Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.

Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.

EGFR mutants found in non-small cell lung cancer show different levels of sensitivity to suppression of Src: implications in targeting therapy.

Mutations in epidermal growth factor receptor (EGFR) kinase domain associate with clinical responses to EGFR inhibitors and are frequently observed in non-small cell lung cancer (NSCLC) patients in East Asian populations. Clinically identified EGFR mutations cause constitutive receptor activation. The activating mechanisms were unclear but appeared to be different among EGFR mutants. We found that EGFR mutants had different sensitivity to an Src inhibitor PP2. S768I and L861Q mutants were less sensitive to Src suppression than others. Mutation at tyrosine 869 (845) residue, an Src phosphorylation site, decreased the phosphorylation levels of wild-type EGFR and other mutants, but not that of S768I and L861Q mutants, suggesting that S768I and L861Q mutants became Src independent for their activation and biological functions. In contrast, cells expressing EGFR-L858R or exon 19 deletion mutants were more sensitive to PP2 than cells expressing wild-type EGFR. Interestingly, EGFR with exon 19-deletion/T790M double mutations, which was resistant to gefitinib, remained sensitive to PP2. Taken together, our data indicate that Src inhibitors might be effective in treating NSCLC harboring specific types of EGFR mutations.

Epitaxial growth of InN films by molecular-beam epitaxy using hydrazoic acid (HN3) as an efficient nitrogen source.

Epitaxial InN films have been successfully grown on c-plane GaN template by gas-source molecular-beam epitaxy with hydrazoic acid (HN3) as an efficient nitrogen source. Results in residual-gas analyzer show that the HN3 is highly dissociated to produce nitrogen radicals and can be controlled in the amounts of active nitrogen species by tuning HN3 pressure. A flat and high-purity InN epifilm has been realized at the temperature near 550 degrees C, and a growth rate of 200 nm/hr is also achieved. Moreover, the epitaxial relationship of the InN(002) on the GaN(002) is reflected in the X-ray diffraction, and the full-width at half-maximum of the InN(002) peak as narrow as 0.05 degrees is related to a high-quality crystallinity. An infrared photoluminescence (PL) emission peak at 0.705 eV and the integrated intensity increasing linearly with excitation power suggest that the observed PL can be attributed to a free-to-bound recombination.

Effects of glutamine-supplemented total parenteral nutrition on cytokine production and T cell population in septic rats.

BACKGROUND: This study was designed to investigate the effects of total parenteral nutrition (TPN) enriched with glutamine (GLN) on in vivo cytokine production and cellular immune response in early and late septic stages of rats. METHODS: Male Wistar rats were divided into 2 experimental groups and received TPN solution at an energy level of 270 kcal/kg body weight. The TPN solutions were isonitrogenous and identical in nutrients composition except for differences in amino acid content. One group received 2% GLN, whereas the other group received glycine (Gly) instead. TPN was maintained for 5 or 6 days according to the sacrifice schedule of the rats. On day 5, sepsis was induced by cecal ligation and puncture (CLP). Respective groups of rats were sacrificed 2, 4, 6, and 24 hours after CLP. RESULTS: Sepsis resulted in a negative nitrogen balance in both groups, and nitrogen loss was significantly lower in the GLN than the Gly group. Interleukin (IL)-2 and interferon (IFN)-gamma in most of the samples collected at various time points were not detectable in plasma or peritoneal lavage fluid. No differences in plasma IL-6 and TNF-alpha concentrations were observed between the GLN and Gly groups. Also, there were no significant differences in IL-1beta, IL-6, and TNF-alpha concentrations in peritoneal lavage fluid between the 2 groups at various time points. The CD4+/CD8+ ratio was significantly higher in the GLN group than in the Gly group only at 4 hours after CLP, and no difference was observed at 24 hours after CLP. CONCLUSIONS: TPN preinfused with a GLN-supplemented solution had a beneficial effect in ameliorating the extent of negative nitrogen balance in septic rats. However, parenterally administered GLN did not reduce the production of inflammatory mediators systemically or at the site of injury, and the influence on enhancing cellular immunity was not obvious.

Preserved esophagogastric manometric motility in patients after distal gastrectomy.

BACKGROUND/AIMS: A prospective study resolved whether commonly employed distal gastrectomies could influence the esophagogastric manometric measurements and the role of vasoactive intestinal polypeptide in mediating motility after surgery. METHODOLOGY: Studied groups consisted of 20 patients following radical subtotal gastrectomy for gastric cancer, 20 patients after subtotal gastrectomy for duodenal ulcer and 20 controls. Fasting blood was obtained to measure serum vasoactive intestinal polypeptide levels. A pneumohydraulic infusion system measured esophagogastric motility parameters. RESULTS: Measured lower esophageal sphincter pressures in subjects of gastric cancer surgery, duodenal ulcer surgery and controls were 15.3 +/- 4.7, 13.1 +/- 5.3 and 12.6 +/- 5.0 mmHg, respectively (NS), while the sphincter lengths were 3.15 +/- 0.81, 3.22 +/- 0.79 and 2.86 +/- 0.85 cm, respectively (NS). In addition, other parameters including lower esophageal body remained unchanged. The serum vasoactive intestinal polypeptide levels of three groups were 24.1 +/- 10.8, 22.5 +/- 9.5 and 21.3 +/- 7.8 pg/ml, respectively (NS). CONCLUSIONS: Neither gastric cancer nor duodenal ulcer in distal stomach removal can alter the lower esophageal body and LES manometric motilities. Unchanged serum VIP levels after gastric surgery are likely one of the mechanisms preserving esophagogastric integrity.

Alteration of distal esophageal motor functions on different body positions.

BACKGROUND/AIMS: This study tried to resolve whether changed body position influences esophageal manometric parameters. MATERIAL AND METHODS: A pneumohydraulic infusion system was employed to measure esophageal parameters for 32 healthy volunteers. They underwent two consecutive manometries on both supine and sitting positions in a random order. These motility measurements included lower esophageal sphincter pressure, dry/wet swallow induced contractile amplitude and interval of distal esophageal body, and its peristaltic speed. RESULTS: Sitting position evoked a higher lower esophageal sphincter pressure than the supine measurement (Mean +/- SD: 14.6 +/- 4.0 mmHg vs. 11.9 +/- 4.2 mmHg, p < 0.01). At the distal esophagus, a swallow led to a stronger contractile amplitude and longer interval on supine measurement. CONCLUSIONS: Recorded peristaltic speeds in various esophageal segments resulted in a difference while this result was mainly due to the different recorded body positions (p < 0.01). Partial esophageal manometric parameters recorded on sitting position are different from the supine measurement. Hence altered body position may modulate some distal esophageal motor functions.

Correlation of esophageal manometry and radionuclide esophageal transit in normal subjects.

What was the correlation of esophageal manometry and scintigraphy in Chinese was studied. Thirty-two volunteers (M/F: 18/14, age: 20-57) without evident esophageal motor disturbance and chest deformity underwent manometric measurement in the spine position using a low compliance pneumohydraulic infusion system. These measurements included the location of both upper and lower esophageal sphincter from nostril, and dry or wet swallow elicited peristaltic speed in the lower esophageal segment. Within one week after manometry, they swallowed a technetium-99m colloid bolus to measure radionuclide manifested esophageal transit time in the supine position beneath a gamma-camera. Body heights of enrolled subjects exhibited a significant positive correlation (r = 0.458, p < 0.01) with manometry measured esophageal lengths. Mean radionuclide esophageal transit time was 7.61 +/- 2.51 sec (3.1-13.57 sec). These transit times exhibited a positive correlation with esophageal lengths (r = 0.6, p < 0.001). Radionuclide transit speed was actually slower than either dry swallow or wet swallow elicited speed (p < 0.05). In conclusion, either manometry or scintigraphy manifests their specific benefits to diagnose esophageal motility disorders. Some correlations of measured variables can be obtained if they are simultaneously employed.

Radial asymmetry characterized the upper esophageal sphincter pressures.

The characteristics of the upper esophageal sphincter (UES) motor functions remain unknown in Chinese. Twenty-three volunteers (M/F: 10/13, age: 19-40) without any pharyngeal/esophageal motor disturbance underwent UES measurement in the left decubitus position using a low compliance pneumohydraulic infusion system. These measurements included the location of UES from nostril, its resting pressure, and the responses to swallow. Mean UES resting pressures measured with three 120 degrees oriented manometric orifices were 22.6 +/- 7.7 mmHg, 16.9 +/- 8.6 mm Hg and 20.7 +/- 9.6 mmHg respectively (p < 0.05). In regard with the swallow-induced UES relax ability, the relax interval, the post-relax contractile amplitude and interval, neither dry swallow nor wet swallow led to a different result. Mean measured UES location from the nostril with the most proximal orifice of probe was 29.3 +/- 2.3 cm. This location did correlate very well with body height (r = 0.60, p < 0.01). In conclusion, this study demonstrates that the UES resting pressures exhibit a radial asymmetry, and that the type of swallow does not influence UES responses. Furthermore, an equation based on the body height may predict the most appropriate UES position.

Effect of H3PO4 concentration on bond strength.

Prior to bonding, the enamel surface of the tooth is normally etched using a solution of 37%-50% phosphoric acid (H3PO4) for 60 seconds. The purpose of this study was to evaluate the tensile bond strength, debonding interface distribution and enamel surface detachment of various concentrations of H3PO4 solution, from 2% to 80%, applied for 15 seconds. Statistically significant differences in bond strength were found among the various concentrations tested: concentrations in the 10% to 60% range produced greater bond strengths than both the weaker and stronger concentrations. The weaker the bond strength, the greater the debonding interface between resin and enamel. The greater the bond strength, the greater the debonding interface between the bracket and resin. Enamel detachment occurred as the H3PO4 concentration rose above 30%. To obtain greater bond strength and less enamel detachment, 10%-30% concentrations of phosphoric acid for 15 seconds etching are suggested for clinical bonding.

Abnormal thyroid hormone levels in critical nonthyroidal illness.

Low levels of thyroid hormone in the absence of clinical hypothyroidism often happen to patients with critical non-thyroidal illnesses (NTI). Low thyroid hormone concentrations in serum do not necessarily mean hypofunction of the thyroid gland; rather it is a helpful adaptation of the human body to the underlying diseases. We collected 133 hospitalized cases of critical NTI and analyzed the incidence of this phenomenon. Fifty-three per cent of the patients had T3 level lower than 60 ng/dl (normal:85-165 ng/dl) and 60% had T4 level lower than 6 ug/dl (normal:6-12 ug/dl). The lowest levels were observed in patients who had sepsis, were aged over 70 or died in this admission. Free T4 and TSH levels were within normal range in most cases. There is a strong negative correlation between the prognosis and the level of T4 in these patients. Those patients with markedly low levels of T3 and T4 should be treated more sophisticatedly.

[The efficacy of sonic and ultrasonic appliances on root canal debridement].

The purpose of this study was to compare the debridement efficacy of hand, sonic (MM-3000), and ultrasonic (Cavi-Endo) appliances, utilizing the same K-type files and a constant flow irrigation system, in the mesial root canals of extracted human mandibular 1st and 2nd molars. Only those roots with a canal curvature of between 10 and 30 degrees, by Schneider's method, were used in this study. The instrumentation time per mesial root canal for each treatment group was also evaluated. Following canal preparation and histological processing, the middle and apical cross-sections were examined to determine the percentage of canal and isthmus cleanliness, and the percentage of planed canal walls in the main canal area. Statistical analysis indicated no significant difference in canal and isthmus cleanliness at the middle and apical levels. All techniques achieved a high level of canal cleanliness. However, step-back hand instrumentation had the greatest percentage of planed canal walls in the main canal area at every portion of the root. Sonic instrumentation, in this study, was significantly faster than hand instrumentation in preparing the root canal system.

Long-term immunogenicity and efficacy of hepatitis B vaccine in infants born to HBeAg-positive HBsAg-carrier mothers.

In an attempt to evaluate the long-term immunogenicity and efficacy of plasma-derived hepatitis B vaccine in preventing hepatitis B virus infection, 199 infants born to hepatitis B e antigen-positive hepatitis B surface antigen-carrier mothers were found to be antibody to HBsAg-positive (greater than or equal to 10 mIU per ml) 2 months after the first booster of hepatitis B vaccination at age 1, and their serum HBsAg and anti-HBs were rechecked annually to ages 3 to 5. Of the nine infants whose initial anti-HBs were low (10 to 100 mIU per ml) in concentration, four (44%) were found to be anti-HBs seronegative at age 3, while none of the 127 vaccine responders with high anti-HBs levels (greater than 1,000 mIU per ml) lost their anti-HBs during the 4-year follow-up period. Also, in 63 infants whose initial anti-HBs titers were around 101 to 1,000 mIU per ml, only two lost their anti-HBs at age 4, and another two at age 5, respectively. Whether the vaccine responders lost their anti-HBs or not, no hepatitis B virus infection occurred in these vaccinees during the follow-up period. Thus, in the first 5 years of life, the protective efficacy in the high-risk infants who responded to plasma-derived hepatitis B vaccine was 100%. Because of the diversity of anti-HBs response in individuals, we suggest testing anti-HBs titer in all vaccinated infants after the first booster vaccination in order to calculate the time of next booster before the minimal protective level is reached.

Cockroach hypersensitivity: preliminary study of allergic cockroach asthma in Taiwan.

One hundred eight-two atopic patients were skin tested with cockroach antigen. Of these 182 patients, 54.9% gave positive immediate skin reaction by intracutaneous test. Among those atopic patients tested, 57.5% of patients with asthma and 50.7% of patients with allergic rhinitis were sensitive to cockroach extracts. The specific IgE antibody was determined by fluoroallergosorbent test. Of 79 cockroach-positive atopic patients, 39.2% were found to contain IgE antibodies against cockroach. No specific IgE was detected in cockroach-negative atopic and nonatopic subjects. Bronchial provocation test with cockroach antigen was performed on 15 subjects. Immediate asthmatic response was detected in six of nine cockroach-positive subjects with asthma. Two cockroach-negative subjects with asthma and four nonatopic subjects demonstrated no significant decrease in FEV1. The results indicate that cockroach induces antigen-specific IgE-mediated bronchial asthma, and cockroach is one of the major causes of allergic asthma.

Histologic and clinicopathologic features of Chinese patients with HBsAg-positive chronic active hepatitis.

Needle biopsies of both the right and left lobes of the liver were performed during peritoneoscopy in 20 male patients with chronic active hepatitis B in Taiwan. Microscopic study of these biopsy specimens led to the recognition of three groups: 1) five patients in whom the lobular architecture was easily recognizable but in whom necrosis and early intralobular fibrosis were present, along with severe chronic inflammation of the portal tracts; 2) seven patients in whom the livers were characterized by early septal formation and a good regenerative response, but few recognizable lobules with normal architecture; and 3) eight patients in whom the disease had progressed to severe fibrosis with septal formation and tiny pseudolobules, indicative of early cirrhosis. The left lobe was the more severely damaged in 16 of the 20 patients.

The hemodynamic effect of verapamil on portal hypertension in patients with postnecrotic cirrhosis.

Wedged hepatic venous pressure, free hepatic venous pressure and cardiac index were measured before and 1 hr after i.v. administration as well as 1 month and 3 months after chronic oral administration of verapamil in 10 patients with HBsAg-positive cirrhosis. The gradient between wedged hepatic venous pressure and free hepatic venous pressure was decreased 14% at 1 hr after i.v. administration of 10 mg verapamil, and the sustained decrease in hepatic venous pressure gradient was also demonstrated in the patients after 1 month, and in six patients after 3 months of continuous oral administration of verapamil. The mean arterial pressure significantly decreased (p less than 0.01) 1 hr after the administration of verapamil. There was no significant change in other hemodynamic values. We conclude that chronic oral administration of verapamil can reduce the hepatic venous pressure gradient in patients with compensated HBsAg-positive cirrhosis and portal hypertension.

Immunoprophylaxis of infection with hepatitis B virus in infants born to hepatitis B surface antigen-positive carrier mothers.

Infants born to carrier mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) received 5 micrograms of hepatitis B virus (HBV) vaccine on four occasions. Group 1 received vaccine only, group 2 received vaccine plus hepatitis B immune globulin (HBIG) at birth, and group 3 received vaccine plus HBIG at birth and at one month. Infants born to HBeAg-positive mothers (group 4) received a reduced dose of vaccine (2.5 micrograms) on three occasions as well as HBIG at birth. As compared with 78.4% of the control group (infants whose parents refused vaccination) who became chronic HBV carriers at the age of 14 months, the protective efficacy rate of vaccination was 75.3% in group 1,85.5% in group 2,89.7% in group 3, and 87.2% in group 4. HBV vaccine (5 micrograms) was also given to infants born to HBsAg-positive, HBeAg-negative mothers on four on four occasions. The antibody response to HBsAg in vaccine recipients was 12% after the first dose, 44% after the second dose, and 75% and 100% at six months and 1.5 years of age, respectively.