Treatment efficiency and stability of skeletal Class III malocclusion with a surgery-first approach.

OBJECTIVES: To compare treatment duration in skeletal Class III malocclusion patients managed with a 2-step treatment (surgery-first approach, SFA) and conventional 3-step treatment, and to compare stability of surgical outcomes between segmentation and non-segmentation in the 2-step treatment group. SETTING AND SAMPLE POPULATION: The sample population consisted of 37 patients who completed orthognathic surgery (OGS) and orthodontic correction at the Charm Aesthetic Surgery Clinic (Taipei, Taiwan) between 2012 and 2015. Of these, 26 received 2-step treatment and 11 received 3-step treatment. MATERIALS AND METHODS: To compare treatment efficiency and stability, three time points were analysed: T0 , before treatment (before OGS in the 2-step group and before orthodontic treatment in the 3-step group); T1 , after OGS but before orthodontic correction (cone beam computed tomography (CBCT) was obtained within 2 weeks of OGS); and T2 , after orthodontic correction (CBCT was obtained on the day of bracket removal). The post-OGS (T1 ) CBCT items were individually superimposed on the pre-treatment (T0 ) CBCT items to determine the distance of B point migration. RESULTS: A significant difference was found in treatment times between 2-step treatment and conventional 3-step treatment. In addition, no significant difference was found when comparing B-X (mm) and B-Y (mm) at T2 -T1 for the segmentation and non-segmentation groups. CONCLUSIONS: Using SFA for skeletal Class III malocclusions saves approximately 6 months of treatment time over 3-step treatment; the stability of the segmentation group was comparable to that of the non-segmentation group, a result that is possibly associated with the fixation of 2 miniplates.

Risks and predictors of osteoporosis in patients with inflammatory bowel diseases in an Asian population: a nationwide population-based cohort study.

BACKGROUND: We investigated the inflammatory bowel disease (IBD) specific predictors of osteoporosis and pathological fracture by analysing the Taiwan National Health Insurance Research Database. METHODS: Totally, we enrolled 3141 IBD patients and 12,564 age- and sex-matched controls. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of osteoporosis and pathological fracture in both cohorts. RESULTS: Inflammatory bowel disease patients had significantly higher comorbidity-adjusted rates of osteoporosis and pathological fracture compared with controls [adjusted hazard ratio (aHR), 1.31; 95% CI, 1.09-1.60, p = 0.004]. Further analysis indicated that women (aHR, 1.36; 95% CI, 1.09-1.70, p = 0.008), middle-aged patients (aHR, 1.74; 95% CI, 1.25-2.41, p = 0.001), patients with Crohn's disease (aHR, 1.33; 95% CI, 1.09-1.64, p = 0.006) and patients without comorbidities (aHR, 1.81; 95% CI, 1.23-2.67, p = 0.003) exhibited excessive risks of osteoporosis. Moreover, patients requiring hospitalisation for IBD exhibited the highest risk of developing osteoporosis (aHR, 4.46; 95% CI, 2.74-7.27, p < 0.001) and pathological fracture (aHR, 17.1; 95% CI, 5.78-50.9, p < 0.001). CONCLUSIONS: Patients with IBD, particularly women, middle-aged patients and patients without comorbidities, are associated with a long-term risk of osteoporosis. The risks of osteoporosis and pathological fracture were highest in patients requiring hospitalisation for IBD.

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

BACKGROUND: An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. METHODS: A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. RESULTS: The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. CONCLUSION: Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance.

Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma.

BACKGROUND: We have previously demonstrated that overexpression of ankyrin repeat-rich membrane spanning (ARMS) protein facilitates melanoma formation via conferring apoptotic resistance. This study aims to investigate whether ARMS contributes to melanoma progression. METHOD: Using immunohistochemistry, we graded the expression level of ARMS in 54 cases of primary melanoma and 46 cases of metastatic melanoma. The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics. By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment. RESULTS: Stronger immunointensity of ARMS was observed mostly in melanomas with Breslow tumour thickness >1.0 mm (Fisher's exact test, P=0.002) or with nodal metastasis (Fisher's exact test, P=0.026), and was correlated with a worse overall survival in melanoma patients (log-rank test, P=0.04). Depletion of ARMS inhibited migration, invasion, and metastatic potential of melanoma cells in vitro and in vivo. Moreover, ARMS mediated melanoma cell migration and invasion through activation of the extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signalling pathway. CONCLUSION: Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes.

BACKGROUND: Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ- and NA-treated animals, using modern spectral estimation technique. DESIGN: An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4- and 8-week STZ-NA rats with anaesthesia. The power of low-frequency and high-frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed-loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low-frequency band. RESULTS: Compared with the age-matched controls, both the 4- and 8-week STZ-NA diabetic rats had significantly decreased low-frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0.451 +/- 0.060 and 0.484 +/- 0.056 vs. 1.196 +/- 0.064 ms mmHg(-1), P < 0.05). On the other hand, the low frequency-high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho-vagal balance of the heart control (0.472 +/- 0.109 and 0.504 +/- 0.090 vs. 1.857 +/- 0.336, P < 0.05). CONCLUSIONS: The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ- and NA-treated rats.

Interactions of the fucose-specific Pseudomonas aeruginosa lectin, PA-IIL, with mammalian glycoconjugates bearing polyvalent Lewis(a) and ABH blood group glycotopes.

Pseudomonas aeruginosa Fuc > Man specific lectin, PA-IIL, is an important microbial agglutinin that might be involved in P. aeruginosa infections in humans. In order to delineate the structures of these lectin receptors, its detailed carbohydrate recognition profile was studied both by microtiter plate biotin/avidin-mediated enzyme-lectin-glycan binding assay (ELLSA) and by inhibition of the lectin-glycan interaction. Among 40 glycans tested for binding, PA-IIL reacted well with all human blood group ABH and Le(a)/Le(b) active glycoproteins (gps), but weakly or not at all with their precursor gps and N-linked gps. Among the sugar ligands tested by the inhibition assay, the Le(a) pentasaccharide lacto-N-fucopentaose II (LNFP II, Galbeta1-3[Fucalpha1-4]GlcNAcbeta1-3Galbeta1-4Glc) was the most potent one, being 10 and 38 times more active than the Le(x) pentasaccharide (LNFP III, Galbeta1-4 [Fucalpha1-3]GlcNAcbeta1-3Galbeta1-4Glc) and sialyl Le(x) (Neu5Acalpha2-3Galbeta1-4[Fucalpha1-3] GlcNAc), respectively. It was 120 times more active than Man, while Gal and GalNAc were inactive. The decreasing order of PA-IIL affinity for the oligosaccharides tested was: Le(a) pentaose > or = sialyl Le(a) tetraose > methyl alphaFuc > Fuc and Fucalpha1-2Gal (H disaccharide)>2'-fucosyllactose (H trisaccharide), Le(x) pentaose, Le(b) hexaose (LNDFH I) and gluco-analogue of Le(y) tetraose (LDFT)>H type I determinant (LNFP I)>Le(x) trisaccharide (Galbeta1-4[Fucalpha1-3]GlcNAc) > sialyl Le(x) trisaccharide >> Man >>> Gal, GalNAc, and Glc (inactive). The results presented here, in accordance with the crystal 3D structural data, imply that the combining site of PA-IIL is a small cavity-type best fitting Fucalpha1- with a specific shallow groove subsite for the remainder part of the Le(a) saccharides, and that polyvalent glycotopes enhance the reactivity. The Fuc > Man Ralstonia solanacearum lectin RSL, which resembles PA-IIL in sugar specificity, differs from it in it's better fit to the B and A followed by H oligosaccharides vs. Fuc, whereas, the second R. solanacearum lectin RS-IIL (the structural homologue of PA-IIL) binds Man > Fuc. These results provide a valuable information on PA-IIL interactions with mammalian glycoforms and the possible spectrum of attachment sites for the homing of this aggressive bacterium onto the target molecules. Such information might be useful for the antiadhesive therapy of P. aeruginosa infections.

Expression and function of CYR61, an angiogenic factor, in breast cancer cell lines and tumor biopsies.

We have previously shown that expression of heregulin (HRG) is closely correlated with breast cancer progression. We have subsequently isolated Cyr61, a ligand for the alpha(v)beta3 integrin that is differentially expressed in HRG-positive cells, and have shown that it is expressed in all of the invasive and metastatic breast cancer cell lines tested. Preliminary evaluation of Cyr61 expression in breast tumor biopsies revealed expression of Cyr61 in about 30% of invasive breast carcinomas. Significantly, we demonstrated that Cyr61 is a downstream effector of HRG action, because a Cyr61-neutralizing antibody abolished the ability of HRG-expressing cells to migrate in vitro. Furthermore, we have shown that HRG-expressing cells denote higher levels of alpha(v)beta3 expression, and we have established that Cyr61 action is mediated, at least in part, through its receptor alpha(v)beta3, because a functional blocking antibody of the alpha(v)beta3 blocked the Matrigel outgrowth of HRG-expressing cells. These results strongly suggest that Cyr61 is necessary for HRG-mediated chemomigration and that Cyr61 plays a functional role in breast cancer progression, possibly through its interactions with the alpha(v)beta3 receptor.

Establishment and characterization of a tumor cell line from human nasopharyngeal carcinoma tissue.

An epithelial tumor cell line, CG1, was established from human nasopharyngeal carcinoma tissues. The CG1 cells are of an epithelial origin as shown by their reactivities with the epithelial-specific antikeratin antibodies and by the presence of the desmosome structure at cell-cell junctions. CG1 cells possess characteristics of tumor cells because these cells are tumorigenic in nude mice and also have reduced serum requirements for in vitro cultivation. The doubling time of CG1 cells is 20 h and these cells have been successfully cultured in vitro for more than 200 generations. The average chromosome number of these cells is 60. Slot and Southern blot hybridizations showed the presence of Epstein-Barr virus-DNA sequences in CG1 cells. This cell line provides us an in vitro system for the study of the role of Epstein-Barr virus in nasopharyngeal carcinoma.

Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome.

Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.

Identification of multiple endocrine neoplasia, type 2 gene carriers using linkage analysis and analysis of the RET proto-oncogene.

Ten kindreds (95 individuals) with multiple endocrine neoplasia, type 2 (MEN 2) were analyzed by linkage analysis using four highly polymorphic (CA)n-repeat markers (sTCL-1, D10S141, ZNF22, and sJRH-1). Additionally, we examined the RET proto-oncogene for specific mutations by DNA sequence analyses in these 10 plus 14 members of 3 additional kindred. Nine families had MEN 2A, two had MEN 2B, and two had medullary thyroid cancer alone (FMTC). Using these four markers, all 10 kindreds were informative, with 10 individuals predicted to be presymptomatic MEN 2 gene carriers and 23 individuals predicted not to be carriers. DNA sequence analysis of exons 10 and 11 of the RET proto-oncogene revealed a mutation in all nine MEN 2A kindreds. A missense mutation was found in each case, leading to a loss of a cysteine residue (codon 618 of exon 10 or codon 634 of exon 11). In the MEN 2A families, the linkage analysis and RET mutation analysis gave concordant results for prediction of gene carriers in 100% of the individuals tested. No mutations were found in the two kindreds with FMTC or the two MEN 2B kindreds. Two individuals from two different MEN 2A kindreds were identified who had abnormal calcitonin stimulation tests but were not MEN 2A gene carriers by both linkage analysis and RET mutation analysis. These individuals presumably represented the sporadic occurrence of abnormal calcitonin stimulation tests in the general population. These studies provide further support for a role of the RET proto-oncogene in the pathogenesis of MEN 2A. Additionally, in the absence of identifiable RET proto-oncogene mutations, linkage analysis using (CA)n-repeat markers is a highly accurate alternative for the identification of MEN 2 or FMTC gene carriers.

Familial medullary thyroid cancer and prominent corneal nerves: clinical and genetic analysis.

A unique kindred manifesting medullary thyroid carcinoma and corneal nerve thickening without other aspects of the multiple endocrine neoplasia syndrome (MEN) was analyzed by linkage analysis using four highly polymorphic (CA)n repeat markers (sTCL-1, D10S141, ZNF22, and sJRH-1). Additionally, the RET protooncogene was examined for specific mutations by DNA sequence analyses in all affected family members. Screening of 11 family members spanning 4 generations revealed 7 subjects with corneal nerve thickening; of these subjects, 3 had abnormal pentagastrin-stimulated calcitonin studies, and these 3 subjects were each found to have C-cell hyperplasia or medullary thyroid carcinoma at surgery. Linkage analysis showed cosegregation of alleles (as defined by the above markers), with the presence of both corneal nerve thickening and medullary thyroid carcinoma/C-cell hyperplasia (maximum LOD score, 2.69; consistent with, but not proving linkage). DNA sequence analysis showed that none of the affected individuals had mutations in either exon 10 or 11, or in exon 16 of the RET protooncogene, regions where mutations have been described for MEN type 2A (MEN-2A) and MEN-2B families, respectively. Thus, compared to the defined syndromes of MEN-2A and MEN-2B, this kindred appears to represent a true clinical overlap syndrome whose genetic basis may be distinct from these two syndromes.

Studies on the binding of wheat germ agglutinin (Triticum vulgaris) to O-glycans.

The binding profile of Triticum vulgaris (WGA, wheat germ) agglutinin to 23 O-glycans (GalNAc alpha1-->Ser/Thr containing glycoproteins, GPs) was quantitated by the precipitin assay and its specific interactions with O-glycans were confirmed by the precipitin inhibition assay. Of the 28 glycoforms tested, six complex O-glycans (hog gastric mucins, one human blood group A active and two precursor cyst GPs) reacted strongly with WGA and completely precipitated the lectin added. All of the other human blood group A active O-glycans and human blood group precursor GPs also reacted well with the lectin and precipitated over two-thirds of the agglutinin used. They reacted 4-50 times stronger than N-glycans (asialo-fetuin and asialo-human alpha1 acid GP). The binding of WGA to O-glycans was inhibited by either p-NO2-phenyl alpha,betaGlcNAc or GalNAc. From these results, it is highly possible that cluster (multivalent) effects through the high density of weak inhibitory determinants on glycans, such as GalNAc alpha1-->Ser/Thr (Tn), GalNAc at the nonreducing terminal, GlcNAc beta1--> at the non-reducing end and/or as an internal residue, play important roles in precipitation, while the GlcNAc beta1-->4GlcNAc disaccharide may play a minor role in the precipitation of mammalian glycan-WGA complexes.

Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system.

WW domain-containing oxidoreductase WOX1, also known as WWOX or FOR, is a proapoptotic protein and a putative tumor suppressor. Hyaluronidases such as PH-20, Hyal-1 and Hyal-2 induce the expression of WOX1, and hyaluronidases and hyaluronan are involved in the embryonic development. In the present study, we document the expression of WOX1 in the developing murine nervous system. Immunohistochemical analysis revealed that WOX1 was differentially expressed in early dividing cells from all three germ layers from embryonic to perinatal stages. In murine fetuses, WOX1 was present prevalently in the brainstem, spinal cord and peripheral nerve bundles, but its expression decreased after birth. In parallel, the expression of WOX1, as determined by Western blotting, was significantly reduced in the brain stem and spinal cord of adult mice. Notably, high levels of WOX1 immunoreactivity was observed in the neural crest-derived structures such as cranial and spinal ganglia and cranial mesenchyme during the late fetal stage. In the adult brain, WOX1 is abundant in the epithelial cells of the choroids plexus and ependymal cells, while a low to moderate level of WOX1 is observed within white matter tracts, such as axonal profiles of the corpus callosum, striatum, optic tract, and cerebral peduncle. WOX1 is shown to mediate apoptosis synergistically with p53 in vitro. Nonetheless, the expression profiles of WOX1 were found to be similar in both p53 wild type and knockout mice, suggesting that WOX1 expression is not controlled by p53-mediated gene transcription. Taken together, in this study we have shown the expression and distribution of WOX1 in developing and adult murine nervous system. The potential role of WOX1 in the neuronal differentiation is discussed.

Detection of mutations in the p53 gene in human head and neck carcinomas by single strand conformation polymorphism analysis.

Using the polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis, we have examined the highly conserved regions of the p53 gene in 58 biopsy samples of head and neck tumors. Mutations were found in 13/58 (23%) tumor specimens, but not in 6 normal tissues. Ten of 13 mutations were due to single base changes and the remaining 3 were 1- or 8-base deletion mutants. These mutations were clustered in exons 5 and 7 and resulted in amino acid changes. Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies. The relationship of Epstein-Barr virus or human papillomavirus and p53 gene mutations in this group of cancers was also analyzed and discussed.

Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth.

Black cohosh is an increasingly popular alternative to estrogen replacement therapy for the relief of menopausal symptoms, primarily hot flushes. However, an important consideration for long-term therapy is potential toxicity and carcinogenicity. Therefore, we undertook a study to assess the estrogenic activity of black cohosh to examine its safety for those with, or at high risk of developing, breast cancer. Several assays were utilized as listed: RNAse protection assays, which ascertain the regulation of the expression of E2-responsive genes; estrogen-responsive-element (ERE)-luciferase, which determines modulation of the ER function by transactivation of the ERE; the Ishikawa cell system, which has an E2-regulated endogenous alkaline phosphatase; and colony formation of ER-expressing breast cancer cells, which indicates possible progression of early stage breast cancer into a more aggressive state. Black cohosh extracts did not demonstrate estrogenic activity in any of these assay systems. This is an encouraging step in the assessment of the safety of black cohosh for treatment of menopausal hot flushes.

Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3.

We have previously reported that Heregulin (HRG)/neu differentiation factor (NDF) induced growth arrest and cellular differentiation in breast cancer cells overexpressing erbB-2 receptor. To elucidate the cellular mechanisms underlying the growth inhibition by HRG, we developed an in vitro model by transfection of HRG cDNA into the erbB-2 overexpressing breast cancer cell line, SKBr-3. We showed that the enforced expression of HRG in SKBr-3 cells induces dramatic morphological changes and pronounced inhibition of anchorage-dependent and -independent growth. Most SKBr-3/HRG-transfected (SK/HRG) cells exhibited about 15-fold increase in size and persisted as multinucleated cells with extended flattened vacuole-filled cytoplasm with reduced cell attachment. The growth suppression of SK/HRG cells was accompanied by a reduction in S phase, the presence of a G2-M cell cycle delay, and an increase in DNA aneuploid components. In addition, DNA fragmentation assays showed that HRG induced apoptosis of SKBr-3 cells. In contrast, while HRG treatment of other erbB-2 overexpressing breast cancer cell lines led to growth arrest and cell detachment, it did not induce apoptotic features. Thus, this study demonstrates that while growth arrest and cell detachment are general effects of HRG towards erbB-2 overexpressing cells, the ability of HRG to induce apoptosis is a phenomenon confined to selective cells including SKBr-3 cells.

Distribution of FMRFamide-like immunoreactivity in the central nervous system of the Formosan monkey (Macaca cyclopsis).

The distribution of FMRFamide-like immunoreactivity in the central nervous system of the Formosan monkey (Macaca cyclopsis) was investigated employing immunohistochemical techniques. FMRFamide-containing cells were found to be widely distributed throughout the forebrain. Principal densities of FMRFamide neuronal perikarya were observed in the following areas: the amygdaloid complex, the olfactory tubercle, the cerebral cortex, the basal ganglia, the septum, the caudate-putamen and the arcuate nucleus. A large number of immunoreactive fibers were observed in areas ranging from the cerebral cortex to the spinal cord, and were noted in the following locations: the preoptic area, the tuberal and posterior hypothalamic areas, the bed nucleus of the stria terminalis, the nuclei of the spinal trigeminal nerve, the hypoglossal nucleus, the nucleus of the solitary tract, and the dorsal horn of the spinal cord. The results generally parallel those described in the rat and guinea pig.

Tuberculous wrist in the era of effective chemotherapy: an eleven-year experience.

BACKGROUND: The chronic course and non-specific clinical manifestations of tuberculous (TB) wrist often cause failure to make a timely diagnosis. OBJECTIVE: To better understand the rarely encountered TB wrist. PATIENTS AND METHODS: Retrospective review and analysis of cases of TB wrist between 1986 and 1997 in a medical centre in southern Taiwan. RESULTS: Thirty-seven cases (16 definitive, 13 probable and eight possible) of TB wrist (25 men, 12 women; mean age, 56.3 +/- 13.0 years) were found among a total of 4970 cases of tuberculosis. The most common presenting sign and symptom (mean duration 9.4 months) were local swelling and pain over the affected wrist. The mean white blood cell (WBC) count in peripheral blood was 7.04 x 10(9)/l, and the erythrocyte sediment rates (ESR) in seven of 31 patients who had ESR assayed were normal. Forty-six per cent of the patients had abnormal chest X-ray, and 35% had had previous manipulation of the affected wrist. CONCLUSION: Physicians should have a high index of suspicion for TB wrist among patients with chronic arthritis, even when their peripheral WBC count and ESR are normal. An abnormal chest X-ray and/or a history of previous manipulation of the affected wrist could be important clues for possible TB wrist.

Signaling molecules implicated in heregulin induction of growth arrest and apoptosis.

Heregulin (HRG) is one of the groups of polypeptide growth factors that activate the erbB-2 receptor via induction of heterodimerization with erbB-3 and erbB-4 receptors. The biological effects of HRG have been extensively studied. The vast majority of the reports indicate that HRG induces cell growth in breast cancer cells expressing normal levels of erbB-2 and growth inhibition and apoptosis in cells over-expressing erbB-2. However, the mechanism by which HRG promotes cell growth inhibition and apoptosis is still unknown. Previously we reported that constitutive expression of HRG in an erbB-2-overexpressing cell line (SKBr-3) induced growth arrest and apoptosis. We also demonstrated that constitutive expression of HRG promoted a marked morphological change, G2/M delay of the cell cycle, and DNA fragmentation. In this study, we demonstrate the mechanism by which HRG induces these cellular effects. The doubling time of the SK/HRG cells increased in relation to the level of HRG expression, and the level of HRG expression dictates the morphological change of the cells as well as their ability to grow or not grow in an anchorage-independent manner. We demonstrate that these effects are accompanied by downregulation of both erbB-2 and erbB-3 receptors at the transcriptional and translational levels and that down-regulation of the erbB-receptors results in reduced receptor tyrosine phosphorylation. The decrease in erbB-receptor phosphorylation in turn results in a marked reduction of ERK activity and a significant increase in JNK activity. Consequently, overexpression of HRG promoted the expression of PEA3, an Ets nuclear transcription factor. Taken together, our data demonstrate that the cellular effects induced by constitutive expression of HRG in SKBr-3 cells are correlated with the level of HRG expression. This is a first report demonstrating that HRG induction of apoptosis is directly correlated with decreased MAPK activity, increased JNK activity resulting in upregulation of PEA3 and down-regulation of the erbB-2 receptor. Overall, these data provide important clues regarding the mechanism and downstream molecules involved in HRG induction of apoptosis that can be used as targets for therapeutic prevention.

Carbohydrate specificity of an agglutinin isolated from the root of Trichosanthes kirilowii.

The root of Trichosanthes kirilowii, which has been used as Chinese folk medicine for more than two thousand years, contains a Gal specific lectin (TKA). In order to elucidate its binding roles, the carbohydrate specificities of TKA were studied by enzyme linked lectinosorbent assay (ELLSA) and by inhibition of lectin-glycoform binding. Among glycoproteins (gp) tested, TKA reacted strongly with complex carbohydrates with Galbeta1-->4GlcNAc clusters as internal or core structures (human blood group ABH active glycoproteins from human ovarian cyst fluids, hog gastric mucin, and fetuin), porcine salivary glycoprotein and its asialo product, but it was inactive with heparin and mannan (negative control). Of the sugar inhibitors tested for inhibition of binding, Neu5Ac alpha2-->3/6Galbeta1-->4Glc was the best and about 4, 14.6 and 27.7 times more active than Galbeta1-->4GlcNAc(II), Galbeta1-->3GalNAc(T) and Gal, respectively. From these results, it is suggested that this agglutinin is specific for terminal or internal polyvalent Galbeta1-->4GlcNAcbeta1-->, terminal Neu5Ac alpha2-->3/6Galbeta1-->4Glc and cluster forms of Galbeta1-->3GalNAc alpha residues. The unusual affinity of TKA for terminal and internal Galbeta1-->glycotopes may be used to explain the possible attachment roles of this agglutinin in this folk medicine to target cells.