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Biomedical subjects

J L Smith

Publications and source records attributed to J L Smith.

At least 361 records · Page 20Linked to original sources

Detection of kidney reactive antibodies at crossmatch in renal transplant recipients.

We have investigated retrospectively sera from 70 renal allograft recipients for the presence of antibodies binding to a preanastomosis biopsy of the donor kidney by an indirect immunoperoxidase technique. All recipients had a negative T cell lymphocytotoxic crossmatch. A positive immunoperoxidase crossmatch for kidney-reactive antibodies was seen in 13/70 (18.6%) recipients--6 reacting with endothelium, 4 with epithelium, and 3 with both cell types. Neither the presence of these antibodies nor their pattern of staining correlated with recipient graft outcome. Following transplantation endothelial reactive antibodies developed in 15/43 (35%) patients, whereas tubular epithelial antibodies occurred in 5/43 (12%). The antibodies were persistent and accompanied graft failure in 10/14 (71%) patients, while transient antibodies were only associated with graft failure in 2/12 (17%) recipients. Development of lymphocytotoxic antibodies did not correlate with the presence of renal reactive antibodies or eventual graft outcome. Smooth muscle and antinuclear antibodies in recipient sera prior to transplantation were associated with improved graft survival. Eluates of 8/14 rejected grafts confirmed the presence of renal reactive antibodies, with patterns of staining similar to those observed in recipient sera. Antibodies in 7/8 recipients were shown by absorption studies to have HLA class I and/or II specificity, the remaining recipient having proximal tubular brush border antibodies.

Adolescent↗

Reaction time and strength in pregnant and nonpregnant employed women.

The purpose of this study was to determine whether or not employed women, during pregnancy or the immediate postpartum period, differ from nonpregnant employed women in reaction time and upper extremity strength. Differences in reaction time, strength, and/or physical work capacity during pregnancy could have implications for maternal and fetal safety, and for job assignment, tool design, and work process design for expectant mothers. Balance is affected by changes in weight, body contour, and center of gravity shift (National Safety News 1979; 119:77-80). Awkwardness, fatigue, and tendency toward loss of balance could become critical, especially when rapid movement or reaction is required for safety or task performance.

Analysis of Variance↗

CD3+ CD8+ T cell lymphocytosis masking B cell leukaemia.

A patient with CD3, CD8 positive lymphocytosis presented with features consistent with T cell chronic lymphocytic leukaemia/proliferations of large granular lymphocytes. The marrow and blood lymphoid populations (19.4 x 10(9)/l) contained more than 80% CD3 and CD8 positive cells with no evidence of a monotypic B cell population. A biopsy specimen of a vasculitic rash showed a diffuse infiltrate of CD3, CD8 positive cells into the upper dermis, consistent with T cell lymphocytic disease. After follow up for two years without treatment the blood lymphocyte count was 53 x 10(9)/l and was composed of cytologically small lymphocytes. A monoclonal SIg M D k lymphoid population (more than 90%) was demonstrable in sample blood and marrow aspirate. Gene rearrangement studies carried out on DNA extracted from peripheral blood lymphocytes at presentation and at two year follow up exhibited JH and Ck immunoglobulin gene rearrangement but no rearrangement of T cell receptor TcR gamma and beta genes. It is thought that this is the first well documented case of an aggressive CD8 positive lymphocytosis preceding, or in response to, an underlying B cell neoplasm.

Antigens, Differentiation, T-Lymphocyte↗

MHC class I and class II antigen expression in normal human corneas and in corneas from cases of herpetic keratitis.

The expression of HLA class I and class II antigens in corneas from normal donors and patients with quiescent herpetic keratitis was investigated using specific monoclonal antibodies. Keratocytes from diseased corneas showed aberrant expression of HLA class I and class II (DR, DP and DQ) antigens. The expression of HLA antigens in these corneas was not associated with immune cell infiltrates or viral antigens.

Adult↗

Diagnosis and course of nephrogenic ascites.

Nephrogenic ascites is a complex diagnostic problem with poorly understood pathophysiology. Morbidity and eventual mortality from this ongoing problem are significant. The diagnosis of nephrogenic ascites must be established by exclusion. We report the cases of nine patients investigated between 1978 and 1985. Laparoscopy, which was utilized in all nine patients, led to a specific diagnosis in two. We believe that a vigorous diagnostic evaluation, including laparoscopy, is essential in patients with chronic renal failure who develop persistent ascites.

Adult↗

An immunohistological study of CD4+ lymphocyte subsets within inflammatory lesions with special reference to rheumatoid arthritis and inflammatory bowel disease.

The monoclonal antibodies (mAbs) WR16, UCHL1 and WR19 identify subsets of CD4+ lymphocytes that have been functionally characterized as suppressor inducer cells or helper inducer cells. These were applied as components of a panel of lymphocyte-specific mAbs for the phenotypic analysis of lymphocyte populations within biopsies taken from rheumatoid synovial membrane and normal and inflamed gut. The phenotype of peripheral blood lymphocytes from patients with rheumatoid arthritis were also compared to normal controls. The rheumatoid synovium was characterized immunohistologically by a lymphocytic infiltrate composed predominantly of CD4+ lymphocytes and a CD4:CD8 ratio of 2.4. The CD4+ population was composed of UCHL1+ cells to the exclusion of WR16+ cells. This finding was confirmed by double immunofluorescence staining using directly conjugated Leu-3a and WR16. The UCHL1+/WR16-/CD4+ phenotype was maintained in the synovial biopsies regardless of whether the patient had commenced treatment with disease modifying drugs. The absence of WR16+ cells within the rheumatoid synovium was shown to be a localized phenomenon as there was a slight elevation of circulating WR16+ lymphocytes in the peripheral blood of rheumatoids whilst the levels of UCHL1+ and WR19+ lymphocytes remained unchanged. As no appropriate normal control tissue is available for comparison to the rheumatoid synovium we also examined the lymphocytes present within Crohn's disease-involved bowel biopsies and compared them to normal gut tissue lymphocytes using WR16 and UCHL1 mAbs. The CD3+ lymphocytes present within normal tissue comprised a mixture of WR16+ and UCHL1+ cells. In contrast the CD3+ lymphocytes within Crohn's involved tissue were exclusively UCHL1+ as previously observed in the rheumatoid synovium. These data indicate that the CD4+ lymphocyte infiltrate present within inflammatory lesions of presumed distinct aetiology exhibit a localized selective loss of cells with the CD45R+/CD4+ suppressor inducer phenotype. This may be a consequence of the selective extravasation of CD4+ helper induced cells or more likely, in view of the previously documented loss of the p220 molecule identified by CD45R mAbs upon T-cell activation, the result of CD4+ T-cell activation at sites of inflammation.

Arthritis, Rheumatoid↗

Gastroduodenal complications of chronic NSAID therapy.

The fact that nonsteroidal anti-inflammatory drugs (NSAIDs) damage the gastroduodenal mucosa is no longer contested. Endoscopic studies in normal volunteers after NSAID administration have failed to predict which NSAIDs would be safest when administered chronically. NSAID use has been associated with a disproportionately high frequency of upper gastrointestinal bleeding and perforation of ulcers. All of the newer NSAIDs appear to be similar in their propensity to cause mucosal damage, including peptic ulceration. On any given day, more than 10% of patients receiving NSAIDs chronically will have a gastric ulcer, a point prevalence of ulcer disease at least 5 to 10 times higher than in patients who are not taking NSAIDs. The dose-response relationship between anti-inflammatory activity and untoward events, coupled with increased use of newer more potent NSAIDs, explains, in part, the increased incidence of NSAID-associated ulcer complication of bleeding and perforation. The possible association of the increase in prevalence of Campylobacter pylori gastritis with aging and the apparent increase in NSAID-associated complications in the elderly is discussed. The current status of nonsteroidal drug therapy can be summarized as follows: 1) new NSAIDs are not safer than the old NSAIDs, as far as major gastrointestinal side effects are concerned, 2) NSAIDs should be avoided when analgesia is the main goal, 3) if NSAIDs are required, the lowest possible dose that achieves pain relief should be used, 4) newer NSAIDs available only in relatively high anti-inflammatory activity dosages should be restricted to those patients in whom high levels of anti-inflammatory activity are desired.

Anti-Inflammatory Agents, Non-Steroidal↗

Gastric adaptation. Studies in humans during continuous aspirin administration.

To study the process of gastric mucosal adaptation to aspirin administration, 14 normal men underwent a study with continued administration of aspirin. Endoscopic assessment, biopsies, and gastric wash collections for acid, mucus, and deoxyribonucleic acid recovery were performed weekly; aspirin was continued until the endoscopy showed minimal damage. Six subjects took 650 mg of aspirin b.i.d., and 8 took 650 mg q.i.d.; adaptation and resolution took longer with the higher dose (median 4.5 wk vs. 1 wk, p less than 0.01). Despite improvement in mucosal appearance, gastric microbleeding remained elevated throughout aspirin administration. In contrast, deoxyribonucleic acid recovery (a marker for cellular exfoliation and regeneration) increased significantly just before the time of resolution, when, on average, it more than doubled. As no other biochemical or histologic changes could be associated with the resolution of damages, we conclude that gastric adaptation to chronic injury may involve increased cellular regeneration.

Adaptation, Physiological↗

Arthritogenic effects of Mycoplasma arthritidis T cell mitogen in rats.

The intraarticular injection of Mycoplasma arthritidis T cell mitogen (MAM) produced significant joint swelling with inflammation in DA rats. Histologic examination of the joint initially showed edema below the synovial surface layer with light polymorphonuclear and focal lymphoid cell infiltration. Widespread but incomplete shedding of the surface layer of the synovial membrane and hypertrophy and hyperplasia of the subsynovium with fibroblasts and macrophages were observed subsequently. The hyperplastic process began to resolve by Day 5 and almost completely disappeared by Day 7 with healing of the surface layer, leaving virtually no trace of the preceding acute episode. Arthritis in animals with previous adjuvant induced arthritis was not exacerbated by the intraarticular injection of MAM.

Animals↗

Iatrogenic Campylobacter pylori infection is a cause of epidemic achlorhydria.

On a number of occasions, there have been descriptions of epidemic achlorhydria in subjects undergoing repeated gastric secretory studies, typically as part of research protocols. We observed a case in a 37-yr-old healthy man undergoing weekly gastric analyses, along with endoscopy and gastric biopsy, as part of a research protocol studying gastric adaptation to aspirin. In the middle of the 2nd wk of aspirin administration, he developed severe nausea and epigastric discomfort. Aspirin administration was discontinued, but, as per protocol, gastric analyses, endoscopies, and biopsies were continued. Compared to the week preceding the acute illness, biochemical analyses showed a transient 7.4-fold increase in basal gastric acid, 3.6-fold increase in pepsin secretion, 8.8-fold increase in DNA loss, 5.6-fold increase in mucus secretion, and 12-fold increase in gastric bleeding. Basal acid secretion was zero, and pepsin secretion was one-third of control during the 2nd wk of the infection. Endoscopy at the time of symptoms showed erosions in the gastric body and antrum, as well as numerous mucosal hemorrhages and an acute ulcer in the antrum. Endoscopy 7 days later revealed that the gastric mucosa had almost completely recovered, with only a shallow erosion seen at the site of the previous ulcer. Gastric biopsies were normal before and during the first 2 wk of aspirin ingestion. Gastric biopsies taken at the time of the acute illness (associated with increased basal acid secretion) showed marked acute inflammation of the antrum with many Campylobacter pylori bacilli. At that time, neither acute inflammation nor C. pylori were found in biopsies from the body of the stomach. Biopsies obtained 1 wk later (zero basal acid) showed acute inflammation of both the gastric body and antrum. One week later, biopsies from the gastric body showed mild focal acute inflammation, moderate chronic inflammation, and an occasional lymphoid follicle; the gastric antrum showed chronic inflammation. Antral biopsies obtained 2 yr later showed persistent chronic gastritis with prominent lymphoid follicles and scattered foci of acute inflammatory cells; C. pylori bacilli were still present, but were less apparent. We believe that the syndrome of acute (epidemic) gastritis is often iatrogenic C. pylori infection. Our case shows that increased basal acid and pepsin secretion occur before onset of basal acid hypochlorhydria in the acute phase of C. pylori infection.

Achlorhydria↗

Hypertension management in a Cape Peninsula coloured community. A retrospective medium-term assessment.

A retrospective study of the records of a large hypertension clinic at a primary care centre was carried out for the period 1975-1984. A total of 250 patients were selected from a systemic 1-in-2 sample. The objectives were to establish the degree of control, compare the use of a large arm blood pressure (BP) cuff with a standard one, and determine the prevalence of associated diseases and the cost of drug therapy. The mean systolic BP was 163.2 mmHg, with 45% of patients having a systolic BP below 160 mmHg. The mean diastolic BP was 101.2 mmHg with 13% of patients having a diastolic BP below 95 mmHg. The majority of patients were overweight and the large BP cuff was found to be useful.

Adult↗

Structure of myohemerythrin in the azidomet state at 1.7/1.3 A resolution.

The molecular model of myohemerythrin, an oxygen-carrying protein from sipunculan worms, has been refined by stereochemically restrained least-squares minimization at 1.7/1.3 A resolution to a conventional R-value of 0.158. The estimated positional standard deviation is better than 0.15 A for most of the 979 protein atoms. The average isotropic displacement parameter, B, for the protein atoms is 23.1 A2. This high average B parameter appears to be due to the overall motion of the molecule, which correlates with the observed anisotropic diffraction. The side-chains of seven residues were modeled in two conformations, i.e. the side-chains were discretely disordered, and B parameters for several lysine and glutamate side-chains indicate that they are poorly localized. Of the residues in myohemerythrin, 66% are helical, with 62% occurring in four long alpha-helices with mean values for the backbone torsion angles of phi = -65 degrees, psi = -42 degrees, and for the hydrogen bonds distances of N ... O, 3.0 A and H ... O, 2.1 A, and angles of N ... O = C, 153 degrees, N-H ... O, 157 degrees, and H ... O = C, 147 degrees. For two-thirds of the alpha-helical residues, the torsional rotation of the C alpha-C beta bond, chi 1, is approximately -60 degrees, and for one-third chi 1 is approximately 180 degrees. Although most turns in myohemerythrin are well-categorized by previous classification, two do not fit in established patterns. Also included in the refined model are three sulfate ions, all partially occupied, and 157 water molecules, 40% of which are modeled fully occupied. Only one water molecule is internal to the protein, the remainder occur on the surface and are observed principally between symmetry-related molecules contributing, along with van der Waals' contacts, most of the interactions between molecules. There are eight intermolecular protein-protein hydrogen bonds, of which only four are between well-located atoms.

Amino Acid Sequence↗

Cell cycle and neuroepithelial cell shape during bending of the chick neural plate.

Neuroepithelial cells change shape from spindle-like to wedge-like within three restricted areas (hinge points) of the bending neural plate. The mechanisms underlying these localized cell shape changes and the specific role that these changes play in bending are unclear. This study was designed to determine whether changes in neuroepithelial cell shape involve basal cellular expansion owing to alteration of the cell cycle. Neurulating chick embryos were treated with colchicine to arrest and accumulate cells in metaphase, and colchicine indices and cell generation times were calculated for the neural plate. During bending of the neural plate, cell generation time in the median hinge point, which contains predominantly wedge-shaped cells, was significantly longer than that in adjacent lateral areas of the neural plate, which contain predominantly spindle-shaped cells. In addition, cell generation time in the flat neural plate, which contains predominantly spindle-shaped cells and has not yet differentiated into the median hinge point and lateral subdivisions, was identical to that in lateral areas of the bending neural plate but was significantly shorter than that in the median hinge point. These results support the hypothesis that changes in neuroepithelial cell shape from spindle-like to wedge-like involve basal cellular expansion owing to alteration of the cell cycle. Additional tests of this hypothesis and studies on the role of localized cell shape changes in neurulation are in progress.

Animals↗

Peritoneal dialysis catheter sepsis: a medical and surgical dilemma.

Peritoneal dialysis remains a viable and valuable alternative to hemodialysis in selected patients; however, the development of intraperitoneal sepsis should raise serious questions as to whether a particular patient should remain with this particular mode of dialysis. Six conclusions can be drawn from this retrospective review. (1) Vancomycin appears to be the first single drug of choice, especially in cases of gram-positive peritonitis. (2) In our experience, the dialysis catheter should be removed in patients who do not demonstrate major resolution of their peritoneal sepsis by 3 to 4 days. (3) If removal of the dialysis catheter does not resolve the issue within 2 to 3 days, exploratory laparotomy should be seriously considered. (4) If fungal organisms are present, exploration and debridement of the peritoneal cavity should be carried out and the patient should be aggressively treated with systemic amphotericin. This should be undertaken early in the course of the peritonitis. (5) Patients with polycystic kidney disease may be better served by hemodialysis. (6) Patients who experience multiple septic episodes should be, when feasible, electively converted to hemodialysis or should undergo transplantation.

Adolescent↗