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Biomedical subjects

M Wada

Publications and source records attributed to M Wada.

At least 217 records · Page 12Linked to original sources

Spontaneous gastrointestinal perforation in patients with lymphoma receiving chemotherapy and steroids. Report of three cases.

Spontaneous gastrointestinal perforations in three patients with lymphoma were considered to be treatment-related conditions. All three were diagnosed as having malignant lymphoma by histological examination, and treated with chemotherapy and steroids. Four to 14 days after the start of chemotherapy, they complained of abdominal pain and plain roentgenograms revealed pneumoperitoneum. The interval between the onset of peritonitis and operation was almost 24 h. Emergency operations were carried out; one patient with a jejunal perforation underwent resection of the jejunum, another with a gastric perforation received a simple closure with omental patch, and the third with a gastric perforation underwent gastrectomy. Two patients recovered from the surgery, while the gastrectomy patient died due to sepsis. The favorable outcome of the surgical intervention is attributed to early diagnosis, prompt exploration, and selective operative procedures. We recommended a simple closure with omental patch for gastroduodenal perforation. Resection and primary anastomosis are possible only in the small bowel.

Adult↗

Analysis of binding properties between 20 kDa human growth hormone (hGH) and hGH receptor (hGHR): the binding affinity for hGHR extracellular domain and mode of receptor dimerization.

It has recently been shown that 20 kDa human growth hormone (hGH) forms the 1:2 hGH:hGH receptor (hGHR) complex and expresses full agonistic activity, although it hardly forms the 1:1 GH:GHR complex as compared with 22 kDa hGH. To clarify this mechanism, we analyzed the mode of receptor dimerization of 20 kDa hGH using the intact form and mutants. Complex formation analysis between hGHR extracellular domain (hGHBP) and either site1 mutant (K157A) or site2 mutant (G105R) by gel-filtration showed that the site1 mutant apparently formed no 1:1 complex and that the site2 mutant formed only the 1:1 complex. Cell proliferation analysis revealed that the activity curve (vs ligand concentration) of 20 kDa hGH showed a bell-shaped pattern. This indicates that the receptor dimerization of 20 kDa hGH proceeds in a sequential manner. Based on this sequential binding we have produced a mathematical model for receptor dimerization as a function of [hGH], [hGHBP], K(d) values for the first hGHBP binding (K(d1)) and the second hGHBP binding (K(d2)). The result of 20 kDa hGH binding to (S201C) hGHBP immobilized on biosensor tip showed that the K(d1) value was 1. 6x10(-8) M. Adopting this value as a constant in the function described above, we have obtained calculative hGHR dimerization curves vs hGH concentration. Since the K(d2) value could not be experimentally determined, the curves were simulatively obtained with varied K(d2) values. The simulated curve pattern coincided with the experimental result of the cell proliferation in Ba/F3-hGHR when the value 2.5x10(-10) M was adopted as K(d2). In conclusion, although the affinity of 20 kDa hGH for the first hGHR binding is reduced to one-tenth, that for the second binding is increased ten-fold in comparison with those of 22 kDa hGH, indicating that 20 kDa hGH can be an effective hGH isoform in the presence of hGHBP.

Alternative Splicing↗

A simple food frequency questionnaire for Japanese diet--Part I. Development of the questionnaire, and reproducibility and validity for food groups.

We developed a simple food frequency questionnaire (FFQ) based on one-day dietary records (DRs) among 1001 subjects in Nagoya, Japan. A total of 97 foods and dishes were selected through a two-step procedure; first by ranking food items according to the contribution to the population intake of nutrient variables, and second by stepwise multiple regression analyses of individual food items as the independent variables and of total nutrient intake as the dependent variables. For simplicity, questions on portion sizes were not included except for a few selected food items, which resulted in short time (about 20 minutes) to complete the questionnaire. This FFQ was validated for food groups by referring to four 4-day DRs among 88 men and women in central Japan, from 1996 to 1997. The energy-, sex- and age-adjusted test-retest correlation coefficients between the two FFQs administered at an one year interval ranged from 0.34 to 0.78. The de-attenuated, energy-, sex- and age-adjusted correlation coefficients between the second FFQ and the DRs were larger than 0.40 for most food groups, indicating the usefulness of this simple FFQ with its sufficient validity in epidemiological surveys.

Adult↗

A simple food frequency questionnaire for Japanese diet--Part II. Reproducibility and validity for nutrient intakes.

A self-administered 97-item simple food frequency questionnaire (FFQ), without portion size questions for most items, was completed twice at an one-year interval by 88 men and women in central Japan to evaluate its reproducibility. This FFQ was further validated by referring to four 4-day weighed dietary records (DRs) which were performed at 3-month intervals. Mean energy and 18 nutrient intakes measured by the first and the second FFQs were quite similar to those measured by the DRs. In our reproducibility study, Pearson and intraclass correlation coefficients, adjusted for energy intake, sex and age, ranged from 0.48 to 0.82 (median = 0.67). In the validation study, adjusted and de-attenuated correlation coefficients between the second FFQ and the DRs ranged from 0.42 for iron to 0.83 for calcium (median = 0.61). The proportion of subjects classified by the FFQ into the same or adjacent quintiles defined by the DRs was between 65.9% and 83.0% (median = 69.9%). These findings essentially suggested that our FFQ is well reproducible and sufficiently valid, and therefore, reasonably useful for nutritional epidemiological studies for Japanese diets, particularly for those of Tokai Area.

Adult↗

Secretion and excretion of immunoglobulin A to cecum and feces differ with type of indigestible saccharides.

The study was conducted to elucidate the effects of orally administered indigestible saccharides (IDS) on immunoresponses of the intestinal tracts, especially secretion and excretion of immunoglobulin A (IgA). Male 4-week-old Sprague-Dawley rats were fed diets containing several kinds of IDS (cellulose, corn husk, glucomannan, curdlan and lactulose) at 5% for three weeks. The results indicated that the proportion of IgA-presenting lymphocytes in the cecal mucosa of the tested IDS groups increased significantly or tended to increase compared with that of the cellulose group. No significant differences among the experimental groups were observed in the CD4(+)- and CD8(+)-presenting lymphocytes and the CD4+/CD8+ ratios in the small intestine, cecum and mesenteric lymph nodes. IgA amounts in the cecal contents increased significantly in the glucomannan and curdlan groups as compared with that in the cellulose group. The inconsistent results were observed in the cecal IgA amounts of the lactulose group. Although IgA excretion into feces increased periodically in the cellulose, hardly any changes were observed in the glucomannan and curdlan groups. These results revealed that IgA secretion from cecal mucosa to contents was promoted, and its excretion to feces was decreased by the oral administration of highly fermentable IDS, respectively, while non- or low-fermentable IDS functioned adversely to IgA responses in the intestinal tract. It is suggested that the response of IgA in the intestinal immune system differs with the type of IDS ingested.

Administration, Oral↗

Curdlan and gellan gum, bacterial gel-forming polysaccharides, exhibit different effects on lipid metabolism, cecal fermentation and fecal bile acid excretion in rats.

The effects of curdlan (CD) and gellan gum (GG), bacteria-producing polysaccharides, on lipid concentrations of serum and liver, fecal bile acid composition and intestinal fermentation products were studied in rats fed diets containing cellulose powder (CP), CD or GG at 5% for 4 wk. The cecal weight of the CD group increased significantly as compared to that of the other two groups and the pH of its contents was significantly low. The gastrointestinal transit time in the GG group was significantly shorter than that in the CP and CD groups. No significant inter-group differences were observed in the serum concentrations of total cholesterol and HDL-cholesterol, but a significant decrease was observed in the hepatic total cholesterol concentration of the CD group as compared to that of the CP and GG groups. No significant difference in the total bile acid excretion in feces was observed among the groups, but significantly low values were observed in the proportion of secondary bile acids in the CD group as compared to those of the CP and GG groups. Amounts of short-chain fatty acids (acetic, propionic and butyric acid) and lactic acid in the cecal contents were significantly higher in the CD group than in the other two groups. These results reveal that dietary CD is easily degraded and fermented by intestinal bacteria in the cecum and lowers cholesterol concentration in the liver, while dietary GG shortens the gastrointestinal transit time, suggesting the promotion of evacuation.

Animals↗

Measurement of olfactory threshold using an evoked potential technique.

A new device introducing brief pulses of odorised air synchronous with the inspiration of the test subject was developed. Responses to skatole were distinguishable as an evoked response by using the superimposition technique before averaging. The olfactory threshold measured by the chemosensory event-related potentials to olfactory stimulations according to our ascending method was found E-2 or E-1 and was equal to the detection olfactory threshold in each of the eight normal test subjects.

Electric Stimulation↗

[Six-months chemotherapy (2HRZS or E/4HRE) of new cases of pulmonary tuberculosis--six year experiences on its effectiveness, toxicity, and acceptability].

The incidence of tuberculosis in Japan, 33.7 per 100,000 in 1997, is very high compared with USA or Western European countries. The decrease in the incidence has slowed down from the early 1980s, and the average annual rate of decrease has been 3.8% in the last 5 years. About 9 percent of tuberculosis patients defaulted from the nine-month regimen (6HRS or E/3HR) in urban areas. Regimens shorter than nine-month are needed to achieve high effectiveness of tuberculous chemotherapy. Out of 1128 new pulmonary tuberculosis patients, six-hundred twenty started treatment with six-month (2HRZS or E/4HRE) in Fukujuji Hospital, JATA, in Tokyo from January 1991 to December 1996. Out of 620, four-hundred twenty eight were both smear and culture positive, 136 were smear negative and culture positive and 56 were bacilli negative. Out of 564 bacilli positive cases, 530 were susceptible to INH and RFP. Out of 530 drug susceptible cases three hundred ninety-three patients completed the regimen. Ninety-three percent of these patients had converted to negative at two months of chemotherapy and all of them at five months. Out of 450, two-hundred ninety five completed 6-month regimen, one-hundred fifty-five were changed their regimen or prolonged duration of chemotherapy. Out of 295, nine patients (3.1%) relapsed after the completion of 6-month chemotherapy. Mean follow-up period was 17.2 months and the median was 15.5 months. The relapse rate was 2.2 per 100 person-years. Six of the relapsed cases were complicated with Diabetes Mellitus. Relapse rate was higher in patients with Diabetes Mellitus than in patients without (6/54, 7.9 per 100 person-years vs 3/237, 0.8 per 100 person-years) (p < 0.001). Drug-induced hepatotoxicity was defined as elevated serum transaminase level with clinical symptoms of hepatitis or elevated serum transaminase level more than 5 times of upper limit of normal range with or without symptoms. Drug-induced hepatotoxicity developed in 43 (8.0%) of 535 with initial normal liver function test results, this rate was similar to that in patients treated with nine-month regimen (34/420, 8.1%). But the frequency of hepatotoxicity of more than 400 IU/ml of serum transaminase level was higher in patients treated with PZA-containing regimen than with nine-month regimen (16/536, 3.0% vs 4/420, 1.0%), but this deference was not statistically significant. Hepatotoxicity developed in 13/85 (15.3%) of patients treated with PZA-containing regimen with abnormal liver function tests at the beginning of chemotherapy, and this frequency was similar to 7/65 (10.8%) in patients with nine-month regimen. The relapse rate in patients with Diabetes Mellitus was statistically higher than in without Diabetes Mellitus (7.9 vs 0.8 per 100 person-years). We concluded that the six-month regimen was highly effective, but the frequency of severe hepatotoxicity was relatively higher than in nine-month regimen and the duration of chemotherapy was not enough for patients complicated with Diabetes Mellitus. Further study is needed for sufficient chemotherapy in patients with Diabetes Mellitus.

Adult↗

Multidrug resistance-associated protein subfamily transporters and drug resistance.

Multidrug resistance-associated protein gene MRP/MRP1, and its family genes, including MRP2/cMOAT, have been isolated and characterized. These ATP-binding cassette (ABC) superfamily transporter genes are differentially expressed in various normal tissues and multidrug-resistant cell lines. Transfection of MRP/MRP1 and MRP2/cMOAT cDNA confers drug resistance on different spectra of anticancer agents from that of MDR1 coding P-glycoprotein. Although it remains unclear how MRP/MRP1 and related family genes are specifically involved in drug resistance in clinical cancers, current knowledge of the MRP subfamily suggests the importance of this class of transporters as a molecular target for drug sensitivity to anticancer agents.

ATP-Binding Cassette Transporters↗

[Vascular endothelial growth factor promotes experimental choroidal neovascularization in monkey eyes].

PURPOSE: To evaluate the effect of vascular endothelial growth factor (VEGF) on experimental choroidal neovascularization (CNV) in monkey eyes through clinical, morphometric, and histological observations. METHOD: CNV was induced in both eyes of 6 rhesus monkeys by intense photocoagulation by red krypton laser. Immediately after photocoagulation, 2.5 micrograms of exogenous human VEGF was injected into the vitreous of the left eye in each animal. The right eyes served as controls. The eyes were enucleated 3 days to 12 weeks after photocoagulation and were examined by light and electron microscopy. RESULTS: VEGF-treated eyes developed remarkable serous retinal detachment around the sites of photocoagulation with manifest CNV one week after photocoagulation. Although there was no difference in the incidence of CNV between the treated and control eyes, the treated eyes showed more intense leakage of fluorescein from the CNVs for up to 4 weeks after treatment. Morphometrically, the CNVs were significantly larger and continued to grow longer in the treated than in the control eyes after one week of photocoagulation. Histologically, newly formed vessels with a distinct lumen were present in the treated eyes after 3 days of photocoagulation. CONCLUSION: Intravitreal injection of human VEGF promotes experimental choroidal neovascularization in monkey eyes.

Animals↗

[Cytopathology of the breast--benign and malignant neoplastic conditions].

Breast cancer is one of the most common malignancies in women and the incidence has been increasing. Cytology plays a very important role not only in the diagnosis of breast lesions, but also in keeping the benign-to-malignant biopsy ratio low, so that unnecessary surgery is not performed. A fundamental feature of a benign aspirate is the presence of a dual population of ductal epithelial cells (variable within limits, but cohesive and orderly) and myoepithelial cells (naked, bipolar nuclei). Several cytologic features must be assessed to make the diagnosis of malignancy, including high cellularity, cell dissociation, large nuclear and cell size, cell pleomorphism, intracytoplasmic lumens (containing mucin), irregular nuclear margin, coarse chromatinic pattern, prominent nucleoli, and the presence of abnormal mitoses. Other criteria of lesser importance include necrosis, absence of myoepithelial cells and intranuclear inclusions. However, breast carcinomas do not always show every feature of malignancy. The well-differentiated or low-grade carcinomas are often difficult to differentiate from benign cells. It may be helpful to consider the clinical and radiological findings. We reported here, typical neoplastic lesions of the breast by correlating cytological with histopathological features.

Biopsy↗

[Comparison of the newly developed MB redox system with mycobacteria growth indicator tube (MGIT) and 2% Ogawa egg media for recovery of mycobacteria in clinical specimens].

The rate of recovery and the mean time to detection of mycobacteria in clinical specimens were determined in a newly-developed MB Redox system based on liquid medium, and the results were compared with those of MGIT and 2% Ogawa egg media. From 587 sputum specimens processed, totally 203 mycobacterial isolates were detected, of which 177 (87.2%) with MB Redox, 185 (91.1%) with MGIT and 133 (65.6%) with 2% Ogawa medium. The difference in the percentages of positive cultures between either of the two liquid media and 2% Ogawa medium was significant (p < 0.0001). The mean time to detection of the Mycobacterium tuberculosis complex was 17.5 days with MB Redox, 18.7 days with MGIT, and 26.2 days with 2% Ogawa medium. The contamination rates were 1.5, 1.7, and 4.1% for MB Redox, MGIT, and 2% Ogawa medium, respectively. In conclusion, both MB Redox and MGIT systems, based on liquid medium, are more efficient than 2% Ogawa medium for the recovery of mycobacteria in clinical specimens.

Bacteriological Techniques↗

[Interhemispheric subdural empyema in a patient with allergic rhinitis, pansinusitis and acute excerbation of frontal sinusitis].

We reported a 10-year-old boy with an interhemispheric subdural empyema caused by acute excerbation of frontal sinusitis. He has suffered from allergic rhinitis and pansinusitis for years. He had fever and a generalized tonic-conic seizure, followed by prolonged consciousness disturbance and right hemiparesis. CT and MRI were useful to diagnose an interhemispheric subdural empyema, which showed a characteristic double-layer fluid collection pattern. Prompt diagnosis and treatment with craniotomy resulted in recovery without any neurological sequelae. His basic disorders, allergic rhinitis and pansinusitis, were successfully treated with macrolides and antiallergic drugs: pranlukast hydrate and sodium cromoglicate, administered per os and by inhalation, respectively.

Acute Disease↗

[Cross-contamination of Mycobacterium tuberculosis culture in clinical laboratories].

For many years, it has been thought that positive culture of M. tuberculosis is a definitive diagnostic evidence of tuberculosis and cross-contamination of M. tuberculosis culture in clinical laboratories is rare. However recently introduced RFLP analysis has enabled us to identify a strain of M. tuberculosis, and many cases of the cross-contamination in clinical laboratories confirmed by RFLP analysis have been reported. In this report, we present the first case of the cross-contamination confirmed by RFLP in Japan. In our case, 5 patients without any personal link to each other were suspected based on clinical findings to have cross-contaminated results of M. tuberculosis culture. All their specimens were processed on the same day, and were smear negative and culture positive with only a small number of colonies (less than 8 colonies). The sputum from the suspected source of contamination processed on the same day was strongly positive for AFB smear and heavily culture positive. The RFLP patterns of these 6 patients were identical, so it was concluded that the positive cultures of the sputum from the 5 patients who were not expected to be culture positive on clinical findings were caused by the cross-contamination in our hospital laboratory. We review all the charts of patients with M. tuberculosis culture positive results in the same year of this case, but we didn't find no other cases suspected of the cross-contamination. Then we reviewed the literature of M. tuberculosis culture cross-contamination. The patterns of the cross-contamination are divided into two. One is associated with malfunction of a sampling needle in the BACTEC 460 system and the other associated with the initial processing of the specimens, mostly involving reagents such as NaOH solution. Cross-contaminated specimens are usually smear negative with only a few colonies (less than 5), and processed just after the source specimen of the contamination in most reported cases, but not in all. In almost half of them the cross-contamination results had significant influence on the clinical management. The frequency of the cross-contamination is estimated around 1% of the patients with M. tuberculosis culture positive results. For early detection of the cross-contamination, not only clinicians but also laboratory staffs have important role and close cooperation between them is mandatory. To prevent the contamination, it is advisable to process smear positive and probable culture positive specimens separately from others, and not to use a large same container of reagents for processing of different specimens.

Adult↗

[MR imaging of the posterolateral aspect of the knee].

The structures of the posterolateral aspect of the knee were evaluated with axial MR images. One hundred twelve knees of clinical cases without posterolateral injury were retrospectively reviewed, and 30 knees of 15 volunteers with no history of knee injury or pain were evaluated. The amount of joint effusion and visualization of the lateral collateral ligament (LCL) and popliteal tendon were classified according to three grades. The LCL and popliteal tendon were identified in 111 clinical cases (99%) and 28 volunteer knees (93%). Visualization of the LCL and popliteal tendon was facilitated in the presence of both joint effusion and fluid collection between the LCL and popliteal tendon. Fluid collection posterior to the femoral attachment of the popliteal tendon was seen in 79 clinical cases (71%) and 20 volunteer knees (67%). Based on cadaveric study, this was considered to be a potential fluid space for communication to the joint space.

Adolescent↗

A phytochrome from the fern Adiantum with features of the putative photoreceptor NPH1.

In plant photomorphogenesis, it is well accepted that the perception of red/far-red and blue light is mediated by distinct photoreceptor families, i.e., the phytochromes and blue-light photoreceptors, respectively. Here we describe the discovery of a photoreceptor gene from the fern Adiantum that encodes a protein with features of both phytochrome and NPH1, the putative blue-light receptor for second-positive phototropism in seed plants. The fusion of a functional photosensory domain of phytochrome with a nearly full-length NPH1 homolog suggests that this polypeptide could mediate both red/far-red and blue-light responses in Adiantum normally ascribed to distinct photoreceptors.

Amino Acid Sequence↗

Localization of the Rab3 small G protein regulators in nerve terminals and their involvement in Ca2+-dependent exocytosis.

The Rab3 small G protein subfamily (Rab3) consists of four members, Rab3A, -B, -C, and -D. We have recently isolated and characterized the Rab3 regulators, GDP/GTP exchange protein (GEP) and GTPase activating protein (GAP), both of which are specific for the Rab3 subfamily. Rab3 GEP stimulates the conversion of the GDP-bound inactive form to the GTP-bound active form, whereas Rab3 GAP stimulates the reverse reaction. Of the four members of the Rab3 subfamily, evidence is accumulating that Rab3A is involved in Ca2+-dependent exocytosis, particularly in neurotransmitter release. We first analyzed the subcellular localization of Rab3 GEP and GAP in rat brain. Subcellular fractionation analysis showed that both Rab3 GEP and GAP were enriched in the synaptic soluble fraction. Immunocytochemical analysis in primary cultured rat hippocampal neurons showed that both Rab3 GEP and GAP were concentrated at the presynaptic nerve terminals. We then examined whether Rab3 GEP and GAP were involved in Ca2+-dependent exocytosis by use of human growth hormone (GH) co-expression assay system of cultured PC12 cells. Overexpression of the deletion mutant of Rab3 GEP possessing the catalytic activity reduced the high K+-induced GH release without affecting the basal GH release, whereas that of the deletion mutant lacking the catalytic activity showed no effect on the high K+-induced GH release. In contrast, overexpression of Rab3 GAP or its deletion mutant possessing the catalytic activity did not affect the high K+-induced GH release or the basal GH release. These results indicate that Rab3 GEP and GAP are colocalized with Rab3A at the synaptic release sites and suggest that they regulate the activity of Rab3A and are involved in Ca2+-dependent exocytosis.

Animals↗

Hypomethylation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukemias.

Selection of human cells for resistance to vincristine or doxorubicin often induces overexpression of the multidrug resistance 1 gene (MDR1), which encodes the cell surface P-glycoprotein, as a result of gene amplification or transcriptional activation. Moreover, overexpression of the MDR1 gene has been shown to be associated closely with clinical outcome in various hematological malignancies, including acute myeloid leukemia (AML). However, the precise mechanism underlying overexpression of the MDR1 gene during acquisition of drug resistance remains unclear. We recently described an inverse correlation between the methylation status of CpG sites at the promoter region and expression of the MDR1 gene in malignant cell lines. In this study, we expanded this analysis to 42 clinical AML samples. We adapted a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay for gene expression and a quantitative PCR after digestion by Hpa II for methylation status of the MDR1 gene. We observed a statistically significant inverse correlation between methylation and MDR1 expression in clinical samples. The hypomethylation status of the MDR1 promoter region might be a necessary condition for MDR1 gene overexpression and establishment of P-glycoprotein-mediated multidrug resistance in AML patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗