Clinical and epidemiological findings during a measles outbreak occurring in a population with a high vaccination coverage

Malignant mesothelioma is caused almost exclusively by occupational exposure to asbestos. During the past few years, however, increasing evidence has mounted that background exposure to asbestos could be sufficient to cause mesothelioma. Treatment of malignant mesothelioma remains a big problem. Some new approaches are on their way, and the most exciting ones are local immunotherapy in very early cases. Some success has been reported with local interferon treatment. As for treatment of metastatic pleural disease, the main purpose is symptomatic relief of dyspnea caused by fluid accumulation. The best way to achieve a lasting palliation is pleurodesis, and the most common way to do this, is by chemical means. The drug of choice in the United States has for many years been tetracycline, but since injectable tetracycline is no longer available, some substitute must be found. The substance that will "win" is not yet clear, but the two leading contestants are talc and doxycycline. Bleomycin also has its supporters, and a dark horse is quinacrine, which although not easily available in the United States, has been used in many European centers for decades.     

Panic and phobic anxiety: defining phenotypes for genetic studies

OBJECTIVE: With recent advances in molecular genetics, the rate-limiting step in identifying susceptibility genes for psychiatric disorders has become phenotype definition. The success of psychiatric genetics may require the development of a "genetic nosology" that can classify individuals in terms of the heritable aspects of psychopathology. The authors' aim is to begin to apply this analysis to the anxiety disorders, focusing on panic and phobic disorders. METHOD: Two parallel traditions of defining anxiety phenotypes are reviewed: the first, more closely identified with clinical psychiatry, has identified categorical diagnoses (e.g., panic disorder and social phobia). The other, more closely identified with psychological studies of personality development, has examined dimensional traits (e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition). RESULTS: The authors suggest that a genetic nosology of panic and phobic disorders may incorporate features of both traditions and discuss strategies for optimizing genetic approaches to anxiety including 1) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci. CONCLUSIONS: An important dividend from the effort to define the boundaries of heritable phenotypes for genetic studies of anxiety may be a refinement of the nosology of anxiety disorders.     

Rerouting of the intratemporal facial nerve: an analysis of the literature

Anterior rerouting of the intratemporal facial nerve in the infratemporal fossa approach is employed to access to the jugular bulb, hypotympanum, and lateral skull base, whereas posterior rerouting of the facial nerve, as employed in the transcochlear craniotomy, is most frequently used for surgery of the posterior fossa, cerebellopontine angle, prepontine region, and petrous apex. Facial nerve rerouting may lead to facial paresis or paralysis. This review of the literature is intended to define the physiologic "cost" of these procedures, so that the neurotologic surgeon can determine if the morbidity incurred in these techniques is worth the resultant exposure. Inconsistencies in reporting facial function places into question the validity of some of the cumulative data reported. Postoperatively, grades I-II facial nerve function was seen in 91% of patients undergoing short anterior rerouting, 74% of patients undergoing long anterior rerouting, and 26% of patients undergoing posterior complete rerouting. Although facial nerve rerouting allows unhindered exposure to previously inaccessible regions, it is achieved at the cost of facial nerve function. Facial nerve dysfunction increases with the length of facial nerve rerouted.     

Redox properties of human medium-chain acyl-CoA dehydrogenase, modulation by charged active-site amino acid residues

The modulation of the electron-transfer properties of human medium-chain acyl-CoA dehydrogenase (hwtMCADH) has been studied using wild-type and site-directed mutants by determining their midpoint potentials at various pH values and estimating the involved pKs. The mutants used were E376D, in which the negative charge is retained; E376Q, in which one negative charge (pKa approximately 6. 0) is removed from the active center; E99G, in which a different negative charge (pKa approximately 7.3) also is affected; and E376H (pKa approximately 9.3) in which a positive charge is present. Em for hwtMCADH at pH 7.6 is -0.114 V. Results for the site-directed mutants indicate that loss of a negative charge in the active site causes a +0.033 V potential shift. This is consistent with the assumption that electrostatic interactions (as in the case of flavodoxins) and specific charges are important in the modulation of the electron-transfer properties of this class of dehydrogenases. Specifically, these charge interactions appear to correlate with the positive Em shift observed upon binding of substrate/product couple to MCADH [Lenn, N. D., Stankovich, M. T., and Liu, H. (1990) Biochemistry 29, 3709-3715], which coincides with a pK increase of Glu376-COOH from approximately 6 to 8-9 [Rudik, I., Ghisla, S., and Thorpe, C. (1998) Biochemistry 37, 8437-8445]. From the pH dependence of the midpoint potentials of hwtMCADH two mechanistically important ionizations are estimated. The pKa value of approximately 6.0 is assigned to the catalytic base, Glu376-COOH, in the oxidized enzyme based on comparison with the pH behavior of the E376H mutant, it thus coincides with the pK value recently estimated [Vock, P., Engst, S., Eder, M., and Ghisla, S. (1998) Biochemistry 37, 1848-1860]. The pKa of approximately 7.1 is assigned to Glu376-COOH in reduced hwtMCADH. Comparable values for these pKas for Glu376-COOH in pig kidney MCADH are pKox = 6.5 and pKred = 7.9. The Em measured for K304E-MCADH (a major mutant resulting in a deficiency syndrome) is essentially identical to that of hwtMCADH, indicating that the disordered enzyme has an intact active site.     

Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes

Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS.     

Molecular cloning, sequencing, and expression of the 36 kDa protein present in pars planitis. Sequence homology with yeast nucleopore complex protein

PURPOSE: Patients with active pars planitis have increased levels of a 36 kDa protein (p-36) in their circulation. The current studies were undertaken to determine the primary structure of this protein. METHODS: A degenerate oligonucleotide probe based on the amino terminal sequence of p-36 was used to identify a clone from a human spleen cDNA library. The cDNA insert was subcloned into the EcoR1 site of pUC-19, and both strands were sequenced. Southern blot analysis was used to study the genomic hybridization pattern. p-36 cDNA was subcloned in a pSG5 expression vector, and the construct was used to transfect COS-7 cells. RESULTS: The cDNA sequence contained an open reading frame of 966 base pairs encoding a protein of 322 amino acids, an untranslated region of 322 base pairs, and 2693 base pairs at the 5' and 3' ends, respectively. The deduced amino acid sequence showed 96.8% identity with the carboxy-terminal region of a yeast nucleopore complex protein, nup 100. Southern blot analysis of human genomic DNA revealed a simple hybridization pattern. Transfection of p-36 cDNA in COS-7 cells resulted in the presence of p-36 mRNA and expression of protein. CONCLUSIONS: The 36 kDa protein (p-36) detected at increased levels in the blood of patients with active pars planitis was cloned from a human spleen cDNA library. Its deduced amino acid sequence is homologous with the carboxy-terminal region of a nucleopore complex protein. Thus, we refer to this protein as nup36.     

Criterion validity and the utility of reactive and proactive aggression: comparisons to attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, and other measures of functioning

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is a clinicopathologic entity that includes proteinuria, azotemia, focal segmental glomerulosclerosis or mesangial hyperplasia, and tubulointerstitial disease. The incidence of HIVAN is increased in black patients and variable depending on the age and geographic area. The objective of this study was to describe relevant clinical and pathological findings in 30 children with HIVAN followed at the Children's National Medical Center in Washington, D.C. Our experience of the last 12 years showed a spectrum of HIVAN that seems to be coincident with the degree of acquired immunodeficiency syndrome (AIDS) symptomatology. By renal sonograms and frequent urinalysis, we identified children undergoing the early stages of HIVAN with enlarged echogenic kidneys, proteinuria, and "urine microcysts". HIVAN did not necessarily progress rapidly to end-stage renal disease. Nephrotic syndrome or chronic renal insufficiency were late manifestations of HIVAN. Children with HIVAN were likely to develop transient electrolyte disorders, heavy proteinuria, and acute renal failure due to systemic infectious episodes or nephrotoxic drugs. HIVAN was associated with other HIV-induced illnesses and high mortality rates. Early detection and careful clinical follow-up of children with HIVAN may reduce the incidence of renal-cardiovascular complications and improve their quality of life.     

The use of irreversible ligands to inactivate receptor subtypes: 4-DAMP mustard and muscarinic receptors in smooth muscle

Irreversible ligands are useful tools for investigating the function of receptor subtypes in various physiological processes. The mechanism for alkylation involves the formation of a reversible receptor complex followed by a covalent reaction. The extent of receptor alkylation is determined by the dissociation constant of the reversible complex and the rate constant for conversion to the covalent complex. Selectivity can be achieved if the irreversible ligand exhibits a difference in its dissociation constants for receptor subtypes. Selective alkylation can also be achieved using a selective competitive inhibitor to protect the desired receptor subtype. By using the non-M2-selective irreversible antagonist, 4-DAMP mustard, in combination with the competitive M2-selective antagonist, AF-DX 116, it has been possible to achieve a highly selective inactivation of all non-M2 subtypes of the muscarinic receptors in smooth muscle and has enabled the discovery of the functional role of M2 receptors in smooth muscle.     

Antimicrobial susceptibilities of Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens spp. isolated in Spain

The susceptibilities of 143 Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens isolates to 18 antimicrobial agents were tested. All P. gingivalis isolates were susceptible. In contrast, some Prevotella spp. (17%) were resistant to beta-lactams, erythromycin, clindamycin, or tetracycline and carried resistance genes, ermF or tetQ, or beta-lactamases.     

Familial influences on gambling behavior: an analysis of 3359 twin pairs

BACKGROUND: Pathological gambling is becoming an increasing problem in the United States as the number of legalized gambling establishments grows. To examine vulnerability to pathological gambling, we estimated the familial contributions (i.e. inherited factors and/or experiences shared by twin siblings during childhood) to DSM-III-R pathological gambling symptoms and disorder. METHODS: Data were obtained from a telephone interview performed in 1991-92 utilizing the Diagnostic Interview Schedule Version III-Revised. Interviews were administered to 6718 members of the nationally distributed Vietnam Era Twin Registry of male-male monozygotic and dizygotic twin pairs who served in the military during the Vietnam era. RESULTS: Inherited factors explain between 35% (95% CI: 28%, 42%) and 54% (95% CI: 39%, 67%) of the liability for the five individual symptoms of pathological gambling behavior that could be estimated statistically. In addition, familial factors explain 56% (95% CI: 36%, 71%) of the report of three or more symptoms of pathological gambling and 62% (95% CI: 40%, 79%) of the diagnosis of pathological gambling disorder (four or more symptoms). CONCLUSIONS: Familial factors have an important influence on risk for pathological gambling behavior. The increasing access to legalized gambling is likely to result in a higher prevalence of pathological gambling behavior among individuals who are more vulnerable because of familial factors.