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Biomedical subjects

K M Brown

Publications and source records attributed to K M Brown.

88 records · Page 5Linked to original sources

Genetic abnormalities of immunoregulation in primary biliary cirrhosis.

Patients with primary biliary cirrhosis have an abnormality of lymphocyte suppressor cell function that could play a role in the pathogenesis of their disease. To investigate this possibility, suppressor cell function in patients with primary biliary cirrhosis, in their healthy first-degree relatives, in unrelated household contacts, in patients with other types of cirrhosis, and in normal control subjects was studied. The method used is based on the finding that the in vitro addition of concanavalin A to pokeweed mitogen-stimulated lymphocytes activates suppressor cells, which in turn inhibit immunoglobulin synthesis. Thirteen of 16 patients with primary biliary cirrhosis and six of 23 healthy relatives had significant impairment of IgG suppression. All six of these relatives were female. No abnormal suppression was found in unrelated household contacts of patients with primary biliary cirrhosis, in patients with other types of cirrhosis, or in healthy control subjects. There was no correlation between results of the IgG suppressor cell assay and the disease activity in patients with primary biliary cirrhosis. These data suggest that the abnormal suppressor cell function is not a direct cause of primary biliary cirrhosis; however, it may be a genetic marker for susceptibility to this disease.

Adult↗

Plasmodium berghei malaria: blockage by immune complexes of macrophage receptors for opsonized plasmodia.

Immune complexes produced in vitro by mixing immune serum and soluble Plasmodium berghei antigens and immune complexes precipitated from serum of acutely infected rats blocked macrophage receptor sites for opsonized plasmodia. The immune complexes were precipitated from acute-phase serum, using polyethylene glycol, and their composition was determined by using a Raji cell immunofluorescence assay. The immune complexes contained immunoglobulin G (IgG), IgM, and malarial antigens. These results indicate that immune complexes in the serum of acutely infected animals may protect the plasmodia from the activities of macrophages.

Animals↗

The forensic laboratory evaluation of evidence in alleged rape.

Serial vaginal fluid samples were obtained for laboratory analysis in 15 couples after voluntary intercourse. These samples were analyzed to determine the rate of decay of sperm and prostatic acid phosphatase as it pertains to alleged rape. An attempt was made to identify the male partner by laboratory examination of pubic hair combings and for foreign ABO antigens in vaginal fluid. If consideration is given to proper laboratory controls, examination for spermatozoa and prostatic acid phosphatase remains the primary test in alleged rape.

ABO Blood-Group System↗

The spectrum of alleged rape.

A prospective series of 110 alleged rape victims from July through November 1974 at Denver General Hospital is presented. The victims and assailants are characterized. The laboratory established proof of recent coitus in 68%. Four-fifths of the victims presented within 12 hours of the alleged incident. The analysis of ABO vaginal antigens appears to be promising for assailant identification. Follow-up by appointment in this group was successful in only 5%. Only a minority of cases led to arrest and criminal proceedings. Suggestions are made for alternative approaches to victims based on new developments in forensic laboratory procedures.

ABO Blood-Group System↗

A case of paraquat poisoning and subsequent fatality presenting to an emergency department.

Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is an herbicide associated with both accidental and intentional ingestion, leading to severe and often fatal toxicity. Prognosis is largely dependent on the amount of paraquat absorbed. Rapid identification of the symptoms of paraquat toxicity (burns or ulceration at the site of ingestion or injection, acute respiratory distress, and renal failure) can facilitate early treatment intervention to limit absorption. We report a case of a 71-year-old man with a suicidal ingestion of paraquat 2 days prior to presentation. Serum paraquat levels, time elapsed since ingestion, and clinical symptoms all indicated poor prognosis. The patient developed severe respiratory distress and progressive renal failure, and died 6 days after admission to the hospital.

Aged↗

Automated detection of prevalent mutations in BRCA1 and BRCA2 genes, using a fluorogenic PCR allelic discrimination assay.

Mutations in the genes BRCA1 and BRCA2 account for 5%-10% of familial early onset breast cancer. Identification of these mutations allows molecular diagnosis for breast cancer susceptibility. A high through-put automated PCR allelic discrimination assay (ADA) was developed to detect the prevalent mutations in these genes. Two allele specific oligonucleotides (ASO) are directly used in the PCR reaction, in both of which the fluorescent reporter and quencher dyes are attached to the 5' and 3' ends, respectively. During PCR, fluorescence is generated after cleavage of the annealed ASO by the 5' nuclease activity of Taq polymerase. The wild-type BRCA sequence is distinguished from the mutant sequence by the differential fluorescence emission of two different reporter dyes. The sensitivity of ADA is at the level of a single cell following a nested PCR. Eighty-six patient samples can be analyzed for each mutation in 15-min post-PCR without the need for radioactivity, gel electrophoresis, or membrane blotting/hybridization.

Alleles↗

Human urine-derived inhibitors of interleukin 1.

Human urine has been found to contain several different substances that are capable of inhibiting the in vitro effects of interleukin 1 (IL-1). The urine of febrile individuals contains elevated levels of a 30-40 kilodalton (kdal) glycoprotein that is a potent inhibitor of IL-1-induced proliferation of murine thymocytes. This inhibitor from febrile individuals also blocks antigen-induced activation of human peripheral blood lymphocytes in vitro but increases, rather than decreases IL-1-induced production of prostaglandin E2 by fibroblasts. Uromodulin, an 85-kdal glycoprotein derived from the urine of pregnant women, is also a potent inhibitor of IL-1-induced thymocyte proliferation and human lymphocyte activation. Differences in molecular weight, biologic activity, and antigenicity suggest that uromodulin and the febrile inhibitor are distinct entities. Urine of some individuals has also been found to contain large amounts of a third IL-1 inhibitor that is 20-25 kdal in size. Unlike the febrile inhibitor and uromodulin, this 25-kdal molecule has been found to be a potent inhibitor of IL-1-induced production of prostaglandin E2 by fibroblasts as well as of the proliferation of thymocytes. The biologic activities of these three inhibitors indicate that they may be part of an important physiologic system for the regulation of immunity and inflammation in humans.

Female↗

Toxic epidermal necrolysis: does immunoglobulin make a difference?

Experimental evidence implicates Fas ligand-mediated keratinocyte apoptosis as an underlying mechanism of toxic epidermal necrolysis syndrome (TEN). In vitro studies indicate a potential role for immunoglobulin (Ig) therapy in blocking Fas ligand signaling, thus reducing the severity of TEN. Anecdotal reports have described successful treatment of TEN patients with Ig; however, no study to date has analyzed outcome data in a large series of patients treated with Ig using institutional controls. The SCORTEN severity-of-illness score ranks severity and predicts prognosis in TEN patients using age, heart rate, TBSA slough, history of malignancy, and admission blood urea nitrogen, serum bicarbonate, and glucose levels. A retrospective chart review was performed that included all patients treated for TEN at our burn center since 1997. Ig therapy was instituted for all patients with biopsy-proven TEN beginning in January 2000. Twenty-one TEN patients were treated before Ig (no-Ig group), and 24 patients have been treated with Ig. SCORTEN data were collected, as well as length of stay (LOS) and status upon discharge. Each patient was given a SCORTEN of 0 to 6, with 1 point each for age greater than 40, TBSA slough greater than 10%, history of malignancy, admission BUN greater than 28 mg/dl, HCO3 less than 20 mg/dl, and glucose greater then 252 mg/dl. Outcome was compared between patients treated with Ig and without Ig. Overall mortality for patients treated before Ig was 28.6% (6/21), and with Ig, mortality was 41.7%% (10/24). There was no significant difference in age or TBSA slough. The average SCORTEN between the groups was equivalent (2.2 in no-Ig group vs 2.7 in Ig group, P = 0.3), and no group of patients with any SCORTEN score showed a significant benefit from Ig therapy. Overall LOS as well as LOS for survivors was longer in the Ig group. This series represents the largest single-institution analysis of TEN patient outcome after institution of Ig therapy. Our data do not show a significant improvement in mortality for TEN patients treated with Ig at any level of severity and may indicate a potential detriment in using Ig. Ig should not be given to TEN patients outside of a clinical trial. A multicenter, prospective, double-blinded randomized trial is necessary and urgently indicated to determine whether Ig therapy is beneficial or harmful in the care of TEN patients.

Adult↗

A performance-based lottery to improve residential care and training by institutional staff.

Two experiments were conducted on four units of a residential facility for the multiply-handicapped retarded in an attempt to improve daily care and training services. Experiment I compared the effects of two procedures in maintaining the work performance of attendants, using an A-B design on two units. One procedure consisted of implementing specific staff-resident assignments, the other consisted of allowing attendants who had met performance criteria to be eligible for a weekly lottery in which they could win the opportunity to rearrange their days off for the following week. Results showed that the lottery was a more effective procedure as measured by the per cent of time attendants engaged in predefined target behaviors, and by their frequency of task completion in several areas of resident care. Experiment II replicated and extended these results to the area of work quality on two additional units, using a multiple-baseline design. The performance lottery was found to be an effective econimical procedure that could be implemented by supervisory staff on a large scale.

Adult↗