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Silylene-spaced donor-acceptor divinylarene copolymers are synthesized by hydrosilylation of bisalkynes 7 with bisvinylsilanes 3; efficient intrachain energy transfer between donor-acceptor chromophores is observed.

Recent work identifies the AKT kinase as a potential mediator of tumor expansion in multiple myeloma. The finding of PTEN mutations in several myeloma cell lines suggests that loss of PTEN function may be one mechanism by which AKT activity is increased in this disease. Because PTEN-deficient myeloma cells may have up-regulated activity of the mammalian target of rapamycin (mTOR), downstream of AKT, they may be particularly sensitive to mTOR inhibition. To test this hypothesis, we challenged myeloma cell lines with CCI-779, a newly developed analogue of rapamycin and an efficient inhibitor of mTOR. Three of four PTEN-deficient cell lines with constitutively active AKT were remarkably sensitive to cytoreduction and G(1) arrest induced by CCI-779 with ID(50) concentrations of <1 nM. In contrast, myeloma cells expressing wild-type PTEN were >1000-fold more resistant. Acute expression of a constitutively active AKT gene in CCI-779-resistant myeloma cells containing wild-type PTEN and quiescent AKT did not convert them to the CCI-779-sensitive phenotype. Conversely, expression of wild-type PTEN in CCI-779-sensitive, PTEN-deficient myeloma cells did not induce resistance. Differential sensitivity did not appear to be due to differences in the ability of CCI-779 to inhibit mTOR and induce dephosphorylation of p70S6kinase or 4E-BP1. However, CCI-779 inhibited expression of c-myc in CCI-sensitive PTEN-null myeloma cells but had no effect on expression in CCI-resistant cells. In contrast, cyclin D1 expression was not altered in either sensitive or resistant cells. These results indicate that PTEN-deficient myeloma cells are remarkably sensitive to mTOR inhibition. Although the results of transfection studies suggest that the level of PTEN and AKT function per se does not regulate sensitivity, PTEN/AKT status may be a good predictive marker of sensitivity.

Transcatheter occlusion of a small or moderate patent ductus arteriosus (PDA) using Gianturco coils is safe and effective. Several investigators have reported using different techniques with variable results. To eliminate the serious potential complications of inadvertent coil embolization to undesirable sites and to improve control of the coil throughout the procedure, a modified snare-assisted method with approach from the main pulmonary artery was developed. However, articles discussing this technique are still limited. Herein, we report our successful experience of the snare-assisted technique to occlude small or moderate PDAs in three children aged from 1 to 8 years old. We achieved immediate total occlusion in all three cases with no complications. All three patients were discharged the next day and there was no coil dislodgement, left pulmonary stenosis, or residual shunting during the follow-up period of up to 3 years. This technique had the advantages of safety, optimal positioning, and improved stability of coil implantation.

Pulmonary radionuclide studies provide reliable information on regional lung perfusion and ventilation. In children of focal pneumonia with consolidation on the chest radiographs, we determined the association between the initial pneumonia sites and the late lung ventilation-perfusion (V-P) scan abnormalities six months to one year later. Totally fifteen children, 9 males and 6 females, aged 2 to 12 years, were enrolled. All cases had normal chest radiographs in follow up, and had unremarkable respiratory symptoms or signs. Both of 99mTc MAA perfusion scintigraphy and 99mTc DTPA radioaerosol ventilation scintigraphy were performed in 12 cases while the other 3 cases had only perfusion studies. As results of these findings, there were 10 abnormal lung scans, including 9 cases at comparable areas (66%) and one at incomparable area with the initial pneumonia sites. Among those 9 comparable cases, we found 6 ventilation/perfusion (V/Q) matched defects, 2 high V/Q mismatched defects and one decreased perfusion defect. We concluded that abnormal lung V-P scans were frequently after uncomplicated pneumonia in childhood, mostly being matched defects, which may be secondary to local bronchial obstruction and decreased perfusion. However, they seem not always to correlate with the initial pneumonia sites.

Interleukin-6 (IL-6) is a prominent tumor growth factor for malignant multiple myeloma cells. In addition to its known activation of the Janus tyrosine kinase-STAT and RAS-MEK-ERK pathways, recent work suggests that IL-6 can also activate the phosphatidylinositol 3-kinase (PI3-K)/AKT kinase pathway in myeloma cells. Because activation of the PI3-K/AKT as well as RAS-MEK-ERK pathways may result in downstream stimulation of the p70(S6K) (p70) and phosphorylation of the 4E-BP1 translational repressor, we assessed these potential molecular targets in IL-6-treated myeloma cells. IL-6 rapidly activated p70 kinase activity and p70 phosphorylation. Activation was inhibited by wortmannin, rapamycin, and the ERK inhibitors PD98059 and UO126, as well as by a dominant negative mutant of AKT. The concurrent requirements for both ERK and PI3-K/AKT appeared to be a result of their ability to phosphorylate p70 on different residues. In contrast, IL-6-induced phosphorylation of 4E-BP1 was inhibited by rapamycin, wortmannin, and dominant negative AKT but ERK inhibitors had no effect, indicating ERK function was dispensable. In keeping with these data, a dominant active AKT mutant was sufficient to induce 4E-BP1 phosphorylation but could not by itself activate p70 kinase activity. Prevention of IL-6-induced p70 activation and 4E-BP1 phosphorylation by the mammalian target of rapamycin inhibitors rapamycin and CCI-779 resulted in inhibition of IL-6-induced myeloma cell growth. These results indicate that both ERK and PI3-K/AKT pathways are required for optimal IL-6-induced p70 activity, but PI3-K/AKT is sufficient for 4E-BP1 phosphorylation. Both effects are mediated via mammalian target of rapamycin function, and, furthermore, these effects are critical for IL-6-induced tumor cell growth.

A total of 110 central venous access procedures using Port-A catheters were performed in our center for pediatric patients with oncologic or hematologic diseases over a period of 6 years from November 1994 to June 2000. Spontaneous dislodgement of the outlet catheters was noted in two cases. Both dislodged catheters were located in the left pulmonary artery and were successfully retrieved via the right femoral vein by nonsurgical transvenous snares. Awareness of the possibility of spontaneous catheter dislodgement and embolization of Port-A catheters is important as prompt retrieval will prevent further serious complications. When the procedure is performed by an open surgical method, to reduce the possibility of spontaneous catheter dislodgement, the use of a guidewire is recommended while a Port-A catheter is being inserted into the subclavian vein.

IL-6 is an established growth factor for multiple myeloma tumor cells, stimulating proliferative and survival responses. Recent work indicates that IL-6 can activate the AKT kinase in myeloma cells. Thus, to test a potential role for AKT in IL-6-induced cellular responses, we transfected myeloma cell lines with an active 'E40K' or dominant negative'PH AKT construct using an adenoviral vector. Transfection of the E40K into myeloma cells resulted in enhanced tumor cell growth and expression of the PH dominant negative AKT resulted in both inhibition of the IL-6-dependent proliferative response and a decrease in S phase distribution. While transfection of E40K protected myeloma cells from dexamethasone-induced apoptosis, the dominant negative PH had no effect on the ability of IL-6 to protect these cells from dexamethasone. These results clearly demonstrate that AKT activation is critical for the IL-6 proliferative response. In addition, although the level of AKT activation can regulate sensitivity to dexamethasone-induced apoptosis, additional cytokine-induced AKT-independent pathways can mediate IL-6 protection against dexamethasone. DOI: 10.1038/sj/onc/1205194

The purpose of this investigation is to establish a practical method to predict and create surface a profile of bone defects by a well-trained 3-D orthogonal neural network. First, the coordinates of the skeletal positions around the boundary of bone defects are input into the 3-D orthogonal neural network to train it to learn the scattering characteristic. The 3-D orthogonal neural network avoids local minima and converges rapidly. After the neural network has been well trained, the mathematic model of the bone defect surface is generated, and the pixel positions are derived. Herein, to verify its performance the proposed method is applied on a patient with a craniofacial defect.

Background and Purpose: During the period from August 1994 to October 1998, a total of 19 isolates of Exophiala jeanselmei were recovered from 17 patients with various underlying thoracic diseases treated at National Taiwan University Hospital. The purpose of this study was to describe the clinical characteristics of these patients and to determine the microbiologic relatedness of the E. jeanselmei., Methods: Of the 19 isolates, 11 from nine patients were preserved and were identified based on their biotypes as determined by the API ID32C System, their cellular fatty acid profiles by gas-liquid chromatography, their antibiotypes to five antifungal agents by the E-test, and their random amplified polymorphic DNA (RAPD) patterns by arbitrarily primed PCR. Extensive environmental surveillance cultures and cultures from the skin of eight patients and hands of one physician were also performed., Results: One of the 17 patients had E. jeanselmei isolated from cutaneous phaeohyphomycosis (3 isolates), and the other 16 patients had isolations from pleural effusion specimens (15 isolates) or lung mass (1 isolate) following sonography-guided aspiration. The latter 16 patients had no clinical or pathologic evidence of fungal infection. Isolates (clone 1) from aspirated specimens had identical biotypes, antibiotypes, and RAPD patterns, which were different from those of the three isolates (clone 2) from the patient with a cutaneous lesion. All specimens from environmental sources, patients' skin, and the hands of the physician were negative for E. jeanselmei., Conclusion: This series of patients demonstrates the difficulty in identifying the sources of a nosocomial pseudoinfection due to this slow-growing microorganism when isolated from pleural effusion specimens.

Image segmentation is the partition of an image into a set of non-overlapping regions that comprise the entire image. The image is decomposed into meaningful parts, which are uniform with respect to certain characteristics, such as grey level or texture. This study presents a novel methodology to evaluate ultrasound image segmentation algorithms. The sonographic features can differentiate between various sized malignant and benign breast tumours. The clinical experiment can determine whether a tumour is benign or not, based on contour, shape, echogenicity and echo texture. Further study of the standardized sonographic features, especially the tumour contour and shape, will improve the positive predictive value and accuracy rate in breast tumour detection. The effectiveness of using this methodology is illustrated by evaluating image segmentation on breast ultrasound images. Via definite segmentation, the appreciated tumour shape and contour can be ascertained. Furthermore, this method can enhance the ability of ultrasound to distinguish between benign and malignant breast lesions.

This research was conducted to study the influence of composting on the concentrations, water solubility, and phase association of Cu, Mn, and Zn from swine (Sus domesticus) feces. Composting of separated swine manure was performed in two piles for 122 days. The metal concentrations increased rapidly during the first 49 days and leveled off thereafter. All metal concentrations increased approximately 2.7-fold in the final compost due to decomposition of organic matter. A sequential extraction protocol was used to evaluate the humification process and partition metals into water-soluble, exchangeable, organically complexed, organically bound, solid particulate, and residual fractions. Temporal changes in the water-soluble fractions of Cu, Mn, and Zn were reflected by water-soluble organic C concentrations, which rapidly increased to a maximum at Day 18 and declined thereafter. An increase in the humic acid/fulvic acid ratio in Na4P2O7 or NaOH extracts at various stages of composting represented the humification process. During composting, the major portions of Cu, Mn, and Zn were in the organically-bound, solid particulate, and organically complexed fractions, respectively. Metal distributions in different chemical fractions were generally independent of composting age and, thus, independent of respective total metal concentrations in the composts.

Traditionally, the orthopaedist, according to their past experience, reconstructs damaged area while the operation is in progress. This may prolong the operation and cause the wound to become infected. Most importantly it is difficult to precisely match the skeletal defect. A well-disciplined network of prediction re-fabricates the damaged area through automation. This research is based on the CT image file, which is the product of X-ray computed tomography (CT), and computes the skeletal positions around the damaged area through image processing and boundary detection. The skeletal positions are inputted into the orthogonal neural network and discipline the network so that it possesses the scattering characteristic of bone. The network then calculates skeletal positions in the damaged area and revises the former CT image file to rebuild a 3D model. Accordingly, in comparison with a manual sketch, the orthogonal neural network forecast is more geometrically precise. Moreover, the forecast satisfies the second order derivative, which is a continuous function, and the edge of the fabricated bone is therefore kept smoother.

From January 1987 through December 1998, Penicillium marneffei infection (23 patients) or colonization (1 patient) was diagnosed in a total of 24 patients in Taiwan. Of these 24 patients, 16 (67%) had AIDS and 20 (83%) had disseminated P. marneffei infection. The majority (63%) of the infections were considered indigenous. The number of cases has increased markedly in recent years, with 17 of the 24 cases diagnosed from 1996 through 1998. Twenty preserved isolates of P. marneffei, recovered from 11 patients treated at National Taiwan University Hospital during the period of January 1996 through December 1998, were studied to determine the epidemiology of P. marneffei infections. Among the 20 isolates, a total of 8 strains (highly related isolates) were identified on the basis of tests for susceptibility to 5 antifungal agents, for chromosomal DNA restriction fragment-length polymorphism types, and for randomly amplified polymorphic DNA patterns. One of the strains (6 isolates) was isolated from 4 patients treated in 1997 and 1998. Strain spreading of P. marneffei may partially contribute to the increased number of infections caused by this organism in immunosuppressed patients in Taiwan.

Background: From October 1990 to January 1999, 11 of 2237 hepatoma patients at our hospital had gastrointestinal tract metastasis. We describe the radiological and endoscopic features, clinical course and prognoses of those patients., Methods: All patients were male. Six patients were hepatitis B carriers, and cirrhosis was noted in eight patients on admission. We reviewed all available radiological, endoscopic and pathological features., Results: The commonest clinical presentation was frank gastrointestinal bleeding. Histological proof of gastrointestinal involvement was seen in six patients. Endoscopic features included ulcerative tumours mimicking advanced gastric carcinoma (43%) and submucosal tumours (29%). The sites of organ involvement were stomach (five), duodenum (two), colon (three) and duodenum and colon (one). Direct invasion by a contiguous neoplasm was the major route of gastrointestinal tract metastasis. Portal vein thrombosis may be the key point of haematogenous spread to other sites., Conclusions: The prognosis in these patients was extremely poor. Almost all patients died within 5 months if no further aggressive management was performed. Surgical intervention may be the optimal choice for palliative treatment of HCC with gastrointestinal tract involvement.

Background: Chronic Helicobacter pylori infection leads to the development of mucosa-associated lymphoid tissue (MALT), gland atrophy, intestinal metaplasia, and in certain individuals, gastric lymphoma and adenocarcinoma. We conducted a prospective study to determine the effect of H pylori eradication on the development of MALT, gland atrophy and intestinal metaplasia., Methods: From July 1995 to October 1996, 63 consecutive patients with H pylori-associated peptic ulcer disease were enrolled in a bacterial eradication trial. The grade of MALT and the degree of gastritis of the antrum were assessed using Wotherspoon's scale and the Sydney system before treatment, and at eight weeks and one year after H pylori eradication therapy., Results: During the study period, 43 patients received complete follow-up. In the patient group with eradication failure (n = 22), MALT score was significantly decreased at the end of the eighth week (p < 0.05) but returned to the initial level by one year of follow-up. There were no changes in the scores for inflammation, neutrophil activity, gland atrophy or intestinal metaplasia at the end of the eighth week and at one year following H pylori eradication therapy. In contrast, there was a marked reduction in the MALT, inflammation, and activity scores at eight weeks (p < 0.01, < 0.05 and < 0.05, respectively) and one year after treatment (p < 0.05, < 0.001 and < 0.001, respectively) in the patient group with successful eradication (n = 21). However, no significant changes in gland atrophy and intestinal metaplasia were observed during the follow-up period., Conclusions: Eradication of H pylori leads to regression of MALT in the stomach, but the degrees of gland atrophy and intestinal metaplasia remain unchanged, even after one-year of follow-up.

Background: This study investigates the cell proliferation and the expression of p53 protein in Helicobacter pylori (H. pylori)-associated gastritis and assesses the effect of bacterial eradication on these epithelial factors., Material and Methods: Seventy-nine patients with H. pylori-associated gastritis were randomized into the control group (n = 38) and anti-H. pylori group (n = 41). Each patient received endoscopic examinations with gastric biopsy before and 8 weeks after the treatment. The specimens from gastric antrum were immunostained for monoclonal antibodies against the proliferating cell nuclear antigen (PCNA) and p53 protein., Results: In the control group, the total labeling index (L.I.) of PCNA and the positive index (P.I.) of p53 in the whole foveolar epithelium were unchanged after treatment. In the anti-H. pylori group, 35 of 41 cases (85.3%) achieved eradication of H. pylori. Amongst the H. pylori-eradicated cases, the total L.I. of PCNA in the whole foveolar epithelium did not meaningfully alter after H. pylori elimination (p > 0.05). However, a significant reduction of L.I. was observed in the middle compartments of the gastric pits (before vs. after treatment: 14.0 vs. 7.3, p < 0.05). With regard to the p53 expression, the P.I.s were significantly decreased in the whole foveolar epithelium (before vs. after treatment: 0.57 vs. 0.17, p < 0.05) and in each compartment of the gastric pits (before vs. after treatment: [upper compartment]: 0.34 vs. 0.15, p < 0.05; [middle compartment]: 0.67 vs. 0.23, p < 0.05; [lower compartment]: 0.71 vs. 0.20, p < 0.05) after eradication of H. pylori., Conclusions: Bacterial eradication reverses the hyperproliferating status of the foveolar epithelium in patients with H. pylori gastritis and leads to a decrease in p53 accumulation in the epithelial cells.

The diffusiophoretic motion of a long circular cylinder in a transversely imposed gradient of a nonionic solute near a large plane wall parallel to its axis is analyzed. The range of the interaction between the solute and the solid surfaces is assumed to be small relative to the particle radius and to the gap width between the particle and the wall, but the polarization effect of the mobile solute in the thin diffuse layers adjacent to the solid surfaces caused by the strong adsorption of the solute is incorporated. A normal flux of the solute and a slip velocity of the fluid at the outer edge of the diffuse layers are used as the boundary conditions for the fluid domain outside the diffuse layers. Through the use of cylindrical bipolar coordinates along with these boundary conditions, a set of transport equations governing this problem is solved in the quasisteady situation and the wall effects on the diffusiophoresis of the cylinder are computed for various cases. For the diffusiophoretic motion of a cylinder normal to a plane, the particle mobility decreases monotonically with the decrease of the distance of the particle axis from the wall. The stronger the polarization effect in the diffuse layer, the weaker the wall effect on the diffusiophoresis. The effect of the normal plane on the diffusiophoresis of a cylinder is much more significant than that for a sphere at the same separation. For the diffusiophoresis of a cylinder parallel to a plane, the boundary effect is a complicated function of the relevant parameters (not necessarily varies monotonically with the extent of separation) mainly due to the existence of a diffusio-osmotic flow caused by the tangential fluid velocity at the plane wall. Copyright 2000 Academic Press.

Background: Endoscopic sphincterotomy and basket extraction are currently used to remove bile duct stones, with a duct clearance rate of 85% to 90%. A biliary endoprosthesis (stent) is an alternative method to treat difficult cases, especially high-risk surgical patients. The aim of this study was to investigate the long-term effect of biliary endoprostheses in patients with irretrievable common bile duct stones., Methods: From December, 1990, to November, 1998, 546 patients were referred to the Veterans General Hospital-Kaohsiung for endoscopic removal of common bile duct stones. Of them, 12 received long-term biliary endoprosthesis because endoscopic removal or surgery was not suitable. Large-caliber stents (> 10 French) were inserted into 12 patients (5 women and 7 men, mean age, 78.4 years) and they were followed up with regular clinical visits. Quantitative cholescintigraphy was performed in four patients to evaluate biliary emptying after liver function returned to normal., Results: No early complications from stent insertion occurred and a satisfactory resolution of jaundice, pain and fever were noted in all patients. One patient had repeated cholangitis due to stent occlusion and five died from unrelated causes. The median effective period of stent placement was 11 months (range, 1-38 months). Quantitative cholescintigraphy revealed delayed biliary drainage in four patients despite an absence of symptoms after their liver function returned to normal., Conclusions: Large-caliber stents are a safe and effective treatment for long-term palliation in high-risk patients with retained common bile duct stones.

Cobra cardiotoxins (CTXs) are able to adopt a three-fingered beta-strand structure with continuous hydrophobic patch that is capable of interacting with zwitterionic phospholipid bilayer. In addition to the four disulfide bonds that form the rigid core of CTXs, Asp57 near the C-terminus interacts electrostatically with Lys2 near the N-terminus (Chiang et al. 1996. Biochemistry. 35:9177-9186). We indicate herein, using circular dichroism and the time-resolved polarized tryptophan fluorescence measurement, that Asp57 to Asn57 (D57N) mutation perturbs the structure of CTX molecules at neutral pH. The structural stability of the D57N mutant was found to be lower, as evidenced by the reduced effective concentration of the 2,2,2-trifluoethanol (TFE)-induced beta-sheet to alpha-helix transition. Interestingly, the single mutation also allows a greater degree of molecular unfolding, because the rotational correlation time of the TFE-induced unfolding intermediate is larger for the D57N mutant. It is suggested that the electrostatic interaction between N- and C-termini also contributes to the formation of the functionally important continuous hydrophobic stretch on the distant end of CTX molecules, because both the binding to anilinonaphthalene fluorescent probe and the interaction with phospholipid bilayer were also reduced for D57N mutant. The result emphasizes the importance of the hydrophobic amino acid residues near the tip of loop 3 as a continuous part of the three-fingered beta-strand CTX molecule and indicates how a distant electrostatic interaction might be involved. It is also implicated that electrostatic interaction plays a role in expanding the radius of gyration of the folding/unfolding intermediate of proteins.

Background: The pathogenesis of cirrhotic ascites and hepatorenal syndrome remains unresolved. The involvement of both endothelin-1 and atrial natriuretic peptide have recently been suggested. This study investigated the concentrations of serum endothelin and atrial natriuretic peptide in cirrhotic patients., Methods: Seven healthy subjects and 31 cirrhotic patients were studied. Cirrhotic patients were divided into three groups: Group I, 16 cirrhotic patients without ascites; Group II, 10 cirrhotic patients with ascites, but without hepatorenal syndrome; and Group III, five cirrhotic patients with hepatorenal syndrome and ascites. Their sera were analyzed for endothelin-1 and atrial natriuretic peptide concentrations., Results: Cirrhotic patients with ascites, Group II and Group III, had higher plasma endothelin-1 concentrations (15.9 +/- 2.3 pg/ml and 24 +/- 2.1 pg/ml, respectively) than normal subjects and compensated cirrhotics (3.8 +/- 0.7 pg/ml and 6.4 +/- 1.1 pg/ml, respectively); p < 0.001). Atrial natriuretic peptide concentrations were also significantly higher in cirrhotic patients than in normal subjects (p < 0.025). Plasma endothelin-1 concentration had a negative correlation with creatinine clearance (r = -0.65, p < 0.001), as did atrial natriuretic peptide concentrations (r = -0.44, p = 0.012). Plasma endothelin-1 correlated significantly with atrial natriuretic peptide concentrations (r = 0.38, p = 0.035)., Conclusions: Both endothelin-1 and atrial natriuretic peptide concentrations were elevated in cirrhotic patients with ascites and hepatorenal syndrome. Endothelin-1 may have a negative impact on renal function. Our data also suggested that impaired responsiveness rather than impaired secretion of atrial natriuretic peptide is responsible for sodium retention in cirrhotic patients with ascites.

The thyroid hormone receptor genes, TRalpha and TRbeta, differ in developmental expression and tissue distribution. TRbeta knockout mice have goiter, elevated thyroid hormone and TSH levels, and a functional auditory defect. In contrast, mice with TRalpha 1/alpha2 inactivation have thyroid hypoplasia, low serum thyroid hormone levels, growth arrest and delayed small intestine maturation. Mice with selective TRalpha1 inactivation have apparent normal growth and development, but have bradycardia and reduced body temperature. The dramatic differences between these mice with TRbeta and TRalpha gene inactivations indicate the differential function of these genes. The influence of these gene inactivations on thyroid-stimulating hormone regulation is central to the resulting phenotypes.

We report the studies of conjugated polymers, polyaniline thin films, with a near-field scanning optical microscope. Because of the absorption variation in different oxidation states, transmission-mode near-field scanning optical microscope images were employed to map out the distribution of the oxidation states on a submicrometer scale. When the near-field wavelength is varied (between 632.8 and 543.5 nm), the phase separation between the oxidized and the reduced repeated units, with domain sizes on a nanometer-length scale, is observed.

Background and Purpose: Anorexia is a common problem in cancer patients who receive radiotherapy. In this current study, we attempt to determine the effect of megestrol acetate and prepulsid on appetite and nutritional improvement in patients with head and neck cancers undergoing radiotherapy., Materials and Methods: One hundred twenty-nine consecutive patients with head and neck cancers treated between July 1993 and June 1994 were prospectively randomized to receive either megestrol acetate, 40 mg qid (megace group), prepulsid, 5 mg tid (cisapride group), or a placebo treatment (control group) during radiotherapy. Before radiotherapy, body weight (kg), appetite score, performance status, biochemical parameters and hematological parameters were evaluated, and the above-noted clinical and biochemical parameters were assessed and recorded every other week. All patients received 6- 10 MV X-rays or Co-60 gamma-ray to head and neck region for a full course of radiotherapy, 61.2-75.6 Gy/7-9 weeks., Results: Forty-eight patients were enrolled in the megace group, 41 patients in the cisapride group, and 40 patients in the control group. At the 2nd, 4th, 6th and 8th week, as the radiation dose escalated, the megace group had significantly less body weight loss than did the cisapride and control groups (P = 0.045, 0.024, 0.006, 0.003, respectively). The appetite scores of the megace group were significantly higher than those of the cisapride and control groups (P = 0.0001). However, there were no statistically significant differences in the change of albumin level among these three groups at the 2nd, 4th, 6th and 8th week (P > 0.05, respectively)., Conclusions: Megestrol acetate can significantly decrease the degree of body weight loss, and can prevent the deterioration of appetite in patients with head and neck cancers receiving radiotherapy. However, prepulsid lacks the above-mentioned clinical benefits.

The near-field intensity distribution perpendicular to the light-propagation direction was measured by photochemical processes on conjugated-polymer thin films. The shape of the distribution is elliptical, with the long axis along the direction of the incident polarization. The results are compared with calculations based on the realistic tapered probe geometry. The asymmetry distribution is due to the simultaneous presence of horizontal and vertical electric fields in the near field.

The simultaneous operation of near-field scanning optical microscopy (NSOM) in reflection and transmission modes is demonstrated. In the transmission mode, a low-noise, large-area silicon photodetector was mounted between the piezoelectric transducer scanning stage and the sample. In the reflection mode, either a photomultiplier tube or two large-area silicon detectors was used for signal collection. The reflection-mode setup consisting of two silicon detectors provides a large numerical aperture of 0.9 as well as symmetrical detection of emitting photons. The dielectric thin films and the light-emitting polymers were used to demonstrate the capability of these two modes of NSOM. A comparison between these two different setups is also presented.

Retinoid-X receptor (RXR) forms heterodimers with thyroid hormone receptor (TR) and significantly enhances binding to thyroid hormone response elements (TREs). Expression of RXR in a transient transfection assay augments the T3 response, but the influences of the specific cell line and TRE used have not been systematically studied. We determined RXR alpha and -beta augmentation of the TR alpha-mediated T3 response in transient transfection assays of COS, JEG, and mouse embryonic stem (ES) cell lines for a series of eight wild-type thyroid hormone (T3) and retinoic acid response elements (previously shown to bind TR). RXR augmented T3-induced expression in COS and ES cells (1.5- to 4-fold greater expression with added RXR compared to TR alone), but had minimal effect on augmentation of response in JEG cells. For most elements studied there was a proportional augmentation of basal and T3-stimulated expression. TREs from rat GH and laminin-B1, however, had relatively higher levels of T3-induced expression as a result of RXR cotransfection (T3 induction ratios increased 2-fold or greater). Previous characterization of these elements demonstrates that they contain more than two hexameric binding domains, all of which can simultaneously bind TR. The influence of endogenous RXR expression in a cell line on RXR augmentation of the T3 response was determined. RXR alpha and -beta messenger RNA (mRNA) expression was quantitated by Northern blot in each cell line. COS and JEG cells expressed almost exclusively RXR alpha mRNA, although expression was almost 2-fold higher in JEG compared to COS cells (12 +/- 2.5 vs. 6.8 +/- 0.5 density units relative to actin; mean +/- SE; P < 0.05). ES cells expressed only RXR beta mRNA, but at a very low level (0.4 +/- 0.1). Nuclear extracts prepared from JEG and COS cells augmented TR binding proportional to the endogenous RXR mRNA expression, and the heterodimer band was supershifted by the addition of antibody to RXR alpha. Nuclear extracts from ES cells had no detectable TR heterodimer binding to a range of response elements. RXR augmentation of the T3 response differs among cell lines and is greater in those with reduced endogenous RXR. Furthermore, the functional augmentation of the T3 response ratio by RXR is likely to require additional sequences contained in only a subset of elements in which RXR augments TR binding.

Objective: After the advent of selective serotonin reuptake inhibitors on the U.S. market in 1988, American psychiatrists have been faced with more choices of antidepressants for the treatment of depression. The prescribing of SSRIs has been increasing in popularity because they are easily titrated by the physicians and tolerated by patients. However, the SSRI use is frequently associated with female sexual dysfunction. The aim of this study was to describe these SSRI-associated female sexual side effects., Methods: In a retrospective series, clinic records of 110 female SSRI-treated outpatients were reviewed for loss of or decreased libido, orgasmic disturbances (anorgasmia or delayed orgasm), as well as clinical management patterns to alleviate sexual side effects., Results: Twenty-one fluoxetine-, nine paroxetine-, and five sertraline-treated cases with female sexual inhibition were identified. The fates of SSRI-associated sexual adverse effects and clinical managements of restoring these side effects were described., Conclusions: With some limitations in interpreting the data, the findings of this study suggest that SSRI-associated female sexual dysfunction occurs at a higher rate than we previously thought, equal potentials in implicating female sexual side effects among three SSRIs, and the absence or the low incidence of female sexual adverse effects from bupropion, and that these side effects can be managed by waiting for a spontaneous remission, dosage reduction of SSRIs, substitution with bupropion and other antidepressants, or the use of an antidote.

Objective: This is a retrospective study to add to the existing body of clinical information regarding male sexual side effects associated with antidepressants. From the chart review, thirty-four out of eighty male patients were identified to have reported loss of libido, erectile difficulty, anorgasmia, and delayed ejaculation while receiving pharmacotherapy of selective serotonin reuptake blockers (fluoxetine, paroxetine, and sertraline); tricyclic antidepressants (nortriptyline, imipramine, amitriptyline, desipramine, and clomipramine); and a monoamine oxidase inhibitor (phenelzine)., Method: The authors also discussed the management of these sexual side effects by waiting for spontaneous remission, reducing the dosage level, and substituting the offending drug with other antidepressants., Results: This article underscores the underreported nature of antidepressant-associated sexual dysfunction, the high incidence of SSRI-associated sexual side effects, equal potentials in causing sexual side effects among the three SSRI's, the low incidence rate of sexual adverse effects from bupropion, and the minimal need to add an antidote if the side effects are to be managed systematically., Conclusions: Finally, male sexual side effects can occur randomly and involve any sexual phase randomly, and the treatment approaches are similar, regardless of the types of sexual dysfunction associated with antidepressants.

By use of restriction fragment length polymorphism analysis, we examined the liver mitochondrial DNA amplified by polymerase chain reaction from 60 Chinese subjects of 31 to 78 years of age. We found nine specific mtDNA polymorphisms that had never been reported before. Eleven subjects had an Alu I polymorphic site in the subunit 2 gene of NADH dehydrogenase, five had a Hae III polymorphic site in the cytochrome oxidase subunit 2 gene, and five had a Hinf I polymorphic site in the subunit 3 gene of cytochrome oxidase. No polymorphic site was found in the structural genes coding for subunits 1, 3, 4, 4L and 6 of NADH dehydrogenase, cytochrome b, and subunit 8 of ATP synthase. Detailed analysis of the RFLP data did not show age-dependent mtDNA polymorphisms. In addition, the analysis of the restriction patterns of all the mtDNAs revealed 12 mtDNA haplotypes in all the Chinese subjects examined. Among them, type 1 mtDNA was found to be the most predominant and comprised 63.3% of the total study subjects. The restriction patterns of type 1 mtDNA generated by all restriction enzymes were identical to those deduced from the Cambridge sequence of human mtDNA. About 8.3% of the subjects exhibited type 2 mtDNA, and 5% had types 3, 5 and 8 mtDNA, respectively. Each of the rest seven mtDNA types comprised about 2% of the samples. Moreover, type 1 mtDNA was found in the platelets of three white Americans. These findings suggest that type 2 to type 12 mtDNAs have come into existence through the generation or loss of specific polymorphic restriction sites in the mtDNA of the Chinese.

The effect of leucine limitation and of restricted leucine tRNA charging on the expression of the ilvGEDA operon of Serratia marcescens was examined. In this organism, the ilv leader region specifies a putative peptide containing only a single leucine codon that could be involved in leucine-mediated control by attenuation (E. Harms, J.-H. Hsu, C. S. Subrahmanyam, and H. E. Umbarger, J. Bacteriol. 164:207-216, 1985). A plasmid (pPU134) containing the DNA of the S. marcescens ilv control region and three of the associated structural genes was studied as a single chromosomal copy in an Escherichia coli strain auxotrophic for all three branched-chain amino acids. The S. marcescens ilv genes responded to a multivalent control similar to that found in other enteric organisms. Furthermore, the S. marcescens ilv genes were derepressed when the charging of leucine tRNA was restricted in a leuS derivative of E. coli that had been transformed with pPU134. It was concluded that ribosome stalling leading to deattenuation is not dependent on either tandem or a consecutive series of codons for the regulatory amino acid. However, the fact that the single leucine codon is a less frequently used codon (CUA) may be important. The procedure for obtaining the cloned ilv genes in single chromosomal copy exploited the dependence of ColE1 replicons on the polA gene. The cloning experiments also revealed a branched-chain amino acid-glutamate transaminase in S. marcescens that is different from transaminase B.

The nucleotide sequence preceding the ilvGEDA operon has been examined and compared in five enteric organisms. The sequence in Escherichia coli B was identical to the earlier-described strain K-12 sequence. The sequences of Salmonella typhimurium and Klebsiella aerogenes were remarkably similar to that of E. coli and identical in that part of the leader region that specified the putative 32-amino-acid peptide. Thus, identical secondary structures could be postulated for the leaders of all three organisms, and regulation of operon expression could be like that postulated earlier for E. coli. Different secondary structures had to be postulated for the leader transcripts of Edwardsiella tarda and Serratia marcescens. Control of attenuation of the operon in these organisms by the level of leucyl tRNA could be explained only if ribosome stalling occurred at a single leucine codon. In both organisms, that single leucine codon is the rarely used CUA rather than the CUG that is in E. coli, S. typhimurium, and K. aerogenes.