cells and extracellular matrix overlying a core formed by macrophage foam cells were observed in the lesion. Gelatin proteolytic activities were found in homogenates containing either media or intima from the injured artery, and activated matrix metalloproteinase-2 (MMP2) was detected. With prolongation of the HCD feeding period (interval between injuries) from 2 weeks to 4 weeks, typical plaque was observed more frequently. Furthermore, the neointimal area and the macrophage foam cells area increased, as did gelatin-proteolytic activity. Since the typical atherosclerotic plaques observed in the present study have some histopathological and pathogenic characteristics in common with unstable atherosclerotic plaque, we expect that the typical atherosclerotic plaque found in the present study will be useful for basic studies of plaque stabilization and prevention of acute coronary syndromes.

Animals↗

Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer.

Although recent studies have demonstrated that cyclooxygenase (COX)-2 is overexpressed in various cancers including gastric cancer, the mechanisms underlying the contribution of COX-2 to tumorigenesis and tumor promotion still remain unclear. To determine the role of COX-2, we investigated the COX-2 expression, the prostaglandin (PG) levels, and the microvessel density in 42 patients with primary gastric adenocarcinoma. COX-2 protein was over-expressed in 31 (74%) of 42 gastric cancers based on an immunoblot analysis. The intensity of COX-2 expression was found to significantly correlate with lymph node involvement. The COX-2 overexpressed cases showed significantly elevated levels of prostaglandin E2 (PGE2) in cancer tissues in comparison with the normal gastric mucosa by an immunoassay (201 +/- 90 versus 161 +/- 57 ng/mg protein; P < 0.05). However, the COX-2 overexpression was not related to the levels of thromboxane B2 and 6-keto-prostaglandin F1alpha. The density of microvessel immunostained with CD34 was significantly higher in patients demonstrating COX-2 overexpression than in those without such expression (63 +/-21 versus 45 +/- 17/200 x; P < 0.01). Our data thus suggested COX-2 overexpression to be associated with increased PGE2 biosynthesis and angiogenesis in gastric cancer, which indicates that COX-2 may play a role in the development of gastric cancer.

Adenocarcinoma↗

[A case of rhabdomyolysis with water intoxication confirmed by muscle biopsy].

A 32-year-old woman with chronic schizophrenia who took 8-10 liters of water for three years due to thirsty, admitted to our hospital because of convulsion and muscle weakness. Neurological finding on admission showed a mild disturbance of consciousness, moderate proximal muscle weakness, and muscle pain. Laboratory examination revealed marked serum hyponatremia(102 mEq/l) and high value of creatin kinase (1,259 IU/l). The level of creatin kinase reached a peak(39,700 IU/l) at the 5th hospital day. An analysis of the muscle biopsy specimen showed necrotic muscle fibers and opaque fibers, that was compatible with rhabdomyolysis. T 2 weighted magnetic resonance imaging of the brain showed a transient high signals in bilateral putamen but not in pons. She was diagnosed to have rhabdomyolysis due to water intoxication. The present case is the first rhabdomyolysis in Japan that was confirmed by muscle biopsy at an acute stage of water intoxication related with schizophrenia.

Adult↗

[Diffuse Lewy body disease searched out from 114 patients with parkinsonism].

From 114 patients who had been previously diagnosed as Parkinson's disease, we diagnosed six cases as clinically definite "diffuse Lewy body disease (DLBD)" according to McKeith's criteria with more strict modifications. Besides a central feature, dementia, and core features including parkinsonism, fluctuating cognition, and recurrent visual hallucinations, the patients presented some of supportive features, that is, repeated falls (4 cases), syncope (5 cases), and transient loss of consciousness (all cases). Autopsy, which was performed in 2 of the cases, revealed Lewy bodies in various nervous tissues including autonomic nervous systems in both cases. 7 cases of probable DLBD and 8 cases of possible DLBD, which lacked fluctuating cognition and/or visual hallucinations, demonstrated neither of repeated falls, syncope, nor transient loss of consciousness. Episodes of these supportive features, which seem to be associated with autonomic dysfunctions and/or fluctuating cognition, should be important in the differential diagnosis of DLBD.

Adult↗

[Cytokine production in surgical stress].

Surgical injury influences the function of mononuclear cells, leading to various systemic responses. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1, -6, -8, and the antiinflammatory cytokine IL-10, which are mainly produced by mononuclear cells, are known to play an important role in the response to and pathogenesis of surgical stress. TNF alpha production by monocytes is extremely upregulated, but monocyte HLA-DR antigen expression is suppressed in patients with surgical stress. While production of Th1 cytokines such as IL-12 and interferon-gamma by mononuclear cells is suppressed, production of Th2 cytokines and IL-10 is upregulated during surgical stress. Immune suppression following surgical stress has been clarified recently in terms of Th1 and Th2 cytokine production balance mainly caused by mononuclear cells. It is thought to be very important to maintain immunological function after surgical stress by controlling cytokine production and balance.

Cytokines↗

[Progressive limb-kinetic apraxia with myoclonus focal atrophy in the postcentral gyrus and the supplementary motor area].

We report a 70-year-old right handed man with a 5-year history of slowly progressive clumsiness of his left hand. A neurological examination disclosed mild rigidity and myoclonus in his left hand. He showed limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was present. Aphasia and agnosia were also absent. He was thought to have the primary progressive limb-kinetic apraxia clinically. Brain CT and MRI revealed focal atrophy in the right postcentral gyrus and the supplementary motor area. A positron emission tomography (PET) study showed diffuse decrement of cerebral blood flow, predominantly in the right hemisphere. The decrease in the uptake of [18F]-Fluoro-deoxyglucose also revealed glucose hypo-metabolism, especially in the right frontal and parietal lobe. Striatal [11C]NMSP and [18F]FDOPA uptake were also reduced in an asymmetric pattern. These findings suggest that our patient is likely to have corticobasal degeneration. Transcranial magnetic stimulation using double pulse paradigm revealed a decrease in the level of cortico-cortical inhibition in the motor cortex on the affected side. Our results indicate increase in the excitability of motor cortical neurons in primary progressive limb-kinetic apraxia, likely due to a decreased excitability of cortico-cortical inhibitory mechanism as a result of focal degeneration of cortical neurons.

Aged↗

[Objective evaluation of treatment for sleep apnea syndrome].

CPAP treatments for sleep apnea syndrome (SAS) are being established; however, there is no established evaluation method to scale the long-lasting effectiveness of the treatment. The only available method is to judge the results from each patient's subjective symptoms. We therefore tested a self-contained microcomputer with an acceleration sensor (Lifecorder) in an attempt to evaluate the effectiveness of treatments objectively. Fifteen patients with OSAS were the subjects. We keep the records of Lifecorders that were worn by the subjects a month before and a month after nasal CPAP treatment. We also assessed their daily physical activity levels; the number of steps taken, calories consumed, intensity of each activity along with improvement in their subjective symptoms. The number of steps taken in a day increased as did the calories consumed after treatment in 9 subjects. Moderate and intensive activities also increased among those 9 subjects. Our results indicate that evaluation with a Lifecorder, which is simple and inexpensive, can provide objective indicators to assess the effectiveness of treatments in patients' daily activities.

Adult↗

Increased polyploid incidence is associated with abnormal copper accumulation in the liver of LEC mutant rat.

Long-Evans Cinnamon (LEC) rats are deleted at the p-type copper transport ATPase gene (Atp7b), so that they exhibit abnormal hepatic copper concentration. In this study, it was confirmed that LEC rat liver possesses a feature of increase in polyploid. Furthermore, a segregation analysis using backcrosses between LEC and F344 normal rats showed that the increased polyploid incidence is strongly associated with excessive copper content in their liver. These results should demonstrate that copper cytotoxicity leads to the impairment of mitotic progression, resulting in the increase of polyploid in the liver of LEC rats.

Animals↗

Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme.

We have determined the nucleotide sequence of the clone pAL2 obtained from Porphyromonas gingivalis 381 in the previous study [Ansai et al. (1995) Microbiology 141, 2047-20521. The DNA sequence analysis of this fragment revealed one complete ORF and one incomplete ORF. The ORF encoded a protein (PgPepO) of 690 amino acids with a calculated molecular weight of 78796. The deduced amino acid sequence exhibited a significant homology with human endothelin-converting enzyme (ECE)-1. Recombinant PgPepO was purified to homogeneity and characterized. The purified enzyme was strongly inhibited by phosphoramidon, and converted big endothelin-1 to endothelin-1. Furthermore, the purified PgPepO strongly cross-reacted with a monoclonal antibody against rat ECE-1. These results indicate that PgPepO has striking similarity to mammalian ECE in structure and function.

Amino Acid Sequence↗

Evaluation of the New American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification.

BACKGROUND: A new system for the classification of gastric carcinoma, based on the number of metastatic lymph nodes, has been adopted by the current American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) TNM system (1997). The purpose of this study was to evaluate the rationality of this classification in comparison with the Japanese classification, which is based on the location of positive lymph nodes. METHODS: The authors analyzed 587 patients who underwent clinically curative gastrectomy with D2 lymphadenectomy for gastric carcinoma and each had 15 or more lymph nodes histologically examined from 1982 to 1992. Multivariate analysis with the Cox proportional hazards model was carried out to determine which classification was more effective. RESULTS: Within the pN1 or pN2 category of the new AJCC/UICC system, no significant difference in the survival rates existed between n1 patients and n2 patients of the Japanese classification. On the other hand, the survival rates significantly decreased, in the order of pN1, pN2, and pN3 (from greatest to smallest decrease), within the n1 and n2 categories. In multivariate analysis, lymph node involvement by the AJCC/UICC classification was selected as the most significant prognostic determinant, whereas the Japanese lymph node classification was not significantly prognostic. When survival rates were calculated within the pT1, pT2, and pT3-4 categories, no differences existed between pN0 and pN1. There was some discrepancy between the survival rate for each pT and pN category and the corresponding stage. CONCLUSIONS: The new AJCC/UICC classification for lymph node involvement of gastric carcinoma is basically acceptable and considered superior to the Japanese classification. Further analysis involving a greater number of cases may be necessary to confirm the applicability of this staging system.

Adult↗