Expression of CA III in rodent models of obesity.

To achieve a better understanding of the biochemical basis of obesity, we have undertaken comparative analyses of adipose tissue of lean and obese mice. By two-dimensional gel analysis, carbonic anhydrase-III (CA III) has been identified as a major constituent of murine adipose tissue. Quantitative comparisons of CA III protein and mRNA levels indicate that this enzyme is expressed at lower levels in adipose tissue from animals that were either genetically obese or had experimentally induced obesity compared to levels in the corresponding lean controls. This decrease in CA III expression was unique to adipose tissue, since other CA III-containing organs and tissues did not show a change when lean and obese animals were compared. Additionally, levels of CA III in adipose tissue from obese animals responded to acute changes in energy balance of the animal. These results are discussed in light of possible metabolic roles for CA III.

Dimorphic markers for the human apolipoprotein CII gene locus.

Two restriction-site polymorphisms (RSP) have been detected when using a human apolipoprotein CII (apoCII) cDNA clone as a hybridization probe. These include a BanI and a TaqI RSP. Frequencies of the more common allele have been determined in a German population of 100 individuals and are 0.66 (BanI RSP) and 0.56 (TaqI RSP). Corresponding polymorphic information content (PIC) values are 0.36 and 0.37 for individual sites, and 0.58 for the BanI-TaqI pair of sites, making this locus a very informative (PIC-rich) marker for this region of chromosome 19. Haplotype studies also indicate the presence of allelic association (linkage disequilibrium) at the human apoCII gene locus.

Comparison between cefprozil and penicillin to eradicate pharyngeal colonization of group A beta-hemolytic streptococci.

BACKGROUND: Our objective was to perform a prospective, randomized, double blinded study of cefprozil and penicillin therapy to eradicate group A beta-hemolytic streptococci (GABHS) in children who were bacteriologic failures after receiving a standard 10-day course of penicillin treatment for GABHS pharyngitis. METHODS: Children and adolescents 2 to 18 years of age were eligible for the study. From 3 to 7 days after completing oral penicillin therapy for pharyngitis caused by GABHS, the study was explained, informed consent was obtained, a history and physical examination were completed and a throat culture was performed. Children with throat cultures positive for GABHS were randomized to receive either cefprozil or penicillin for 10 days. Children who were bacteriologic failures after administration of the first study drug were crossed over to receive the alternate drug. RESULTS: Of 180 enrolled children 66 (37%) had throat cultures positive for GABHS. Seventeen were excluded from the study, leaving 49 who completed the protocol. Of the 49 participants 26 received cefprozil initially whereas 23 received penicillin. GABHS were eradicated from the pharynx of 73% of children who received cefprozil as the first antibiotic compared with 39% of penicillin recipients (chi square, 5.748, 0.01 < P < 0.025). After crossover of failures, the final efficacy rate for cefprozil was 65% compared with 36.7% for penicillin (chi square, 5.523, 0.01 < P < 0.025). CONCLUSIONS: Cefprozil was more effective than penicillin in treating children who were bacteriologic failures after a standard 10-day course of oral penicillin.

Cloning and characterization of human tissue inhibitor of metalloproteinases-3.

The tissue inhibitors of metalloproteinases (TIMPs) comprise a family of proteins, of which two members have so far been described in humans. We have cloned and sequenced a third human TIMP (hTIMP-3) from phorbol ester-differentiated THP-1 cells stimulated with bacterial lipopolysaccharide. The open reading frame encodes a 211-amino-acid precursor including a 23-residue secretion signal. The mature polypeptide has a calculated molecular weight of 21.6 kD and includes an N-linked glycosylation site near the carboxyl terminus. The protein is quite basic, having a predicted isoelectric point of 9.04. We have mapped the single gene encoding human TIMP-3 to chromosome 22. By Northern analysis, transcripts for TIMP-3 were identified in a broad cross-section of tissues examined from both embryonic and adult origin. In all tissues except the placenta, the predominant transcript was 5.0 kb in size, with minor bands around 2.4 and 2.6 kb comprising no more than about 10% of the signal. In the placenta, the smaller bands accounted for close to 50% of the signal. Human TIMP-3 shows slightly closer amino acid sequence similarity to TIMP-2 (44.3%) than to TIMP-1 (38.4%), but is most closely related to a recently reported chicken TIMP, chIMP-3 (80.8% amino acid; 77.7% nucleic acid similarity.

Prevention of neonatal group B streptococcal infections: advances in maternal vaccine development.

OBJECTIVE: We describe the current state of prevention of neonatal group B streptococcal infections and present recent advances toward the development of a maternal vaccine for prevention of this disease. DATA SOURCES: We used a MEDLINE search of the Index Medicus from 1976-1992 for articles regarding group B streptococcus classification and immunology. Group B streptococcus was also cross-referenced with bacterial antigens, antibodies, and vaccines. Relevant textbooks were reviewed. METHODS OF STUDY SELECTION: Fifty-seven articles were selected as providing important background and new findings pertinent to this topic. DATA EXTRACTION AND SYNTHESIS: The literature supports prophylactic use of intrapartum antibiotics in mothers who are known carriers of group B streptococcus but highlights the need for more sensitive rapid screening techniques to identify this high-risk population. The promise of intravenous immunoglobulin for neonatal prophylaxis has not been borne out, although hyperimmune and monoclonal preparations offer renewed hope for prophylaxis and adjuvant therapy. Native bacterial polysaccharides, conjugated oligosaccharides and polysaccharides, and C proteins have been investigated as antigens for candidate vaccines. Antibodies elicited in human and animal studies provide protection against bacterial strains possessing these determinants. The theoretical existence of a "universal antigen" is significant because polysaccharide and C protein formulations are required to be polyvalent. CONCLUSIONS: The development of a vaccine for prevention of neonatal group B streptococcal sepsis is an attainable goal. Further study of the immunogenic properties of bacterial-cell-wall polysaccharides and their conjugates, C proteins, and the potential universal antigen is required.

Molecular processing of adenovirus proteins.

Late in adenovirus infection, a virus-encoded protease processes several viral structural proteins. The maturation cleavages are a prerequisite for full viral infectivity. The peptide fragment removed during processing is located at the amino end of the major core protein VII. The structure of the precursor peptide sequence was determined by both protein and nucleotide sequencing. Two processing events were elucidated. First, during protein biosynthesis, the initiator methionyl residue is removed and the penultimate seryl residue is acetylated. Second, the resulting NH2-terminal 23-residue fragment is removed during virus assembly. The specificity of the viral endoprotease was investigated by isolating and characterizing another viral proprotein precursor, Pro-VI. The propeptide of VI was also found to be extended at the amino end of the molecule. Comparison of the two propeptide sequences at the cleavage site revealed a consensus amino acid sequence of Gly-Gly-Ala. In addition, there is extensive similarity in the precursor sequences of both proteins. The analogous constitution of the precursor fragments in Pro-VI and Pro-VII suggests that a common mechanism is implicated in controlling the reorganization of VI and VII during virion assembly.

Gene and protein sequences of adenovirus protein VII, a hybrid basic chromosomal protein.

The sequences of both the gene and the corresponding protein of adenovirus major core protein VII have been determined. The precise location of this gene is between 43.37 and 44.90 map coordinates on the viral genome. Protein VII is 173 residues long and has a molecular weight of 19,258. Detailed analysis of its sequence has revealed four basic domains separated by several predicted alpha helices. It is proposed that intrachain folding of protein VII is driven by hydrophobic interactions of the alpha helices, leaving the basic domains of the protein to interact with DNA phosphates. Protein monomers may further associate with each other in the formation of hexameric nucleosome-like particles. The displacement and replacement of protein VII during the viral infectious cycle in the host cell appears to mimic the biology of nucleoprotamine during the processes of spermatogenesis and fertilization. The presence of a protamine-like domain affirms a hybrid histone/protamine molecular structure for protein VII, although it may resemble the protamine in function.

Polymorphisms in the apolipoprotein AI-CIII gene complex.

We report the presence of five restriction fragment length polymorphisms in the apolipoprotein AI-CIII (apo AI-CIII) gene complex as well as their respective allelic frequencies in a German population (pi) that we studied: an SstI (BanII) polymorphism in the 3' non-coding region of apo CIII q1(pi) = 0.13); an MspI polymorphism in the third intron of apo AI (q2(pi) = 0.12); a PvuII polymorphism in the first intron of apo CIII (q3(pi) = 0.30); and two XmnI polymorphisms in the 5' side of apo AI (q4(pi) = 0.20 and q5(pi) = 0.05).