[Effects of antibiotics on the liver].
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Biomedical subjects
Publications and source records attributed to K Shimada.
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A method for the determination of dehydroepiandrosterone sulphate (DHEA-S) in biological samples is described. [7,7,16,16-2H4]-Dehydroepiandrosterone sulphate (2H4-DHEA-S) was synthesized and its applicability was examined as an internal standard with liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS). Deuterium atoms in 2H4-DHEA-S molecules were not exchanged to hydrogen atoms during the extraction procedure from biological specimens in the determination of DHEA-S with LC/MS. The calibration curve of DHEA-S was linear over the range of 2-500 ng on-column. The detection limit of DHEA-S was 0.5 ng on-column with a signal-to-noise ratio of 3. The relative standard deviations of intra- and inter-assay with 200 ng of standard sample were 3.3 and 5.0%, respectively. These results were better than a similar method reported on previously (Nakajima et al., 1996). The proposed method was successfully developed for the determination of DHEA-S in biological samples.
The quantitative determination of 25-hydroxyvitamin D3 3-sulphate in human plasma was completed using reversed phase high performance liquid chromatography with UV detection (265 nm) and an internal standard method. The vitamin D sulphate fraction was obtained from a plasma specimen with the combined use of a Bond Elut C18 cartridge for solid-phase extraction and a piperidinohydroxypropyl Sephadex LH-20 column for lipophilic ion-exchange chromatography. Separation of the compounds was performed on a YMC-Pack ODS-AM column. The limit of quantitation was 5 ng/mL and the assay was linear from 5 to 50 ng/mL. The proposed method is satisfactory in its accuracy and precision.
A retrospective study was made of the correlation between preoperative clinical or histologic findings and the prevalence of lymph node metastasis in 60 patients with squamous cell carcinoma of the oral cavity who had histologically confirmed neck metastasis. Of these 60 patients, 39 with clinically N+ necks underwent immediate therapeutic neck dissection, and 21 whose necks were initially N0 but progressed to N+ during observation underwent subsequent therapeutic neck dissection. The primary site, TNM staging, histologic grade of malignancy of biopsy specimen, and location and number of histologically positive lymph nodes were reviewed in each case. The results were as follows: (1) The prevalence of neck metastasis was not significantly correlated with primary site and T stage; however, there was an apparent correlation between histologic grade of malignancy and the prevalence of neck metastasis. Patients with grade I-II histologic malignancy showed limited metastases that involved lymph nodes in levels I-II. On the other hand, patients showing grade III-IV histologic malignancy often had metastases that extended beyond level III, regardless of T stage. These results suggest that histologic grade of malignancy, as well as clinical features, must be taken into consideration when deciding whether supraomohyoid neck dissection is indicated. (2) The group that underwent subsequent neck dissection exhibited less advanced neck metastasis and a better prognosis than the group which underwent immediate neck dissection. These findings show that if they are closely followed up, it is possible to delay neck dissection in N0 patients until a neck metastasis is detected.
Three cases of liver granuloma mistakenly diagnosed as metastases from breast cancer are described. No common cause for granuloma formation in the liver was evident among the patients. Although surgical intervention to obtain a definitive diagnosis may occasionally be necessary, care needs to be exercised in the preoperative diagnosis of liver tumors. The growth rate of the lesions may be an important factor to consider.
A total of 754 patients were treated intravenously with sulbactam/ampicillin, in a clinical trial to determine the efficacy and safety of the drug. The majority of patients were treated with 3 g/day by intravenous infusion for 4 to 14 days. Clinical response was evaluated in 689 of 754 patients. In the treatment of respiratory and urinary tract infections, efficacy was 82.5% and 77.1%, respectively. Overall, sulbactam/ampicillin was effective in 80.4% of all evaluable patients. Of 175 patients who failed to respond to prior antibiotic therapy, 135 patients (77.1%) were effectively treated with sulbactam/ampicillin. The overall bacteriological eradication rate was 91.8% against Gram-positive organisms, 75.9% against Gram-negative organisms, and 90% against anaerobes. In addition, 166 of 221 strains that were beta-lactamase producers were eradicated after treatment with sulbactam/ampicillin. Side effects such as rash, fever, itching, urticaria, and diarrhea occurred in only 2.65%, 20 of 754 cases. Laboratory abnormalities were similar to those reported for other beta-lactam antibiotics, including increases in levels of SGOT (4.9%), SGPT (5.7%), and eosinophilia (3.4%) counts. The study showed that sulbactam/ampicillin has a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms as well as anaerobes. There was a high degree of safety. Thus, sulbactam/ampicillin is effective and safe as a treatment for medical, surgical, urological, and gynecological infections.
We reviewed computed tomography (CT) in eight patients with sclerosing hepatocellular carcinoma who underwent resection. Dynamic CT was performed 25-40 s (rapid phase) and 5-10 min (late phase) after injection of contrast medium. Most of the lesions were round and homogeneous. Tumors tended to show density equal to the liver. The relative density of the tumors in the rapid phase, however, tended to be higher than in other phases. A peripheral low-density area was absent. Dynamic CT was thus important in the diagnosis of sclerosing hepatocellular carcinoma.
Although the birth of homozygous alpha1, 3 galactosyltransferase gene-knockout pigs raised hopes for an imminent breakthrough in the prevention in the antibody-mediated rejection of pig to human discordant xenotransplants, human CD8(+) cytotoxic T lymphocyte (CTL)-mediated killing may represent a new immunological barrier to long-term survival in xenograft recipients. In this study, we demonstrated that the cytotoxicity of human CD8(+) CTL against swine endothelial cells (SEC) is highly detrimental and mediated at least in part by the Fas/FasL pathway. To prevent this CTL-mediated xenocytotoxicity, we overexpressed the human decoy Fas antigen, which does not contain a death domain in its cytoplasmic region, by means of binding competition with endogenous pig Fas antigen on SEC for the common ligand, human FasL. Furthermore, we generated a membrane-bound form of human FasL that cannot be cleaved by a putative metalloproteinase to produce a soluble form, which was assessed as an inhibitor of CTL cytotoxicity. Both human decoy Fas and membrane-bound FasL were effective to prevent CTL-mediated killing, suggesting that these novel molecules may represent a step forward toward preventing CD8(+) CTL-mediated xenograft rejection. The combined expression of both molecules may be more beneficial to protect xenograft cells.
AIMS: Type 2 diabetes is characterized by a combination of insulin resistance and pancreatic beta-cell dysfunction. Although pancreas transplantation (PTx) is mainly performed in patients with type 1 disease, both clinical and experimental data have demonstrated that PTx improves insulin sensitivity in type 2 diabetic recipients. However, it remains unclear whether PTx has the potential to induce islet neogenesis in a recipient's native pancreas. METHODS: Nondiabetic 10-week-old and diabetic (defined as blood glucose level >250 mg/dL) 25-week-old (average onset age of diabetes) male spontaneously diabetic Torii (SDT; RT1(a)) rats served as donors and recipients, respectively. RESULTS: In nontreated control SDT rats, beta-cell mass gradually decreased and blood glucose levels progressively increased (>600 mg/dL after 40 weeks of age). In PTx rats, however, the onset of diabetes was significantly delayed (>47.5 +/- 18.2 [graft age] versus 25.2 +/- 3.9 weeks in control rats). On immunohistochemical staining, insulin-secreting islets were observed in the naive pancreata of 40-week-old recipients with PTx (PTx40w), whereas no islets were found in 40-week-old control SDT rats. Moreover, the islets in the native pancreata of PTx40w recipients were located close to ductal structures, and PDX-1 (pancreatic duodenal homeobox-1)-positive cells were more clearly visible. These results indicate the possibility of beta-cell regeneration in the recipient native pancreas by avoiding glucose toxicity under normoglycemic condition achieved by PTx. CONCLUSIONS: Pancreas transplantation has beneficial effects on impaired islet, inducing regeneration in the spontaneously diabetic Torii rat.
We estimated the severity of coronary artery disease by the continuous-recording method of exercise two-dimensional echocardiography (Ex.2DE) in 56 patients with angiographically significant coronary artery stenosis ( > 50% diameter narrowing) who had undergone both Ex.2DE and coronary angiography. Patients were divided into two groups on the basis of findings of coronary angiography: group 1 had 50% to 89% stenosis (n = 24) and group 2 had 90% or greater stenosis (n = 32). The sensitivity and specificity of Ex.2DE for the detection of ischemic segments were 82% and 88%, respectively in the overall patient population. The sensitivity was 67% in group 1 and 94% in group 2. Hyperkinesis occurred at the beginning of exercise in 21 (88%) of 24 patients in group 1 and 15 (47%) of 32 patients in group 2 (p < 0.05). Our findings demonstrated that patients who did not show hyperkinesis at the beginning of exercise had more severe coronary artery disease. Careful observation of serial wall motion during exercise by the continuous-recording method may provide important information about myocardial ischemia.
To obtain an antibody which is useful for developing a selective immunoaffinity chromatography (IAC) of 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], which is an effective pretreatment tool for determining this metabolite in biological fluids, a variety of monoclonal antibodies have been produced against a novel haptenic derivative, 11alpha-hemiglutaryloxy-1alpha,25-dihydroxyvitamin D3, linked to bovine serum albumin. BALB/c, A/J and C57BL/6 mice, as well as Wistar and SD rats, were immunized with the hapten-carrier conjugate and the titer of the anti-1,25(OH)2D3 antibody in serum was examined. Spleen cells from A/J mice or SD rats, which showed a high titer, were fused with P3/NS1/1-Ag4-1 myeloma cells. After serial screening by enzyme-linked immunosorbent assay and radioimmunoassay, sixteen kinds of hybridoma clones secreting different anti-1,25(OH)2D3 antibodies were established. Scatchard analysis revealed that 12 antibodies out of 16 have enough affinity to 1,25(OH)2D3 (Ka>10(9) M[-1]). By a cross-reaction study using various related compounds, two antibodies, M114 and M129, both derived from A/J mice, were found to have suitable specificity. Although they showed relatively high cross-reactivities with the 1,25(OH)2D3 derivatives having 24-hydroxylated (both 20%) or lactonized (30%, 8.9%) side chain, all the tested 1alpha-deoxy-type metabolites, some of which interfere with the 1,25(OH)2D3 assays, were successfully discriminated [25(OH)D3: 0.67%, 0.40%; 24,25(OH)2D3: 0.27%, 0.24%; 25(OH)D3 3-sulfate: 0.11%, 0.14%]. These monoclonal antibodies will be applicable for developing not only IAC but also various immunoassay procedures.
AIM: To determine whether plasma vascular endothelial growth factor (VEGF) level is elevated in Type 2 diabetic patients with an early stage of diabetic nephropathy. METHODS: We studied 71 Japanese Type 2 diabetic patients with normal serum creatinine level (<100 micromol/l) (age 63.0 [60.3-65.6] years old, diabetes duration 15.6 [14.0-17.3] years, HbA1c 7.36% [7.06-7.66%], mean [95% confidence interval, CI]): normoalbuminuric patients (n=36); microalbuminuric patients (n=21); and proteinuric patients (n=14). Plasma VEGF concentration was measured by a quantitative sandwich enzyme immunoassay technique. RESULTS: Plasma VEGF concentration was not related to the degree of albuminuria: normoalbuminuric patients (25 [13-95] ng/l, median [25th-75th percentile]); microalbuminuric patients (33 [15-120] ng/l); and proteinuric patients (54 [17-107] ng/l). Plasma VEGF level in patients with retinopathy (25 [15-95] ng/l, n=30) was not elevated as compared to those without retinopathy (53 [14-126] ng/l, n=34). Plasma VEGF tended to correlated negatively with diabetes duration (R's=-.217, P=.0690) and HbA1c (R's=-.221, P=.0647), whereas there was no correlation between plasma VEGF level and age, serum creatinine or urinary albumin to creatinine ratio (ACR) of the patients, respectively. Plasma VEGF level in the group of patients with HbA1c equal to or below the median (<7.2%) was significantly higher than that in the group of patients with HbA1c above the median (>7.2%) (P<.05). CONCLUSIONS: The results suggested that Type 2 diabetic patients with microalbuminuria and those with retinopathy are not necessarily associated with an elevation of circulating plasma VEGF concentration. Plausible association between plasma VEGF level and glycemic control remains to be seen.
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BACKGROUND: It has been reported that nicorandil restores blood flow to reperfused myocardium in patients with acute myocardial infarction. However, whether nicorandil might decrease infarct size remains unclear. The aim of this study was to assess the effect of nicorandil on infarct size with thallium-201/beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) dual-isotope single photon emission computed tomography. METHODS: A total of 62 patients were randomly assigned to receive intravenous nicorandil (4 mg in 5 minutes at admission, immediately followed by 6 mg/hr over a 24-hour period) or placebo. All patients were divided into 4 groups: Group N-a, 16 patients with preexisting angina treated with nicorandil; N-b, 15 patients without preexisting angina treated with nicorandil; C-a, 14 patients with preexisting angina given placebo; C-b, 17 patients without preexisting angina given placebo. Tl-201/BMIPP imaging was performed in the 62 patients within 7 days after admission. Dual-isotope single photon emission computed tomographic images were quantified by severity index with a polar map. RESULTS: The BMIPP severity index was similar among the 4 groups. Only the thallium severity index in the N-a group was significantly less (P<.05). The ratio of the thallium severity index to that of BMIPP in the N-a group was significantly decreased compared with those of the other groups. CONCLUSION: Nicorandil has a protective effect in patients with acute myocardial infarction and preexisting angina treated with primary balloon angioplasty.