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Samuel Kaplan

Publications and source records attributed to Samuel Kaplan.

29 records · Page 2Linked to original sources
PubMed2003

A second and unusual pucBA operon of Rhodobacter sphaeroides 2.4.1: genetics and function of the encoded polypeptides.

A new operon (designated the puc2BA operon) displaying a high degree of similarity to the original pucBA genes of Rhodobacter sphaeroides 2.4.1 (designated puc1) was identified and studied genetically and biochemically. The puc2B-encoded polypeptide is predicted to exhibit 94% identity with the original beta-apoprotein. The puc2A-encoded polypeptide is predicted to be much larger (263 amino acids) than the 54-amino-acid puc1A-encoded polypeptide. In the first 48 amino acids of the puc2A-encoded polypeptide there is 58% amino acid sequence identity to the original puc1A-encoded polypeptide. We found that puc2BA is expressed, and DNA sequence data suggested that puc2BA is regulated by the PpsR/AppA repressor-antirepressor and FnrL. Employing genetic and biochemical approaches, we obtained evidence that the puc2B-encoded polypeptide is able to enter into LH2 complex formation, but neither the full-length puc2A-encoded polypeptide nor its N-terminal 48-amino-acid derivative is able to enter into LH2 complex formation. Thus, the sole source of alpha-polypeptides for the LH2 complex is puc1A. The role of the puc1C-encoded polypeptide was also determined. We found that the presence of this polypeptide is essential for normal levels of transcription and translation of the puc1 operon but not for transcription and translation of the puc2 operon. Thus, the puc1C gene product appears to have both transcriptional and posttranscriptional roles in LH2 formation. Finally, the absence of any LH2 complex when puc1B was deleted in frame was surprising since we know that in the presence of functional puc2BA, approximately 30% of the LH2 complexes normally observed contain a puc2B-encoded beta-polypeptide.

Amino Acid Sequence↗
PubMed2002

Cardiovascular status of infants and children of women infected with HIV-1 (P(2)C(2) HIV): a cohort study.

BACKGROUND: Data from cross-sectional and short-term longitudinal studies have suggested that children infected with HIV-1 might have cardiovascular abnormalities. We aimed to investigate this hypothesis in a long-term cohort study. METHODS: We measured cardiovascular function every 4-6 months for up to 5 years in a birth cohort of 600 infants born to women infected with HIV-1. We included 93 infants infected with HIV-1 and 463 uninfected infants (internal controls) from the same cohort. We also included a cross-sectionally measured comparison group of 195 healthy children born to mothers who were not infected with HIV-1 (external controls). FINDINGS: Children infected with HIV-1 had a significantly higher heart rate at all ages (mean difference 10 bpm, 95% CI 8-13) than internal controls. At birth, both cohort groups of children had similar low left ventricular (LV) fractional shortening. At 8 months, fractional shortening was similar in internal and external controls, whereas in children infected with HIV-1, fractional shortening remained significantly lower than in controls for the first 20 months of life (mean difference from internal controls at 8 months 3.7%, 2.3-5.1). LV mass was similar at birth in both cohort groups, but became significantly higher in children with HIV-1 from 4-30 months (mean difference 2.4 g at 8 months, 0.9-3.9). CONCLUSIONS: Vertically-transmitted HIV-1 infection is associated with persistent cardiovascular abnormalities identifiable shortly after birth. Irrespective of their HIV-1 status, infants born to women infected with HIV-1 have significantly worse cardiac function than other infants, suggesting that the uterine environment has an important role in postnatal cardiovascular abnormalities.

Cardiovascular Abnormalities↗
PubMed2002

The incidence of congenital heart disease.

This study was designed to determine the reasons for the variability of the incidence of congenital heart disease (CHD), estimate its true value and provide data about the incidence of specific major forms of CHD. The incidence of CHD in different studies varies from about 4/1,000 to 50/1,000 live births. The relative frequency of different major forms of CHD also differs greatly from study to study. In addition, another 20/1,000 live births have bicuspid aortic valves, isolated anomalous lobar pulmonary veins or a silent patent ductus arteriosus. The incidences reported in 62 studies published after 1955 were examined. Attention was paid to the ways in which the studies were conducted, with special reference to the increased use of echocardiography in the neonatal nursery. The total incidence of CHD was related to the relative frequency of ventricular septal defects (VSDs), the most common type of CHD. The incidences of individual major forms of CHD were determined from 44 studies. The incidence of CHD depends primarily on the number of small VSDs included in the series, and this number in turn depends upon how early the diagnosis is made. If major forms of CHD are stratified into trivial, moderate and severe categories, the variation in incidence depends mainly on the number of trivial lesions included. The incidence of moderate and severe forms of CHD is about 6/1,000 live births (19/1,000 live births if the potentially serious bicuspid aortic valve is included), and of all forms increases to 75/1,000 live births if tiny muscular VSDs present at birth and other trivial lesions are included. Given the causes of variation, there is no evidence for differences in incidence in different countries or times.

Ductus Arteriosus, Patent↗
PubMed2002

Oxygen adaptation. The role of the CcoQ subunit of the cbb3 cytochrome c oxidase of Rhodobacter sphaeroides 2.4.1.

The cbb(3) cytochrome c oxidase of Rhodobacter sphaeroides consists of four nonidentical subunits. Three subunits (CcoN, CcoO, and CcoP) comprise the catalytic "core" complex required for the reduction of O(2) and the oxidation of a c-type cytochrome. On the other hand, the functional role of subunit IV (CcoQ) of the cbb(3) oxidase was not obvious, although we previously suggested that it is involved in the signal transduction pathway controlling photosynthesis gene expression (Oh, J. I., and Kaplan, S. (1999) Biochemistry 38, 2688-2696). Here we go on to demonstrate that subunit IV protects the core complex, in the presence of O(2), from proteolytic degradation by a serine metalloprotease. In the absence of CcoQ, we suggest that the presence of O(2) leads to the loss of heme from the core complex, which destabilizes the cbb(3) oxidase into a "degradable" form, perhaps by altering its conformation. Under aerobic conditions the absence of CcoQ appears to affect the CcoP subunit most severely. It was further demonstrated, using a series of COOH-terminal deletion derivatives of CcoQ, that the minimum length of CcoQ required for stabilization of the core complex under aerobic conditions is the amino-terminal approximately 48-50 amino acids.

Amino Acid Sequence↗
PubMed2002

Photosynthesis genes and their expression in Rhodobacter sphaeroides 2.4.1: a tribute to my students and associates.

This minireview traces the photosynthesis genes, their structure, function and expression in Rhodobacter sphaeroides 2.4.1, as applied to our understanding of the inducible photosynthetic intracytoplasmic membrane system or ICM. This focus has represented the research interests of this laboratory from the late 1960s to the present. This opportunity has been used to highlight the contributions of students and postdoctorals to this research effort. The work described here took place in a much greater and much broader context than what can be conveyed here. The 'timeline' begins with a clear acknowledgment of the work of June Lascelles and William Sistrom, whose foresight intuitively recognized the necessity of a 'genetic' approach to the study of photosynthesis in R. sphaeroides. The 'timeline' concludes with the completed genome sequence of R. sphaeroides 2.4.1. However, it is hoped the reader will recognize this event as not just a new beginning, but also as another hallmark describing this continuum.

Journal Article↗
PubMed2002

The opgGIH and opgC genes of Rhodobacter sphaeroides form an operon that controls backbone synthesis and succinylation of osmoregulated periplasmic glucans.

Osmoregulated periplasmic glucans (OPGs) of Rhodobacter sphaeroides are anionic cyclic molecules that accumulate in large amounts in the periplasmic space in response to low osmolarity of the medium. Their anionic character is provided by the substitution of the glucosidic backbone by succinyl residues. A wild-type strain was subject to transposon mutagenesis, and putative mutant clones were screened for changes in OPGs by thin layer chromatography. One mutant deficient in succinyl substitution of the OPGs was obtained and the gene inactivated in this mutant was characterized and named opgC. opgC is located downstream of three ORFs, opgGIH, two of which are similar to the Escherichia coli operon, mdoGH, governing OPG backbone synthesis. Inactivation of opgG, opgI or opgH abolished OPG production and complementation analysis indicated that the three genes are necessary for backbone synthesis. In contrast, inactivation of a gene similar to ndvB, encoding the OPG-glucosyl transferase in Sinorhizobium meliloti, had no consequence on OPG synthesis in Rhodobacter sphaeroides. Cassette insertions in opgH had a polar effect on glucan substitution, indicating that opgC is in the same transcription unit. Expression of opgIHC in E. coli mdoB/mdoC and mdoH mutants allowed the production of slightly anionic and abnormally long linear glucans.

Bacterial Proteins↗
PubMed2002

Incidence of cardiac abnormalities in children with human immunodeficiency virus infection: The prospective P2C2 HIV study.

OBJECTIVE: To describe the 5-year cumulative incidence of cardiac dysfunction in human immunodeficiency virus (HIV)-infected children. STUDY DESIGN: We used a prospective cohort design, enrolling children at 10 hospitals. Group I included 205 vertically HIV-infected children enrolled at a median age of 1.9 years. Group II consisted of 600 HIV-exposed children enrolled prenatally or as neonates, of whom 93 were ultimately HIV-infected. The main outcome measures were echocardiographic indexes of left ventricular dysfunction. RESULTS: In group I, the 5-year cumulative incidence of left ventricular fractional shortening </=25% was 28.0%. The 5-year incidence of left ventricular end-diastolic dilatation was 21.7%, and heart failure and/or the use of cardiac medications 28.8%. The mortality rate 1 year after the diagnosis of heart failure was 52.5% [95% CI, 30.5-74.5]. Within group II, the 5-year cumulative incidence of decreased fractional shortening was 10.7% in the HIV-infected compared with 3.1% in the HIV-uninfected children (P =.01). Left ventricular dilation, heart failure, and/or the use of cardiac medications were more common in infected compared with uninfected children. CONCLUSIONS: During 5 years of follow-up, cardiac dysfunction occurred in 18% to 39% of HIV-infected children and was associated with an increased risk of death. We recommend that HIV-infected children undergo routine echocardiographic surveillance for cardiac abnormalities.

Disease Progression↗
PubMed2002

Interdependent expression of the ccoNOQP-rdxBHIS loci in Rhodobacter sphaeroides 2.4.1.

The rdxBHIS gene cluster of Rhodobacter sphaeroides 2.4.1, located downstream of the ccoNOQP operon encoding the cbb(3) cytochrome c oxidase, is required for the posttranscriptional modification of the cbb(3) cytochrome c oxidase. The cbb(3) cytochrome c oxidase is the main terminal oxidase under microaerobic conditions, as well as a component of the signal transduction pathway controlling photosynthesis gene expression. Because of the intimate functional and positional relationships of the ccoNOQP operon and the rdxBHIS gene cluster, we have examined the transcriptional activities of this DNA region in order to understand their expression and regulation. Northern blot analysis and reverse transcription-PCR, together with earlier complementation analysis, suggested that the ccoNOQP-rdxBHIS cluster is transcribed as ccoNOQP-, ccoNOQP-rdxBH-, rdxBH-, and rdxIS-specific transcripts. Multiple transcriptional start sites have been identified by primer extension analyses: five for ccoN, four for rdxB, and one for rdxI. Transcription from P1(N) of ccoN and P1(B) of rdxB is dependent on the presence of FnrL. LacZ fusion analysis support the above-described studies, especially the importance of FnrL. Expression of the cco-rdx cluster is closely related to photosynthesis gene expression, suggesting that transcript stoichiometry and presumably the stoichiometry of the gene products are critical factors in controlling photosynthesis gene expression.

Bacterial Proteins↗
PubMed1995

Isolation of regulatory mutants in photosynthesis gene expression in Rhodobacter sphaeroides 2.4.1 and partial complementation of a PrrB mutant by the HupT histidine-kinase.

The photosynthetic bacterium Rhodobacter sphaeroides responds to the transition from aerobiosis to anaerobic photosynthesis by increasing the expression of the photosynthesis genes. Mutants have been isolated based on their inability, following such a transition, to increase transcription of the puc operon encoding the apoproteins of the light-harvesting complex II. Mutant D5, a representative of one mutant class, described here, although remaining photosynthetically competent, produced only low levels of the photosynthetic spectral complexes. Complementation analysis revealed that either the gene for the photosynthesis response regulator prrA or the gene encoding its cognate sensor kinase, prrB, was capable of rescuing this mutant. However, partial complementation of this mutant was achieved by placing in trans additional copies of other defined genes from the cosmid library of R. sphaeroides. We describe this effect in detail, attributable to the hupT gene, which has been proposed to encode a histidine-kinase for the hydrogen uptake system in Rhodobacter capsulatus. The effect of HupT on the expression of the photosynthesis genes was mediated through PrrA and independent of a functioning hydrogen uptake system. Thus, we raise the possibility that HupT can participate in phosphorylation of the heterologous response regulator PrrA by so-called cross-talk and therefore partially compensate for the defect in the mutant described. The observation of cross-talk, together with the complementation analysis, allowed us to assign the original mutation to the prrB gene; this was confirmed by DNA sequencing. Analysis of cross-talk in the wild-type, prrB and prrA genetic backgrounds suggested that besides kinase activity, PrrB may possess phosphatase activity toward PrrA. We also report the cloning, organization and structure of some of the hup genes from R. sphaeroides and construction of a Hup- strain.

Amino Acid Sequence↗
PubMedDate not supplied

Postmortem cardiomegaly and echocardiographic measurements of left ventricular size and function in children infected with the human immunodeficiency virus. The Prospective P2C2 HIV Multicenter Study.

BACKGROUND: Cardiomegaly, seen postmortem in over 50% of HIV-infected children, may occur in the absence of clinical or histopathologic cardiac disease. Premortem echocardiography has also demonstrated clinical and subclinical cardiac disease, including increased left ventricular mass (LVM) and functional abnormalities. No studies have compared these echocardiographic measures of heart size and function with postmortem findings in this population. We sought to determine the postmortem prevalence, clinicopathologic relationships and importance of cardiomegaly in HIV-infected children. METHODS: We reviewed clinical and postmortem cardiac findings in 30 HIV-infected children who were part of the Prospective P(2)C(2) HIV Study. Postmortem heart weight was compared with clinical measures of heart size and function, with cardiac pathology and with clinical measures reflecting chronic effects of HIV disease. RESULTS: Postmortem cardiomegaly (heart weight z score >/=2) was identified in 53% of the children. Children with cardiomegaly had increased LVM, increased heart rate, more frequent clinical chronic heart disease and a higher prevalence of postmortem pericardial effusions compared to children without cardiomegaly (P</=.05). The association with LV end-diastolic dimension (LVEDD) did not reach statistical significance (P=.08). No association was found with LV posterior wall thickness (LVPWT), CD4(+) T-cell counts, HIV-1 viral load, hemoglobin, encephalopathy, myocardial histology or myocardial organisms. CONCLUSIONS: Postmortem cardiomegaly was associated with echocardiographic measures of increased LVM. The pathogenesis appears not to be related to chronic anemia, HIV viral load, the degree of immune suppression or encephalopathy. Autonomic dysregulation, reflected by chronically increased heart rate, may be of pathoetiologic significance.

Child↗