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Biomedical subjects

M S Gelfand

Publications and source records attributed to M S Gelfand.

At least 19 recordsLinked to original sources

Statistical analysis and prediction of the exonic structure of human genes.

Nonhomologous fully sequenced human protein-coding genes were studied. Three sets of exon-exon junctions were formed defined by the intron (shadow) position relative to the reading frame. For the analysis of intron shadow signals in exons, information content and discrimination energy approaches were used with the correction allowing one to ignore the influence of a protein-coding message. The corrected formulas allow one to define the consensuses for the three types of intron shadow signals as a AG/guwn, cAG/GUnn, and cAG/gunU, and provide better recognition than the original formulas. The analysis of the codon usage in the signal positions leads to the conclusion that the prevalence of some amino acids in corresponding protein sites is caused by the signal requirements and not vice versa. The distribution of potential intron shadow signals in exons contradicts the hypothesis of intron insertion into suitable preexisting sites. There exists a correlation between the intron types and/or the exon length modulo 3.

Amino Acid Sequence

Subacute bacterial endocarditis secondary to Streptococcus pneumoniae.

Pneumococcal endocarditis characteristically presents as an acute illness, often accompanied by purulent meningitis, rapid destruction of the heart valves, congestive heart failure, and high mortality. We describe two patients with subacute pneumococcal endocarditis without a known primary source of pneumococcal bacteremia, fever, meningitis, or congestive heart failure. Both patients were cured with medical therapy. Pneumococcal endocarditis can present as an indolent illness resembling viridans streptococcal endocarditis.

Aged

In vitro activity of various antimicrobial agents against Staphylococcus aureus isolates including fluoroquinolone- and oxacillin-resistant strains.

To determine susceptibility to 31 old and new antimicrobials, 44 strains of Staphylococcus aureus, most resistant to oxacillin and ciprofloxacin and isolated in a community hospital, were tested in vitro. For the peptide/peptide-derivative compounds, with the exception of mersacidin, all strains were inhibited by less than or equal to 2 micrograms/ml. Minimum inhibitory concentration (MIC)90 values indicated mupirocin, teicoplanin, and MDL 62211 to be fourfold more active than vancomycin, ramoplanin, and decaplanin. For fluoroquinolones, ciprofloxacin-resistant S. aureus exhibited high-level cross-resistance to ofloxacin, norfloxacin, fleroxacin, enoxacin, and Ro 23-9424. WIN 57253, a new fluorinated naphthyridine, showed good activity against these strains. Among the beta-lactams, the penem-derivative compounds (imipenem, meropenem, FCE 22101, and HRE 664) had the greatest activity, although resistance to each compound was detected among oxacillin-resistant S. aureus. The presence of tazobactam reduced the piperacillin MIC90 fourfold. Oxacillin-susceptible strains were susceptible to cephalosporins/cephamycins, whereas most oxacillin-resistant strains exhibited resistance. This study has shown that certain old and new quinolones and peptide-derivative compounds have good in vitro activity against multiply resistant strains of S. aureus.

Aminoglycosides

Extendable words in nucleotide sequences.

Previous statistical analyses revealed several peculiarities of nucleotide sequences that preclude their description by existing models and thus allow one to distinguish DNA and RNA sequences from random A,T,G,C-texts. This is a consequence of the unusual distribution of certain words in nucleotide sequences: while the distribution of (most) words is consistent with Markov models of small orders, the distribution of certain words cannot be described by any previous model (anomalies in distribution of homonucleotide/homopurine/homopyrimidine runs, complementary and mirror palindromes, and non-stationary words). In this work we introduce a probabilistic approach that is partly motivated by analogy with linguistics. We also describe another important feature of DNA/RNA sequences: anomalies in distribution of words of poor nucleotide composition. We show that some classes of these words are the major obstacle for the simple Markov description of nucleotide sequences.

Base Sequence

Computer prediction of the exon-intron structure of mammalian pre-mRNAs.

A novel approach to the problem of prediction of protein-coding regions is suggested. This approach combines the site prediction methods to predict splicing sites and the global coding region prediction methods to choose the best variant of spliced mRNA. One of the advantages of the suggested algorithm is that the resulting mRNA or protein sequence may then be immediately analyzed further. The true mRNA either coincides with the predicted one or ranks high in the list of variants. In the latter situation the predicted mRNA usually differs from the true one in only one or two of several exons. The combined approach allows the use of a priori information (e.g. the putative protein length or the number of exons). It is possible to use additional parameters not considered here, such as the preferred lengths of exons and introns, and particularly the preferred position of introns in the reading frame and the preferred codon position of exon termini.

Actins

Cefamandole versus cefonicid prophylaxis in cardiovascular surgery: a prospective study.

We randomized 400 patients who were scheduled for an elective cardiovascular operation involving median sternotomy to receive cefamandole nafate or cefonicid in a prospective double-blind study. Three hundred fifty-seven patients were evaluable for prophylactic efficacy. Chest wound and donor site infections and early prosthetic valve endocarditis occurred more frequently with cefonicid (11 patients, 6.3%) than with cefamandole (4 patients, 2.2%) (p = 0.05). Three patients, all in the cefonicid group, required sternal debridement to control postoperative deep wound infections. Twenty-five miscellaneous postoperative infections (urinary tract infection, pneumonia, intravenous site infection, bacteremia, sepsis, Clostridium difficile diarrhea) occurred in 16 patients (9.19%) in the cefonicid group and four in 4 patients (2.19%) in the cefamandole group (p = 0.003). These data indicate that cefamandole is superior to cefonicid in preventing both surgical wound infections and miscellaneous nonsurgical infections after cardiovascular operations.

Cardiac Surgical Procedures

Candidal meningitis following bacterial meningitis.

Patients with bacterial meningitis and posttraumatic and/or postsurgical access to the CSF are at risk for superinfection with Candida species. Patients who are not improving on appropriate antimicrobial chemotherapy for bacterial meningitis or are deteriorating after initial improvement should have a CSF reexamination for Candida superinfection.

Adult

Invasive pulmonary penicilliosis: successful therapy with amphotericin B.

We have described a patient with invasive pulmonary penicilliosis, documented by thoracotomy and cured with amphotericin B. Penicillium sp isolates in immunosuppressed patients should not be disregarded without a thorough investigation, especially if normally sterile sites are involved. Amphotericin B therapy may be successful, especially if accompanied by a reversal or moderation of immunosuppression.

Amphotericin B

Characterization of mechanisms of resistance to beta-lactam antibiotics in methicillin-resistant strains of Staphylococcus saprophyticus.

The resistance mechanisms of methicillin-resistant strains of Staphylococcus saprophyticus were characterized. Penicillin-binding protein (PBP) studies demonstrated an inducible PBP identical to PBP 2a in the membranes of these isolates. The amount of beta-lactamase produced was minimal. PBP 2a is responsible for the methicillin resistance observed in these strains of S. saprophyticus.

Anti-Bacterial Agents

Fungal pseudomeningitis superimposed on Escherichia coli meningitis.

Pseudomeningitis is the demonstration of microorganisms from the cerebrospinal fluid by stain or culture in a patient with symptoms suggesting meningitis. This is a report of fungal pseudomeningitis superimposed on a case of nosocomial Escherichia coli meningitis resulting from a neurosurgical procedure. Critical care personnel need to be aware of the possibility of pseudomeningitis with or without associated meningitis in the appropriate setting.

Cefotaxime

Statistical analysis of mammalian pre-mRNA splicing sites.

222 donor and 222 acceptor (including 206 pairs) non-homologous splicing sites were studied. Well known features of these were confirmed and some novel observations were made. It is (1) cCAGGGag signal in (-60)-(-58) region of acceptor sites; (2) strong complementarity between regions (-69)-(-55) and (-36)-(-22) of some of the acceptor sites, and (3) small but statistically significant correlation between discrimination energies of corresponding donor and acceptor sites.

Animals

Spatial rotational alignment of identical particles in the case of (almost) coaxial projections.

Knowledge of projection directions is essential to the 3D reconstruction of biological objects from electron micrographs. In the general case, mutual orientation of the particles lying randomly on a support film can be found by the geometrical method described elsewhere. In the case of coaxial projections, the geometrical method finds the rotation axis but cannot find tilting angles. We propose here a new method to solve this problem, which requires no a priori information. The method uses the first moments of plane sections of the object, and it is both simpler and more effective than the previously proposed methods [A.B. Goncharov and M.S. Gelfand, Ultramicroscopy 25 (1988) 317]. Thus we have a general solution of the stated problem. We report the results of the computer experiment and describe how the noise and deviations of the rotation axis affect the results.

Computers

Candida tropicalis.

C tropicalis is a frequent and virulent pathogen in neutropenic patients. Infection control personnel should be familiar with this microorganism and the significance of a positive culture for C tropicalis in a setting of poor host resistance.

Amphotericin B

Enterobacter sakazakii infections in neonates associated with intrinsic contamination of a powdered infant formula.

We report an outbreak of Enterobacter sakazakii infection and colonization in neonates related to an infant formula contaminated during the manufacturing process. The outbreak occurred in a 20-bed neonatal intensive care unit during a six-week period in 1988, and involved a total of four infants. Three infants had sepsis and three had bloody diarrhea; all patients responded to intravenous antibiotics and recovered without complications. The E sakazakii isolated from the formula had the same plasmid and multilocus enzyme profile as those isolated from patients. This outbreak demonstrates the significance of commercially contaminated formulas and emphasizes the need to limit contamination and multiplication of bacteria in enteral formulas.

Cross Infection

Ticarcillin-clavulanate therapy for infections with ticarcillin-resistant microorganisms.

In a prospective study, 46 episodes of serious infection with ticarcillin-resistant microorganisms were treated with the combination ticarcillin disodium and clavulanate potassium (Timentin). Clinical cure was achieved in 35 of the 46 episodes (76%), and microbiologic eradication was achieved in 30 (65%). We found no development of resistance to ticarcillin-clavulanate and observed no serious side effects.

Adult

CDC group HB-5 as a cause of genitourinary infections in adults.

Isolates from five patients with genitourinary infections diagnosed over a 7-week period were identified as CDC group HB-5. The organisms caused clinical presentations of pelvic inflammatory disease in three women and urethritis in the only male in the series. The remaining patient received surgical treatment for a Bartholin gland abscess. Since the clinical and temporal presentations were remarkable and the questions of sexual mode of transmission and strain relatedness were of concern, the five strains were examined further by multilocus enzyme electrophoresis and ribosomal DNA typing. Overall, the five clinical isolates were more closely related to each other than to the control strains. This is the first report describing genitourinary infections caused by group HB-5. While the pathophysiology of group HB-5 infections remains to be fully elucidated, the possibility that this organism may be sexually transmitted deserves further study.

Abscess