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Biomedical subjects

W Williams

Publications and source records attributed to W Williams.

At least 109 records · Page 6Linked to original sources

Analysis of autoantibody reactivity and common idiotype PR4 expression of myeloma proteins.

Sera from 75 patients with monoclonal gammopathies and with no clinical evidence of autoimmune disease have been screened for a wide range of autoreactivity including binding to DNA, cardiolipin, extractable nuclear antigen (ENA), rheumatoid factor activity and the presence of the common anti-DNA antibody idiotype PR4. The sera of 17/75 (23%) patients possessed autoreactivity: six were positive for anti-DNA activity, two had anticardiolipin activity and the PR4 ID was found in two sera (both of which possessed anti-DNA activity). Antibodies to ENA were found in one serum (anti-Ro) and anti-organ-specific antibodies in five. Using iso-electric focusing and immunoblotting we have shown that the PR4 ID and DNA binding activity are carried on the paraprotein and not on some other serum constituent. The IgG subclass distribution of 55 IgG paraproteins has also been investigated. The majority of IgG paraproteins belong to IgG1 subclass (55%), with the others, being IgG2 (4%), IgG3 (9%) and IgG4 (27%). In this study we have shown that sera from myeloma patients frequently possess autoreactivity, and that in many cases this can be attributed to the paraprotein.

Antibodies, Antinuclear↗

Radioscintigraphic demonstration of unsuspected urine extravasation.

Three cases of unsuspected urine extravasation first detected by radionuclide scintigraphy are presented with subsequent confirmation by CT and, retrograde pyelograms. A renal study done to rule out acute transplant rejection demonstrates gallbladder uptake which was initially thought to be consistent with urine extravasation.

Adolescent↗

As sick as a pigeon--psittacosis myelitis.

An association between acute transverse myelitis and psittacosis in a teenage boy is described. Closer collaboration between doctors and vets might have made the diagnosis sooner. A full paediatric history should include details of contact with pets and other animals.

Acute Disease↗

Serological abnormalities, including common idiotype PR4, in families with rheumatoid arthritis.

A broad range of autoreactivity among a group of 12 French patients with rheumatoid arthritis (RA) and 58 of their healthy first degree relatives has been identified. Over 15% of the patients were found to have antibodies to ssDNA, histone H1, H2A, and H2bB. Among the relatives, IgG and IgM rheumatoid factor and antibodies to ssDNA, H2A, and H4 were present in more than 10%. Even more remarkable, a common anti-DNA antibody idiotype designated PR4, known to be present in 70% of patients with systemic lupus erythematosus (SLE), was found in approximately 30% of both patients with RA and their healthy relatives. This is quite different from its lack of increased expression in relatives of patients with SLE and suggests that in the family members of those with RA a particular combination of environmental influence on germline gene expression is responsible.

Antibodies, Anti-Idiotypic↗

Preservation of myocardial ultrastructure after 24 hours of Klebsiella sepsis: histologic, functional, and biochemical correlations.

Myocardial function with ultrastructure and high energy phosphate levels in dogs was correlated after 24 hours of sepsis using live Klebsiella aerogenes. All animals developed progressive hemodynamic deterioration over a 24 hour period. Mean arterial pressure decreased from 148 +/- 7 mmHg to 85 (P less than 0.01) and cardiac output decreased from 3.43 +/- .31 to 1.6 +/- 0.5 L/min. Left ventricular stroke work decreased from 48.2 +/- 5 to 18.1 +/- 6 gm-meters (P less than 0.001). Systemic and pulmonary vascular resistances were increased at 24 hours (3,538 +/- 27 to 7,404 +/- 1,400 dyne/sec/cm-5 (P less than 0.01), and 185 +/- 20 and 619 +/- 90 dyne/sec/cm-5 (P less than 0.001), respectively. Left ventricular function curves at 24 hours showed a fixed low output. However, myocardial ultrastructure was preserved and high energy phosphate levels remained normal. These observations correlate well with the changes seen clinically in early gram negative sepsis in hypovolemic patients. Thus, this appears to be a suitable model for further investigation of the effects of gram negative sepsis on myocardial performance, ultrastructure, and maintenance of energy stores.

Animals↗

Massive lymphocele following pelvic lymphadenectomy for staging of prostatic cancer.

Two patients developed massive pelvic lymphoceles within 30 days of retroperitoneal node dissection for staging of prostatic cancer. Excised lymph nodes were negative for metastases. Both patients developed severe bilateral peripheral edema, and one developed pulmonary thromboembolism from intraluminal thrombi in the adjacent, compressed inferior vena cava. Each patient responded to unroofing of the cyst wall with either concomitant external or internal drainage.

Aged↗

Use of naloxone in septic shock.

Experimental and clinical evidence show that endogenous opiates (endorphins) contribute to the pathophysiology of circulatory shock. The authors evaluated the effectiveness and safety of continuous infusion of naloxone in five septic patients with prolonged hypotension unresponsive to volume replacement and dopamine infusion. Naloxone (2 mg bolus) was intravenously administered and continued at 0.25 mg/hr for 24 to 48 hours. All five patients had significant increase in mean arterial pressure of between 20 and 30 mmHg (P less than 0.0012). Cardiac index, systemic vascular resistance, and pulmonary arterial pressure were not significantly altered; however, there was a significant difference in pulmonary capillary wedge pressure (P less than 0.034) and urinary output (P less than 0.0273). Subjects did not experience side effects with naloxone. We conclude that continuous infusion of naloxone can reverse endorphin-mediated hypotension in septic shock patients.

Aged↗

Relation between lymphocytotoxic antibodies, anti-DNA antibodies and a common anti-DNA antibody idiotype PR4 in patients with systemic lupus erythematosus, their relatives and spouses.

Forty-two patients with systemic lupus erythematosus (SLE), 65 of their healthy relatives and 20 spouses were studied for the presence of lymphocytotoxic antibodies (LCA), anti-lymphocyte antibodies (ALA), antibodies to DNA and a common idiotype (Id) PR4. Seventy-one per cent of the patients had positive levels of LCA, and in 34% the PR4 Id was detected; normal levels were found in their families. Anti-PR4, an anti-Id, failed to block the lymphocytotoxic activity in those nine patients who both carried the Id and had LCA. This indicates that the Id was not present on LCA. There was no correlation between anti-DNA antibodies and LCA, suggesting that different mechanisms are involved in their expression.

Antibodies, Antinuclear↗

DSM-III diagnosis and code types of the Diagnostic Inventory of Personality and Symptoms.

The relationships of high-point code types of the Diagnostic Inventory of Personality and Symptoms (DIPS) to the Diagnostic and Statistic Manual III of the American Psychiatric Association (DSM-III) were explored for patients (N = 316) in private mental health settings. Sixteen DIPS code types that relate code types to Axis I diagnoses are presented. The three DIPS personality disorder cluster scales and the eight combinations thereof are presented as well. Five of the personality disorder cluster scale code types that relate to DSM-III Axis II categories are identified. Finally, a narrative summation of each of the code types is given.

Humans↗

Studies of a common idiotype PR4 in autoimmune rheumatic disease.

A new common idiotype, designated PR4, is described. This idiotype was originally identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy, which binds the major Mycobacterium leprae-derived antigen, phenolic glycolipid-1, poly(ADP)-ribose, DNA, and poly(dT). The PR4 idiotype was found in patients with systemic lupus erythematosus (SLE) (70%), rheumatoid arthritis (40%), and Sjögren's syndrome (15%). It was not, however, found in the spouses of the SLE patients or (unlike other lupus idiotypes) in their healthy first-degree relatives. Although no correlation between PR4 idiotype levels and disease activity in SLE was found, a subset of rheumatoid arthritis patients with high levels of the idiotype was identified.

Antibodies, Anti-Idiotypic↗

A comparison of autoantibodies and common DNA antibody idiotypes in SLE patients and their spouses.

In order to determine whether environmental influence per se might influence autoantibody production, sera from the spouses of 20 SLE patients were examined. No antibodies to cardiolipin, poly (ADP-ribose), or ENA were detected and none had detectable rheumatoid factor. One weakly positive ANA reaction was noted, one had anti-DNA antibodies (by RIA and ELISA) and in two sera the common DNA antibody idiotype 16/6 was found. The idiotype was not, however, present on either anti-DNA or anti-K30 antibodies. Although long-term analyses are required, it is evident that sharing the same environment with patients who commonly express a wide range of autoantibodies and common idiotypes rarely leads to their expression in non-autoimmune subjects.

Antibodies, Antinuclear↗

Bilateral Warthin's tumor.

A case report of bilateral mixed Warthin's tumors with nonuniform uptake demonstrated by Tc-99m pertechnetate imaging is presented. The findings are compared to CT, surgical, and pathology results.

Adenolymphoma↗

Disease activity in systemic lupus erythematosus related to a range of antibodies binding DNA and synthetic polynucleotides.

Antibodies to dDNA, nDNA, Z-DNA, poly(dT), poly(I), poly(dG.dC), poly(dA.dT), and total IgG and IgM were measured in five serial bleeds from 39 patients with systemic lupus erythematosus (SLE). The main findings were that those patients with renal disease form a distinct subset whose antibody levels correlate well with disease activity; anti-poly(dT) antibodies showed the best overall correlation with disease activity; and discriminant functional analysis demonstrated a major improvement in correlation of disease activity with combinations of antibodies to dDNA/nDNA/Z-DNA/poly(dT) (generally 50% or more were correctly classified) than with dDNA or nDNA alone (generally less than 25% correct). Serum IgG (but not IgM) correlated significantly (p less than 0.01) with six antibodies, suggesting that polyclonal activation plays a part in the development of these antibodies, though antibody cross reactivity is not excluded.

Antibodies↗

Human monoclonal antibodies to phenolic glycolipid-1 from leprosy patients cross react with poly(ADP-ribose), polynucleotides and tissue bound antigens.

Antibodies which bind to poly(ADP-ribose) have been described in Systemic Lupus Erythematosus (SLE) and a variety of infectious diseases. Two IgM kappa human monoclonal antibodies (MAbs), TH3 and PR4, produced from the fusion of peripheral blood lymphocytes of leprosy patients with the GM4672 lymphoblastoid cell line, were found to bind to poly(ADP-ribose) in direct binding and inhibition ELISAs. Significant inhibition of binding of these MAbs to poly(ADP-ribose) occurred with phenolic glycolipid-1, the M. leprae specific glycolipid, ssDNA, dsDNA, poly(dT), as well as poly(ADP-ribose) itself. Up to 80% of binding of TH3, and 90% of binding of PR4, to poly(ADP-ribose) was inhibited by 10 mcg of ssDNA suggesting that there may be sharing of some conformational determinants. Although the serological binding profiles of TH3 and PR4 are similar, only PR4 was found to bind to basal keratinocytes of normal human interfollicular epidermis and astrocyte cytoplasm in normal brain tissue. These results support the concept that an antibody binding site may accommodate more than one epitope. Furthermore, small differences in antigen binding potential may distinguish relatively innocuous antibodies from those which may be more pathogenic.

Antibodies, Monoclonal↗

Lack of relation between human T-lymphotropic virus type I infection and systemic lupus erythematosus in Jamaica, West Indies.

To determine whether systemic lupus erythematosus (SLE) is associated with human T-lymphotropic virus, type I (HTLV-I) infection in Jamaica, an endemic area for the virus, we studied 63 patients with SLE at the University Hospital of the West Indies in Kingston. Antibodies to HTLV-I were measured by an enzyme-linked immunosorbent assay (ELISA) technique using purified disrupted whole virus as antigen, with confirmation by p24 protein RIA or competitive binding. Four of 63 SLE patients were HTLV-I seropositive (6.3%). There was no evidence for excess HTLV-I infection in SLE patients when their age- and sex-standardized HTLV-I seroprevalence rate was compared to that of a large group of healthy food service employees. None of 13 patients with rheumatoid arthritis were seropositive for HTLV-I. We conclude that HTLV-I infection does not appear to be linked with SLE in Jamaica.

Adolescent↗

Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi.

Whole body lymphangioscintigraphy was performed after intradermal injection of 99mtechnetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.

Animals↗