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Biomedical subjects

M Haga

Publications and source records attributed to M Haga.

At least 37 records · Page 2Linked to original sources

Outbreak of cryptosporidiosis after contamination of the public water supply in Saitama Prefecture, Japan, in 1996.

An outbreak of cryptosporidiosis occurred in Ogose Town, Saitama Prefecture. Japan, in June 1996. Of 12,345 respondents to a questionnaire sent to households in the town (population; 13,809), 8,812 (71.4%) reported an acute gastrointestinal illness some time between May and July. In addition, 274 traceable visitors at local inns, golf courses, and the like during this period and 54 employees from out of town were infected. Cases of cryptosporidiosis were estimated to 9,140. Of these, 2,856 subjects were treated at outpatient clinics and 24 subjects were hospitalized (some subjects counted twice). No deaths were attributed to the outbreak. Among the visitors to Ogose who were traced, 7 persons who stayed only one day during the outbreak and drank half a glass to 2 glasses (100 to 360 ml) of tap water had cryptosporidiosis confirmed by laboratory tests. The median incubation period for the 14 persons for whom this calculation was possible was 6.4 days (range, 5 to 8 days). Of 469 pupils reporting details of their fever and diarrhea, abdominal cramps, or these combined signs and symptoms, the median maximum body temperature was 37.8 degrees C (range, 36.7 to 40.3 degrees C). The duration of illness, reported by 608 of the pupils, was 5.2 days (range, 1 to 15 days), and that reported by 187 employees was 4.8 days (range, 1 to 18 days). The longest known time for discharge of oocysts after onset was 44 days. Blood was not found in the 609 stool specimens examined. The outbreak was caused by contamination of the town's potable water by Cryptosporidium parvum oocysts. The town's water treatment plant treated river water by coagulation, sedimentation, sand filtration, and chlorination. Contamination arose because of various natural and artificial factors: one was that the monthly precipitation in May was much lower than average, causing the river water level to drop. Another factor was heavy rainfall one night in May that increased water turbidity. The amounts of the coagulant added seemed to be insufficient. There are two inns, three public lavatories, and two small-scale wastewater treatment plants upstream 400 m and 1,200 m of the intake point of the town's water treatment plant. However, there are no farms with livestock in the area. We suggest that the location of the water treatment facilities was inappropriate, and that oocysts had circulated from the potable water to humans to sewage to the river and back to the potable water.

Adolescent↗

In vitro absorption and metabolism of a citrus chemopreventive agent, auraptene, and its modifying effects on xenobiotic enzyme activities in mouse livers.

We previously reported that auraptene (7-geranyloxycoumarin, AUR), widely occurring in citrus fruit, is a structurally novel type of effective cancer-preventive agent, as manifested in several rodent models. However, its bio-availability and metabolism in biological systems have yet to be investigated. In the present study, we examined the chemical stability of AUR at pH 1.57 and 37 degrees C (as a stomach digestion model) and observed its stoichiometric conversion to umbelliferone [7-hydroxycoumarin, UMB; half-life (t1/2) = 15 h; 7-ethoxycoumarin (ETC) was stable for 24 h]. Differentiated Caco-2 cells, a human colorectal adenocarcinoma cell line, were used as a small intestine model. ETC permeated the basolateral (portal vein) side of Caco-2 cells in a time-dependent manner; AUR slightly permeated the cells, but with an intracellular accumulation. Epoxyauraptene and UMB were detected when AUR was treated with the rat liver S-9 mixture. ETC was also converted to UMB, but its t1/2 of two hours was much shorter than that of AUR (> 24 h). This suggests that AUR, bearing a geranyloxyl side chain, is a relatively metabolism-resistant substrate for cytochrome P-450 enzymes and, thus, is stable in the liver compared with ETC. Oral administration of AUR by gavage at 50-200 mg/kg body wt dose dependently induced glutathione S-transferase (GST) activity in mouse livers without affecting cytochrome P-450 activity. Using 10 coumarin-related compounds, we found that only those coumarins having a 7-alkyloxyl group induced GST, but not cytochrome P-450, activity. The present study presumes that AUR accumulates in the epithelial cells of the small intestine and then gradually permeates into the portal vein. Stable localizability of AUR in the colon and liver may be associated with the induction of GST activity, which is important as the action mechanism for suppression of rodent chemical carcinogenesis.

Absorption↗

Anti-CD2 monoclonal antibodies prevent the induction of experimental autoimmune myocarditis.

We investigated the effect of a monoclonal antibody against CD2 molecules (OX34) in preventing the induction of experimental autoimmune myocarditis (EAM) induced by immunizing Lewis rats with cardiac myosin. Administration of OX34 before immunization, on Days -6, -4, -2 and 0, completely prevented EAM. On the other hand, treatment with OX34 just before the appearance of myocardial lesions, on Days 9, 11, 13 and 15, had only a partial effect in preventing the disease. Flow cytometric analysis of lymph node cells showed that CD3+ T cells were immediately depleted with the administration of OX34 but had largely recovered on Day 21. Lymph node cells in OX34-treated rats had no proliferative responses to cardiac myosin-rod, but the proliferation was restored when recombinant IL-2 was added. Ultimate production of the anti-myosin antibody was not inhibited by the treatment with OX34. These results suggest that the prevention of EAM by administering the anti-CD2 monoclonal antibody OX34 resulted from T cell depletion during the induction phase, and might in addition result from T cell anergy of Th1, but not Th2 cells.

Animals↗

An experience of a case with perforation of an aneurysm in the anterior mitral cusp developing after aortic valve replacement.

Mitral valve aneurysm is a rare disease and in Japan, cases of perforation which is considered to be mainly caused by infectious endocarditis is usually only encountered through case reports. We experienced a case who received aortic valve replacement and mitral valve annuloplasty for combined valvular heart disease of aortic insufficiency and mitral insufficiency followed by mitral valve replacement for severe mitral valve regurgitation subsequent to perforation of the anterior mitral cusp, leading to recovery.

Aneurysm, Ruptured↗

Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain.

We have previously demonstrated that bilobalide, a constituent of the Ginkgo biloba extract, possesses anticonvulsant activity, and suggested that the mechanism of its anticonvulsant action involves modulation of y-aminobutyric acid (GABA)-related neuronal transmission. This study examined the effects of bilobalide on the level of GABA and glutamate, the activity and the amount of glutamic acid decarboxylase (EC 4.1.1.15), and the function of GABA(A) receptors in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels, glutamic acid decarboxylase activity, and the protein amount of 67 kDa glutamic acid decarboxylase in the hippocampus of mice treated with bilobalide (30 mg/kg, p.o., once a day for 4 days) were significantly higher than those in controls. However, there were no significant differences in glutamate levels or, the number and the dissociation constants of GABA(A) receptors in the hippocampus between control and bilobalide-treated mice. These results suggest that the anticonvulsant effect of bilobalide is due to elevation of GABA levels, possibly through potentiation of glutamic acid decarboxylase activity and enhancement of the protein amount of 67 kDa glutamic acid decarboxylase by bilobalide.

Animals↗

Pulmonary function after segmentectomy for small peripheral carcinoma of the lung.

OBJECTIVE: The aim of this study is to compare the pulmonary function after a segmentectomy with that after a lobectomy for small peripheral carcinoma of the lung. PATIENTS AND METHODS: Between 1993 and 1996, segmentectomy and lobectomy were performed on 48 and 133 good-risk patients, respectively. Lymph node metastases were detected after the operation in 6 and 24 patients of the segmentectomy and lobectomy groups, respectively. For bias reduction in comparison with a nonrandomized control group, we paired 40 segmentectomy patients with 40 lobectomy patients using nearest available matching method on the estimated propensity score. RESULTS: Twelve months after the operation, the segmentectomy and lobectomy groups had forced vital capacities of 2.67 +/- 0.73 L (mean +/- standard deviation) and 2.57 +/- 0.59 L, which were calculated to be 94.9% +/- 10.6% and 91.0% +/- 13.2% of the preoperative values (P =.14), respectively. The segmentectomy and lobectomy groups had postoperative 1-second forced expiratory volumes of 1.99 +/- 0.63 L and 1.95 +/- 0.49 L, which were calculated to be 93.3% +/- 10.3% and 87.3% +/- 14.0% of the preoperative values, respectively (P =.03). The multiple linear regression analysis showed that the alternative of segmentectomy or lobectomy was not a determinant for postoperative forced vital capacity but did affect postoperative 1-second forced expiratory volume. CONCLUSION: Pulmonary function after a segmentectomy for a good-risk patient is slightly better than that after a lobectomy. However, segmentectomy should be still the surgical procedure for only poor-risk patients because of the difficulty in excluding patients with metastatic lymph nodes from the candidates for the procedure.

Aged↗

The influence of lung cancer mass screening on surgical results.

BACKGROUND: After the introduction of the mass screening program for lung cancer, the number of patients detected by mass screening increased as well as the number of early staged patients. Therefore, we examined the influence of lung cancer mass screening on surgical results. METHODS: A total of 1177 primary lung cancer cases, who underwent surgery from 1963 to 1992, were retrospectively reviewed. They were grouped according to the changes in the mass screening system: the first period (1963-1977) before lung cancer screening started, the second period (1978-1986) when mass screening was conducted by the local government, and the third period (1987-1992) after the launching of the national screening program. RESULTS: The rate of cases detected by mass screening increased over time and the 5-year survival rate improved significantly, from 33.7% in the first period, to 51.8% in the second period and finally, to 58.4% in the third period. The improvement is attributable to a relative increase of rate of stage I cases and better stage I survival rate. Specifically, in stage I cases, improvement resulted from a relative increase of stage IA in peripheral type and roentgenographically occult lung cancer cases and from better survival rate of these two groups. CONCLUSION: As lung cancer screening has come into widespread use, detection of peripheral small-sized lung cancer and roentgenographically occult lung cancer have increased and consequently, surgical results have improved.

Adenocarcinoma↗

Effects of bilobalide, a sesquiterpene in Ginkgo biloba leaves, on population spikes in rat hippocampal slices.

The effects of bilobalide, a sesquiterpene isolated from the leaves of Ginkgo biloba L., were investigated in a rat hippocampal slice preparation. Bilobalide (10-500 microM) significantly increased the amplitude of population spikes evoked by electrical stimulation of Schaffer collateral/commissural fibers in a concentration-dependent manner. Paired-pulse inhibition at interpulse intervals of 10-50 ms was significantly reduced in the presence of bilobalide (50 microM). The inhibitory action of muscimol (1 microM) was attenuated by bilobalide (100 microM). These results suggest that bilobalide induces an enhancement of excitability of CA1 pyramidal neurons, which involves, at least in part, a reduction in GABAergic inhibition in rat hippocampus.

Action Potentials↗

Vesicular monoamine transporter 1 is responsible for storage of 5-hydroxytryptamine in rat pinealocytes.

Vesicular monoamine transporters (VMATs) are involved in chemical transduction in monoaminergic neurons and various endocrine cells through the storage of monoamines in secretory vesicles. Mammalian pinealocytes contain more 5-hydroxytryptamine (5-HT) than any other cells and are expected to contain VMAT, although no information is available so far. Upon the addition of ATP, radiolabeled 5-HT was taken up by a particulate fraction prepared from cultured rat pinealocytes. The 5-HT uptake was inhibited significantly by bafilomycin A1 (an inhibitor of vacuolar H+-ATPase), 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (a proton conductor), or reserpine (an inhibitor of VMAT). RT-PCR analysis suggested that VMAT type 1 (VMAT1), but not type 2, is expressed. Antibodies against VMAT1 recognized a single polypeptide with an apparent molecular mass of approximately 55 kDa, and specifically immunostained pinealocytes. VMAT1 immunoreactivity was high in the vesicular structures in the varicosities of long branching processes and was associated with 5-HT, but not with synaptophysin, a marker protein for microvesicles. The 5-HT immunoreactivity in the long branching processes disappeared upon incubation with reserpine. These results indicate that 5-HT, at least in part, is stored in vesicles other than microvesicles in pinealocytes through a mechanism similar to that of various secretory vesicles.

Adenosine Triphosphate↗

Successful surgery for an acute type A aortic dissection following repair of a descending thoracic aortic aneurysm.

Acute type A aortic dissection in the presence of a previously repaired atherosclerotic descending thoracic aortic aneurysm is rarely reported. We experienced a patient who underwent an ascending aortic replacement with reconstruction of the aortic arch 16 months after repair of a descending thoracic aortic aneurysm. We succeeded in the redo operation with comprehensive techniques involving selective cerebral perfusion, deep hypothermia, early antegrade systemic circulation for cerebral protection, and femoro-femoral bypass with occlusion of the descending aorta for lower systemic perfusion as well as renal perfusion. The patient recovered and is doing well one year after the redo operation.

Acute Disease↗

Improvement of intestinal absorption of peptide drugs by glycosylation: transport of tetrapeptide by the sodium ion-dependent D-glucose transporter.

A tetrapeptide (Gly-Gly-Tyr-Arg, GGYR), which is not transported by di- or tripeptide transporters, was glycosylated with p-(succinylamido)phenyl alpha- or beta-D-glucopyranoside (alpha,beta-SAPG) to investigate whether these glycosylated molecules are transported by the Na+-dependent D-glucose transporter. Their uptake into brush border membrane vesicles (BBMVs) and transport through the intestinal membrane were examined using the rapid filtration technique and the everted sac method. It was observed that glycosylation at the alpha-amino position of GGYR increased resistance to aminopeptidase activity and inhibited its degradation. When alpha- and beta-SAPG-GGYR were incubated with BBMVs, overshoot uptake was observed about 2 min after the start of incubation in the presence of an inward Na+ gradient. This uptake remained unaffected by the addition of GGYR while it was significantly inhibited when Na+ was replaced with K+ or alpha- and beta-SAPG-GGYR were incubated with BBMVs at 4 degrees C. Uptake was also markedly inhibited either with 1 mM phloridzin or 10 mM D-glucose. These findings suggested that the Na+-dependent glucose transporter (SGLT-1) played an important role in the uptake of both alpha- and beta-SAPG-GGYR into BBMVs. A comparison of alpha- with beta-SAPG-GGYR revealed that the amount of beta-SAPG-GGYR taken up was greater than that of alpha-SAPG-GGYR. From the everted sac method data, it was shown that the elimination clearance from the mucosal side, CLel, and permeation clearance to the serosal side, CLp, were 15.82+/-6.83 and 0.83+/-0.06 microL/min/cm for alpha-SAPG-GGYR and 44.52+/-3.61 and 3.50+/-0.81 microL/min/cm for beta-SAPG-GGYR, respectively, and that alpha-SAPG-GGYR was more resistant to enzymatic degradation than beta-SAPG-GGYR. Permeation of both alpha- and beta-SAPG-GGYR was inhibited in the presence of D-glucose and in the absence of a Na+ gradient, suggesting that both alpha- and beta-SAPG-GGYR were transported by the Na+-dependent D-glucose transporter. The permeation clearance transported by the Na+-dependent D-glucose transporter, (CLp)Na+, of beta-SAPG-GGYR was about 5 times greater than that for alpha-SAPG-GGYR. This result may be ascribable to the fact that the beta-form of glucose has higher affinity to SGLT-1 than the alpha-form. The results of the present study encourage further investigations on improvements in intestinal absorption of peptide drugs by glycosylation.

Animals↗

Complete intercostal artery reimplantation using a method of aneurysmoplasty.

We report the case of a 58-year-old woman who underwent repair of a chronic dissecting thoracoabdominal aortic aneurysm. Using a method of aneurysmoplasty under normothermic cardiopulmonary bypass, all intercostal arteries were quickly reperfused, and the spinal cord ischemic time was minimized. No neurological deficits developed in our patient using this method.

Aortic Dissection↗

Intermediate TCR cells in mouse lung: their effector function to induce pneumonitis in mice with autoimmune-like graft-versus-host disease.

The lung comprises lymphocytes even under noninflammatory conditions. We investigated the presence of NK cells, extrathymic T cells, and thymus-derived T cells in this organ. As shown previously in mouse liver, two-color staining for CD3 and IL-2R beta-chain (IL-2Rbeta) identifies CD3- IL-2Rbeta+ NK cells, CD3int IL-2Rbeta+ cells (int indicates intermediate; of extrathymic origin), and CD3high IL-2Rbeta- cells (high indicates high; of thymic origin). These populations were present in the lungs of normal mice in a unique manner (i.e., NK cells > CD3high cells > CD3int cells). The proportion of CD3int cells increased in the lung with age. In athymic mice, only CD3int cells were detected in the lung. In contrast to CD3int cells in the liver, the majority of these cells in the lung did not express NK1.1 Ags. Other properties of CD3int cells in the lung were the same as those in the liver, e.g., double-negative CD4- 8- cells and gammadelta T cells. CD3int cells in the lung contained forbidden clones similar to those in other organs. When (B6 x bm12) F1 mice (Ly5.2) were injected with CD3high cells of B6-Ly5.1 origin, F1 mice fell victim to chronic graft-vs-host disease and pneumonitis, showing the expansion of CD3int cells. Almost all of them were of recipient origin (Ly5.2+). More importantly, such CD3int cells induced autoimmune-like pneumonitis when injected into irradiated F1 mice. CD3int cells isolated from the lung in mice with graft-vs-host disease exerted autologous cytotoxicity against thymocytes in vitro. These results suggest that extrathymic T cells exist in the lung and that their expansion may be responsible for inflammatory lung diseases.

Adoptive Transfer↗

Rheumatoid arthritis and the risk of malignancy.

OBJECTIVE: To determine the relative risks of malignancy and of site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: In a prospective cohort study, 862 patients with RA (96% white) were enrolled from 1966 to 1974 and were followed up for up to 35 years (mean 17.4 years) at the University of Saskatchewan Rheumatic Disease Unit. All diagnoses of cancer were cross-referenced with the Provincial Cancer Registry. Expected cancer incidence rates were determined based on province of Saskatchewan population statistics matched to each study patient for age, sex, and calendar year. Standardized incidence ratios (SIRs) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. RESULTS: A total of 136 cases of cancer were observed compared with 168 expected (SIR 0.80, P = 0.011 [95% CI 0.67-0.95]). The relative risk of colorectal malignancy was significantly reduced in the RA study population (SIR 0.52, P = 0.037 [95% CI 0.25-0.96]). A significant excess of leukemia was found (SIR 2.47, P = 0.026 [95% CI 1.12-4.69]), whereas the incidence rates for Hodgkin's disease and non-Hodgkin's lymphoma and all other site-specific malignancies were not found to be significantly different from general population rates. CONCLUSION: In our cohort of RA patients, colorectal cancer was detected in only half the expected number of patients. This risk reduction may be related to long-term nonsteroidal antiinflammatory drug (NSAID) use in RA, as has been suggested in several other studies of long-term NSAID use. An increased risk of leukemia was confirmed. This may be due to the persistent immune stimulation associated with RA itself, since other potential explanatory factors for increased leukemia were not apparent. Despite the excess of hemopoietic malignancy and despite treatment of RA with potentially oncogenic agents, the overall risk of malignancy was reduced in this RA cohort.

Adolescent↗

Analysis of urinary red blood cells of healthy individuals by an automated urinary flow cytometer.

A newly developed automated urinary flow cytometer allows clear discrimination of erythrocytes from other solid components of urine. In this study, the normal range of the urinary erythrocyte count and the source of urinary erythrocytes in healthy individuals were investigated using this analyzer. For the diagnosis of the source of the urinary erythrocytes, Kitasato University Kidney Center criteria for this analyzer were applied. The subjects were 133 regularly employed volunteers (age range 20-48 years, mean 30.5) who noted no urinary tract symptoms and showed normal blood pressure, consisting of 41 females not in their menstrual period (age range 20-39 years, mean 24.8) and 92 males (age range 20-48 years, mean 33.1). Mid-stream voided urine was collected from these subjects using urine sampling cups, immediately transferred to 50-ml sterilized Spitz tubes, and analyzed within 30 min using the automated urinary flow cytometer. Urinary erythrocytes were derived from glomeruli in all samples of healthy subjects. The urinary erythrocyte count showed a logarithmic normal distribution. Values 2 SD of the urinary erythrocyte count in healthy individuals or higher were regarded as abnormal, and hematuria was considered to be positive when 11.0/microliter or more erythrocytes were observed by this analyzer. The finding by this analyzer corresponded to the report of Birch et al.

Adult↗

Effect of cardiopulmonary bypass on cytokine release and adhesion molecule expression in alveolar macrophages. Preliminary report in six cases.

Although recent studies have shown that adhesion molecules on alveolar macrophages are important in a variety of pulmonary diseases, there have been few studies on the phenotypic and functional changes of alveolar macrophages during cardiopulmonary bypass. To investigate the possible role of alveolar macrophages in activating pulmonary immunity during cardiopulmonary bypass, we measured the expression of adhesion molecules on alveolar macrophages and peripheral blood monocytes in patients undergoing cardiopulmonary bypass. Antigens were stained with monoclonal antibodies against adhesion molecules, and the expression of antigens was quantified by flow cytometry as the ratio of specific to nonspecific linear fluorescence. On alveolar macrophages obtained after the release of aortic cross-clamp, macrophages as compared with alveolar macrophages obtained before cardiopulmonary bypass, there was a significant enhancement of CD11a, CD11b, CD11c, and CD18. In addition, alveolar macrophages, but not peripheral monocytes, produced higher levels of TNF-alpha and IL-8 when they were cultured in vitro. A higher expression of CD11 and CD18 on alveolar macrophages and enhanced production of cytokines after release of the aortic cross-clamp may contribute to immune activation in lung by macrophage-lymphocyte interaction.

Adult↗