Genome maps 7. The human transcript map. Wall chart.
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Biomedical subjects
Publications and source records attributed to D Page.
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OBJECTIVE: To determine whether a continuous intravenous infusion of pentoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Sixteen patients with septic shock. INTERVENTIONS: Patients were randomly assigned to receive either pentoxifylline (1 mg/kg) followed by an infusion of 1.5 mg/kg/hr for 24 hrs (n = 8), or placebo (n = 8). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations were measured by radioimmunoassays; IL-8 concentrations by an enzyme-linked immunosorbent assay (ELISA) and pentoxifylline concentrations by high-performance liquid chromatography at 0, 3, 6, 12, 18, 24 and 48 hrs after study entry. Pulmonary artery catheter-derived hemodynamics were measured at 0, 0.75, 3, 6, 12, 18, and 24 hrs. In pentoxifylline-treated patients, at 24 hrs, serum concentrations of TNF were significantly lower compared with controls (12 +/- 2 vs. 42 +/- 12 pg/mL, respectively, p = .04). Serum concentrations of IL-6 and IL-8 did not differ between the two treatment groups. There were also no significant differences in any hemodynamic and oxygenation measurements comparing the two treatment groups. Pentoxifylline concentrations were 1,544 +/- 241 ng/mL after the initial dose, and 5,776 +/- 1,781 ng/mL at the end of the 24-hr infusion. Five patients in the pentoxifylline group and four patients in the placebo group died. CONCLUSIONS: Pentoxifylline is able to decrease serum TNF but not IL-6 or IL-8 serum concentrations during septic shock. Pentoxifylline was well tolerated by all eight patients with no adverse effect. Further studies are needed to determine if pentoxifylline's ability to lower circulating TNF concentration without altering hemodynamics will improve outcome in septic shock.
The security of several types of laparoscopic and open knots and varying suture materials was tested in an attempt to improve suture and knot selection for advanced laparoscopic procedures. Six different types of knots and five suture materials were tested. All sutures were of 2-0 size, and laparoscopic knots were tied using a pelvic trainer. A typical number of square throws was used for each suture. Stress was gradually applied by withdrawing the ends of a manual digital tensiometer until either the knot slipped or the suture parted. The maximum stress withstood by the knot-suture complex was recorded, as was whether the knot was secure (i.e., whether the knot held until the suture broke). The data were analyzed using analysis of variance to compare the knot security of the various knot types and the different sutures using a given knot. No significant difference was found in security or stress resistance between laparoscopic square and open square knots or in the Dacron, polypropylene, and expand polytetrafluoroethylene (ePTFE) extracorporeal and intracorporeal knots, with the exception of ePTFE intracorporeal knots, which were significantly less secure (p = 0.028). Silk suture was significantly less secure than all the other sutures tested for all knots tested (p < 0.0001). The Roeder's and Fisherman's knots were the least secure of all laparoscopic knots in all sutures tested (p < 0.0001), with the exception of polyglactin tied with a fisherman's knot, which was as secure as the extracorporeal and intracorporeal polyglactin knots. These experiments showed laparoscopic square knots to be as secure as open square knots; removing the operating finger from the knot does not seem to affect the security of a well-tied square knot. Furthermore, of the permanent sutures tested, there was no substantive difference in the security of laparoscopic intracorporeally and extracorporeally tied knots, except that ePTFE was more secure when tied with extracorporeal throws. Our data also suggest that silk is not as secure as other permanent suture materials.
Due to its unique biology of partial sex linkage and high recombination rates, the pseudoautosomal region (PAR1) on both X and Y chromosomes has attracted considerable interest. In addition, an extremely high level of YAC instability has been observed in this region. We have derived 82 YAC clones from six different YAC libraries mapping to this 2.6-Mb region. Of these a subset of 22 YACs was analyzed in detail. YAC contigs were assembled using 67 pseudoautosomal probes, of which 64 were unambiguously ordered. All markers are well distributed over the entire region, including the middle part of the region, which has previously been found difficult to contig. Two gaps of less than 50 kb within the genomic locus of CSF2RA and around XE7 remain, which could not be covered with YACs, cosmids, or phages. This YAC contig anchored on the physical map of PAR1 represents one of the best characterized large regions of the human genome with a map completion greater than 90% at 100-kb resolution and has permitted the accurate localization of all known genes within this region.
This study was undertaken to investigate a number of immune parameters which may be compromised with exposure to morphine sulfate. Mice were implanted subcutaneously with 8-, 25-, or 75-mg morphine sulfate pellets. Placebo pellets of identical makeup to the 75-mg morphine pellet (without morphine of course) were used as a control. Twenty-four hours after implantation of a 75-mg morphine pellet, blood levels reached a peak of 1610 ng/ml. Corticosterone increased in parallel with morphine and reached a peak level of 966 ng/ml 24 hr after implantation. The dose response of morphine to increase corticosterone, however, was flat. The weight of the lymphoid organs, spleen and thymus, and the liver were significantly reduced in the morphine-treated groups. Morphine treatment was associated with an increase in serum albumin, SGPT, BUN, and alkaline phosphatase indicative of hepatic damage. In contrast to increased serum proteins, the C3 component of complement was reduced in a dose-dependent manner. Leukocyte number in the peripheral blood was significantly reduced, while erythrocyte number and hematocrit were both increased. The number of B cells and T cells was decreased in morphine-treated animals. However, the percentage of T cells relative to B cells was increased. The primary IgM antibody response to the T-dependent antigen, sheep red blood cells, was decreased. Natural killer cell activity was reduced in response to morphine, as was the phagocytic capacity of Kupffer cells. Host-resistance models of Listeria monocytogenes or Streptococcus pneumoniae showed an increased resistance following administration of morphine. This increased host resistance, however, was not due to an increase in antimicrobial action of sera obtained from mice treated with morphine. The majority of morphine's effects on the immune system exhibited a flat dose response, suggesting that these effects may be mediated secondarily through corticosterone.
Necrosis that occurs in a salivary gland neoplasm is usually considered to be an ominous sign, suggesting malignant transformation, particularly in lesions that have had no prior manipulation such as fine-needle aspiration. We describe five pleomorphic adenomas and two canalicular adenomas of salivary gland origin that exhibited necrosis, yet were otherwise benign. All lesions displayed a distinctive histopathologic pattern characterized by a narrow rim of viable tumor tissue at the periphery of the neoplasm combined with a diffuse central region that demonstrated apparent ischemic necrosis. No invasion of adjacent normal tissue was identified, and no recurrence or metastasis has been seen with these lesions. Caution should be exercised in the evaluation of salivary gland neoplasms with central necrosis to avoid misdiagnosis of all such lesions as malignant.
RATIONALE AND OBJECTIVES: A prior study indicated that differences in the x-ray linear attenuation coefficients of cancerous and normal breast tissues tend to increase as the energy of the incident beam decreases. The authors investigated x-ray energies down to 20 keV. In the current study, the linear attenuation coefficients for normal and selected cancerous breast tissues within the energy range of 14 to 18 keV were determined. METHODS: Fifty breast biopsy specimens consisting of a mixture of breast malignancies, normal tissues, fat specimens, and tumors grown in rats were used. X-ray linear attenuation coefficients were measured for each sample within the energy range of 14.15 to 18 keV, using monoenergetic x-rays from beamline X-19A at the National Synchrotron Light Source at Brookhaven National Laboratory. Each sample was measured at 130 different energies starting at 14.15 keV with step sizes of 0.030 keV. Correlation of the measured attenuation coefficients for cellular makeup was performed. RESULTS: The mean of linear attenuation coefficients for samples classified as "cancers" was 10.9% higher than the mean of samples classified as "normal" breast tissues and was 66.5% higher than the mean of samples classified as normal breast fat. CONCLUSIONS: Differences in the linear attenuation coefficients of monochromatic x-rays between 14.15 and 18 keV do exist between normal and cancerous tissues, but there is some degree of overlap.
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Asthma morbidity and mortality are increasing despite the availability of antiasthma medicines and a broader understanding of the pathology of the disease. In an attempt to enhance the understanding of asthma and to aid in appropriate asthma management, the National Heart, Lung and Blood Institute assembled an expert panel, which developed a report titled "Guidelines for the Diagnosis and Management of Asthma." These guidelines are designed to facilitate patient and health-care-provider education, and diagnosis and management of asthma. Proper diagnosis of the disease is a frequent problem in children and adults. For proper diagnosis of asthma, a complete patient history, physical examination and specific laboratory tests are required. Health care providers who educate patients and their families about common symptom triggers, encourage avoidance techniques and who incorporate state-of-the-art treatment for acute and chronic asthma management may reduce the recent increases in asthma morbidity and mortality while maintaining normal growth and development of the child.
A retrospective study of 536 needle-localization biopsies of nonpalpable breast lesions and 623 excisional biopsies of palpable breast lesions was performed. Carcinoma was present in 17.9% of needle-localization biopsy specimens and in 11.1% of excisional biopsy specimens. Noninvasive carcinoma constituted 50% of carcinomas detected by needle-localization biopsy and only 7.3% of carcinomas detected by excisional biopsy (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was associated with axillary lymph node metastasis in 9.8% of patients who had axillary dissection, compared with 37.7% of patients with invasive carcinoma detected by excisional biopsy of a palpable mass (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was less than 2 cm in size (T1) in 93.5% of biopsy specimens; in contrast, invasive carcinoma detected by excisional biopsy was less than 2 cm in size in only 54.7% of biopsy specimens (p less than 0.005). Nonpalpable breast lesions that proved to be invasive carcinoma were pathologic stage I in 82.9% of patients. Palpable breast lesions that proved to be invasive carcinoma were pathologic stage I in only 47.2% of patients. Survival benefits of mammographic screening and biopsy of nonpalpable lesions are likely the result of detection of invasive carcinoma at an early stage and detection of noninvasive carcinoma that may later develop into or mark increased risk of invasive carcinoma.
This report describes a French Canadian family whose members exhibit a high incidence of allo- and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, P1A1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia.
The mouse X-inactivation center lies just distal to the T16H breakpoint. Utilizing pedigree analysis of backcross progeny from a Mus domesticus/Mus spretus interspecific cross, we have mapped a number of genetic loci, gene probes, microclones, and EagI linking clones distal to the T16H breakpoint. The genetic analysis provides a detailed genetic map in the vicinity of the mouse X-inactivation center. Comparative mapping data from the human X chromosome indicate that the most probable location of the mouse X-inactivation center is distal to Ccg-1 and in the region of the Pgk-1 locus. We report the assignment of two new loci, EM13 and DXSmh44, to the Ccg-1/Pgk-1 interval.
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