Search PubMed⌕ Search

Biomedical subjects

Y T Chen

Publications and source records attributed to Y T Chen.

At least 91 records · Page 5Linked to original sources

Expression of MAGE-antigens in normal tissues and cancer.

The human MAGE gene family encodes products that can be recognized by autologous cytotoxic T cells. Because MAGE genes are silent in most normal tissues except testis but are activated in a variety of neoplastic lesions, MAGE antigens represent ideal targets for immunotherapy. Current knowledge of MAGE gene expression is based primarily on mRNA typing and relatively little is known about MAGE protein expression. Monoclonal antibody (MAb) 57B, originally thought to be specific for MAGE-3, but now known to be reactive with other MAGE components, was used in the present study to analyze MAGE expression in a panel of normal and malignant tissues. In tests with a wide range of normal tissues, only spermatogenic cells of testis were reactive with 57B. In tumor tissues, significant immunoreactivity was observed in malignant melanomas and carcinomas of the lung, head and neck as well as urinary bladder. No 57B reactivity was seen with colorectal, prostatic or renal cell carcinomas. Lipo- and myosarcomas, as well as malignant fibrous histiocytoma (MFH), were negative, but synovial sarcomas showed intense immunoreactivity. A subset of seminomas was also strongly reactive with 57B. Tumor specimens showed great variability in the number of tumor cells showing 57B reactivity, with some tumors showing only small isolated clusters of positive cells to other tumors with uniform staining throughout the tumor.

Antigens, Neoplasm↗

A new positive/negative selectable marker, puDeltatk, for use in embryonic stem cells.

A novel positive/negative selection cassette, puDeltatk, was generated. pu(Delta)tk is a bifunctional fusion protein between puromycin N-acetyltransferase (Puro) and a truncated version of herpes simplex virus type 1 thymidine kinase (DeltaTk). Murine embryonic stem (ES) cells transfected with pu(Delta)tk become resistant to puromycin and sensitive to 1-(-2-deoxy-2-fluoro-1-beta-D-arabino-furanosyl)-5-iodouracil (FIAU). Unlike other HSV1 tk transgenes, puDeltatk is readily transmitted through the male germ line. Thus pu(Delta)tk is a convenient positive/negative selectable marker that can be widely used in many ES cell applications.

Acetyltransferases↗

Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease.

Deficiency of glycogen debranching enzyme (AGL) activity causes glycogen storage disease type III (GSD-III). Generalized loss of AGL activity results in GSD-IIIa, and muscle-specific retention of AGL activity results in GSD-IIIb. To date, no common mutation has been described among GSD-III patients, except for three alleles; two linked specifically with GSD-IIIb, and the third found only in North African Jews with GSD-IIIa. Here we report two frequent mutations, each of which was found in the homozygous state in multiple patients, and each of which was associated with a subset of clinical phenotype in those patients with that mutation. A novel point mutation of a single T deletion at cDNA position 3964 (3964delT) was first detected in an African American patient, who has a severe phenotype and early onset of clinical symptoms. The second mutation was an A to G transition at position -12 upstream of the 3' splice site of intron 32 (IVS32-12A > G). This lesion, previously implicated as a IIIb mutation in a Japanese patient, was identified in a confirmed GSD-IIIa Caucasian patient presenting with mild clinical symptoms. These two mutations together account for more than 12% of the molecular defects in the GSD-III patients tested. Our molecular and clinical data suggest a genotype-phenotype correlation for each of these mutations. Furthermore, this current study, coupled with our previous reports, describes the molecular tools necessary for the development of a DNA-based diagnostic test for GSD-III.

Adult↗

SEREX analysis of gastric cancer antigens.

Stomach cancer is the major malignancy in Japan and one of the most common cancers worldwide. To establish the basis for an immunotherapeutic approach to stomach cancer, we have initiated an analysis of stomach cancer antigens recognized by human immunoglobulin G (IgG) antibodies using SE-REX, a powerful expression cloning method developed by Dr. M. Pfreundschuh's group. Five stomach cancer cDNA libraries have been screened with autologous patient sera: one moderately differentiated adenocarcinoma; two poorly differentiated adenocarcinomas; and two scirrhous-type poorly differentiated adenocarcinomas of Borrmann type 4, the most devastating form of stomach cancer. Based on the reactivities of clones with autologous IgG antibodies, an average of 50 independent clones from each library and a total of 297 clones were isolated. DNA sequencing revealed that these 297 clones were derived from 136 different genes. Comparison of the 136 genes to sequences in DNA databases showed that 95 are previously identified genes and 41 are newly identified in this study. The antigens are derived from various genes including a chimeric gene between E-cadherin and an unknown gene Y, AKT oncogene, genes overexpressed in stomach cancers, genes of which the transcripts are alternatively or aberrantly spliced, and genes known to be involved in autoimmune diseases. Thus stomach cancer patients can generate an immune response against a surprisingly diverse set of gene products. To identify antigens potentially useful in the diagnosis and therapy of gastric cancer, all 136 genes were tested for their reactivities with a panel of sera from 44 gastric cancer patients (17 women and 27 men, aged 35-81 years) and with a panel of sera from 100 control individuals with no previous history of cancer but some of whom had gastritis (55 women and 45 men, aged 30-69 years). Eleven antigens showed reactivity only with a certain proportion of cancer patient sera but not with any control sera. An additional 12 antigens elicited antibody production at a much higher frequency in cancer patients than in control individuals. To evaluate the clinical usefulness of these antigens we are now examining their expression in normal and malignant tissues.

Adult↗

Predictors of readmission among elderly survivors of admission with heart failure.

BACKGROUND: Readmission rates for patients discharged with heart failure approach 50% within 6 months. Identifying factors to predict risk of readmission in these patients could help clinicians focus resource-intensive disease management efforts on the high-risk patients. METHODS: The study sample included patients 65 years of age or older with a principal discharge diagnosis of heart failure who were admitted to 18 Connecticut hospitals in 1994 and 1995. We obtained patient and clinical data from medical record review. We determined outcomes within 6 months after discharge, including all-cause readmission, heart failure-related readmission, and death, from the Medicare administrative database. We evaluated 2176 patients, including 1129 in the derivation cohort and 1047 in the validation cohort. RESULTS: Of 32 patient and clinical factors examined, 4 were found to be significantly associated with readmission in a multivariate model. They were prior admission within 1 year, prior heart failure, diabetes, and creatinine level >2.5 mg/dL at discharge. The event rates according to number of risk predictors were similar in the derivation and the validation sets for all outcomes. In the validation cohort, rates for all-cause readmission and combined readmission or death were 26% and 31% in patients with no risk predictors, 48% and 54% in patients with 1 or 2 risk predictors, and 59% and 65% in patients with 3 or all risk predictors. CONCLUSIONS: Few patient and clinical factors predict readmission within 6 months after discharge in elderly patients with heart failure. Although we were unable to identify a group of patients at very low risk, a group of high-risk patients were identified for whom resource-intensive interventions designed to improve outcomes may be justified.

Aged↗

Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.

A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5'-non-coding region (5'-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.

5' Untranslated Regions↗

T311--an anti-tyrosinase monoclonal antibody for the detection of melanocytic lesions in paraffin embedded tissues.

Tyrosinase is a key enzyme in melanin biosynthesis and represents a marker of melanocytic differentiation. We previously generated T311, a murine monoclonal antibody to the tyrosinase recombinant protein. This study was performed to evaluate T311 as a diagnostic immunohistochemical reagent for use on formalin-fixed paraffin-embedded pathological material. We analyzed the specificity of the antibody on a panel of normal and neoplastic tissues, and we assessed its sensitivity in a large number of metastatic and primary malignant melanomas, nevi, three angiomyolipomas, and two vitiligo specimens. T311 revealed intense reactivity on paraffin-embedded material. Immunoreactivity was limited to cells of melanocytic differentiation and no immunostaining was present in unrelated normal tissues and tumors. Eighty-four percent of metastatic malignant melanomas were immunoreactive with T311 and showed predominantly a homogeneous expression pattern. However, in primary melanomas of the desmoplastic/spindle cell type, T311 revealed a poor immunoreactivity. Nevi showed intense staining at the junctional zone, while the dermal component revealed decreasing reactivity towards deeper areas. Only one angiomyolipoma was focally immunoreactive with T311. Vitiligo specimens were immunonegative. We conclude that T311 is a specific and sensitive marker for the detection of melanocytic lesions in formalin-fixed paraffin-embedded tissues and a useful serological reagent for diagnostic pathology.

Antibodies, Monoclonal↗

Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations.

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.

Adult↗

Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects.

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean +/- SEM, 8.1 +/- 0.6 v 6.8 +/- 0.2 micromol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 +/- 0.5 v 7.2 +/- 0.5 v 8.4 +/- 0.6 micromol/L; P = .148) or normotensive subjects (6.3 +/- 0.4 v 8.0 +/- 0.8 v 7.0 +/- 0.8 micromol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.

Blood Glucose↗

Towards a molecular therapy for glycogen storage disease type II (Pompe disease).

Glycogen storage disease type II (GSD-II), also known as Pompe disease, is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. Currently, there is no treatment for this fatal disorder. However, several lines of research suggest the possibility of future treatment. Enzyme replacement strategies hold the greatest hope for patients currently affected by GSD-II, but future strategies could include in vivo or ex vivo gene therapy approaches and/or mesenchymal stem cell or bone-marrow transplantation approaches. Each of the approaches might eventually be combined to further improve the overall clinical efficacy of any one treatment regimen. The lessons learned from GSD-II research will also benefit a great number of individuals affected by other genetic disorders.

Animals↗

Acylcarnitines in fibroblasts of patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and other fatty acid oxidation disorders.

Mitochondrial fatty acid oxidation disorders cause hypoglycaemia, hepatic dysfunction, myopathy, cardiomyopathy and encephalopathy. Despite their recognition for more than 15 years, diagnosis and treatment remain difficult. To help design rational diagnostic and therapeutic strategies, we studied the pathophysiology of accumulating metabolites in a whole-cell system. Acylcarnitines were quantified in cells and media of cultured fibroblasts after incubation with L-carnitine and fatty acids. Following incubation with palmitate, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)-deficient fibroblasts compared with controls showed elevation of hydroxypalmitoyl- and palmitoyl-carnitine and reduction of C10- and shorter acylcarnitines, and following incubation with linoleate an increase in C14:2-, C18:2- and hydroxy-C18:2- acylcarnitines and reduction in C10:1-acylcarnitines. Hydroxyacylcarnitines remained more intracellular compared to corresponding saturated acylcarnitines. Incubation with decanoate and octanoate showed absence of hydroxylated acylcarnitines and correction of secondary metabolic disturbances, suggesting that optimal treatment should include medium-chain triglycerides of these chain lengths. Fibroblasts of patients with other fatty acid oxidation disorders showed distinct elevations of disease-specific acylcarnitines. This acylcarnitine analysis allows the diagnosis of LCHAD deficiency and its differentiation from other fatty acid oxidation disorders, which can pose difficulties in vivo. The strategy has allowed in-depth analysis with different substrates, providing suggestions for the rational design of treatment trials.

3-Hydroxyacyl CoA Dehydrogenases↗

Effects of areca nut extracts on the functions of human neutrophils in vitro.

Aqueous extracts of ripe areca nut without husk (ripe ANE) and fresh and tender areca nut with husk (tender ANE) were examined for their effects on the defensive functions of human neutrophils. Exposure of peripheral blood neutrophils to ripe ANE and tender ANE inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose-dependent manner. At the concentrations tested, ripe and tender ANEs did not significantly affect the viability of neutrophils as verified by their ability to exclude trypan blue dye. However, both ANEs inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction. Moreover, the ripe ANE inhibited neutrophils more effectively than did tender ANE. Arecoline, a major alkaloid of areca nut, only exhibited an inhibitory effect on the functions of neutrophils when high concentrations were used. Therefore, arecoline could not be used to explain the inhibitory effects observed for ANEs. In conclusion, our results demonstrated that ripe and tender ANEs reduced the antibacterial activity and the superoxide anion production of neutrophils. This effect may contribute to a less efficient elimination of bacteria from the periodontal environment. Inhibition of the antimicrobial functions of neutrophils may alter the microbial ecology of the oral cavity, and this may be one possible mechanism by which areca nut compromises the oral health of users of areca nut products.

Aggregatibacter actinomycetemcomitans↗

Genetic screening for patients with azoospermia and severe oligo-asthenospermia.

In order to explore the genetic defects of patients with azoospermia or severe oligo-asthenospermia, screening examinations were carried out for the chromosome disorder and gene deletion of the Y chromosome for 220 male infertility patients. The present results show that the total prevalence of genetic defects is 23.6%, including 38 patients (28.4%) with chromosome disorder and 14 patients (16.8%) with gene deletion in the Yq arm. The most prevalent chromosome anomaly is 47XXY (Klinefelter's syndrome), which includes 18 cases of pure type and three cases of mosaic type. Variable autosomal translocations occurred in both the azoospermia group (5.2%) and the oligo-astheno-spermia group (5.8%) with similar prevalence. A total of 22 patients had deletions of the variable, interstitial portion of the Yq arm. These gene deletions are distributed not only inside the AZF region, but also outside of this region. The severity of deletions is not well correlated to the clinical testicular function of the patients. We conclude that chromosome disorder and gene deletions are the causative factors of patients with azoospermia and oligo-asthenospermia. Genetic screening should be a routine examination for them before the use of assisted-reproductive technologies.

Adult↗

Tubularized incised plate urethroplasty for proximal hypospadias.

OBJECTIVE: To review our experience of using the tubularized incised plate (TIP) urethroplasty (useful in the treatment of distal hypospadias) to treat proximal hypospadias. MATERIALS AND METHODS: From March 1997 to March 2000 primary repairs were carried out on 40 boys (mean age 4.5 years) with proximal hypospadias. After degloving the penile skin the meatus was at the mid-shaft in 10 boys, at the proximal penile shaft in 11, at the penoscrotal junction in 16, at the scrotum in two and at the perineum in one. The 21 patients with a mid or proximal shaft meatus were categorized as having mid-shaft and the other 19 as having posterior hypospadias. Tunica albuginea plication (TAP) was used to correct residual ventral curvature. The method of urethroplasty was adapted from that described by Snodgrass. The key step of the TIP repair is a midline incision of the urethral plate; a subcutaneous tissue flap dissected from the inner prepuce is used to cover the neourethra. An 8 or 10 F nasogastric tube is used as a urethral stent and removed 7 or 8 days after surgery. Follow-up endoscopy and urethral sounding were carried out in 17 of the patients aged < 6 years; the mean follow-up was 12.5 months. RESULTS: TAP was used to correct penile curvature in nine (23%) of the patients. Excluding stenosis, the TIP repair was successful in 20 (90%) of those with mid-shaft and in 16 of the 19 with posterior hypospadias; for all complications the respective rates were 19 of 22 and 15 of 19. The overall success rate was 88% for all 40 patients with proximal hypospadias; a urethrocutaneous fistula occurred in two of those with mid-shaft and three of those with posterior hypospadias. Urethral meatal stenosis occurred in four (12%) of the patients (two in each group); two were associated with a fistula and the other two had only mild meatal stenosis. The overall complication rate was 17.5% (three and four in the mid and the posterior hypospadias groups, respectively). The meatal stenosis was managed by simple dilatation in three and meatoplasty in one patient. Endoscopically, the mucosa of neourethra was pink and smooth in all 17 patients assessed. The calibre of all 17 neourethra was > or = 8 F and in 13 was > or = 10 F. CONCLUSION: TIP repair is a reliable method for treating both mid-shaft and posterior hypospadias.

Child, Preschool↗

Monoclonal antibody MA454 reveals a heterogeneous expression pattern of MAGE-1 antigen in formalin-fixed paraffin embedded lung tumours.

Cancer/testis (CT) antigens such as those encoded by the MAGE-gene family are expressed in a wide variety of malignant neoplasms. In normal tissues, expression is generally restricted to testis. Current knowledge of the expression pattern of CT antigens is mainly based on mRNA analysis. Little is known about actual protein expression. We previously developed MA454, a monoclonal antibody (mAb) to MAGE-1 recombinant protein. By employing antigen retrieval techniques, we show that MA454 is reactive on formalin-fixed paraffin-embedded tissues. Immunohistochemical (IHC) analysis of a normal tissue panel revealed staining solely in germ cells of testes. A series of 59 lung tumours was co-typed for MAGE-1 expression by RT-PCR and by immunohistochemistry with MA454. MA454 was positive in 19/59 cases (32%). MAGE-1 mRNA was found in 17 of the 54 cases (32%) available for RT-PCR. Of the 19 MA454-reactive tumours, 15 showed a highly heterogeneous pattern of expression. The other 4 MA454 positive cases revealed immunoreactivity in >25% of tumour areas. Of the 53 cases typed for both, mRNA and protein expression, 48 co-typed whereas 5 cases were discrepant, a likely consequence of heterogeneous MAGE-1 expression. The predominantly focal expression of MAGE-1 suggests that this antigen might not be sufficient as a sole target for immunotherapeutic approaches.

Antibodies, Monoclonal↗

Cervical cancer practice patterns and appropriateness of therapy.

OBJECTIVE: This study was undertaken (1) to describe practice patterns for treatment of cervical cancer on a national scale, including patient characteristics associated with receiving appropriate versus inappropriate therapy, and (2) to determine whether mortality rate differences exist between patients who were treated appropriately and those who were treated inappropriately. STUDY DESIGN: We defined treatment appropriateness in cases of cervical cancer according to general recommendations for therapy for each International Federation of Gynecology and Obstetrics stage. In an analysis of data obtained from the Surveillance, Epidemiology, and End Results Program for 1988 through 1994 we determined the associations of patient demographic characteristics and tumor characteristics with treatment appropriateness. The association between treatment appropriateness and overall mortality for as long as 7 years of follow-up was adjusted for age; marital status; Surveillance, Epidemiology, and End Results Program location; International Federation of Gynecology and Obstetrics stage of disease; lymph node status; tumor grade; and histologic classification. RESULTS: Overall 90% of all patients were found to have received appropriate therapy. Important variables significantly associated with being treated inappropriately versus appropriately included age <40 years, positive nodal status, and International Federation of Gynecology and Obstetrics stage IB disease. Important variables significantly associated with receiving no therapy versus receiving appropriate therapy were age >/=60 years, International Federation of Gynecology and Obstetrics stage IV disease, positive nodal status, and unknown nodal status. In a comprehensive model that included demographic factors and tumor characteristics, the adjusted hazard ratio for mortality among patients who were treated inappropriately versus appropriately was 0.87 (95% confidence interval, 0.70-1.09). The adjusted hazard ratio for mortality among patients who did not receive therapy versus those who were treated appropriately was 2.92 (95% confidence interval, 2.44-3.48). CONCLUSIONS: In an analysis of data from a tumor registry, cervical cancer practice patterns were generally found to follow accepted treatment guidelines. Appropriateness of therapy did not vary widely according to demographic variables. Although patients who received no therapy had an elevated risk of death with respect to that of patients who were treated appropriately, patients who were treated inappropriately had a mortality rate similar to that among those who were treated appropriately (perhaps because of limitations in Surveillance, Epidemiology, and End Results Program data). Results of this preliminary study suggest a need for further research on effectiveness of cervical cancer therapies in the general population.

Adult↗

Accuracy of computerized automatic identification of cephalometric landmarks.

Computerized cephalometric analysis can include both landmark identification and determination of linear or angular measurements. Although its use is time saving compared with a manual method, the accuracy of automatic landmark identification remains unclear. The purpose of this study was to evaluate the accuracy of a computerized automatic landmark identification system that used an edge-based technique. The technique divides the scanned cephalogram into 8 rectangular subimage regions. After the resolution of these subimages is reduced, the edges are detected and the landmarks are located automatically. Thirteen landmarks were selected for assessment on a set of 10 test cephalograms. The results showed that the errors between manual and computerized identification for landmarks were not significantly different (P > .05) for 5 of 13 landmarks: sella, nasion, porion, orbitale, and gnathion. These results suggest that the accuracy of computerized automatic identification is acceptable for certain landmarks only. Further studies to improve the accuracy of computerized automated landmark identification are needed.

Cephalometry↗

Plasma tumor necrosis factor alpha levels and insulin sensitivity in hypertensive subjects.

Recent studies have shown that tumor necrosis factor-alpha (TNFalpha), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFalpha levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFalpha levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9 +/- 0.6 vs 7.4 +/- 0.7 ng/ml, p=0.190). Fasting plasma TNFalpha concentrations were not different between subjects with hypertension and normotension (10.5 +/- 0.5 vs 9.8 +/- 0.4 pg/ml, p=0.360). Fasting plasma TNFalpha concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4 +/- 0.4 vs. 10.9 +/- 1.6 vs. 9.9 +/- 1.0 pg/ml, p=0.297) and normotensive subjects (9.2 +/- 0.7 vs. 9.3 +/- 0.9 vs. 9.7 +/- 0.9 pg/ml, p=0.875). Fasting plasma TNFalpha values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFalpha did not differ between hypertensive subjects and normotensive controls. Plasma TNFalpha concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFalpha on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.

Cholesterol, HDL↗