Miracle-dz/UniFAR-FTUs huggingface dataset:
Myoepithelial and basement membrane antigens in benign and malignant human breast tumors

Serial cryostat sections of 160 human breast lesions and of 9 lymph‐node metastases were studied by indirect immunofluores‐cence. We used monoclonal antibodies (MAbs) to lining‐epithelium‐specific keratin 8 and to myoepithelium‐specific keratin 17 in combination with polyclonal and monoclonal antibodies to major basement membrane components, laminin, collagen type IV, entactinhidogen, and large heparan sulfate proteoglycan (perlecan) core protein. Continuous basement membranes adjacent to a basal layer of keratin‐17‐positive myoepithelial cells were typical for normal, benign and in situ carcinomatous structures. In invasive and metastatic structures, always formed by keratin‐8‐positive tumor cells, basement membranes were found only rarely and with conspicuous fragmentations. This lack of basement membranes correlated with loss of myoepithelium identified by staining for keratin 17. In comedo structures of invasive ductal carcinomas and in papillary carcinomas, fibrovascular complexes with numerous blood vessels and deposition of basement membrane material were often seen in the stroma. lmmunomorphological analysis of 41 cases of doubtful diagnosis at intra‐operative biopsy was also performed. A combination of MAbs to keratins 8 and 17, and to basement membrane components, made it possible to distinguish between morphologically similar benign and malig‐nant proliferations and to detect single‐cell invasion of the stroma. This combination of antibodies may be recommended as an auxiliary immunomorphological tool for differential diagno‐sis of intra‐operative breast biopsies in dubious cases.
MOLECULAR MECHANISMS OF ULTRAVIOLET RADIATION CARCINOGENESIS

UV radiation is a potent DNA damaging agent and a known inducer of skin cancer in experimental animals. There is excellent scientific evidence to indicate that most non-melanoma human skin cancers are induced by repeated exposure to sunlight. UV radiation is unique in that it induces DNA damage that differs from the lesions induced by any other carcinogen. The prevalence of skin cancer on sun-exposed body sites in individuals with the inherited disorder XP suggests that defective repair of UV-induced DNA damage can lead to cancer induction. Carcinogenesis in the skin, as elsewhere, is a multistep process in which a series of genetic and epigenetic events leads to the emergence of a clone of cells that have escaped normal growth control mechanisms. The principal candidates that are involved in these events are oncogenes and tumor suppressor genes. Oncogenes display a positive effect on transformation, whereas tumor suppressor genes have an essentially negative effect, blocking transformation. Activated ras oncogenes have been identified in human skin cancers. In most cases, the mutations in the ras oncogenes have been localized to pyrimidine-rich sequences, which indicates that these sites are probably the targets for UV-induced DNA damage and subsequent mutation and transformation. The finding that activation of ras oncogenes in benign and self-regressing keratoacanthomas in both humans and in animals indicates that they play a role in the early stages of carcinogenesis (Corominas et al., 1989; Kumar et al., 1990). Since cancers do not arise immediately after exposure to physical or chemical carcinogens, ras oncogenes must remain latent for long periods of time. Tumor growth and progression into the more malignant stages may require additional events involving activation of other oncogenes or deletion of growth suppressor genes. In addition, amplification of proto-oncogenes or other genes may also be involved in tumor induction or progression. In contrast to the few studies that implicate the involvement of oncogenes in UV carcinogenesis, the role of tumor suppressor genes in UV carcinogenesis is unknown. Since cancer-prone individuals, particularly XP patients, lack one or more repair pathways, one can speculate that DNA repair enzymes would confer susceptibility to both spontaneous and environmentally induced cancers. Another potential candidate that can function as a tumor suppressor gene is the normal c-Ha-ras gene. Spandidos and Wilkie (1988) have shown that the normal c-Ha-ras gene can suppress transformation induced by the mutated ras gene. (ABSTRACT TRUNCATED AT 400 WORDS)
Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study.

PURPOSE The purpose of this study was to investigate the effect of acitretin on the development of keratotic skin lesions, and on squamous cell carcinomas and basal cell carcinomas in a group of renal transplant recipients. PATIENTS AND METHODS Forty-four renal transplant recipients with more than 10 keratotic skin lesions on the hands and forearms were enrolled onto a randomized, double-blind, placebo-controlled trial to test the possible skin cancer-preventing effect of a 6-month treatment with acitretin 30 mg/d. RESULTS No deterioration in renal function occurred in any of the 38 assessable patients treated. During the 6-month treatment period, two of 19 patients (11%) in the acitretin group reported a total of two new squamous cell carcinomas, compared with nine of 19 patients (47%) in the placebo group who developed a total of 18 new carcinomas (chi 2 = 6.27, P = .01). The relative decrease in the number of keratotic skin lesions in the acitretin group was 13.4%, as compared with a relative increase in the placebo group of 28.2% (difference, 41.6%; 95% confidence interval, 11.5 to 71.7). Most patients treated with acitretin had mild mucocutaneous side effects, but these were easily manageable. Some patients experienced mild hair loss. With the exception of three patients, no increase in serum cholesterol or triglyceride above pretreatment levels was observed, and liver function remained unchanged in all patients. CONCLUSION Acitretin 30 mg/d over 6 months had significantly more effect than placebo in the prevention of squamous cell carcinomas and reduced the occurrence of keratotic skin lesions in a group of renal transplant recipients with severe lesions. This effect was most pronounced in patients with a history of squamous cell carcinomas and basal cell carcinomas.
Stages of disease severity and factors that affect the health status of patients with chronic obstructive pulmonary disease.

BACKGROUND We hypothesized that the factors which may influence health status would differ in patients at different disease stages of chronic obstructive pulmonary disease (COPD). The present study investigated how impairments in health status were distributed in male patients at each disease stage according to the British Thoracic Society (BTS) guidelines, and analysed the contribution of the clinical indices, the dyspnoea rating and the psychological status to the health status of patients at the three disease stages of COPD. METHODS A total of 218 consecutive male patients with stable COPD were recruited from our outpatient clinic. All eligible patients completed pulmonary function testing, progressive cycle ergometry, a dyspnoea rating [Medical Research Council (MRC) dyspnoea scale], an assessment of their anxiety and depression [Hospital Anxiety and Depression Scale (HADS)], and an assessment of their health status [the St. George's Respiratory Questionnaire (SGRQ)]. The patients were categorized into three groups: mild COPD with a FEV1 at 60-79% of the predicted value, moderate COPD at 40-59% of the predicted value, and severe COPD at below 40% of the predicted value. RESULTS Twenty-five patients (11%) had mild COPD, 72 patients (33%) had moderate COPD, and 121 patients (56%) had severe COPD. Significant differences were observed for the total score and for three components on the SGRQ among patients at the three stages (one-way ANOVA, P<0.05). The scores for the total SGRQ and for the activity component were significantly higher for patients with severe COPD than for patients with moderate COPD [Fisher's least-significant-difference (LSD) method, P<0.05], and also significantly higher for moderate COPD patients than for mild COPD patients. The maximal oxygen uptake (VO2 max) correlated significantly with the total SGRQ score in the mild patients [Pearson's correlation coefficient (r) = -0.67], but not in the moderate or severe patients. The MRC dyspnoea scale had strong correlations with the SGRQ in all patient groups (r = 0.53 to approximately 0.70). Anxiety and depression on the HADS showed moderate correlations with the SGRQ score in the mild and severe patients (r = 0.51 to approximately 0.57). Multiple regression analysis showed that in patients with mild COPD, the MRC and VO2 max accounted for the total score on the SGRQ. Anxiety on the HADS plus the MRC scale accounted for the total score on the SGRQ in patients with moderate COPD, and anxiety on the HADS, the MRC scale and the FEV1 significantly influenced the SGRQ severe COPD patients. CONCLUSIONS The disease staging proposed by the BTS guidelines can separate patients with COPD according to impairments in their health status. Furthermore, the factors that influence health status differed in patients at the three disease stages. Our findings support the boundaries used in disease staging and some recommendations from the BTS guidelines.
Relationship Issues of Women With Breast Cancer

This in-depth, qualitative pilot study explored the impact of breast cancer on specific dimensions of the relationships and roles of women. It included interaction within the partner relationship as well as with family, friends, and colleagues. Data were obtained by individual and group interviews from 10 women with a diagnosis of breast cancer and 5 male partners. Both partnered and single women participated. There were four major findings seldom discussed in the literature, which have important implications for preventive intervention. First, partner relationships troubled before the diagnosis as well as those characterized by mutual caring faced challenges and negative changes. Second, in an effort to protect each other, communication within the partner dyad became less open, and there were changes in the usual manner of conflict resolution. Third, unpartnered women appeared to be more vulnerable to problems of negative adjustment, largely because of relationship issues. Fourth, participants confirmed the need for a comprehensive intervention to facilitate coping with issues relative to relationships, intimacy, and sexuality. Although the sample was small, in-depth data were obtained that provide a basis for specific areas in which further empirical investigation is needed, and they indicate that preventive intervention may well be warranted.
Retinal venous oxygen saturation increases by flicker light stimulation.

PURPOSE Luminance flicker stimulation of the photoreceptors is known to increase retinal blood flow. Elevated blood velocity was determined using laser Doppler velocimetry, and increased vascular diameters during flicker were observed by measurements with a retinal vessel analyzer. Oxygen supply may be the target of the regulation of retinal blood flow. Thus, the oxygen saturation (SO(2)) in retinal arterioles and venules was investigated along with their diameters. METHODS Dual-wavelength (548 nm and 610 nm) fundus images were taken in 19 healthy volunteers (mean age, 26 ± 2.5 years) before (baseline) and during luminance flicker stimulation (12.5 Hz; modulation depth, 1:25). Retinal vessel SO(2) (dual-wavelength optical oximetry) and diameters (central retinal arterial and venous equivalents [CRAE and CRVE]) were determined. RESULTS CRAEs and CRVEs of 193 ± 20 μm and 228 ± 20 μm at baseline increased statistically significant to a maximum of 202 ± 19 μm (P < 0.0005) and 242 ± 17 μm (P < 0.0005), respectively, under flicker stimulation. Although the arterial SO(2) remained unchanged at 98%-99%, an increase of the venous saturation from 60% ± 5.7% to 64% ± 5.9% (P < 0.0005) was found. CONCLUSIONS In agreement with earlier investigations, the vessel dilation found here indicates an elevation of retinal blood flow by luminance flicker stimulation. This increase of the flow should meet the enhanced metabolic need of the neural retina under a physiological stimulus. The augmentation of venous oxygenation may indicate a higher capillary oxygen concentration, necessary to provide a sufficient diffusion rate of oxygen from the capillaries to the inner retinal tissue.
Effect of Turbulent-Flow Pasteurization on Survival of Mycobacterium avium subsp.paratuberculosis Added to Raw Milk

ABSTRACT A pilot-scale pasteurizer operating under validated turbulent flow (Reynolds number, 11,050) was used to study the heat sensitivity ofMycobacterium avium subsp.paratuberculosis added to raw milk. The ATCC 19698 type strain, ATCC 43015 (Linda, human isolate), and three bovine isolates were heated in raw whole milk for 15 s at 63, 66, 69, and 72°C in duplicate trials. No strains survived at 72°C for 15 s; and only one strain survived at 69°C. Means of pooled Dvalues (decimal reduction times) at 63 and 66°C were 15.0 ± 2.8 s (95% confidence interval) and 5.9 ± 0.7 s (95% confidence interval), respectively. The mean extrapolatedD72°C was <2.03 s. This was equivalent to a >7 log10 kill at 72°C for 15 s (95% confidence interval). The mean Z value (degrees required for the decimal reduction time to traverse one log cycle) was 8.6°C. These five strains showed similar survival whether recovery was on Herrold's egg yolk medium containing mycobactin or by a radiometric culture method (BACTEC). Milk was inoculated with fresh fecal material from a high-level fecal shedder with clinical Johne's disease. After heating at 72°C for 15 s, the minimum M. avium subsp.paratuberculosis kill was >4 log10. Properly maintained and operated equipment should ensure the absence of viable M. avium subsp. paratuberculosisin retail milk and other pasteurized dairy products. An additional safeguard is the widespread commercial practice of pasteurizing 1.5 to 2° above 72°C.
The effect of a manual therapy knee protocol on osteoarthritic knee pain: a randomised controlled trial.

BACKGROUND Knee osteoarthritis is a highly prevalent condition with a significant socioeconomic burden to society. It is known to effect sufferers through pain, loss of function and changes in health related quality of life. Management typically involves pharmacologic and/or exercise based therapy approaches to reduce pain. Previous studies have shown multimodal treatment approaches incorporating manual therapy to be efficacious. The aim of this study is to determine if a manual therapy technique knee protocol can alter the self reported pain experienced by a group of chronic knee osteoarthritis sufferers in a randomised controlled trial. METHODS 43 participants with a chronic, non-progressive history of osteoarthritic knee pain, aged between 47 and 70 years were randomly allocated following a screening procedure to an intervention group (n=26; 18 men and 8 women, mean age 56.5 years) or a control group (n=17; 11 men and 6 women, mean age 54.6 years). Participants were matched for present knee pain intensity measured on a visual analogue scale. The intervention consisted of the Macquarie Injury Management Group Knee Protocol whilst the control involved a non-forceful manual contact to the knee followed by interferential therapy set at zero. Participants received three treatments per week for two consecutive weeks with a follow up immediately after the final treatment. Post-treatment Participants completed 11 questions including present knee pain intensity and feedback regarding their response to treatment utilizing a visual analogue scale. Results were analysed using descriptive statistics. RESULTS Prior to the intervention, there was no significant differences in age or present knee pain intensity. Following treatment, the intervention group reported a significant decrease in the present pain severity (mean 1.9) when compared to the control group (mean 3.1). Response to treatment questions indicated that compared to the control group, the intervention group felt the intervention had helped them (intervention mean 7.0; control mean 3.4), felt it decreased their knee symptoms such as crepitus (intervention mean 6.0; control mean 3.4) and improved their knee mobility (intervention mean 6.4; control mean 3.4) and their ability to perform general activities (intervention mean 6.5; control mean 3.8). Importantly the MIMG Knee Protocol intervention group reported no adverse reactions during treatment. CONCLUSIONS A short-term manual therapy knee protocol significantly reduced pain suffered by participants with osteoarthritic knee pain and resulted in improvements in self-reported knee function immediately after the end of the 2 week treatment period.
Agonist-induced Desensitization, Internalization, and Phosphorylation of the sst2A Somatostatin Receptor*

Cellular responsiveness to the inhibitory peptide somatostatin (SRIF) or its clinically used analogs can desensitize with agonist exposure. While desensitization of other seven-transmembrane domain receptors is mediated by receptor phosphorylation and/or internalization, the mechanisms mediating SRIF receptor (sst) desensitization are unknown. Therefore, we investigated the susceptibility of the sst2A receptor isotype to ligand-induced desensitization, internalization, and phosphorylation in GH-R2 cells, a clone of pituitary tumor cells overexpressing this receptor. A 30-min exposure of cells to either SRIF or the analog SMS 201–995 (SMS) reduced both the potency and efficacy of agonist inhibition of adenylyl cyclase. Internalization of receptor-bound ligand was rapid (t½ = 4 min) and temperature-dependent. SRIF and SMS increased the phosphorylation of the 71-kDa sst2A protein 25-fold within 15 min. Receptor phosphorylation was dependent on both the concentration and time of agonist exposure and was not affected by pertussis toxin pretreatment, indicating that receptor occupancy rather than second messenger formation was required. Receptor phosphorylation was also stimulated by phorbol 12-myristate 13-acetate activation of protein kinase C. Both ligand-stimulated and phorbol 12-myristate 13-acetate-stimulated receptor phosphorylation occurred primarily on serine. These studies are the first demonstration of agonist-dependent desensitization, internalization, and phosphorylation of the sst2A receptor and suggest that phosphorylation may mediate the homologous and heterologous regulation of this receptor.
An Eigen Domain Interference Rejection Combining Algorithm for Narrowband Interference Suppression

In this letter, we propose an eigen domain interference rejection combining (E-IRC) algorithm to suppress the narrowband interference (NBI). The proposed E-IRC algorithm explores the difference between the time domain autocorrelation matrices of the NBI and the desired signal and implements the IRC in the eigen domain. Compared with the traditional IRC, which rejects the interference in the spatial domain, the proposed E-IRC algorithm exploits the characteristics of the received signal in both the time and spatial domain to suppress the NBI and thus yields better performance. Simulation results are presented to demonstrate the advantage of the proposed algorithm.
Genetic Analysis of Glutathione Peroxidase in Oxidative Stress Response of Saccharomyces cerevisiae *

Three glutathione peroxidase homologs (YKL026C, YBR244W, andYIR037W/HYR1) were found in theSaccharomyces Genome Database. We named themGPX1, GPX2, and GPX3, respectively, and we investigated the function of each gene product. Thegpx3Δ mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes. Glutathione peroxidase activity decreased approximately 57 and 93% in the gpx3Δ andgpx1Δ/gpx2Δ/gpx3Δ mutants, respectively, compared with that of wild type. Expression of theGPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation. The GPX2 gene expression was induced by oxidative stress, which was dependent upon the Yap1p. The TSA1(thiol-specific antioxidant) gene encodes thioredoxin peroxidase that can reduce peroxides by using thioredoxin as a reducing power. Disruption of the TSA1 gene enhanced the basal expression level of the Yap1p target genes such as GSH1,GLR1, and GPX2 and that resulted in increases of total glutathione level and activities of glutathione reductase and glutathione peroxidase. However, expression of the TSA1gene did not increase in thegpx1Δ/gpx2Δ/gpx3Δ mutant. Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Δ mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase.
A Wideband, Low-Profile, Conical-Beam Antenna With Horizontal Polarization for Indoor Wireless Communications

A novel, horizontally polarized, conical-beam antenna is proposed. The antenna is low in profile (H = 0.1867lambdao) and has about 38% impedance bandwidth (SWR < 2) and average antenna gain of 5 dBi. The radiation patterns are stable across the operating band. Good agreement between simulated and measured results is observed.
Testosterone Metabolism In Rat Brain Is Differentially Enhanced By Phenytoin‐Inducible Cytochrome P450 Isoforms

Many cytochrome P450 (P450) isoforms are selectively inducible by xenobiotics, e.g. pharmaceuticals like the anti‐epileptic drug phenytoin. Some of these P450 enzymes are involved in the metabolism of gonadal hormones and are of great importance, especially in early brain development. In this study, the hydroxylation of testosterone by rat brain microsomes from control and phenytoin‐induced animals was examined by use of high performance liquid chromotography (HPLC) provided with a photodiode array detector (PDA). In control rats, testosterone is converted by cytochrome(s) P450 to 6α‐hydroxytestosterone (OHT) as the main metabolite and 6β‐OHT as well as androstenedione as minor metabolites. After phenytoin treatment, brain microsomes showed a strong increase of testosterone metabolism to 2α‐, 6β‐, 16α‐, 16β‐OHT and androstenedione, whereby 16α‐OHT was the main degradation product. These metabolites indicated the action of isoforms of the P450 subfamilies CYP2B, CYP2C and CYP3A. Inhibition experiments with antibodies against CYP2B1/2 and with the CYP2B specific inhibitor orphenadrine indicated the occurrence of members of this subfamily which are known to catalyse the oxidation of testosterone to 16α‐OHT, 16β‐OHT and androstenedione. Western blots revealed the phenytoin‐inducible expression of CYP2B1 and the constitutive expression of CYP3A. The latter is involved in the 6β‐hydroxylation of testosterone which was found correspondingly in control microsomes. Distinct CYP2C isoforms involved in the hydroxylation of testosterone in phenytoin‐induced microsomes are not yet identified. The highly increased testosterone metabolism by phenytoin‐dependent induction of specific cytochrome P450 isoforms in adult rat brain illustrates the potential influence of exogenous substances on internal regulative and metabolic pathways in the brain.