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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 559 records · Page 31Linked to original sources

Evaluation of urinary cadmium and lead as markers of background exposure of middle-aged women in Korea.

OBJECTIVE: The present study was initiated to investigate the validity of cadmium (Cd) and lead (Pb) in urine in comparison with the metals in blood as a biological marker of nonoccupational exposure of general populations to these metals as environmental pollutants. DESIGN: Peripheral blood samples, morning spot-urine samples, and 24-h total food duplicate samples were collected from 107 nonsmoking women (aged 30-59 years) in four urban and rural survey sites in Korea. METHODS: Portions of the samples were digested by heating in the presence of mineral acids, and the digests were analyzed for Cd and Pb by graphite furnace atomic absorption spectrophotometry. The metal concentrations in urine were adjusted for creatinine concentration and a specific gravity of 1.016. The analyte levels were evaluated on an individual basis (n = 107) and also on a group basis, i.e., in terms of geometric means for the survey sites (n = 4). RESULTS: Cd in urine correlated with Cd in blood on an individual as well as survey-site basis and tended to correlate with Cd in food duplicates on a group basis. The correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood when evaluated on an individual and survey-site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey-site basis. CONCLUSIONS: Cd in urine proved to be valid as a biological marker of environmental exposure of general populations, whereas less support was obtained for Pb in urine as an exposure marker.

Adult↗

High-pressure liquid chromatographic determination of toluene in urine as a marker of occupational exposure to toluene.

OBJECTIVE: To establish a convenient method by high-pressure liquid chromatography (HPLC) to measure toluene in urine as a marker of occupational exposure to toluene. METHODS: As soon after sampling as possible, 1 ml of urine was mixed with an equal volume of acetonitrile in a 2.2-ml HPLC glass bottle, and the bottle was tightly sealed and stored at 4 degrees C. Immediately before HPLC determination, 100 microl methanol was added to the mixture to prevent confounding effects of glycosuria, and the bottle was spun to remove any suspended matter. An aliquot of the supernate was introduced into the HPLC system and analyzed on a PRODIGY column, with an acetonitrile - perchloric acid phosphoric acid - water mixture serving as the mobile phase. The effluent was monitored at 191 nm. RESULTS: The method can measure toluene in urine every 20 min, the detection limit was 2 microg/l, the coefficient of variation was less than 5%, and the recovery rate was 100%. No significant reduction in toluene concentration was observed for 1 week after storage at 4 degrees C. When the method was applied to end-of-shift urine samples from 13 male workers exposed to toluene at 18-140 ppm and also to urine samples from 10 nonexposed male controls, toluene in urine was linearly related to toluene exposure concentration, with a regression line passing close to the origin. The correlation coefficient was as high as 0.97 (n=23). No toluene was detected in control urine samples. Calculations suggest that urinary toluene accounts for as little as less than 0.01% of the toluene absorbed via inhalation and that the absorbed toluene is converted almost quantitatively to hippuric acid and, by less than 0.1%, to o-cresol.

Adult↗

Monitoring of occupational exposure to dichloromethane by diffuse vapor sampling and urinalysis.

OBJECTIVE: The aim of the present study was to develop valid methods for monitoring of occupational exposure to dichloromethane (DCM). METHODS: Carbon cloth as an adsorbent in diffusive sampling was tested for its capacity to adsorb DCM vapor and to retain adsorbed DCM after termination of the exposure. Urine samples collected from DCM-exposed workers were analyzed for DCM by the head-space technique. After extraction with carbon disulfide, DCM in the cloth was analyzed on a DB-WAX capillary column by flame-ionization detection gas chromatography (FID-GC) and DCM in urine was analyzed by electron-capture detection (ECD)-GC. RESULTS: The diffusive sampling with carbon cloth as an adsorbent is applicable to 4-h monitoring of exposure to up to 100 ppm DCM vapor. DCM concentrations detected in end-of-shift urine samples correlated linearly with time-weighted average DCM concentrations measured in the breathing-zone air of the exposed workers; essentially the same exposure-excretion relationship was obtained by vapor monitoring for the afternoon 4-h period as compared with a whole day (8-h) of vapor monitoring. There was no sex difference in the exposure-excretion relation. CONCLUSIONS: Both personal diffusive sampling (at up to 100 ppm DCM and for up to 4 h) and biological exposure monitoring by urinalysis for DCM are applicable in occupational health as reliable measures of exposure to this chlorinated hydrocarbon solvent.

Air Pollutants, Occupational↗

Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma.

We examined the relationship between apoptosis and the progression of human gastric carcinoma. Studies were conducted on a total of 88 surgically removed stomachs, comprising 26 minute (less than 5 mm in diameter), 29 early (limited to the mucosal and submucosal layer) and 33 advanced carcinomas. Apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Serial sections were immunostained for p53 and Ki-67. The mean apoptotic indices (AI: percentage of TUNEL signal positive cells) of minute, early, and advanced carcinomas were 4.1 +/- 0.6, 3.8 +/- 1.2, and 4.0 +/- 1.2 in 46 well differentiated carcinomas, and 2.1 +/- 0.5, 2.7 +/- 0.9, and 2.2 +/- 1.1 in 42 poorly differentiated carcinomas, respectively. Similarly, the mean Ki-67 labelling indices (KI) were 39.2 +/- 7.8, 47.2 +/- 12.8, 52.6 +/- 13.1 in the former, and 35.0 +/- 9.3, 36.9 +/- 10.3, and 40.0 +/- 9.2 in the latter, respectively. Both mean AI and mean KI were significantly higher in well differentiated than in poorly differentiated carcinomas (P < 0.05). However, the value of mean AI did not differ among minute, early, and advanced carcinomas in either histological type, while KI increased gradually with tumour progression. The frequency of nuclear p53 expression did not differ among the three categories, implying that the gene mutation is an early event in gastric carcinogenesis. There was no statistical significance between nuclear p53 expression and mean AI. These results suggest that the progression of gastric cancer is defined by a gradual increase of proliferative activity and constant occurrence of apoptosis and that naturally occurring apoptosis is induced predominantly via a p53-gene-independent pathway.

Adenocarcinoma↗

Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C.

A 57-year-old man had abnormal hepatic function identified in April 1994. In October 1994, chronic hepatitis C was diagnosed. Based on the findings of a liver biopsy, administration of recombinant interferon (rIFN)-alpha2b was begun. In the 16th week of treatment, the patient experienced headache and fever and developed a markedly decreased, platelet count and hemolytic anemia. He was admitted on May 19, 1995 and thrombotic thrombocytopenic purpura (TTP) was diagnosed. He died on the 3rd hospital day. The causes of TTP have yet to be elucidated, but in this patient the occurrence of TTP appeared to be related to the IFN treatment for chronic hepatitis C.

Antiviral Agents↗

Malignant mesothelioma originating in the hepatic falciform ligament: report of a case.

We report herein what to our knowledge is the first documented case of malignant mesothelioma arising from the falciform ligament. A 65-year-old woman was admitted to our department for the evaluation of an epigastric mass. An abdominal computed tomography scan, magnetic resonance imaging, and celiac angiogram showed a tumor originating in the falciform ligament. The tumor was subsequently resected, and pathological examination confirmed a diagnosis of malignant mesothelioma originating in the falciform ligament. A metastatic liver tumor was detected 3 years after this operation and a partial liver resection was performed. She is currently off therapy, and no clinical or radiologic evidence of disease has been found for 1 year since her second operation.

Aged↗

Interferon induces insulin resistance in patients with chronic active hepatitis C.

AIM/METHODS: To elucidate the metabolic effect of interferon alpha, the following tests were performed on 14 patients with chronic active hepatitis C before and after interferon therapy (6 million units/day for 2 weeks): (1) oral glucose tolerance tests to measure insulin secretion; (2) euglycemic hyperinsulinemic clamp with oral glucose load to measure peripheral and hepatic insulin sensitivity (splanchnic glucose uptake); and (3) measurements of plasma levels of glucoregulatory hormones. RESULTS: The oral glucose tolerance test showed that a 2-week treatment with interferon did not induce apparent change in plasma glucose and insulin profiles. Nevertheless, interferon therapy worsened insulin-mediated glucose uptake in the peripheral tissues by 17% from 44.4+/-3.2 to 37.3+/-3.0 micromol x kg(-1) x min(-1) (p<0.05). Furthermore, interferon therapy significantly decreased splanchnic glucose uptake by 38% from 47+/-2% to 29+/-3% (p<0.01). No changes were noted for plasma glucoregulatory hormones, such as epinephrine, norepinephrine, cortisol and growth hormone, after interferon therapy. CONCLUSIONS: These results indicate that interferon therapy for 2 weeks induces insulin resistance in the splanchnic, as well as peripheral tissues, in patients with chronic active hepatitis C. Therefore, more careful observation may be needed during interferon therapy in subjects with impaired glucose tolerance.

Antiviral Agents↗

Thermal imaging of receptor-activated heat production in single cells.

Changes in enthalpy (i.e., heat content) occur during the diverse intracellular chemical and biophysical interactions that take place in the life cycle of biological cells. Such changes have previously been measured for cell suspensions or cell-free biochemical extracts by using microcalorimetry, thermocouples, or pyroelectric films, all of which afford minimal spatial or temporal resolution. Here we present a novel thermal imaging method that combines both diffraction-limited spatial (approximately 300 nm) and sampling-rate-limited time resolution, using the temperature-dependent phosphorescence intensity of the rare earth chelate Eu-TTA (europium (III) thenoyltrifluoro-acetonate). With this thermosensitive dye, we imaged intracellular heat waves evoked in Chinese hamster ovary cells after activation of the metabotropic m1-muscarinic receptor. Fast application of acetylcholine onto the cells evoked a biphasic heat wave that was blocked by atropine, and after a brief delay was followed by a calcium wave. Atropine applied by itself produced a monophasic heat wave in the cells, suggesting that its interactions with the receptor activate some intracellular metabolic pathways. The thermal imaging technique introduced here should provide new insights into cellular functions by resolving the location, kinetics, and quantity of intracellular heat production.

Animals↗

Monocyte-vascular smooth muscle cell interaction enhances nitric oxide production.

OBJECTIVE: The adhesive interaction of monocytes and vascular smooth muscle cells (VSMCs) has been suggested to be a regulatory signal in the cellular activation that is involved in the pathogenesis of atherosclerosis. We investigated the effects of monocyte-VSMC interaction on inducible nitric oxide (NO) synthase expression. METHODS: NO production by the cultured cells was determined by measuring the nitrite content of the culture media using the Griess reagent. The expression of inducible NO synthase protein was assayed by Western blotting. RESULTS: Interleukin-1 beta (IL-1 beta) induced nitrite production by VSMCs in a time-dependent manner. The addition of the mouse monocyte cell line J774 to IL-1 beta-stimulated VSMCs further increased nitrite production in a monocyte number-dependent manner. Enhanced nitrite production by coculture was accompanied by increased inducible NO synthase protein accumulation. Addition of tumor necrosis factor-alpha (TNF-alpha) also enhanced IL-1 beta-induced nitrite production by VSMCs, but TNF-alpha showed no effect in the presence of monocytes. Coculture of monocytes and VSMCs in the presence of IL-1 beta secreted substantial amounts of TNF-alpha. The production of nitrite by coculture was markedly inhibited by an anti-TNF-alpha antibody. CONCLUSIONS: The present study revealed that direct cell-to-cell interaction between monocytes and VSMCs enhances NO production, suggesting an important role for their interaction in the pathogenesis of atherosclerosis.

Animals↗

Prior muscular contraction enhances disposal of glucose analog in the liver and muscle.

To noninvasively investigate in vivo glucose disposal in muscle and liver after exercise, 19F magnetic resonance spectroscopy (19F-MRS) was applied using 3-fluoro-3-deoxy-D-glucose (3FDG) as a metabolic probe. After 30 minutes of muscle contraction of rabbit hindlimb by a 1-Hz electrical stimulation, 3FDG 250 mg/kg was injected intravenously and 19F-MRS was performed on the postcontracted hindlimb or the liver. Rabbits subjected to muscle contraction showed 1.5- and 1.7-fold higher peaks for 3FDG signal intensity in the liver and muscle than those not subjected to it. 3FDG was converted to 3-fluoro-3-deoxy-gluconic acid (3FGA) in the muscle and liver, and 3FDG oxidation was not affected by muscle contraction. During intraportal 3FDG infusion for 120 minutes at a dose of 2 mg x kg-1 x min-1 after termination of muscle contraction, the postcontracted rabbits showed a continuous increase in the signal intensity of 3FDG and a 2.1-fold higher total signal intensity of 3FDG than those not subjected to muscle contraction. In conclusion, 19F-MRS allows direct noninvasive observation of 3FDG disposal in rabbit muscle and liver. The increased intensity of 3FDG in the liver after muscle contraction suggests that exercise enhances disposal of the glucose analog in the liver, as well as in muscle, and these effects persist for at least 2 hours after exercise.

Animals↗

A role for local calcium gradients upon hypoxic injury in human umbilical vein endothelial cells (HUVEC).

Upon hypoxic injury, bleb formation is an early event of cell damage observed in a variety of cell types. Although a rise in cytosolic free Ca2+ ([Ca2+]i) has been considered to be involved in this process, the exact relationship between these phenomena remains ill-defined. In order to examine the relationship between bleb formation, and [Ca2+]i or nuclear free Ca2+ ([Ca2+]n), we analyzed [Ca2+]i and [Ca2+]n in HUVEC during hypoxic injury using confocal laser scanning microscopy. [Ca2+]i and [Ca2+]n were measured using Fluo-3, and cell viability and mitochondrial membrane potential were assessed by the exclusion of propidium iodide (PI) and rhodamine 123, respectively. After the initiation of hypoxia, [Ca2+]i and [Ca2+]n rose gradually up to 15 min reaching peak values of 447 +/- 62 and 516 +/- 105 nM, respectively, which was accompanied by a decrease in rhodamine 123 fluorescence and an increase in PI-stained cells. Bleb formation was observed after [Ca2+]i and [Ca2+]n had reached their peak values and the number of blebs increased thereafter. Confocal z-sectioning images revealed a localized increase in [Ca2+]i at the bleb forming site and this localized elevation in [Ca2+]i was observed before bleb formation in the corresponding area. In conclusion, bleb formation induced by hypoxic stress appears to involve Ca(2+)-dependent reactions that are linked to a regional elevation of [Ca2+]i.

Analog-Digital Conversion↗

Detection of negative-stranded hepatitis C virus RNA using a novel strand-specific reverse transcription-polymerase chain reaction.

We developed a novel single-tube reverse transcription-polymerase chain reaction (RT-PCR) for the specific detection of negative-stranded hepatitis C virus (HCV) RNA. By using in vitro synthesized positive- and negative-stranded HCV RNAs, it was demonstrated that as few as 50 copies of negative-stranded HCV RNA could be specifically detected with a set of primers that amplify a 232-base pair sequence unique to the 5'-non-coding region of HCV RNA, while 10(8) copies of positive-stranded HCV RNA were not detected. In addition, we demonstrated that this method allows the detection as few as 100 copies of negative-stranded HCV RNA even with the coexistence of a 100-fold excess of positive-stranded HCV RNA. Furthermore, with this method, negative-stranded HCV RNA was detected in RNAs from liver biopsy specimens obtained from patients with chronic hepatitis C, but not in RNAs from HCV-positive sera.

Hepacivirus↗

Human hepatocyte clonal cell lines that support persistent replication of hepatitis C virus.

We previously found that a human T-cell leukemia virus type I infected T-cell line, MT-2, was susceptible to hepatitis C virus (HCV) infection, and that cloned MT-2C cells could support HCV replication more persistently than the parental MT-2 cells. Recently we found that a non-neoplastic hepatocyte line, PH5CH, showed good susceptibility to HCV infection. In this study, we cloned PH5CH cells to obtain cells that supported more persistent HCV replication, and consequently three clones (PH5CH1, PH5CH7 and PH5CH8) in which intracellular HCV RNA could be detected at least 25 days postinoculation (p.i.) were obtained. Semi-quantitative analysis of HCV RNA indicated that HCV replicated in these cloned PH5CH cells was released into the culture medium. Semi-quantitative analysis of internalized HCV RNA after treatment of cloned PH5CH cells and parental PH5CH cells with proteinase K immediately after virus inoculation revealed that PH5CH1, PH5CH7 and PH5CH8 cells contained 10-fold higher levels of HCV RNA than low susceptible cloned PH5CH or parental PH5CH cells. Furthermore, we demonstrated that HCV replication was maintained for 70-100 days in these three clonal lines when the temperature of cell culture after virus inoculation was reduced from 37 to 32 degrees C. Moreover, we demonstrated that interferon alpha had antiviral effect on HCV-infected PH5CH8 cells. The three PH5CH clones obtained in this study will provide a useful tool for the study of HCV replication and proliferation, and for development of an assay system for antiviral agents.

Antiviral Agents↗

Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group.

To evaluate the effect of pioglitazone on insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) patients, a double-blind placebo-controlled trial was carried out with 30 NIDDM patients. Twenty-one subjects, three on diet alone and 18 on sulfonylurea (SU), orally received 30 mg pioglitazone once daily for 12 weeks. Nine subjects, one on diet alone and eight on SU, received a matching placebo once daily for 12 weeks. Euglycemic (5.2 mmol/l) hyperinsulinemic (1200 pmol/l) clamp combined with an oral glucose load (OGL) was performed before and after 3-month treatment with pioglitazone or placebo to determine insulin-stimulated glucose disposal and splanchnic glucose uptake (SGU). No significant differences existed in the patients' characteristics, including age and body mass index, between the two study groups. The pioglitazone treatment increased the mean glucose infusion rate (GIR) prior to OGL from 8.2 +/- 2.2 to 9.2 +/- 2.0 mg/kg.min (mean +/- SD, P = 0.003) and increased the SGU rate from 28.5 +/- 19.4 to 59.4 +/- 27.1% (P = 0.010). The placebo treatment produced no significant changes in either GIR or SGU after treatment. A significant difference (P = 0.042) was observed in change of SGU between the pioglitazone and placebo treatment groups. In conclusion, the results indicate that pioglitazone is effective for ameliorating insulin resistance in NIDDM by enhancing SGU as well as peripheral glucose uptake.

Blood Glucose↗

Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease.

To determine whether similar abnormalities of various soluble full-length and N-terminal truncated Abeta peptides occur in postmortem cerebral cortex of affected PS1 mutation carriers, we examined the amounts of two amyloid species ending at residue 40 or at residues 42(43) using sandwich ELISA systems. Our results indicate that PS1 mutations effect a dramatic accumulation in brain of the highly insoluble potentially neurotoxic long-tailed isoforms of the Abeta peptide such as Abeta1-42(43) and Abetax-42(43). This enhancing effect of PS1 mutation on Abetax-42(43) deposition was highly similar to that of a betaAPP mutation (Val717Ile) but the effects on Abetax-40 production were significantly different between these two causal genes. In contrast to previous studies of soluble Abeta in plasma and in supernatants from cultured fibroblasts of subjects with PS1 mutations, our studies also show that there is an increase in insoluble Abetax-40 peptides in brain of subjects with PS1 mutations.

Adult↗

Severe antecollis during antipsychotics treatment: a report of three cases.

1. The authors report on three patients with severe antecollis that developed after chronic treatment with antipsychotics. These patients had been treated with neuroleptics for their delusions and hallucinations. Antecollis is a rare form of tardive dystonia that has drawn little attention. To our knowledge, there have been no reports on this disorder. 2. The patients developed the symptom after receiving a number of antipsychotics for 4 months to 14 years. Neither discontinuation of antipsychotics nor administration of anticholinergic agents affected the symptom. 3. Although spontaneous improvement of dystonia was obtained after several months without any specific treatment in one patient, the symptom persisted for several years in another. The last patient could not be followed after discharge from our hospital since she and her family did not come to the hospital. 4. Severe antecollis may cause disturbances in various functions, such as vision, speaking and swallowing. Forward bending of the neck may cause inspiratory obstruction. Severe antecollis may not be unusual and psychiatrists should be aware of this symptom in routine clinical practice.

Aged↗

Cefaclor concentration in radicular granuloma after a single oral administration.

1. Cefaclor concentrations in radicular granuloma and serum in nonfasting patients after a single oral administration of 500-mg cefaclor were assayed. 2. The mean peak concentrations in radicular granuloma and serum were 2.57 mcg/g and 7.41 mcg/ ml, respectively. The mean ratio of granuloma/serum concentration at the peak time was 0.35. 3. All cefaclor concentrations in radicular granuloma at the peak time exceeded the minimal inhibitory concentration for 90% of oral streptococci (1 mcg/ml) isolated from odontogenic infection.

Administration, Oral↗