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Biomedical subjects

P Lane

Publications and source records attributed to P Lane.

At least 19 recordsLinked to original sources

Activated human T cells express a ligand for the human B cell-associated antigen CD40 which participates in T cell-dependent activation of B lymphocytes.

To identify the ligand for the B cell-associated antigen CD40, we constructed a chimeric immunoglobulin molecule where the extracellular portion of the CD40 protein replaced the normal immunoglobulin variable region. No binding was detected on resting peripheral blood T cells. However, following T cell activation with phorbol esters and ionomycin, the chimeric protein bound specifically to activated human T cells and precipitated a 35-kDa protein from such cells. The induction of the CD40 ligand was detectable on the cell surface after 1 h, with maximal expression after 8 h of stimulation. The T cells expressing CD40 ligand were predominantly CD4 positive, although a proportion of CD8-positive cells also expressed the protein. There was no particular correlation with CD45 phenotype. Finally, we found that soluble CD40 inhibited T-dependent B cell proliferation. The results are discussed in the context of cognate interactions between B and T cells.

Adult

Renal structure and function in insulin-dependent diabetes mellitus in man.

PURPOSE: To review renal pathological changes in diabetes, which include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. CRITICAL RENAL LESIONS IN DIABETIC NEPHROPATHY: Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is inversely related to proteinuria, hypertension and a declining glomerular filtration rate. Arteriolar hyalinosis is related to global glomerulosclerosis and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. FUTURE RESEARCH: Longitudinal studies of renal structure and function and a simultaneous study of potential risk factors and pathways of injury are necessary to develop more refined predictors and clearer pathogenic concepts of this important diabetic complication.

Diabetes Mellitus, Type 1

Is a full team required for emergency management of pediatric trauma?

Pediatric trauma centers often do not meet the guidelines requiring a trauma team as recommended by the American Academy of Pediatrics (AAP). We reviewed our experience with a team consisting of a pediatric emergency physician, resident, nurse, and respiratory therapist. The surgical and pediatric critical care residents and staff were available within 5 minutes. We conducted a retrospective chart review of 146 patients (aged 8.1 +/- 4.8 years) between 1987 and 1989, with Injury Severity Scores (ISS) greater than or equal to 16 or admitted to the pediatric critical care unit. The time of presentation, surgical services consulted, and the nature of the injury were obtained from chart review. The Pediatric Trauma Score (PTS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, and Pediatric Risk of Mortality (PRISM) were used to determine the severity of insult and physiologic derangement on admission. The Modified Injury Severity Score (MISS) was determined and the Delta score for Disability Assessment was assigned at discharge. The Delta score was also determined at 3-month intervals up to one year. The probability of survival (Ps) was calculated, using the ISS and RTS. The Z statistic for this group of patients was then determined, using the Major Trauma Outcome Study (MTOS) methodology. The percentages of patients who were normal, disabled, and dead were 61%, 31.5%, and 7.5%, respectively, at 6 months follow-up. Eleven deaths were expected based on PRISM and TRISS analysis. Our mortality and morbidity figures were comparable with those of centers with teams based on AAP guidelines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Renal structure and function in insulin-dependent diabetes mellitus and type I membranoproliferative glomerulonephritis in humans.

Renal pathological changes of diabetes include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is related to proteinuria, hypertension, and declining GFR. Arteriolar hyalinosis is related to global glomerulosclerosis, and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. Parallel findings were documented for type I membranoproliferative glomerulonephritis in which the increased mesangial volume fraction was related to decreased GFR, increased glomerular permeability to protein, and hypertension. As in diabetes, the cortical interstitial volume fraction is correlated with functional abnormalities in type I membranoproliferative glomerulonephritis. Thus, in both of these chronic glomerular disorders, mesangial expansion and interstitial expansion are associated with disordered renal function. Thus, it is not true that glomerular structural changes correlate poorly with glomerular function. Whether it is the glomerular or interstitial pathology or both that is causally responsible for the dysfunction requires further study.

Diabetes Mellitus, Type 1

A single activity carboxyl methylates both farnesyl and geranylgeranyl cysteine residues.

Members of the Ras superfamily of small GTP-binding proteins, gamma-subunits of heterotrimeric G proteins and nuclear lamin B are subject to a series of post-translational modifications that produce prenylcysteine methylester groups at their carboxyl termini. The thioether-linked polyisoprenoid substituent can be either farnesyl (C15) or geranylgeranyl (C20). Small molecule prenylcysteine derivatives with either the C15 or C20 modification, such as N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC), S-trans,trans-farnesylthiopropionate (FTP), as well as the corresponding geranylgeranyl derivatives (AGGC and GGTP) are substrates for the carboxyl methyltransferase. Saccharomyces cerevisiae ste14 mutants that lack RAS and a-factor carboxyl methyltransferase activity are also unable to methylate farnesyl and geranylgeranylcysteine derivatives. Moreover, C20-substituted cysteine analogs directly compete for carboxyl methylation with the C15-substituted cysteine analogs and vice versa. Finally, AGGC is even more effective than AFC as an inhibitor of Ras carboxyl methylation, despite the fact that Ras is methylated at a farnesylcysteine rather than a geranylgeranylcysteine residue.

Animals

The role of the pediatric nephrologist in the care of children with diabetes mellitus.

The pediatric nephrologist has traditionally not been involved in the care of the diabetic child since diabetic nephropathy presents in adulthood. Recent studies suggest that diabetic kidney disease develops silently during childhood. Measurement of urinary albumin excretion (UAE) allows earlier detection of patients at risk of nephropathy, often in adolescence. In addition to diabetic nephropathy, diabetic children are at risk of urinary tract infections, renal papillary necrosis, and various forms of glomerulonephritis. The role of the pediatric nephrologist in the care of the child with diabetes might include advising on the administration and interpretation of screening for UAE and the measurement and interpretation of glomerular filtration rate, and blood pressure. Children with evidence of renal dysfunction should be evaluated and treated by the pediatric nephrologist. Frequently, renal biopsy will be necessary in these patients. Future research may allow the detection of diabetic kidney disease earlier in childhood, further expanding the role of the pediatric nephrologist. In particular, early renal biopsy may eventually be used to select those patients at risk of diabetic nephropathy for specific treatment alterations.

Albuminuria

A study of acne treatments as risk factors for skin cancer of the head and neck.

A retrospective questionnaire was conducted as to the risk factors for facial skin cancer with emphasis on acne and past treatments for acne, in particular use of benzoyl peroxide preparations. The response rate was 90.9% for 964 cases and 79.9% for 3856 controls. There was no association between acne and the use of any acne medication for the risk of facial skin cancer. Cases of skin cancer were significantly more likely to have used phototherapy or sunbeds than the controls (P = 0.024), and more likely to have had radiotherapy prior to diagnosis (P = 0.001). The major risk factors as determined by generalized linear interactive modelling were family history of skin cancer (odds ratio 2.68; 95% confidence interval 2.15, 3.34), light skin (1.54; 1.25, 1.89), sunburning easily (1.43; 1.16, 1.76) and Irish, Scottish, Scandinavian or German mothers (1.33; 1.11, 1.59).

Acne Vulgaris

Human immunodeficiency virus infection and porphyria cutanea tarda.

A recent report documents three homosexual men with porphyria cutanea tarda associated with acquired immune deficiency syndrome (AIDS). We report two brothers with hemophilia and human immunodeficiency virus (HIV) exposure who developed porphyria cutanea tarda. These brothers are heterosexual, have familial porphyria cutanea tarda, and developed overt familial porphyria cutanea tarda in their early twenties. One brother's symptoms were provoked by attending an ultraviolet A suntanning parlor. Our two patients, unlike the previously reported three patients, have not developed AIDS, though one patient has evidence of defective cell-mediated immunity. Three of the five cases of porphyria cutanea tarda associated with HIV infection involved familial porphyria cutanea tarda. It now may be advisable to order HIV serology tests in patients who have porphyria cutanea tarda. We recommend that HIV-positive individuals avoid ultraviolet A radiation because of its immunosuppressive effects in persons already at risk of immunosuppression. Such exposure is further contraindicated in those individuals with porphyria cutanea tarda.

Adult

Erythrocyte phospholipid organization and vesiculation in hereditary high red cell membrane phosphatidylcholine hemolytic anemia.

We have studied the erythrocyte membrane phospholipid organization in hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) and the response of these red cells during incubation with sonicated suspensions of dimyristoylphosphatidylcholine (DMPC). Although both the absolute and relative amounts of phosphatidylcholine were elevated in these red cells, the relative distribution of phosphatidylcholine on both sides of the membrane bilayer and the transbilayer mobility of phosphatidylcholine were normal. HPCHA erythrocytes showed elevated absolute amounts per cell of both protein and lipid and an increased cellular ratio of protein to phospholipid. Incubation of normal red cells with DMPC led to the formation of echinocytes, followed by the release of acetylcholinesterase-containing vesicles. Both echinocyte formation and vesiculation were markedly reduced in red cells from patients with HPCHA. Studies with red cells from patients with liver disease, cells that also have elevated relative amounts of membrane phosphatidylcholine and increased amounts of lipid per cell, revealed normal echinocyte formation and normal DMPC-induced vesiculation. We conclude that the altered lipid composition of HPCHA erythrocytes per se is not responsible for the observed reduction in DMPC-induced vesiculation, but that it is more likely the result of a modification in the protein moiety of these cells. This putative protein abnormality could enhance binding of phosphatidylcholine to red cell membranes and could explain the elevated phosphatidylcholine content of HPCHA erythrocytes and their inability to vesiculate.

Anemia, Hemolytic, Congenital

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Adult

Temperature dependence studies of adriamycin uptake and cytotoxicity.

In order to learn whether a direct relationship exists between cellular uptake and cytotoxicity of Adriamycin, we have compared the temperature dependencies of these two processes in L1210 cells. We find that the equilibrium concentration of drug taken inside the cells varies smoothly with temperature between 37 degrees C and 0 degree C. Even at 0 degree C, however, there is still measurable uptake of the drug into cells. The cytotoxicity index (cloning in soft agar), on the other hand, does not parallel the uptake temperature dependence. Cytotoxicity rapidly diminishes as the temperature of drug exposure is lowered; at all temperatures below about 20 degrees C, Adriamycin is not active. In contrast, other cytotoxic anticancer drugs like mitomycin C, bleomycin, and ARK 73-21 (a platinum analogue) retain cytotoxic potency at low temperatures. The inability of Adriamycin to kill cells at low temperature persists even at very high drug concentrations where substantial quantities of drug enter the cells. The low temperature impotence is not a result of inoperative enzymes which could metabolize Adriamycin to an alkylating species or electron donor to oxygen, since NADH and NADPH dependent reductase activities show linear Arrhenius behavior with no indication of low temperature inactivity. Using purified L1210 plasma membranes with bound Adriamycin as a fluorescence polarization probe, we find evidence of a phase change in the cell surface occurring at the same temperature as the loss of biological activity (approximately equal to 20 degrees C). We conclude that Adriamycin induced cytotoxicity is not dictated solely by uptake, in apparent contradiction with mechanisms requiring an intracellular target. Moreover, the loss of cytotoxicity below 20 degrees C appears to be linked to a structural change in the cell surface membrane, supporting a role other than transport for this membrane in transducing Adriamycin action.

Animals

The superior mesenteric artery fat plane: is obliteration pathognomonic of pancreatic carcinoma?

Obliteration of the fat plane surrounding the superior mesenteric artery has been described as characteristic of pancreatic carcinoma. To determine the specificity of this and other computed tomography findings in the pancreas and peripancreatic region, scans of 86 patients were reviewed without clinical history. Diagnoses included pancreatitis (26 patients); pancreatic adenocarcinoma (14 patients); lymphoma (17 patients); metastatic nonpancreatic carcinoma (14 patients); and normal findings (15 patients). Confluent adenopathy could not be reliably differentiated from a pancreatic mass except when adenopathy separated the common bile duct from the duodenum. Retrocrural adenopathy was unusual with pancreatic carcinoma. The fat plane surrounding the superior mesenteric artery was obliterated with pancreatic carcinoma (36%), nonpancreatic carcinoma (29%), and lymphoma (24%), but not with pancreatitis, although perivascular edema was seen in 19%. Evaluation of the celiac axis was less rewarding. Obliteration of the superior mesenteric artery fat plane is a sign of malignancy, but it is not specific for pancreatic carcinoma. We propose that the superior mesenteric artery origin be considered within a paraaortic space, separate from the anterior pararenal space. This explains its characteristic lack of involvement by pancreatitis.

Adipose Tissue

Quality of care in hospital emergency departments and family physicians' offices.

Indicator conditions were used to evaluate the quality of 686 episodes of care provided in two emergency departments and in five family physicians' offices. Overall, the care was considered adequate in 53% of the emergency department cases and in 40% of the cases dealt with in family physicians' offices, the difference being significant (P less than 0.01). Referrals were very common in both settings, and when quality was assessed solely on the basis of the care actually given by the primary-care providers the difference between the two settings disappeared. Half the observed deficiencies in care related to failure to document the findings from history-taking and physical examination. From these and earlier findings we conclude that the emergency department can be an appropriate setting for the care of nontraumatic illness.

Adolescent

Immunosuppressive alpha globulin from bovine thymus and serum: mode of action upon afferent and efferent arcs of the mouse immune response.

Immunosuppressive bovine alpha globulins of both serum and thymus origin were analyzed for in vitro effects upon the afferent and efferent arcs of the immune system. Although considerable variation in potency occurs between preparations, the functional identity of thymus and serum fractions is apparent. Antigenic recognition and effector capability are not altered whereas the proliferative lymphocyte response is either augmented or suppressed, depending upon the concentration of alpha globulin. A rather selective effect is noted on DNA synthesis and is followed by parallel changes in the development of effector capability, as measured by the development of alloimmune cytotoxic lymphocytes.

Alpha-Globulins