Effect of acute tyrosine depletion in using a branched chain amino-acid mixture on dopamine neurotransmission in the rat brain.

Central dopamine function is reduced by decreasing the availability of the catecholamine precursor, tyrosine, using a tyrosine-free amino acid mixture containing multiple large neutral as well as branched chain amino-acids, which compete with tyrosine for uptake into the brain. Current mixtures are cumbersome to make and administer, and unpalatable to patients and volunteers. Here, we investigate whether individual or limited amino-acid combinations could reduce brain tyrosine levels and hence dopamine function. Measurements of regional brain tyrosine levels, catecholamine and indoleamine synthesis (L-DOPA and 5-HTP accumulation, respectively) were used to identify an effective paradigm to test in neurochemical, behavioral and fos immunocytochemical models. Administration of leucine or isoleucine, or a mixture of leucine, isoleucine, and valine reduced tyrosine and 5-HTP, but not L-DOPA accumulation. A mixture of leucine, valine, and isoleucine supplemented with tryptophan reduced brain tyrosine and L-DOPA, but not 5-HTP. In microdialysis experiments this amino-acid mixture reduced basal and amphetamine-evoked striatal dopamine release, as well as amphetamine-induced hyperactivity. This mixture also reduced amphetamine-induced fos expression in striatal areas. In conclusion, the present study identified a small combination of amino acids that reduces brain tyrosine and dopamine function in a manner similar to mixtures of multiple amino acids. This minimal mixture may have use as a dopamine reducing paradigm in patient and volunteer studies.     

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear: NS may represent another manifestation of CMV disease.     

Pediatric lupus versus adult lupus role of the laboratory

Systemic lupus erythematosus (SLE) is the archetypical immunologic disease. Approximately 20% of patients present in the first two decades of life. This article highlights some of the differences between pediatric and adult onset lupus.Children are defined as different from adults on the basis of age. Lupus presents with different gender ratios based on hormonal or pubertal status with more significant skewing toward female patients in the childbearing years. Female patients in the childbearing years appear to have a higher relative risk for mortality. Despite this, children have greater disease severity at onset based on the number of patients who present with significant organ inflammation, the amount of corticosteroids required and the abnormalities in lupus serologies including autoantibodies and low complements. Children present frequently with congenital and acquired complement defects. Children have an increased risk of infections that can be confused with lupus. They have a higher risk of serious pneumococcal infection and may have less protection from vaccinations received at the time of disease onset.The clinical immunology laboratory is critical in the diagnosis and treatment of pediatric SLE. The rapid analysis and transfer of laboratory results can be life saving for the child with suspected new onset lupus. The laboratory is also helpful in determining disease activity through analysis of immunologic trends over time in pediatric lupus patients. This is especially important in the noncompliant adolescent patient who has a correlation between disease activity and lupus serologic tests. Finally, the clinical immunology laboratory is an important tool for better understanding of the immunologic phenomena associated with lupus and of disease pathophysiology.     

Natural history of colonization with vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and resistant gram-negative bacilli among long-term-care facility residents.

OBJECTIVE: To determine the natural history of colonization with vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and resistant gram-negative bacilli among long-term-care facility (LTCF) residents. DESIGN: Observational cohort study. SETTING: A 355-bed LTCF with a ventilator unit and a subacute unit. PARTICIPANTS: Residents with colonization or infection with VRE, MRSA, or resistant gram-negative bacilli housed at the LTCF between December 1, 1999, and February 29, 2000. METHODS: Cultures of clinical and surveillance sites were performed at regular intervals. Charts were reviewed for clinical characteristics associated with clearance of colonization. Kaplan-Meier curves were constructed to analyze the number of days to clearance of colonization. RESULTS: Forty-nine residents had 65 episodes of colonization (27 VRE, 30 MRSA, and 8 resistant gram-negative bacilli). Eighteen (28%) of the episodes cleared. The clearance rate was 2.7 episodes per 1,000 person-days. Clearance occurred significantly more often with resistant gram-negative bacilli colonization compared with VRE or MRSA colonization (6 [75%] vs 12 [21%]; P = .007; relative risk, 4.17; 95% confidence interval, 1.26 to 11.8). There was a trend toward longer use of antimicrobial agents among residents with persistent colonization. Infections occurred most frequently with MRSA. The urinary tract was the most common site of infection. CONCLUSION: Among LTCF residents, colonization with resistant gram-negative bacilli is four times more likely to clear than colonization with VRE or MRSA. Performance of surveillance cultures at regular intervals may reduce the need for contact precautions for LTCF residents with resistant gram-negative bacilli colonization.     

A clinical, microbiologic, and radiographic study of deep caries lesions after incomplete caries removal.

OBJECTIVE: Clinical, radiographic, and microbiologic changes in deep caries lesions were assessed after incomplete carious dentin removal and tooth sealing. METHOD AND MATERIALS: Thirty-two teeth with deep caries lesions were studied. Treatment consisted of incomplete excavation of the demineralized dentin, application of calcium hydroxide, and sealing for a 6- to 7-month period. The color and consistency of the dentin were clinically assessed. Differences in radiographic density were assessed by digital image subtraction. Microbiologic samples were obtained from the demineralized dentin before the temporary sealing and after the experimental period. The samples were cultivated on blood agar under aerobic and anaerobic conditions, in Mitis Salivarius agar, and Rogosa selective Lactobacillus agar. RESULTS: Two cases were lost during the study; one presented pulpal necrosis. In the other case, there was pulpal exposure during removal of provisional sealing. In all teeth, the initial demineralized dentin was soft and wet; one lesion was yellow, 21 were light brown, and eight were dark brown. After treatment, the dentin was dry, and 80.00% of specimens were hard, 16.67% were leathery, and 3.33% remained soft. The dentin was light brown in five teeth and dark brown in 25. There was a statistically significant mean difference in radiographic density (pixel intensity), 88.77 +/- 7.02 in the control areas and 94.66 +/- 6.75 in the test areas. The counts of anaerobic and aerobic bacteria, lactobacilli, and Streptococci mutans had decreased significantly by the end of treatment. CONCLUSION: Incomplete removal of carious dentin and subsequent tooth sealing resulted in the arrest of the lesions, suggesting that complete dentinal caries lesion removal is not essential to the control of caries lesions.     

Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis

Human lymphoproliferative diseases can be hypothesized to invade locally and to metastatize via mechanisms similar to those developed by a variety of solid tumors, i.e., the secretion of extracellular matrix-degrading enzymes and stimulation of angiogenesis. To assess this hypothesis, Namalwa, Raji, and Daudi cell lines (Burkitt’s lymphoma), LIK and SB cell lines (B-cell lymphoblastic leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266 cell line (multiple myeloma) were evaluated for their capacity to produce matrix metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell lines were also assessed for their ability: (1) to produce the angiogenic basic fibroblast growth factor and vascular endothelial growth factor; (2) to induce an angiogenic phenotype in cultured endothelial cells, represented by cell proliferation, chemotaxis, and morphogensis; (3) to stimulate angiogenesis in different in vivo experimental models. All cell lines expressed the mRNA for one or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the active form of both metalloproteinases, while Daudi, CEM, and Jurkat cells produced metalloproteinase-2 but not -9. In contrast, urokinase-type plasminogen activator was secreted only by SB cells. While Raji, LIK, SB, CEM, and Jurkat cells secreted both basic fibroblast growth factor and vascular endothelial growth factor, Daudi and U266 cells produced only the former, and Namalwa cells only the latter. Accordingly, the conditioned medium of all cell lines stimulated cell proliferation and/or chemotaxis in cultured endothelial cells, with the exception of that of Namalwa cells which was ineffective. The conditioned medium of CEM and Jurkat cells induced morphogenesis in cultured endothelial cells grown on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB, U266, CEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment in the murine Matrigel sponge model and in a chick embryo chorioallantoic membrane assay. The extent of angiogenesis in both models was strictly correlated with the density of the mononuclear cell infiltrate. The results indicate that human lymphoproliferative disease cells possess both local and remote invasive ability via the secretion of matrix-degrading enzymes and the induction of angiogenesis which is fostered by host inflammatory cells and by an intervening ensemble of angiogenic factors.