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J R Weber

Publications and source records attributed to J R Weber.

14 recordsLinked to original sources
PubMed1992

Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor.

Stimulation of the T cell antigen receptor (TCR) activates a protein tyrosine kinase and leads to the tyrosine phosphorylation of phosphoinositide-specific phospholipase C-gamma 1 (PLC gamma 1). The molecular interactions involved in this phosphorylation are not known. After stimulation of the TCR on Jurkat T cells, tyrosine-phosphorylated proteins of 36, 38, 58, and 63 kD coprecipitate with PLC gamma 1. An identical pattern of proteins precipitate with TrpE fusion proteins that contain the Src homology (SH) 2 domains of PLC gamma 1, indicating that these regions of PLC gamma 1 are responsible for binding. TCR stimulation leads to an association between the SH2 domains of PLC gamma 1 and a protein tyrosine kinase, which, by peptide mapping, is identical to p56lck. These studies establish that p56lck associates with PLC gamma 1 as a result of TCR stimulation of Jurkat cells, suggesting that p56lck plays a central role in coupling the TCR to the activation of PLC gamma 1.

Cell Line↗
PubMed1992

Immunodominant structures of human growth hormone identified by homolog-scanning mutagenesis.

Homolog-scanning mutagenesis has been reported to be useful in elucidating the antigenic epitopes recognized by monoclonal antibodies and hGH binding to its receptor. However, little is known about which structures are recognized as immunodominant by murine serum antibodies. Therefore, the previously published series of hGH homologs and additional mutants of human placental lactogen (hPL), porcine growth hormone (pGH), and human prolactin (hPRL) were examined for their interaction with murine serum derived anti-hGH antibodies. As compared to wild-type hGH, nine of the nineteen segment substituted mutants tested showed a significant reduction in binding to anti-hGH sera. These disruptive substitutions mapped to 5 regions on a structural model of hGH: the length of helix 1 (residues 11-33), the loop between the first disulfide bond and helix 2 (residues 54-74), the beginning of helix 3 (residues 109-112), the carboxyl half of helix 4 (residues 167-182), and the final carboxyl terminus segment of the molecule (residues 184-191). In terms of the current structural model, three of the five immunodominant regions (the loop between residues 54-74, central portion of helix 4 to the carboxyl terminus and part of the amino terminus region of helix 1) closely overlaps the hGH receptor binding epitopes.

Amino Acid Sequence↗
PubMed1992

Teaching moral reasoning to student nurses.

Teaching moral reasoning to students is a challenge for all nursing educators. The National League for Nursing and American Nurses' Association emphasize the importance of ethical content within the curriculum. Review of the literature indicates that ethics has been part of the nursing curriculum since the early 1900s. However, the focus of nursing ethics has changed to more critical reflective thinking versus duties and etiquette. Educators have used a variety of methods for teaching ethics and integrating it into the curriculum. Yet nursing graduates still lack adequate skills to be morally accountable practitioners. This creates a dilemma for the educator to find ways to integrate more ethics content into an already crowded curriculum. The code of ethics of holistic nurses may serve as a basis to guide nurse educators in resolving some of the problems encountered in promoting moral education.

Codes of Ethics↗
PubMed1988

Left ventricular hypertrophy: its prime importance as a controllable risk factor.

Left ventricular hypertrophy, which is defined as an abnormal increase in the mass of the left ventricle, has become recognized as an important independent risk factor for predicting several untoward cardiac events, including myocardial infarction, congestive heart failure, and sudden death. The presence of left ventricular hypertrophy is difficult to detect by electrocardiography but can be accurately assessed by echocardiography. Left ventricular hypertrophy can be detected in about 5% of all hypertensive patients by electrocardiography but is found in about 50% by echocardiography. Although it is possible to restore left ventricular mass to normal by controlling hypertension with pharmacotherapy, several commonly prescribed antihypertensive medications, including diuretics and vasodilators, have failed to demonstrate the ability to reverse left ventricular hypertrophy. Other agents, including most beta-blockers, have been found to reverse it. Reversal may take 18 to 24 months from the initiation of therapy. This reversal may be accompanied by an increase in cardiac index, reductions in total peripheral resistance, and improvements in the diastolic properties of the left ventricle. It has yet to be determined whether these improvements reduce the risk of myocardial infarction, heart failure, and sudden death. However, it is likely that some antihypertensive medications may be superior to others in reducing long-term cardiac risks.

Antihypertensive Agents↗
PubMed1986

Expression of three cross-reactive idiotypes on rheumatoid factor autoantibodies from patients with autoimmune diseases and seropositive adults.

Approximately one-half of human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors (RF] from unrelated individuals with cryoglobulinemia coordinately express three cross-reactive idiotypic antigens (CRI). The CRI are detected with: 1) monoclonal antibody 17.109, which recognizes a conformation-dependent CRI on K-light chains; and 2) two rabbit anti-peptide antibodies that react with primary sequence-dependent CRI (PSL2 and PSL3) corresponding to the conserved second and third K-chain complementarity-determining regions, respectively. In the present experiments, the structural features of polyclonal RF autoantibodies from diverse patients with rheumatoid arthritis and from those with primary Sjögren's syndrome, and from seropositive elderly subjects without overt autoimmune diseases, were investigated with these three defined anti-CRI reagents. The pattern of expression of the CRI differed among patient groups. Only the RF autoantibodies from Sjögren's syndrome patients frequently displayed all three CRI. However, the RF from nearly every subject tested, including patients with rheumatoid arthritis, were enriched in the primary sequence-dependent PSL2-CRI as compared to RF-depleted Ig from the same subjects. Amino acid sequence analysis of monoclonal IgM-RF indicates that PSL2-CRI-positive light chains probably represent the products of a single Vk gene. Therefore, a proportion of the polyclonal RF from different autoimmune states may represent somatic variants of this germ-line RF Vk gene which retain the PSL2 sequence as a common element.

Adult↗
PubMed1986

Immunoelectron microscopic localization of HLA-DR antigen in control small intestine and colon and in inflammatory bowel disease.

We have elucidated the distribution of I2 (HLA-DR) antigen in control and inflammatory bowel disease specimens, using immunoelectron microscopic methods. Control small intestinal epithelium and inflammatory bowel disease epithelium expressed 12 antigen, while control colonic epithelium did not. I2 expression by enterocytes was more frequent on the lateral and basal surface than on the microvillus surface. Two of three M cells in control ileum expressed I2 antigen. I2-positive intraepithelial lymphocytes were rarely detected in both control and disease specimens. I2-positive lamina propria lymphocytes were significantly increased in inflammatory bowel disease, while I2-positive lamina propria lymphocytes were virtually absent in control specimens. I2-positive mononuclear cells in the intestinal lamina propria were largely macrophages and monocytes in both control and inflammatory bowel disease specimens. I2-positive mononuclear cells resembling dendritic cells were not detected in control or disease specimens. Furthermore, there were no significant morphological differences in I2-positive or -negative macrophages and monocytes in control and disease specimens. The expression of I2 antigen on Schwann cells was detected more frequently in disease specimens than in control specimens. Capillary endothelia of both control and disease specimens expressed I2 antigen. We demonstrate that I2 expression is present on surface membranes of both immune and nonimmune cells of the intestine and colon and show that this expression is more prominent in inflammatory bowel disease than in control intestine and colon. Further studies are required to determine whether this finding is meaningful in terms of antigen presentation and whether this apparent "immune activation" is involved in the pathogenesis of inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed1986

The intestinal and rectal epithelial lymphocyte in AIDS. An electron-microscopic study.

Injury to the gastrointestinal tract may be mediated in part by the intraepithelial lymphocyte. In this study, we utilized electron microscopy to define the morphological appearance of 86 intestinal and 55 rectal intraepithelial lymphocytes observed in 11 patients with acquired immunodeficiency syndrome (AIDS), and one patient with AIDS-related lymphadenopathy syndrome. The data obtained from intraepithelial lymphocytes of AIDS are compared to those from 106 normal intestinal epithelial lymphocytes and 52 untreated celiac sprue epithelial lymphocytes. The AIDS epithelial lymphocyte possesses more organelles and appears "activated." Eighty-four percent of AIDS epithelial lymphocytes and 44% of normal epithelial lymphocytes possess lysosomal granules. There are 3.3 lysosomal granules/AIDS epithelial lymphocyte and 1.0 lysosomal granule/normal epithelial lymphocyte. Lymphocytes in AIDS usually possess multiple surface projections, which indent and make point contact with adjacent epithelial cells. Thirty-four percent of AIDS epithelial lymphocytes, 23% of sprue epithelial lymphocytes, and 2% of normal epithelial lymphocytes appear "activated." Lymphocytes in AIDS are "activated" in both the presence and absence of gastrointestinal pathogens. Epithelial lymphocytes are increased in intestinal, but not in rectal, AIDS tissue. Mucosal injury, including single cell necrosis, is minimal in the AIDS tissue. We speculate that the "activated" epithelial lymphocyte in AIDS, often possessing large lysosomes, could function as a cytotoxic effector in the development of gastrointestinal immune injury reported to be present in some patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Problems associated with clinical evaluation of antianginal medications.

Assessing the efficacy of antianginal medications is not as easy as it might first appear. Many factors, including the protocol, the subjects chosen for study and the physicians conducting the trial, may produce study bias and thereby yield equivocal results. Objectively attempting to quantitate a subjective event such as angina inherently poses many difficulties. The variable nature of anginal episodes makes identification of attacks, or conversely, elimination of such attacks, difficult to assess. In terms of the protocol, it is necessary to determine what indexes will be used as criteria of efficacy, what doses, either standard or maximally tolerated, will be used for study and what measures will be taken to nullify placebo effect. In terms of patient selection, the varying methods of confirming the diagnosis of ischemia and the questions of concurrent illness, compliance and life-style alterations are all factors that can make findings difficult to elucidate. Finally, investigator bias may be introduced into study results because of prestudy prejudice, involvement in data acquisition and interpretation of findings. It is unlikely that any investigator or group of investigators will ever produce a protocol applicable to all types of antianginal medications that will be universally convincing. Conclusions regarding the efficacy of any antianginal medication will undoubtedly continue to be predicated on assessments made by independent investigators using a variety of research protocols, none of which is likely to be perfect.

Angina Pectoris↗
PubMedDate not supplied

Esophagogastroduodenoscopy by family physicians: a national multisite study of 717 procedures.

This is the first multisite report of esophagogastroduodenoscopies (EGDs) performed by family physicians. The first 717 EGDs performed by family physicians from 8 separate office practices provide a practical and safe rationale for selected cognitive and psychomotor aspects of continuing medical education after residency training. Although primarily in private practice, these physicians were affiliated with 6 academic institutions. This group of family physicians received training in short courses. The average amount of hands-on training before independent EGD was 8 supervised cases. Cumulatively, these data represent 227 months (18.9 years) of office practice. All cases were collected sequentially from the beginning of each physician's experience, and 454 cases were collected prospectively. Physicians reported excellent patient tolerance. Diagnostic yields were high, and biopsies were performed where appropriate. Pathologists reviewed biopsy specimens from 213 sites. The family physician endoscopic diagnosis agreed with the tissue diagnosis in 188 cases (88 percent). Physicians believed that EGD enhanced management or changed the diagnosis in more than 89 percent of cases. One bleeding complication requiring overnight hospitalization was noted. This complication rate 0.0014 (1/717) compares favorably with published subspecialty complication rates 0.0013 (1.3/1000). These data confirm the ability of some family physicians to perform EGD and suggest that continuation is safe. Biopsy analysis indicates diagnostic accuracy is high. Further study on the cognitive aspects and the defragmentation of care is needed.

Adolescent↗