Miracle-dz/UniFAR-FTUs huggingface dataset:
Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women

Summary. Three analogues of posterior pituitary hormones, 1 ‐ deamino ‐ 2 ‐ D ‐ Tyr(OEt) ‐ 4 ‐ Val ‐ 8 ‐ Om ‐ vasotocin(dE ‐ VVT), l‐deamino‐2‐D‐Tyr(OEt)‐4‐Thr‐8‐Orn‐vasotocin(dE‐TVT) and 1‐deamino‐2‐D‐Tyr(OEt)‐oxytocin(dE‐OXY) were compared for their inhibitory effects on vasopressin (VP)‐induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea‐like symptoms. Intravenous injections of all analogues (10 μg/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE‐TVT was the most effective and dE‐OXY was least active. With dE‐TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40–50 min). Only dE‐OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE‐TVT (10 ng/kg body weight) showed that the plasma half‐life was approximately 16 min and the clearance 30 1/h. The bioavailability of 100 ng/kg given intra‐nasally was about 5·5%. Further studies are recommended.
Multiple cancers. Tumor burden permits the outgrowth of other cancers

We demonstrate that tumor-bearing hosts permit the outgrowth of "potentially malignant" cells that are located at a different site. These second cancers continued to grow and kill their hosts even though they retain the "premalignant" phenotype, even after removal of the original malignancy. The potentially malignant cells used in these experiments were ultraviolet light- or methylcholanthrene-induced regressor tumor cells that are rejected regularly by normal mice at any testable dose, and only form progressive tumors in immunosuppressed individuals. The immunological rejection of these highly immunogenic, potentially malignant cells was suppressed by Thy-1+, Ly-2-, nonadherent, radio-sensitive suppressor cells in the tumor-bearing mice. These suppressor cells were absent in nude tumor-bearing mice. Unlike helper and cytolytic T cell-mediated responses, which are exquisitely tumor specific, the suppression caused by a progressively growing tumor was crossreactive among many syngeneic, independently derived tumors induced by different carcinogens. However, T cell- mediated immune responses to alloantigens, allogeneic tumors, certain syngeneic tumors, and humoral responses to xenogeneic red blood cells were normal in these mice. The immune suppression in the tumor-bearing animals closely simulated that induced by ultraviolet light irradiation, and both types of suppression might therefore share common mechanisms. Our findings may contribute to understanding the growth, development, and possible control of multicentric malignancies and add a precaution to the potential use of strongly immunogenic tumor variants for active immunotherapy in hosts bearing less immunogenic tumors.
Mining an Ostrinia nubilalis midgut expressed sequence tag (EST) library for candidate genes and single nucleotide polymorphisms (SNPs)

Genes expressed in lepidopteran midgut tissues are involved in digestion and Bacillus thuringiensis (Bt) toxin resistance traits. Five hundred and thirty five unique transcripts were annotated from 1745 high quality O. nubilalis larval midgut expressed sequence tags (ESTs). Full‐length cDNA sequence of 12 putative serine proteinase genes and 3 partial O. nubilalis aminopeptidase N protein genes, apn1, apn3, and apn4, were obtained, and genes may have roles in plant feeding and Bt toxin resistance traits of Ostrinia larvae. The EST library was not normalized and insert frequencies reflect transcript levels under the initial treatment conditions and redundancy of inserts from highly expressed transcripts allowed prediction of putative single nucleotide polymorphisms (SNPs). Ten di‐, tri‐ or tetranucleotide repeat unit microsatellite loci were identified, and minisatellite repeats were observed within the C‐termini of two encoded serine proteinases. Molecular markers showed polymorphism at 28 SNP loci and one microsatellite locus, and Mendelian inheritance indicated that markers were applicable to genome mapping applications. This O. nubilalis larval midgut EST collection is a resource for gene discovery, expression information, and allelic variation for use in genetic marker development.
Identification of multi‐SH3 domain‐containing protein interactome in pancreatic cancer: A yeast two‐hybrid approach

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that shows minimal response to chemotherapy. Genetic changes involved in the progression of PDAC concern genes that encode proteins related to signal transduction networks. This fact reveals the importance in identifying the role and the relations between multiple signaling cascades in PDAC. One of the major factors that modulate signaling events is multidomain scaffold proteins that function by binding several proteins simultaneously, inducing their proximity and influencing the outcome of signaling. A particular group among them, containing multiple Src homology 3 (SH3) domains that can bind proteins containing proline‐rich motifs, was associated to different aspects of cancer cell homeostasis. In this work, using a microarray‐based analysis, we have shown that 13 multiple SH3 domain containing scaffold proteins are expressed in PDAC cells. Using a yeast two‐hybrid approach, we have identified proteins that interact with these adaptor proteins. Among them we have found several molecules that modulate cell proliferation and survival (CIZ1, BIRC6, RBBP6), signaling (LTBP4, Notch2, TOM1L1, STK24) and membrane dynamics (PLSCR1, DDEF2, VCP). Our results indicate that interactions mediated by multi‐SH3 domain‐containing proteins could lead to the formation of dynamic protein complexes that function in pancreatic cancer cell signaling. The identification of such protein complexes is of paramount importance in deciphering pancreatic cancer biology and designing novel therapeutic approaches.
Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT.

UNLABELLED A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion. METHODS A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET. RESULTS A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method. CONCLUSION These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF.
The human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein zinc ejection activity of disulfide benzamides and benzisothiazolones: correlation with anti-HIV and virucidal activities

It has been shown previously by our group and others that a series of four disulfide benzamides with cellular anti-human immunodeficiency virus (HIV) activity can eject zinc from HIV type 1 nucleocapsid protein (NCp7) in vitro while analogs without antiviral activity do not. We also found that the zinc ejection activity correlates with the loss of the ability of NCp7 to bind to HIV psi RNA in vitro. These observations indicate that the antiviral disulfide benzamides may act at a novel retroviral target of action, i.e., the nucleocapsid protein. The present studies examine the relationship among disulfide benzamide structure, in vitro NCp7 zinc ejection activity, and antiviral activity for a larger series of compounds. All of the antiviral disulfide benzamides were found to eject NCp7 zinc, while some disulfide benzamides with zinc ejection activity are not antiviral. Utilizing the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid), it was determined that the o-amido-phenyl disulfides being studied cyclize in aqueous solution to form benzisothiazolones. A series of benzisothiazolones, which are stable in solution in the absence of dithiothreitol, were found to eject NCp7 zinc at a rate similar to that of their disulfide benzamide analogs and to possess similar antiviral activity. It was also found that the relative rates of HIV inactivation by various disulfide benzamides and benzisothiazolones correlate with their relative kinetic rates of NCp7 zinc ejection, which is consistent with the nucleocapsid protein being the target of action of these compounds.
Interpretation of Trailing Endpoints in Antifungal Susceptibility Testing by the National Committee for Clinical Laboratory Standards Method

ABSTRACT Trailing endpoints remain a problem in antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards (NCCLS) method. For isolates for which trailing endpoints are found, MICs of ≤1 μg/ml at 24 h and of >64 μg/ml at 48 h are usually observed. In a study of human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis, we identified three patients with multiple serial isolates for which trailing endpoints were observed with fluconazole. At 24 h, MICs were generally ≤1 μg/ml by both broth macro- and microdilution methods. However, at 48 h, MICs were >64 μg/ml, while the organism remained susceptible by agar dilution testing with fluconazole. Most episodes of oropharyngeal candidiasis with trailing-endpoint isolates responded to doses of fluconazole as low as 100 mg/day. Two patients had both susceptible and trailing-endpoint isolates by NCCLS broth macro- and microdilution testing; these isolates were found to be the same strain by pulsed-field gel electrophoresis using restriction fragment length polymorphisms. Another patient had two different strains, one for which trailing endpoints were observed and one which was susceptible at 48 h. Trailing endpoints may be seen with selected isolates of a strain or may be a characteristic finding for most or all isolates of a strain. In addition, with isolates for which trailing endpoints are observed, reading the endpoint for the NCCLS method at 24 h may be more appropriate.
Antibody‐mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background

Antibody‐mediated glomerulonephritis in man may be exacerbated by infection and this effect may be mediated by bacterial endotoxin. There is evidence supporting a role for endotoxin in heterologous nephrotoxic nephritis in rats, but the role of endotoxin in this model in mice has not previously been explored. Previous data in mice on the role of complement in this model are conflicting and this may be due to the mixed genetic background of mice used in these studies. We used the model of heterologous nephrotoxic nephritis in mice and explored the role of endotoxin, complement and genetic background. In this study we show a synergy between antibody and endotoxin in causing a neutrophil influx. We also show that C1q‐deficient mice have an increased susceptibility to glomerular inflammation but this is seen only on a mixed 129/Sv × C57BL/6 genetic background. On a C57BL/6 background we did not find any differences in disease susceptibility when wildtype, C1q, factor B or factor B/C2 deficient mice were compared. We also demonstrate that C57BL/6 mice are more susceptible to glomerular inflammation than 129/Sv mice. These results show that endotoxin is required in this model in mice, and that complement does not play a major role in glomerular inflammation in C57BL/6 mice. C1q may play a protective role in mixed‐strain 129/Sv × C57BL/6 mice, but the data may also be explained by systematic bias in background genes, as there is a large difference in disease susceptibility between C57BL/6 and 129/Sv mice.
Molecular mapping of the origin of postnatal spinal cord ependymal cells: Evidence that adult ependymal cells are derived from Nkx6.1+ ventral neural progenitor cells

Recent studies have suggested that the ependymal cells lining the central canal of postnatal spinal cord possess certain properties of neural stem cells. However, the embryonic origin and developmental potential of the postnatal spinal cord ependymal cells remain to be defined. In this report, we investigated the developmental origin of postnatal spinal ependymal cells by studying the dynamic expression of several neural progenitor genes that are initially expressed in distinct domains of neuroepithelium in young embryos. At later stages of development, as the ventricular zone of the embryonic spinal cord is reduced, expression of Nkx6.1 progenitor gene is constantly detected in ependymal cells throughout chick and mouse development. Expression of other neural progenitor genes that lie either dorsal or ventral to the Nkx6.1+ domain is gradually decreased and eventually disappeared. These results suggest that the remaining neuroepithelial cells at later stages of animal life are derived from the Nkx6.1+ ventral neuroepithelial cells. Expression of Nkx6.1 in the remaining neuroepithelium is closely associated with, and regulated by, Shh expression in the floor plate. In addition, we suggested that the Nkx6.1+ ependymal cells in adult mouse spinal cords may retain the proliferative property of neural stem cells. J. Comp. Neurol. 456:237–244, 2003. © 2003 Wiley‐Liss, Inc.
Essential genes from Arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines

All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 °C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were shown to induce protective immunity after vaccination at a cool body site. About half of the genes that could be tested were unable to mutate to temperature-resistant forms at detectable levels. These results show that psychrophilic essential genes can be used to create a unique class of bacterial temperature-sensitive vaccines for important human pathogens, such as S. enterica and Mycobacterium tuberculosis.
The effect of static stretch and warm-up exercise on hamstring length over the course of 24 hours.

STUDY DESIGN Experimental pretest-posttest control design. OBJECTIVES The purpose of the study was twofold: (1) to determine the lasting effect of static stretch on hamstring length for up to 24 hours and (2) to compare the efficacy of static stretch with and without warm-up exercise on hamstring length. BACKGROUND Research is limited on the lasting effects of static stretching and is controversial on the combined effects of warm-up activities and static stretching on muscle lengthening. METHODS AND MEASURES Fifty-six volunteer subjects (ages 18-42 years) with limited bilateral hamstring length were assigned to 1 of 4 groups: (1) warm-up and static stretch, (2) static stretch only, (3) warm-up only, and (4) control. The warm-up was 10 minutes of stair climbing at 70% of maximum heart rate. Static stretch consisted of a single session of three 30-second passive stretches of the hamstring. Hamstring length was measured preintervention and at several intervals postintervention (immediately and then at 15 minutes, 60 minutes, 4 hours, and 24 hours) using the active knee extension (AKE) test. Data were analyzed using a mixed-model analysis of variance. RESULTS The warm-up-and-static-stretch group and the static-stretch-only group showed a significant increase in hamstring length between preintervention and all postintervention measurements. At 24 hours poststretch, the warm-up-and-static-stretch group had a mean increase of 10.3 degrees (95% confidence interval, 7.7-12.9) and the static-stretch-only group had a mean increase of 7.7 degrees (95% confidence interval, 4.7-10.7) in AKE range of motion (ROM). Both of these groups did show significant decrease (2.9 degrees and 4.0 degrees, respectively) in hamstring muscle length (AKE ROM) at 15 minutes poststretch when compared to immediate poststretch values. The static-stretch-only and the warm-up-and-static-stretch groups did not differ significantly from each other. Control and warm-up-only groups showed no significant increase in hamstring length between preintervention and any of the postintervention measurements. CONCLUSIONS A significant increase in hamstring length can be maintained for up to 24 hours when using static stretching. Muscle length gains are greatest immediately after stretching and decline within 15 minutes. The addition of a warm-up exercise prior to stretching does not appear to significantly increase the effectiveness of static hamstring stretching.
Social Support: Gender Differences in Cancer Patients in the United Kingdom

Social support is an important aspect of psychological functioning during diagnosis and treatment of cancer. Gender has been found to influence support preferences, and previous research suggests that women are more likely to seek and utilize support by comparison to men. This qualitative study explores how patients perceive the support they receive. It also examines patient preferences and satisfaction with information and emotional support provided by staff. Eleven melanoma patients (6 men and 5 women) and 5 breast cancer patients participated in a semistructured interview. Thematic analysis suggests that gender is central to patients' satisfaction and preference for support. Whereas women expected staff to provide information and emotional support, men felt that emotional support from staff was inappropriate and perceived information as supportive in helping them deal with their emotions. Men were also more satisfied with support generally, and women perceived staff to have less time to provide support. Breast cancer patients were more satisfied with access to and the nature of support available to them. Findings suggest that female melanoma patients would benefit from similar services. Meeting the support needs of men appears less clear. If support were available as part of a structured care plan, it is possible that men would also utilize support. Future research is required to gain greater understanding of men's support needs.
Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1.

We have investigated the effect of the administration of mAb against leukocyte function-associated molecule-1 (CD11a/CD18) and intercellular adhesion molecule-1 (CD54) on the delayed-type hypersensitivity reaction in 2,4-dinitro-1-fluorobenzene-sensitized CD2F1 mice. An i.p. injection of the mAb FD441.8 against CD11a at the time of ear challenge led to an almost complete inhibition of ear swelling compared with control animals. Administration of anti-CD54 mAb, 3E2 or YN1/1.7. 4, before challenge, resulted in approximately 50% reduction of the delayed-type hypersensitivity response. The decrease in ear swelling reflected a profound inhibition of the edema and the cell infiltration in ears from animals treated with anti-CD11a, and a partial inhibition with anti-CD54 treatment. In addition, the threefold increase in the number of cells recovered from the draining lymph nodes 24 h after challenge in sensitized mice injected with normal IgG was ablated in mice treated with anti-CD11a and partially reduced in anti-CD54-treated animals. Immunohistochemistry and flow cytometry analysis demonstrated that the in vivo administered anti-CD11a mAb was associated with the surface of the majority of the cells in the lymph nodes 24 h after injection and challenge, whereas the anti-intercellular adhesion molecule-1 mAb reacted preferentially with the vascular endothelium. It is concluded that leukocyte function-associated molecule-1 and intercellular adhesion molecule-1 contribute to the generation of an optimal delayed-type hypersensitivity response.
Skeletal muscle architecture of the rabbit hindlimb: Functional implications of muscle design

The muscle‐fiber architecture of 29 muscles from six rabbits (Oryctolagus cuniculus) was measured in order to describe the muscular properties of this cursorial animal, which possesses several specific skeletal adaptations. Several muscles were placed into one of four functional groups: hamstrings, quadriceps, dorsiflexors, or plantarflexors, for statistical comparison of properties between groups. Antagonistic groups (i.e., hamstrings vs. quadriceps or dorsiflexors vs. plantarflexors) demonstrated significant differences in fiber length, fiber length/muscle length ratio, muscle mass, pinnation angle, and number of sarcomeres in series (P<.02). Discriminant analysis permitted characterization of the “typical” muscle belonging to one of the four groups. The quadriceps were characterized by their large pinnation angles and low fiber length mass ratios, suggesting a design for force production. Conversely, the hamstrings, with small pinnation angles, appeared to be designed to permit large excursions. Similar differences were observed between plantarflexors and dorsiflexors, which have architectural features that suit them for force production and excursion respectively. Although these differences were not absolute, they represented clear morphological distinctions that have functional consequences.