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Biomedical subjects

Y S Ho

Publications and source records attributed to Y S Ho.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lymphangiosis as a predictor of outcome in patients with primary diffusely infiltrative adenocarcinoma of the colon and rectum.

OBJECTIVE: To investigate the relationships between outcome and clinicopathological factors, DNA flow cytometrical characteristics, and postoperative adjuvant therapy in patients with primary diffusely infiltrative colorectal adenocarcinoma. DESIGN: Inception cohort study. SETTING: A medical center that offers a mixture of primary, secondary, and tertiary care services. PATIENTS: Among 7035 patients undergoing resection of primary colorectal adenocarcinoma from 1980 to 1996, 37 patients with a pathological diagnosis of primary diffusely infiltrative tumor were selected. All patients had received regular follow-up until February 28, 1998, or until death. MAIN OUTCOME MEASURES: Cancer-specific survival compared by log-rank test and Cox regression model. RESULTS: Univariate analyses revealed tumor stage (stages II-III vs. stage IV, P = .01) and severity of lymphangiosis (absent/mild vs. moderate/severe, P = .04) were significant in predicting outcome. A proliferative index of greater than 20% was insignificant (P = .08) in predicting outcome. In a Cox regression model, TNM stage and lymphangiosis were independently correlated with a worse outcome. When compared with tumors having less severe lymphangiosis, the odds ratio of death due to cancer in cases of tumors with moderate to severe lymphangiosis was 2.4 (95% confidence interval, 1.0-5.6; P = .05). CONCLUSION: Lymphangiosis and TNM stage were independently predictive of outcome in patients with primary diffusely infiltrative colorectal cancer.

Adenocarcinoma↗
PubMed1999

Glutathione peroxidase-deficient mice are more susceptible to neutrophil-mediated hepatic parenchymal cell injury during endotoxemia: importance of an intracellular oxidant stress.

Neutrophils contribute to hepatocellular injury in a number of acute inflammatory reactions. However, the molecular mechanism of parenchymal cell injury remains controversial. To address the issue of whether or not reactive oxygen species (ROS) are important in the injury process, we used the galactosamine/endotoxin (Gal/ET) model of acute liver failure, which involves a neutrophil-mediated parenchymal cell injury. In C3Heb/FeJ mice, Gal/ET induced a significant increase of hepatic and plasma levels of glutathione disulfide (GSSG), an indicator of oxidant stress, selectively during the neutrophil-mediated injury phase. In glutathione peroxidase-deficient mice (Gpx1(-/-)), Gal/ET or Gal/tumor necrosis factor alpha (TNF-alpha) caused more severe neutrophil-mediated liver injury compared with wild-type animals. However, there was no significant difference in other critical parameters, e.g., activation of the transcription factor, nuclear factor-kappaB (NF-kappaB), and soluble intercellular adhesion molecule-1 (sICAM-1), parenchymal cell apoptosis, and neutrophil sequestration in the liver. Our results suggest that neutrophil-derived ROS are responsible for an intracellular oxidant stress in hepatocytes after Gal/ET treatment. Because of the higher susceptibility of Gpx1(-/-) mice to a neutrophil-mediated injury, we conclude that peroxides generated by neutrophils diffused into hepatocytes and contributed to parenchymal cell death in vivo. Thus, strengthening defense mechanisms against ROS in target cells can attenuate excessive inflammatory injury without affecting host defense reactions.

Animals↗
PubMed1999

Factors related to the survival of papillary and follicular thyroid carcinoma patients with distant metastases.

There is limited clinical information comparing presentations and results of treatment of papillary and follicular thyroid carcinoma patients with distant metastases. We retrospectively analyzed data of 1,257 thyroid cancer patients who received their treatment and follow-up at Chang Gung Memorial Hospital. We found 992 patients with papillary carcinoma and 205 patients with follicular thyroid carcinoma. Of these, 68 patients with papillary thyroid carcinoma (6.9%) had distant metastases at the time of diagnosis or during the follow-up period. Of the follicular thyroid carcinoma patients, 69 (33.7%) had distant metastases. Of the 68 patients with papillary carcinoma, only 33 were categorized as stage IV at the time of diagnosis. Nine of the patients were categorized as clinical stage I carcinoma, 10 as stage II, and 16 as stage III. Sixteen patients (23.5%) died during the study period, all but 2 of thyroid cancer. Twelve of the 68 patients were disease-free after treatment. Of the 69 patients with follicular thyroid carcinoma, 58 were categorized as stage IV at the time of diagnosis. Six of the patients were categorized as clinical stage I carcinoma, 2 as stage II, and 3 as stage III at the time of diagnosis; all of these patients deteriorated to stage IV during the follow-up period. Of the 42 patients with follicular thyroid carcinoma involving bone, 24 presented with bone metastases during the initial diagnosis. After treatment, 25 of 69 patients with follicular carcinoma died of follicular carcinoma. Only 3 patients were disease-free after the treatment. In patients with follicular carcinoma, only tumor size was an important prognostic factor. In this study, 8 patients categorized as clinical stages I to III at the time of operation had thyroglobulin (Tg) levels less than 5 ng/mL and developed distant metastases during the follow-up period. In conclusion, at diagnosis a large group of Asian patients with metastatic well-differentiated thyroid cancer was more likely to have follicular than papillary histology, and that, as expected, metastases from follicular cancer were present earlier and more frequently, were more likely to involve bone, were more likely to be associated with mortality, and were linked to tumor size but not gender. Also unlike some other reports, treatment producing a low Tg did not always produce a good outcome. More aggressive surgical procedures may be able to improve outcomes.

Adenocarcinoma, Follicular↗
PubMed1999

Probing the substrate specificity of the intracellular brain platelet-activating factor acetylhydrolase.

Platelet-activating factor acetylhydrolases (PAF-AHs) are unique PLA2s which hydrolyze the sn-2 ester linkage in PAF-like phospholipids with a marked preference for very short acyl chains, typically acetyl. The recent solution of the crystal structure of the alpha(1) catalytic subunit of isoform Ib of bovine brain intracellular PAF-AH at 1.7 A resolution paved the way for a detailed examination of the molecular basis of substrate specificity in this enzyme. The crystal structure suggests that the side chains of Thr103, Leu48 and Leu194 are involved in substrate recognition. Three single site mutants (L48A, T103S and L194A) were overexpressed and their structures were solved to 2.3 A resolution or better by X-ray diffraction methods. Enzyme kinetics showed that, compared with wild-type protein, all three mutants have higher relative activity against phospholipids with sn-2 acyl chains longer than an acetyl. However, for each of the mutants we observed an unexpected and substantial reduction in the V(max) of the reaction. These results are consistent with the model in which residues Leu48, Thr103 and Leu194 indeed contribute to substrate specificity and in addition suggest that the integrity of the specificity pocket is critical for the expression of full catalytic function, thus conferring very high substrate selectivity on the enzyme.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Prognostic variables of papillary thyroid carcinomas with local invasion.

To evaluate the significance of the extrathyroid extension (ETE) of papillary thyroid carcinoma at the time of diagnosis and the prognostic variables of patients, we retrospectively reviewed 1,013 thyroid cancer patients. Of the 741 papillary thyroid cancer patients, 466 (62.9%) were categorized in clinical stage I and 114 (15.4%) were categorized in clinical stage III. Of the 114 patients in clinical stage III, 81 were female (mean age 44.4 +/- 15.7 years) and 33 were male (mean age 46.9 +/- 18.1 years). Of the clinical stage III patients, 104 patients received post-operative radioactive iodide (131I) therapy while 22 patients received external radiotherapy in the neck and upper mediastinum area post-operatively. In the study, age, gender, 131I accumulated dose, post-operative serum thyroglobulin (Tg) levels, and survival rate were demonstrated to be statistically significant in the groups with no recurrence and recurrence after treatment. The average follow-up period of these patients was 6.0 years. During this follow-up period, 11 patients expired. Eight died of thyroid cancer (7.0%) and 3 died of intercurrent diseases including asthma, renal cell carcinoma and propranolol overdose. Four of the 8 patients (50%) died of airway obstruction due to cancer cell invasion. Another 4 died of distant metastases, including 2 patients with skull metastases and brain invasion. The 5- and 10-year survival rates were 0.981 and 0.956 in clinical stage I and 0.923 and 0.843 in clinical stage III, respectively. In conclusion, the survival rate of the ETE of papillary thyroid cancer was lower when compared with stage I, especially in older male patients with higher post-operative serum Tg levels.

Adult↗
PubMed1999

Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases.

From 1977 through 1995, 1,013 thyroid carcinoma patients received treatment and were followed up at Chang Gung Medical Center in Taiwan. To evaluate the prognostic variables of papillary and follicular thyroid carcinomas with limited lymph node metastases, a retrospective review of these patients was performed. Of these patients, 910 had papillary or follicular thyroid carcinoma, and 119 patients were categorized as clinical stage 2 with limited neck lymph node metastases only at the time of diagnosis. The patients were categorized into two groups as no recurrence and local recurrence or distant metastasis at the end of 1997. After the operations, radioactive iodide (131I) treatments were performed in 114 patients and external radiotherapy for neck region or distant metastases in 18 patients. The median follow-up period of these patients was 5.4 years. Clinical variables were coded in our computer for statistical analysis. After the treatments, 93 patients remained disease-free; 10 were in stage 2; 5 in stage 3; and 11 aggravated to stage 4. Of the clinical variables, age, post-operative first 1311 uptake scans, and 1-month post-operative thyroglobulin levels revealed statistically significant differences between the group which improved and the group which did not. During the follow-up period, five patients died; three patients died of thyroid cancer and two died of intercurrent diseases. Patients with papillary thyroid carcinoma revealed a higher percentage of lymph node metastases. Although limited lymph node metastases did not influence survival rate, patients with poor prognostic factors need more aggressive treatment to avoid progression of the cancer.

Adenocarcinoma, Follicular↗
PubMed1999

Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts.

BACKGROUND: Various periodontal and root canal pathogens, such as the Bacteroides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are still not fully understood. METHODS: We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such as cell growth, protein synthesis, cell adhesion capacity, and cell cycle progression. RESULTS: Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentrations of 4, 8, and 16 mM, butyrate suppressed the cell growth by 11 to 58%, 16 to 60%, and 50 to 71%, respectively. The response of cultured gingival fibroblasts to SCFA showed individual differences. Morphologically, GF became larger and more flattened in appearance following exposure to butyrate (>8 mM) and propionate (>24 mM) for 5 days. Inhibitory effects of butyrate (>2 mM) and propionate (>8 mM) on the growth of GF were due possibly to their inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, butyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 to 24 mM further result in G2/M phase arrest of GF. On the other hand, propionate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Butyrate (>2 mM) inhibited the proline-rich protein synthesis of GF. At concentrations of 4, 8, 16, and 24 mM, butyrate inhibited the protein synthesis of HGF-1 by 42%, 43%, 51%, and 54%, respectively. In all strains of cultured GF, the suppressive effect of propionate is less than that of butyrate. At concentration range of 4 to 24 mM, propionate suppressed the protein synthesis of HGF-1 by 23 to 43%. However, both butyrate and propionate (4 to 48 mM) exerted little effects on the adhesion of GF to type I collagen within 3 hours of incubation. CONCLUSIONS: These results suggested that SCFA released by pathogenic microorganisms can contribute to the gingival tissue dysfunction and breakdown through their actions on specific biological functions of GF.

Butyrates↗
PubMed1999

Induction of apoptosis by S-nitrosoglutathione and Cu2+ or Ni2+ ion through modulation of bax, bad, and bcl-2 proteins in human colon adenocarcinoma cells.

In this study, the amount of S-nitrosoglutathione (GSNO) was measured spectrophotometrically at 334 nm. A spontaneous decrease in absorbency at 334 nm was detected when GSNO was exposed to 37 degrees C and a high pH (pH 8.0). We investigated the catalytic roles of various metal ions on the decomposition of GSNO. The degradation of GSNO (0.5 mM) was enhanced by the presence of Cu(2+) and Ni(2+) ions. The amount of nitric oxide (NO) released from GSNO degradation was estimated by the Griess reaction based on nitrite accumulation. The results indicated that nitrite production was elevated at least twofold in the presence of Cu(2+). Our study further indicated that Cu(2+) enhanced GSNO-induced apoptosis in human colon adenocarcinoma HT 29 cells. We also found that copper ions modulated the expression of bad, bax, and bcl-2 in GSNO-treated HT 29 cells. The levels of bax and bad proteins in treated cells were significantly elevated about fourfold to sixfold when compared with mock-treated cells 24 h after combined treatment with GSNO plus Cu(2+) or Ni(2+). On the other hand, significant inhibition of bcl-2 occurred in HT 29 cells with simultaneous treatment of GSNO with Cu(2+) (or Ni(2+)). It seemed that Cu(2+) and Ni(2+) can enhance the decomposition of GSNO, which liberates NO to activate the pathways. Our results demonstrated that the apoptotic effects induced by GSNO were promoted by Ni(2+) and Cu(2+) through two different mechanisms: depletion of intracellular glutathione and triggering of NO release from GSNO, which then promotes NO-induced apoptosis in human cells.

Adenocarcinoma↗
PubMed1998

Selenium-dependent glutathione peroxidase-GI is a major glutathione peroxidase activity in the mucosal epithelium of rodent intestine.

Gpx2 mRNA, encoding a selenium-dependent glutathione peroxidase (GPX-GI), has been found to be highly expressed in the gastrointestinal tract (GI) mucosal epithelium. In this study, we show that GPX-GI is produced in the mucosal epithelium of the adult rat GI tract and that the activity levels are comparable to that from GPX-1. Post-mitochondrial supernatant GPX activity from the mucosal epithelium of the complete length of the small intestine was partially purified. A sample enriched for putative GPX-GI was fractionated by SDS-polyacrylamide gel electrophoresis. Polypeptides of 21 kDa and 22 kDa were digested with trypsin. After resolving the tryptic peptides by high pressure liquid chromatography (HPLC), the major peaks were analyzed for their amino acid sequence by Microflow-HPLC-Tandem Mass Spectrometry and automated Edman degradation sequencing. Both methods revealed that the 21-kDa sample contained rat GPX-GI determined by the sequence homology with the deduced mouse GPX-GI polypeptide sequence. Rat GPX-1 was also detected in the samples. AntiGPX-GI and antiGPX-1 antibodies were used to determine the distribution of the respective isoenzyme activities along the length of the intestine and with respect to the crypt to villus axis in rats. GPX-GI and GPX-1 activities were uniformly distributed in the middle and lower GI tract and with respect to the crypt to villus axis. GPX-GI activity accounted nearly the same percentage of the total GPX activity as GPX-1 in all of the these compartments. Studies on the distal ileum segment of wildtype and Gpx1 gene knockout mice showed that GPX-GI activity was also at parity with GPX-1 in the mucosal epithelium of this segment.

Amino Acid Sequence↗
PubMed1998

Reduced fertility in female mice lacking copper-zinc superoxide dismutase.

Copper-zinc superoxide dismutase (CuZn-SOD) is believed to play a major role in the first line of antioxidant defense by catalyzing the dismutation of superoxide anion radicals to form hydrogen peroxide and molecular oxygen. Recent studies have shown that missense mutations in this gene contribute, evidently through a gain-of-function mechanism, to about 20% of familial amyotrophic lateral sclerosis. To define further the physiologic role of this enzyme, a model of mice deficient in this enzyme was generated using gene targeting technology. Mice lacking this enzyme were apparently healthy and displayed no increased sensitivity to hyperoxia. However, they exhibited a pronounced susceptibility to paraquat toxicity. Most surprisingly, female homozygous knock-out mice showed a markedly reduced fertility compared with that of wild-type and heterozygous knock-out mice. Further studies revealed that although these mice ovulated and conceived normally, they exhibited a marked increase in embryonic lethality. These data, for the first time, suggest a role of oxygen free radicals in causing abnormality of female reproduction in mammals.

Animals↗
PubMed1998

Acute suppurative thyroiditis and aggressive malignant thyroid tumors: differences in clinical presentation.

BACKGROUND AND OBJECTIVES: Aggressive malignant thyroid tumors (AMTT) may mimic the clinical symptoms and signs of acute suppurative thyroiditis (AST) in the early course of the disease process. Our objective was to analyze the clinical features of these two conditions, to assess the best way of early diagnosis, and to propose proper treatment. METHODS: We retrospectively reviewed and analyzed the clinical features of 30 patients, who had similar clinical pictures of AST and were managed at Chang Gung Memorial Medical Center in Linkou, Taiwan, during the period from 1983 to 1996. These patients were consequently diagnosed as either AST or AMTT. The data were analyzed by the Mann-Whitney U, chi-square and Fisher's exact tests. RESULTS: Among the 30 patients, 25 patients (Male/Female (M/F) ratio = 9/16) were diagnosed as having AST and 5 (M/F ratio = 1/4) as AMTT. After statistical analysis we concluded that the presence of the following factors, namely, older age at diagnosis (P = 0.0155), history of dysphonia (P = 0.0325), right thyroid lobe involvement (P = 0.0151), large size of lesions (P = 0.0013), presence of anemia (P = 0.0075), and sterile pus cultures from thyroid aspirates (P = 0.0013) were cause to suspect a malignancy if the condition did not improve after antibiotics. Delay in diagnosis and management of AMTT may result in a poor prognosis (P = 0.0082). CONCLUSION: Due to the high mortality rate of AMTT, we should closely observe the patients with poor prognostic variables of acute thyroiditis. Earlier detection and aggressive surgical intervention for AMTT might improve the outcome.

Acute Disease↗
PubMed1998

Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice.

Generation of free radicals upon reperfusion has been cited as one of the major causes of ischaemia/reperfusion injury. The following series of experiments was designed to study the effect of manganese superoxide dismutase (MnSOD) overexpression in transgenic mice on ischemia/reperfusion injury. A species of 1.4 kb human MnSOD mRNA was expressed, and a 325% increase in MnSOD activity was detected in the hearts of transgenic mice with no changes in the other antioxidant enzymes or heat shock proteins. Immunocytochemical study indicated an increased labeling of MnSOD mainly in the heart mitochondria of the transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x left ventricular developed pressure, was 52 +/- 4% in the transgenic hearts as compared to 31 +/- 4% in the non-transgenic hearts. This protection was accompanied by a significant decrease in lactate dehydrogenase release from the transgenic hearts. Overexpression of MnSOD limited the infarct size in vivo in a left coronary artery ligation model. Our results demonstrate that overexpression of MnSOD renders the heart more resistant to ischemia/reperfusion injury.

Animals↗
PubMed1998

Ketoconazole-induced apoptosis through P53-dependent pathway in human colorectal and hepatocellular carcinoma cell lines.

In this study, we first demonstrated that the widely used oral antifungal drug, ketoconazole (KT), can induce apoptosis in various type of human cancer cells and in a primary culture of rat liver cells. We further investigated the molecular mechanisms of KT-induced apoptosis. It was found that KT induced nuclear accumulation of p53 protein in a dose- and time-dependent manner. The level of p53 protein was elevated approximately three times as much in treated cells 24 h after KT (5 microM) exposure as in cells receiving mock treatment. We found that cells containing wild-type p53 (COLO 205 and Hep G2) were more sensitive to KT exposure. The bax protein was induced and the bcl-2 protein was inhibited by KT in cells containing wild-type p53 (Hep G2, COLO 205) but not in cells without p53 (Hep 3B). The caspase-3 was activated 24 h after KT treatment. The Poly-(ADP ribose) polymerase (PARP) and the lamin A degradation was induced by KT, which promoted nuclear membrane disassembly and eventually caused apoptosis. Our results also indicated that none of the PKC gene family was involved in KT-induced apoptosis.

Adenocarcinoma↗
PubMed1998

Different prognostic effect of postoperative chemoradiation therapy on diploid and nondiploid high-risk rectal cancers.

PURPOSE: DNA ploidy has been shown to play a role in the response to cytotoxic therapy in a variety of malignancies, including breast cancer and melanoma. However, the importance of DNA ploidy in rectal cancer is unknown. The aim of the present study was to determine whether ploidy status might be associated with response to postoperative chemoradiation in TNM Stages II to III rectal cancer. METHODS: This retrospective study analyzed data from 229 patients with TNM Stages II to III rectal cancer who underwent resection between 1979 and 1984. The ploidy status and treatment modalities in relation to outcome were assessed. RESULTS: The recurrence-free ten-year survival rate was 52.2 percent for patients with diploidy and 50.5 percent for patients with nondiploidy (P = 0.99). The ten-year survival rates for patients with diploidy and patients with nondiploidy were 55 and 19 percent (P = 0.016) in the chemoradiation group, and 51 and 60 percent (P = 0.15) in the nonchemoradiation group, respectively. In the chemoradiation group, DNA nondiploidy was associated with an increased recurrence rate (83.3 vs. 50.0 percent; P = 0.001). The interaction between DNA nondiploidy and chemoradiation remained important in predicting outcome in the Cox regression model. Factors independently correlated with a worse outcome included Stage IIIb (relative risk, 2.9; 95 percent confidence interval, 1.7-5; P = 0.0001), perineural invasion (relative risk, 2.5; 95 percent confidence interval, 1.6-4, P = 0.0001), distal tumor (relative risk, 1.7; 95 percent confidence interval, 1.1-2.7, P = 0.014), and nondiploidy with chemoradiation (relative risk, 2.9; 95 percent confidence interval, 1.2-7.2, P = 0.0213). CONCLUSIONS: These findings suggest that DNA nondiploidy is inversely correlated with long-term outcome among patients with high-risk rectal cancer receiving chemoradiation.

Adult↗
PubMed1998

Nuclear multiparameter flow cytometric DNA analysis of human brain tumors: correlation of DNA content with tumor histology and clinical behavior.

BACKGROUND: Using fresh surgical specimens of brain tumors to investigate cellular DNA content is uncommon. The aim of this study is to elucidate the relationship among cellular nuclear DNA content, tumor histology, and tumor clinical behavior of various tumors of the central nervous system. METHODS: Multiparameter flow cytometry (FACStar, Becton-Dickinson, San Jose, CA) was randomly applied to analyze 40 fresh surgical specimens from brain tumors. Histologically, there were 19 cases of benign tumors and 21 cases of malignant tumors. RESULTS: DNA distribution profiles in the benign tumors revealed 15 cases of diploidy and four cases of aneuploidy, while the malignant tumors had eight cases of diploidy and 13 cases of aneuploidy (p < 0.01). The mean DNA index (DI) in benign tumors was 1.13 +/- 0.27 and in malignant tumors 1.43 +/- 0.48 (p < 0.05). The mean proliferative index (PI) in benign tumors was 10.27 +/- 5.46% and 18.44 +/- 8.98% in malignant tumors (p < 0.05). Clinically, 10 patients had postoperative recurrence. The PI in recurrent and nonrecurrent tumors was 17.83 +/- 11.13% and 13.20 +/- 7.19%, respectively (p < 0.05). The 1-year cumulative survival rate in benign tumors was 78.9%, and 57.1% in malignant tumors (p < 0.05). CONCLUSIONS: Malignant tumors had a significantly higher incidence of aneuploid DNA histograms, a higher DNA index, and a higher proliferative index. Tumors with a high PI had a higher incidence of recurrence and a lower survival rate. Multiparameter DNA analysis by flow cytometry provides a valuable diagnostic aid for the histopathologic differentiation of human brain tumors.

Adolescent↗
PubMed1998

Administration of dexamethasone induces proteinuria of glomerular origin in mice.

The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration. One fourth of mice also intermittently presented with slight hematuria beginning on day 12. Renal lesions in the dexamethasone-treated mice, which were killed on day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme inhibitor. Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Clinical evaluation of C7 spinal nerve transection: 21 patients with at least 2 years' follow-up.

We have performed C7 spinal nerve transfer to treat root injury of the brachial plexus since 1989. Out of a total of 43 patients, 21 have been followed up for at least 2 years. Evaluation of the effect of C7 transection included clinical examination, intraoperative C7 stimulation, LIDO Workset machine and electrophysiological studies to test C7 innervated muscles, and histochemical analysis of the anterior and posterior division of the upper trunk using acetylcholinesterase stain. Nearly half of the study group (48%) reported no significant sensory changes and most patients (81%) did not notice any weakness of the limb following C7 transection. Some patients did experience sensory and motor abnormalities which were most frequent during the first postoperative month, improved during the 2nd month and in most cases resolved in the 3rd postoperative month. The only longer persistent abnormality was the triceps reflex, which becomes weak or absent. We also found that intraoperative C7 stimulation was a useful predictor of possible post-transection morbidity. Subclinical deficits, detected by the LIDO workset machine and by electro-physiological studies, were quite common. Histochemical analysis revealed that the posterior division of C7 had more motor fibres than the anterior division.

Adolescent↗