tbuckley/cabot-search huggingface dataset:
Development of male‐fertility‐regulating agents
Authors: Suprabhat Ray, Parul Verma, Atul Kumar
Journal: Medicinal Research Reviews (1991)

Steroidal, nonsteroidal, plant-derived, gonadotropin-related and immunological agents investigated for control of male fertility are reviewed with brief descriptions of their effects, and illustrations of their structures. The physiology of the male reproductive system is presented as an introduction: an ideal male antifertility agent would inhibit spermatogenesis at the level of the Sertoli cells, without affecting endogenous androgen production by Leydig cells, needed for libido and potency. Androgens down-regulate their own production at physiological levels, but few long-acting orally active derivatives are available. Anti-androgens with mixed androgen and progestin activity, combined with a pure androgen are potentially useful. Androgen-progestin combinations are being tested by WHO as implants. Dozens of miscellaneous nonsteroidal compounds have been discovered serendipitously to have antifertility activity in men or male animals, including alkylating agents antimetabolites, antibiotics, sulfa derivatives, fungicides, trichomonocides, amebicides, alpha blockers, antimalarials, coumarins, and carbohydrate derivatives. Various plant alkaloids have been screened. Those of Hibiscus, Vitex and Plumbago species, as well as Tripterygium wilfordii glycosides, which are being evaluated in combination with gossypol, are mentioned here. Gossypol has been thoroughly tested in China, but rejected because of its side effects, particularly hypokalemic paralysis, its low therapeutic index, and uncertain recovery of fertility. Gonadotropin-releasing hormone (GnRH) agonists and antagonists are being researched in combination with androgens with some success. The GnRH antagonists to date have low activity , or cause histamine-related side effects at higher doses; the androgens require a new route such as a long-acting implant to overcome the need for daily injections. Immunological contraception for males has not progressed beyond the research stage.
Detection of Mononucleotide Repeat Sequence Alterations in a Large Background of Normal DNA for Screening High-Frequency Microsatellite Instability Cancers
Authors: Xiyuan Sun, Yiding Liu, Jim Lutterbaugh, Wei-Dong Chen, Sanford D. Markowitz, Baochuan Guo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Mutations in mononucleotide repeat sequence (MRS) are good indicators of high-frequency microsatellite instability (MSI-H) cancers, but it has been a challenge to detect such mutations in a large background of wild-type DNA; as in this setting, PCR errors often generate false positive mutant alleles. In this study, we developed a general strategy, referred to as probe clamping primer extension-PCR (PCPE-PCR), to detect MRS alterations in a large background of wild-type DNA. Experimental Design: In PCPE-PCR, genomic DNA is first subjected to PCPE, in which mutant single-strand DNA molecules are preferentially produced. Next, genomic DNA is removed to enrich for the mutant DNA fraction. Thereafter, PCR is carried out using the remaining single-strand DNA molecules as templates. Finally, the PCR products are analyzed to reveal the MSI-H status. In this study, the sensitivity of this new method was first examined by spiking mutant DNA into wild-type DNA at specific ratios followed by studying whether this method is applicable to fecal DNA testing. Results: We showed that PCPE-PCR could detect both mutated BAT26 and transforming growth factor-β-RII (A)10 markers in the presence of 500-fold excess of normal DNA and that as few as three copies of mutated DNA could be detected. In addition, we showed that this technology could detect MSI-H colorectal cancer by fecal DNA analysis. Conclusion: PCPE-PCR is sensitive. In addition, PCPE-PCR is simple and amendable to a cost-effective and high-throughput screening operation. This technology may be applicable to noninvasive screening of MSI-H cancer.
"Anomalous" Thy-1+ killer cells in allogeneic and F1-anti-parental mixed leukocyte culture. Relation to natural killer cells and allospecific cytotoxic T lymphocytes.
Authors: K Kärre, J K Seeley, E Eriksson, R C Burton, R Kiessling
Journal: The Journal of Experimental Medicine (1983)

Anomalous killer cells are Thy-1(+) blasts that are cytolytic to the natural killer (NK)-sensitive lymphoma YAC-1, and that can be detected early (day 3-4) in the period preceeding the allospecific cytotoxic T lymphocyte (CTL) response in (CBA x A)F1 {arrow} C57B1 mixed leukocyte culture (MLC). We have investigated the origin and nature of anomalous killing (AK), with special emphasis on its relation to NK-and allospecific CTL-activity. AK was shown to be distinct from the previously described NK(c)-cells induced by cultivation in fetal calf serum (FCS)-supplemented medium when these two reactivities were examined in parallel. AK was detected in either FCS- or normal mouse serum (NMS)-supplemented allogeneic MLC, indicating that the response was not dependent on mitogenic or antigenic properties of heterologous serum. In addition to several H-2-incompatible combinations, AK was also observed in an Mls-incompatible (but H-2 compatible) and two F(1)- antiparental MLC responder/stimulator combinations. AK cells showed a similar selectivity pattern to NK cells, as demonstrated in cold target inhibition and direct cytotoxicity assays using variant or interferon-modulated YAC-1 cells with low expression of NK target structures. The AK-cells were NK- 1.2(-/weak). Thy-l.2(+), although they seem to be derived from non-adherent radiosensitive cells which are closely related, if not identical, to NK-cells (NK-1.2(+). Thy-l.2(-/weak)), as they could not be readily induced in responder populations with low NK-activity but normal allospecific CTL potential. Conversely, an in vivo thymectomy protocol or treatment of normal spleen cells with monoclonal anti-Thy-1.2 + C reduced the allospecific CTL response drastically but did not affect the AK response. Anomalous killers were not observed when MLC were prepared with responder as well as stimulator cells devoid of mature T cells. In such a combination, the AK response could be partially restored by the addition of irradiated +/nu (but not nu/nu) responder cells to the cultures. When normal (non-nude) spleen cells were used as responders, induction of AK did not require the presence of T cells in the stimulator population, whereas the removal of adherent and phagocytic cells from stimulators abrogated the response. 

Taken together, the results suggest that AK represents activation, blast transformation, and surface marker modulation of NK cells induced by alloantigen-stimulated T cells, resulting in Thy-1(+) cytolytic cells with similar properties to those described for NK lines, Although AK cells may be regarded as a more T cell-like NK phenotype, their induction is neither necessary, nor sufficient for generation of specific CTL in MLC.
Preliminary report: imaging of Kaposi sarcoma and lymphoma in AIDS with indium-111-labelled liposomes
Authors: C.A. Presant, D. Blayney, P. Kennedy, C. Wiseman, K. Gala, S.L. Presant, R.T. Proffit, R.J. Crossley, S.J. Preiss, G.E. Ksionski, A.F. Turner, H.I. Nadel, L.E. Williams
Journal: The Lancet (1990)
Does it matter which set of observations are used to calculate the CURB65 score for pneumonia
Authors: Manish Gautam, Katya Lyulcheva, Zahra Estabragh, Josheel Naveed, Paul Deegan
Journal: European Respiratory Journal (2011)

Background:  The British Thoracic Society has recommended that the CURB65 score is applied as the initial severity assessment strategy in hospitals for community acquired pneumonia (CAP), in conjunction with clinical judgement. Evidence for the scoring system is robust and its use at initial presentation enables patients to be stratified according to increasing risk of mortality.   Aim:  To assess whether the CURB65 score was recorded using observations made during the initial hospital assessment or at a later stage.   Methods:  This was a prospective study of random CAP cases (radiologically confirmed) admitted to a large University Hospital between Jan-Feb 2011. CURB65 documentation in the case notes was studied to assess whether the score was performed on the basis of initial observations.   Results:  A total of 55 cases were studied (M: 25, F: 30), mean age 75 years. The CURB65 score was recorded in 44/55 (80%) cases. The score was recorded on the basis of admission observations in 70% of cases (31/44) and in 30% of cases (13/44) observations documented at a later stage. For the latter group, the documented cumulative score was 35, significantly higher than the “actual cumulative score” when calculated retrospectively using admission observations 25 (p value    Conclusions:  Calculation of the CURB65 score using observations made after the initial assessment can significantly affect the score recorded. This may potentially lead to the overuse of antibiotic therapy. In order to improve the quality of care for CAP patients, measures should be taken to ensure that CURB65 is recorded appropriately.
Mechanisms of immune escape in viral hepatitis
Authors: W ROSENBERG
Journal: Gut (1999)

<h3>Objectives</h3> To describe the combination of spinocerebellar ataxia (SCA) types 3 and 6 and sporadic inclusion body myositis (IBM). <h3>Methods</h3> A description of five patients with SCA type 3 and 6 who were diagnosed with IBM. We explore possible mechanisms explaining the coexistence of both diseases. <h3>Results</h3> The patients with SCA-3 (n=4) and SCA-6 (n=1) developed asymmetric muscle weakness in a pattern suggestive of IBM in the course of their disease. Based on findings of neurological examination and additional investigations (muscle ultrasound, muscle biopsy), the diagnosis of IBM was made in all patients. <h3>Conclusion</h3> We report on five patients with concomitant SCA and IBM. Our cases may merely illustrate coincidental co-occurrence of IBM and SCA-3/SCA-6. However, the presence of SCA mutations could predispose to the development of IBM in some SCA patients, or, the presence of toxic aggregates and malfunctioning of cellular quality control processes in both diseases could indicate a convergence of disease mechanisms.
Yet more evidence that osteoarthritis is not a cartilage disease
Authors: K D Brandt
Journal: Annals of the Rheumatic Diseases (2006)

Recurrent abdominal pain accounts for a significant proportion of attenders and high impact users in the emergency department. Due to the heterogeneity of presentation and the broad spectrum of possible causes, abdominal pain presents as a significant clinical challenge within the emergency department, particularly as distress and pain are commonly elevated. Patients in this group are routinely prescribed opiate-based interventions and repeated investigations in a ‘better safe than sorry’ culture which saturates the field of persistent physical symptoms. This approach is contributing to the growing problem, and fuelling a cycle of repeated attendance and failure to resolve. This article reviews the current clinical and psychophysiological understanding of recurrent abdominal pain, critiquing guidelines and approaches to diagnosis and management. We offer an alternative evidence-based biopsychosocial approach using the mnemonic ‘ERROR’, recommending five steps to assessment and clinical management of recurrent abdominal pain in the emergency department.
The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial
Authors: G. F. Snijders, C. H. van den Ende, P. L. van Riel, F. H. van den Hoogen, A. A. den Broeder
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Evidence suggests that doxycycline might have disease-modifying properties in osteoarthritis. However, the clinically relevant question as to whether doxycycline also modifies symptoms in knee osteoarthritis is unanswered. The objective of this study was to investigate the effectiveness of doxycycline on pain and daily functioning in symptomatic knee osteoarthritis. <h3>Methods</h3> A 24-week, randomised, triple-blind, placebo controlled trial on the symptomatic effectiveness of doxycycline twice a day 100 mg in knee osteoarthritis patients according to the clinical and radiological American College of Rheumatology classification criteria. The primary endpoint was the difference in the proportion of participants in both study groups achieving a clinical response defined by the OMERACT–OARSI set of responder criteria. Secondary endpoints included pain, stiffness, daily functioning, patient global assessment, quality of life, osteoarthritis-related medication and side effects. <h3>Results</h3> 232 patients were randomly assigned. At study end, 31% of participants met the primary endpoint in both groups. Except for more adverse events in the doxycycline group, no differences were also found on the secondary endpoints. <h3>Conclusions</h3> Doxycycline is not effective in reducing symptoms in knee osteoarthritis patients over a 24-week study period, but is associated with an increased risk of adverse events. Although a possible structure-modifying effect of doxycycline was previously suggested, this is not accompanied by symptom relief in the short and medium term. Dutch Trial Register no NTR1111.
Perception of airway narrowing in a general population sample
Authors: CM Salome, W Xuan, EJ Gray, E Belooussova, JK Peat
Journal: European Respiratory Journal (1997)

In epidemiological studies, defining asthma as the presence of airway hyperresponsiveness (AHR) plus recent symptoms leaves two groups of subjects whose clinical significance is unclear: those with asymptomatic AHR, and those with symptoms only. The aim of the study was to determine whether subjects with symptoms only differ from the normal and asthmatic groups in the perception of airway obstruction. Six hundred and ninety seven adults completed a questionnaire of symptoms and underwent bronchial challenge with histamine to induce airway obstruction. Recent symptoms included wheeze and morning chest tightness in the last 12 months. AHR was defined as a provoking dose of histamine causing &gt; or = 20% fall in forced expiratory volume in one second (PD20FEV1) &lt;3.9 micromol. At the end of the challenge test, subjects who felt wheezy or tight in the chest marked a value from 0 to 10 on a modified Borg scale, to describe the severity of the sensation. Subjects with asymptomatic AHR did not differ significantly from subjects with AHR plus recent symptoms (current asthma) either in the mean fall in FEV1 or in the median Borg score. In subjects with symptoms only, the mean Borg score was not significantly different from that of the asthmatic subjects, although mean fall in FEV1 differed significantly (p&lt;0.0001). In subjects with symptoms only, chest tightness correlated significantly with the fall in forced vital capacity (FVC) (p= 0.011), but not with the fall in FEV1. Subjects with asymptomatic airways hyperresponsiveness were not poor perceivers of airway narrowing, but may underreport their symptoms. Subjects with symptoms only may have enhanced perception of small changes in lung function, particularly in forced vital capacity.
Metabolically obese status with normal weight is associated with both the prevalence and severity of angiographic coronary artery disease
Authors: Beom-June Kwon, Dae-Won Kim, Sung-Ho Her, Dong-Bin Kim, Sung-Won Jang, Eun-Joo Cho, Sang-Hyun Ihm, Hee-Yeol Kim, Ho-Joong Youn, Ki-Bae Seung, Jae-Hyung Kim, Tai-Ho Rho
Journal: Metabolism (2013)
Angiotensin as a Possible Intrarenal Hormone in Isolated Dog Kidneys
Authors: HAROLD D. ITSKOVITZ, LEE A. HEBERT, JOHN C. MCGIFF
Journal: Circulation Research (1973)

The distribution of renal blood flow was measured in isolated blood-perfused dog kidneys using radioactive labeled microspheres. The kidneys were perfused at a constant systolic pressure of 140 mm Hg. For the first 50 minutes of perfusion, flow to the outer zones of the renal cortex was 79±2% (SE) of the total renal blood flow, and inner cortical blood flow accounted for 21±2%. With continued perfusion, inner cortical blood flow increased progressively, reaching 34±3% by 150 minutes--a time when renin substrate was depleted in the perfusates. Infusions of the tetradecapeptide renin substrate (5-50 µg/min) reestablished the fractional distribution of renal blood flow observed in the initial 50 minutes of perfusion, i.e., inner cortical blood flow was reduced significantly from 36±2% to 23±4% ( P &lt;0.05). In contrast, infusions of angiotensin II (1-10 µg/min) did not reduce the fractional distribution of renal blood flow to the inner cortex. These data provide evidence to support the hypothesis that angiotensin might be formed as an intrarenal hormone which participates in the regulation of deep cortical and medullary vascular resistances. Circulating angiotensin II does not appear to serve a similar function.
Randomised controlled trial of four commercial weight loss programmes in the UK: initial findings from the BBC “diet trials”
Authors: Helen Truby, Sue Baic, Anne deLooy, Kenneth R Fox, M Barbara E Livingstone, Catherine M Logan, Ian A Macdonald, Linda M Morgan, Moira A Taylor, D Joe Millward
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To compare the effectiveness of four commercial weight loss diets available to adults in the United Kingdom. <b>Design</b> Six month multicentre randomised unblinded controlled trial. <b>Setting</b> Community based sample of otherwise healthy overweight and obese adults. <b>Interventions</b> Dr Atkins9 new diet revolution, Slim-Fast plan, Weight Watchers pure points programme, and Rosemary Conley9s eat yourself slim diet and fitness plan. <b>Main outcome measures</b> Weight and body fat changes over six months. <b>Results</b> All diets resulted in significant loss of body fat and weight over six months. Groups did not differ significantly but loss of body fat and weight was greater in all groups compared with the control group. In an intention to treat analysis, average weight loss was 5.9 kg and average fat loss was 4.4 kg over six months. The Atkins diet resulted in significantly higher weight loss during the first four weeks, but by the end was no more or less effective than the other diets. <b>Conclusions</b> Clinically useful weight loss and fat loss can be achieved in adults who are motivated to follow commercial diets for a substantial period. Given the limited resources for weight management in the NHS, healthcare practitioners should discuss with their patients programmes known to be effective. <b>Trial registration</b> Clinical trials NCT00327821[ClinicalTrials.gov].
Management of the sprained ankle
Authors: C N van Dijk
Journal: British Journal of Sports Medicine (2002)

Non-operative treatment with early functional rehabilitation is the treatment of choice

Inversion injuries of the ankle ligament are among the most common injuries, accounting for about 25% of all injuries to the musculoskeletal system. The most commonly injured part of the lateral ligament complex is the anterior talofibular ligament (ATFL). Although ruptures of the ankle ligaments are very common, treatment selection remains controversial. In a recent systematic review of the available literature, it was found that treatment of an acute lateral ligament rupture that was too short in duration or that did not include sufficient support of the ankle joint tended to result in more residual symptoms. It was concluded that a “no treatment” strategy for acute ruptures of the lateral ankle ligament leads to more residual symptoms.1 After a supination trauma, it is therefore important to distinguish a simple distortion from an acute grade II or III ankle ligament rupture, because adequate treatment is associated with a better prognosis.

Although ruptures of the ankle ligament are very common, treatment selection remains controversial. 

Because of the suspected poor reliability of physical diagnosis of ligament ruptures after inversion trauma of the ankle, stress …
Promoting Arab and Israeli cooperation: peacebuilding through health initiatives
Authors: Harvey Skinner, Ziad Abdeen, Hani Abdeen, Phil Aber, Mohammad Al-Masri, Joseph Attias, Karen B Avraham, Rivka Carmi, Catherine Chalin, Ziad El Nasser, Manaf Hijazi, Rema Othman Jebara, Moien Kanaan, Hillel Pratt, Firas Raad, Yehudah Roth, A Paul Williams, Arnold Noyek
Journal: The Lancet (2005)
Human protectin (CD59), an 18-20-kD homologous complement restriction factor, does not restrict perforin-mediated lysis.
Authors: S Meri, B P Morgan, M Wing, J Jones, A Davies, E Podack, P J Lachmann
Journal: The Journal of Experimental Medicine (1990)

Human protectin (CD59) is an 18-20-kD membrane glycoprotein that restricts lysis of human erythrocytes and leukocytes by homologous complement. By directly incorporating protectin into membranes of heterologous cells we observed that protectin did not prevent perforin-mediated killing, whereas complement killing was effectively restricted. Further, no significant enhancement of cell-mediated killing or target killing by purified perforin was observed with anti-protectin antibodies. Thus, in contrast with complement lysis, restriction of lysis by protectin does not apply to cell-mediated killing.
Inflammation-associated lymphangiogenesis: a double-edged sword?
Authors: Honsoul Kim, Raghu P. Kataru, Gou Young Koh
Journal: Journal of Clinical Investigation (2014)

Lymphangiogenesis and lymphatic vessel remodeling are complex biological processes frequently observed during inflammation. Accumulating evidence indicates that inflammation-associated lymphangiogenesis (IAL) is not merely an endpoint event, but actually a phenomenon actively involved in the pathophysiology of various inflammatory disorders. The VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are two of the best-studied pathways in IAL. Methods targeting these molecules, such as prolymphangiogenic or antilymphatic treatments, were found to be beneficial in various preclinical and/or clinical studies. This Review focuses on the most recent achievements in the fields of lymphatic biology relevant to inflammatory conditions. Additionally, preclinical and clinical therapies that modulate IAL are summarized.
Expression of CD44 isoforms in basal cell carcinomas
Authors: H.-P. BAUM, T. SCHMID, G. SCHOCK, J. REICHRATH
Journal: British Journal of Dermatology (1996)

The expression of CD44 isoforms (CD44std, CD44v6, CD44v10) was investigated by an immunohistochemical technique in 42 basal cell carcinomas (BCC) of the superficial and nodular variety. All BCCs studied displayed very low amounts of CD44std, a receptor for hyaluronic acid. Except for single CD44std-positive cells located preferentially in the central parts of the BCC nests, the bulk of the tumour formations were CD44std-negative. CD44v6 showed a heterogeneous distribution pattern accentuated in the peripheral palisading tumour cells. In superficial BCCs, the labelling intensity for CD44v6 increased with the size of the tumour nests. CD44v10 was not detectable in BCCs. Our findings support the notion that CD44v6 is not linked to the metastatic proclivity of tumours originating from keratinocytes. We suggest that the very low expression of the receptor for hyaluronic acid (CD44std) may be one of the factors which block the formation of metastases from BCCs.
OBSERVATIONS ON THE PERSISTENCE OF SKIN SENSITIVITY WITH REFERENCE TO NICKEL ECZEMA.
Authors: J. K. Morgan
Journal: British Journal of Dermatology (1953)

Journal Article OBSERVATIONS ON THE PERSISTENCE OF SKIN SENSITIVITY WITH REFERENCE TO NICKEL ECZEMA. Get access J. K. Morgan, M.R.C.P. J. K. Morgan, M.R.C.P. Lately Tutor and Registrar, Department of Dermatology, Leeds General Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 65, Issue 3, 1 March 1953, Pages 84–94, https://doi.org/10.1111/j.1365-2133.1953.tb13738.x Published: 01 March 1953