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Biomedical subjects

Y Ando

Publications and source records attributed to Y Ando.

At least 91 records · Page 5Linked to original sources

Functional characterization of basolateral and luminal dopamine receptors in rabbit CCD.

Previous studies reported the existence of both D1- and D2-like receptors in the cortical collecting duct (CCD). However, especially with regard to natriuresis, it remains controversial. In the present study, rabbit CCD was perfused to characterize the receptor subtypes responsible for the tubular actions. Basolateral dopamine (DA) induced a dose-dependent depolarization of transepithelial voltage. Basolateral domperidone, a D2-like receptor antagonist, abolished depolarization, whereas SKF-81297, a D1-like receptor agonist, showed no significant change. In addition, bromocriptine, a D2-like receptor agonist, also caused depolarization, whereas SKF-81297, a D1-like receptor agonist, did not depolarize significantly. Moreover, RBI-257, a D4-specific antagonist, reversed the basolateral DA-induced depolarization. In contrast to the basolateral side, luminal DA caused depolarization via a D1-like receptor; however the change was less than that for basolateral DA. For further evaluation, 22Na+ flux (J(Na)) was measured to confirm the effect of DA on Na+ transport. Basolateral DA also caused a suppression of J(Na), and this reaction was abolished by domperidone. These results suggested that the basolateral D2-like receptor is mainly responsible for the natriuretic action of DA in rabbit CCD.

Animals↗

Modulation of endothelin-1-induced cytosolic free calcium mobilization and mitogen-activated protein kinase activation by erythropoietin in vascular smooth muscle cells.

BACKGROUND: It has been reported that human recombinant erythropoietin (rHuEPO) modulates the sensitivity of the cardiovascular system to vasoconstrictors. We investigated whether rHuEPO has modulative effects on the endothelin-1 (ET-1)-induced elevation of cytosolic free calcium concentration ([Ca2+]i) and mitogen-activated protein (MAP) kinase activation in vascular smooth muscle cells (VSMC). METHODS: [Ca2+]i was measured by fura-2/AM, and MAP kinase activation was analyzed by Western blotting. RESULTS: Exposure of VSMC to rHuEPO prior to stimulation with ET-1 enhanced both basal and ET-1-induced elevation of [Ca2+]i in a dose-dependent manner in the presence of extracellular Ca2+. The synergistic effect was also retained in the absence of extracellular Ca2+ after exposure to rHuEPO. However, the effect was diminished in the presence of extracellular Ca2+ combined with the intracellular Ca2+ release inhibitor TMB-8, PKC inhibitor, or PKC depletion. Exposure to rHuEPO also had a synergistic effect on the activation of MAP kinase induced by ET-1; however, this effect was diminished in the presence of the Ca2+ chelator BAPTA-AM. CONCLUSION: The results suggest that rHuEPO has synergistic effects on ET-1-induced [Ca2+]i mobilization, particularly on intracellular Ca2+ release, and MAP kinase activation in VSMC.

Animals↗

Cardiac amyloidosis presenting as microvascular angina--a case report.

Cardiac amyloidosis usually presents with heart failure, but rarely leads to coronary insufficiency. The authors report a case of a 69-year-old Japanese woman with cardiac amyloidosis presenting as microvascular angina. She had exertional angina with positive exercise test and normal coronary angiograms. However, heart failure developed, and she died 3 years after symptom onset. On autopsy, coronary arteries were patent. In contrast to that of the epicardial coronary arteries, histologic examination of the heart revealed severe obstructive alterations of the intramural coronary arteries with amyloid. Furthermore, amyloid was present mainly in the endocardium and the intramural coronary arteries, but there was little present in the myocardium. This case was a rare AL amyloidosis. There have been only 4 reported cases of cardiac amyloidosis that presented with exertional angina, a positive exercise test, and normal coronary angiograms and histologic examination.

Aged↗

Increased frequency of FcgammaRIIIb-NA1 allele in periodontitis-resistant subjects in an elderly Japanese population.

Many elderly people show minimum periodontal tissue destruction, which might be partly due to genetic advantages in host immune response against periodontopathic bacteria. The human IgG Fc receptor IIIb on neutrophils bears a NA1-NA2 polymorphism. The FcgammaRIIIb-NA1 displays a more efficient interaction with IgG1- and IgG3-opsonized bacteria, compared with the FcgammaRIIIb-NA2. We investigated a 70-year-old Japanese population (n = 599) to determine whether the FcgammaRIIIb polymorphism was associated with resistance to periodontitis. Among subjects with > or = 20 teeth present, periodontitis-resistant (n = 46) and periodontitis-susceptible groups (n = 73) were selected based on the percentage of sites with > or = 4 mm probing attachment loss in the entire dentition. The FcgammaRIIIb-NA1 allotype was overrepresented in the periodontitis-resistant group, compared with the periodontitis-susceptible group (chi2 = 4.89, p = 0.03, odds ratio = 1.87, 95% CI, 1.07 to 3.28). This suggests that FcgammaRIIIb-NA1 may be associated with resistance to periodontitis.

Aged↗

Isolation of a bacterium from mangrove soil for degradation of sea sludge.

Sea sludge, which is sediment of fish excrement and sewage on the sea bottom, continues to be a serious environmental problem. It has the potential to cause eutrophication and red tide, resulting in the death of shellfish and leading to an offensive odor. Soil taken from a mangrove swamp was added to sea sludge, which promoted an initial fermentation of the sludge components. This article reports on the isolation of a bacterium from mangrove soil that is involved in that fermentation. Three bacteria were isolated on a marine agar plate after incubating for 12 h at 60 degrees C. One of these bacteria fermented sea sludge. 16S rDNA of this bacterium was sequenced, and it had a high homology with that of Bacillus fumarioli LMG17489 (AJ250056).

Bacteria↗

Clinical investigation of the lesions responsible for sensory disturbance in Minamata disease.

To clarify the lesions responsible for sensory disturbance in Minamata disease (MD), we clinically investigated the characteristics of sensory disturbance. In all patients with the classical type MD, two-point discrimination was severely disturbed, but the involvement of superficial sensation was relatively mild. On short-latency somatosensory evoked potential study, the component corresponding to N20 was completely absent with normal N9, N11, and N13 components. Although 14 of 38 chronic MD patients demonstrated intact superficial sensation, 10 of these 14 showed mild to moderate disturbance in two-point discrimination. The two-point discrimination in chronic MD patients was significantly high irrespective of the disturbance of superficial sensation. These findings suggest that the sensory disturbance of MD patients may mainly be caused by a lesion in the sensory cortex rather than in the peripheral nerves. However, other foci could be also responsible for the sensory impairment, since 9 of 38 chronic MD patients showed intact two-point discrimination.

Adult↗

The effect of calcium on Fas-mediated apoptosis and secondary necrosis of Jurkat cells.

Our previous study using a new microscopic system indicated that apoptotic cells undergo secondary necrosis during treatment with anti-Fas antibody and calcium. In this study, we compared the time-lapse appearance of apoptosis and secondary necrosis of Jurkat cells during treatment with anti-Fas antibody with and without calcium in individual cells. Apoptosis developed in 97% and 81% of cells during 36-hour-treatment with anti-Fas antibody with and without calcium, respectively. The apoptosis of Jurkat cells showed a characteristic pattern of time-lapse morphological change. Less than 1% of the apoptotic cells divided into apoptotic bodies. There was budding in all the other apoptotic cells, but no apoptotic bodies formed. We confirmed that secondary necrosis occurs in individual apoptotic cells during treatment with anti-Fas antibody. Neither the pattern of time-lapse morphological change nor the time interval between the beginning of apoptotic budding and secondary necrosis were related to the presence of calcium. This study clarified the characteristic pattern of time-lapse morphological change in Jurkat cells during treatment with anti-Fas antibody, and presented direct evidence that individual apoptotic cells undergo secondary necrosis. The presence of calcium did not affect the pattern of morphological change or the time interval between the beginning of apoptotic budding and secondary necrosis.

Apoptosis↗

Ultrasonographic differentiation between tuberculous lymphadenitis and malignant lymph nodes.

OBJECTIVE: To assess the usefulness of ultrasonography in the differential diagnosis of cervical tuberculous lymphadenitis versus malignant lymph nodes. METHODS: Ultrasonography of cervical lymph nodes was performed with a real-time linear scanner using a 7.5- or 11-MHz probe or both. Ultrasonographic findings were retrospectively reviewed in 73 patients: 49 with malignant lymphoma, 15 with tuberculous lymphadenitis, and 9 with metastatic lymph nodes. RESULTS: Ultrasonographic features specific to cervical tuberculous lymphadenitis were strong echoes (33.3%) and an echogenic thin layer (86.7%). When the lymph nodes had at least 1 of these 2 features, tuberculous lymphadenitis was diagnosed with a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Ultrasonographic evaluation of cervical lymph nodes can be useful in the diagnosis of cervical tuberculous lymphadenitis.

Adolescent↗

[Whole blood flow cytometry for detection of activated platelets. I. Platelet identification, blood collection and storage].

In order to assess platelet activation by flow cytometry and activation-dependent monoclonal antibodies, a minute volume(2.5 microliters) of citrated whole blood was mixed for 15 minutes with a cocktail of monoclonal antibodies(MoAb), including PAC1, (a MoAb specific for fibrinogen receptors), and a MoAb against CD62P, (an alpha-granule membrane protein which associates with platelet surface membranes when platelets are activated). After fixation with 1% formaldehyde, the percentage of platelets positive for PAC1 and/or MoAb-CD62P was measured by flow cytometry. Even in resting platelets without stimulation, about 15% of platelets were found to be PAC1-positive and 0.6% of platelets were CD62P-positive. If there was a one-minute delay after needle puncture and before blood collection, the number of PAC1-positive platelets was increased compared to that of blood obtained immediately after puncture. If blood was allowed to stand at room temperature, there was a gradual increase in the number of PAC1-positive platelets, and after 60 minutes, this increase became statistically significant. The addition of Iloprost, (a prostacyclin analogue), immediately after venipuncture did not completely prevent the increase in PAC1-positive platelets after 60 minutes. If the inhibitor was added after first incubating for 60 minutes, however, the percentage of PAC1-positive platelets was reduced to preincubation value. Although flow cytometry is a simple and powerful tool to assess platelet activation, there remain several methodological problems to be resolved before this method may be employed in routine clinical use.

Adult↗

[Validity of reticulocyte count testing in reimbursement practice: a cost-effectiveness analysis].

Recently reticulocyte count testing has markedly decreased in Japan. We studied the current status of the reduction of reimbursement for reticulocyte count testing and the cost-effectiveness of the test in an academic hospital. The orders of complete blood counts(CBC) accompanied by reticulocyte count testing in Tokai University Hospital declined from 58.9 to 13.3% during the last decade. Among a total of 15,538 test orders for reticulocyte count in outpatients, full reimbursement was refused in 123(0.79%) during a one year period from April 1999 to March 2000. The cost-effectiveness of reticulocyte count testing was evaluated in 719 new outpatients who visited Tokai University Hospital during this period. A useful result(UR) of testing was defined as that which contributed to a change in a physician's diagnosis- or decision-making, relating to a "tentative initial diagnosis" obtained from patient history and physical examination alone. Cost-effectiveness for either CBC alone or in combination with reticulocyte count testing was evaluated by calculating clinical effectiveness(the number of URs yielded by a test per patient), economic efficiency(cost required for a test per UR generated), and the cost-effectiveness values(cost required for additional test(s) per additional UR generated). There was a wide disparity in the clinical effectiveness of reticulocyte count twisting among the hospital departments, ranging from 0.53 UR/patient(Gastroenterology-2) to 0(Oral Surgery, Neurology, Urology). Poor clinical effectiveness shown in particular hospital departments endorsed the increasing percentages in reimbursement rejection by the payer of health insurance. The test should be ordered more carefully in consideration of reimbursement and in regard to its cost-effectiveness among different patients groups.

Cost-Benefit Analysis↗

The P-glycoprotein antagonist PSC 833 increases the plasma concentrations of 6alpha-hydroxypaclitaxel, a major metabolite of paclitaxel.

PURPOSE: Overexpression of P-glycoprotein (Pgp) is one mechanism of drug resistance in cancer chemotherapy. A Phase I trial was conducted using PSC 833, a Pgp antagonist, in combination with paclitaxel in patients with refractory cancer. The objective of this study was to assess the effect of PSC 833 on the metabolism of paclitaxel and characterize the differences in 6alpha-hydroxypaclitaxel pharmacokinetics. In addition, we examined the possibility of enhanced cytotoxicity of paclitaxel by the coexistence of 6alpha-hydroxypaclitaxel. EXPERIMENTAL DESIGN: Patients received paclitaxel 35 mg/m(2)/day by continuous intravenous infusion (CIVI) x 4 days without PSC 833 in cycle 1 and escalating doses of paclitaxel (13.1, 17.5, or 21.3 mg/m(2)/day CIVI x 4 days) with 5 mg/kg PSC 833 by mouth every 6 h x 7 days in cycle 2. Plasma samples were analyzed for both paclitaxel and its major metabolite with high-performance liquid chromatography methods. Using human liver microsomes, we studied the effect of PSC 833 on the metabolism of paclitaxel. In addition, the in vitro cytotoxicity of 6alpha-hydroxypaclitaxel alone and in combination with paclitaxel was evaluated. RESULTS: Twenty-one of 22 patients had a metabolite peak (6alpha-hydroxypaclitaxel) observed in the chromatogram of plasma samples from cycle 2 when they received paclitaxel in combination with PSC 833. This metabolite was not detectable in plasma obtained during the first cycle when they received paclitaxel without PSC 833. During cycle 2, the mean concentrations of 6alpha-hydroxypaclitaxel and paclitaxel were 0.10 +/- 0.074 and 0.079 +/- 0.041 microg/ml, respectively. A moderate association was observed between total bilirubin and 6alpha-hydroxypaclitaxel concentrations (P = 0.015, r = 0.52; n = 21). Human liver microsome experiments showed that a PSC 833 concentration as high as 10 microM did not affect the production of 6alpha-hydroxypaclitaxel. Paclitaxel cytotoxicity in HL60 and K562 human leukemia cells was increased in the presence of noncytotoxic concentrations of 6alpha-hydroxypaclitaxel. CONCLUSIONS: PSC 833 increases the plasma concentration of 6alpha-hydroxypaclitaxel during paclitaxel therapy. Inhibition of cytochrome P-450 3A4 by PSC 833 may explain this in part, although other mechanisms cannot be excluded.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A scoring system for ultrasonographic differentiation between cervical malignant lymphoma and benign lymphadenitis.

The purpose of our study is to assess the usefulness of a scoring system for ultrasonography using a high-frequency transducer as a non-invasive examination in the differential diagnosis of cervical malignant lymphoma from benign lymphadenitis. Ultrasonography was performed with a real-time linear scanner using 7.5 and/or 11 MHz probes in 66 patients who were presented with cervical lymphadenopathy and were suspected to have malignant lymphoma. Thereafter, a surgical biopsy was performed for histopathological diagnosis, revealing 49 cases of malignant lymphoma and 17 cases of benign lymphadenitis. Ultrasonographic findings were reviewed retrospectively. The incidence of following ultrasonographic features was found to be significantly higher in malignant lymphoma than in benign lymphadenitis. These were; (1) longitudinal and transverse diameter ratio(L/T) < 2.0, (2) a delineation of multiple nodes, (3) a tendency of fusion, (4) an irregular margin, (5) hypoechoic masses with heterogeneous internal echoes, (6) a presence of line echoes and (7) an absence of hilum. These 7 ultrasonographic features were used in combination for a scoring system to discriminate malignant lymphoma from benign lymphadenitis. When ultrasonographic findings of lymph nodes fulfilled more than 3 of the 7 features, malignant lymphoma was diagnosed with a sensitivity of 98.0% and a specificity of 76.5%. Ultrasonographic evaluation of swollen cervical lymph nodes using a high-frequency transducer would be informative and should be performed prior to a surgical biopsy.

Adolescent↗

[Intermittent administration of 5-FU and isovorin to patients with advanced and recurrent colon cancer].

We attempted a new regimen of intermittent administration of 5-FU and low-dose Isovorin (F.I) to four patients with advanced and recurrent colon cancer. A partial response (PR) was achieved in two of four patients who had evaluable lesions for this treatment. We observed few side effects among these patients. Only one patient among four showed grade 1 neuropathy after two administrations of this chemotherapy. However, after a two-week pause in administration, the neuropathy disappeared and we could continue the therapy. This patient with multiple liver metastases achieved a partial response. Other patients had no side effects such as bone marrow suppression or digestive symptoms. This intermittent F.I treatment might be an effective and promising therapy with few side effects even for patients with poorer conditions.

Aged↗

[Prospective evaluation of renal function by serum cystatin-C: comparison with three other parameters of glomerular filtration rate].

Cystatin-C is a low-molecular-weight basic protein produced at a stable rate by all nucleated cells. It is freely filtered through the renal glomeruli and primarily catabolized in the proximal tubule cells. Since the serum cystatin-C concentration is not affected by muscle mass nor inflammation, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with the serum creatinine level. To evaluate the clinical usefulness in terms of estimation of the glomerular filtration rate(GFR), we compared the serum cystatin-C concentration with other markers of GFR, such as serum levels of creatinine(SCr), alpha 1-microglobulin(alpha 1MG), and beta 2-microglobulin(beta 2MG). Their variations were analyzed based on 2-hour creatinine clearance (2hCCr) as a standard marker of GFR. The logarithmic value of serum cystatin-C level showed a stronger negative correlation(-0.959) with the logarithmic value of 2hCCr than that of other markers(-0.924, -0.942, -0.888; SCr, alpha 1MG, beta 2MG, respectively). Although beta 2MG showed the next strongest correlation with 2hCCr, it had a significantly lower sensitivity when detecting mild reduction of GFR. In addition, serum cystatin-C showed the greatest area under the curve of receiver-operating characteristic(ROC) of all GFR markers at both higher(90 ml/min.) and lower(70 ml/min.) cut-off value of 2hCCr. These data suggest that serum cystatin-C is useful for estimating GFR, even if the reduction of GFR is very mild.

Adult↗

Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis.

Irinotecan unexpectedly causes severe toxicity of leukopenia or diarrhea. Irinotecan is metabolized to form active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) 1A1 enzyme. Genetic polymorphisms of the UGT1A1 would affect an interindividual variation of the toxicity by irinotecan via the alternation of bioavailability of SN-38. In this case-control study, retrospective review of clinical records and determination of UGT1A1 polymorphisms were performed to investigate whether a patient with the variant UGT1A1 genotypes would be at higher risk for severe toxicity by irinotecan. All patients previously received irinotecan against cancer in university hospitals, cancer centers, or large urban hospitals in Japan. We identified 26 patients who experienced severe toxicity and 92 patients who did not. The relationship was studied between the multiple variant genotypes (UGT1A1*28 in the promoter and UGT1A1*6, UGT1A1*27, UGT1A1*29, and UGT1A1*7 in the coding region) and the severe toxicity of grade 4 leukopenia (< or =0.9 x 10(9)/liter) and/or grade 3 (watery for 5 days or more) or grade 4 (hemorrhagic or dehydration) diarrhea. Of the 26 patients with the severe toxicity, the genotypes of UGT1A1*28 were homozygous in 4 (15%) and heterozygous in 8 (31%), whereas 3 (3%) homozygous and 10 (11%) heterozygous were found among the 92 patients without the severe toxicity. Multivariate analysis suggested that the genotype either heterozygous or homozygous for UGT1A1*28 would be a significant risk factor for severe toxicity by irinotecan (P < 0.001; odds ratio, 7.23; 95% confidence interval, 2.52-22.3). All 3 patients heterozygous for UGT1A1*27 encountered severe toxicity. No statistical association of UGT1A1*6 with the occurrence of severe toxicity was observed. None had UGT1A1*29 or UGT1A1*7. We suggest that determination of the UGT1A1 genotypes might be clinically useful for predicting severe toxicity by irinotecan in cancer patients. This research warrants a prospective trial to corroborate the usefulness of gene diagnosis of UGT1A1 polymorphisms prior tb irinotecan chemotherapy.

Adult↗

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Amyloid Neuropathies↗