Search PubMed⌕ Search

Biomedical subjects

M Newman

Publications and source records attributed to M Newman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Common causes of neonatal bacteraemia in Accra, Ghana.

This study is a retrospective review of admissions, discharge records and blood culture results of neonates admitted to the Neonatal Intensive Care Unit of Korle Bu Teaching Hospital in Accra, from the first of January 1991 to the 31st of December 1992. During this two year period there were 443 positive blood cultures. Ninety percent of the blood cultures were from babies born in Korle Bu Teaching Hospital, thus making the incidence of neonatal bacteraemia 22.2 per 1000 live births. The overall mortality rate was 37.2%. Gram negative bacteria accounted for 70.9% and Gram positive bacteria for 29.1% of all neonatal bacteraemia. The most common isolates were Enterobacter species 29.6%; Streptococcus faecalis 14.4%; Staphylococcus aureus 10.8%; Acinetobacter species 9.5%; Klebsiella species 9% and Escherichia coli 8.8%. It is concluded that the incidence of neonatal bacterial sepsis is high in our hospital and is associated with a very high mortality rate. There is thus an urgent need to institute appropriate preventive and therapeutic measures.

Bacteremia↗
PubMed1994

Crystallization and preliminary X-ray analysis of restriction endonuclease BamHI-DNA complex.

Restriction endonuclease BamHI from Bacillus amyloliquefaciens has been co-crystallized with a 12 bp DNA fragment that encompasses its recognition site. The co-crystals diffract to at least 1.95 A resolution and belong to space group P2(1)2(1)2(1). The unit cell parameters are a = 108.8 A, b = 81.9 A, c = 68.8 A, consistent with one complex in the crystallographic asymmetric unit. The direction of the DNA appears to be along the b axis. In order to achieve end to end stacking of DNA, the complex must lie on the screw axis along b. A self-rotation function has determined the directions of the non-crystallographic 2-fold axes.

Base Sequence↗
PubMed1994

Structure of restriction endonuclease bamhi phased at 1.95 A resolution by MAD analysis.

BACKGROUND: Type II restriction endonucleases recognize DNA sequences that vary between four to eight base pairs, and require only Mg2+ as a cofactor to catalyze the hydrolysis of DNA. Their protein sequences display a surprising lack of similarity, and no recurring structural motif analogous to the helix-turn-helix or the zinc finger of transcription factors, has yet been discovered. RESULTS: We have determined the crystal structure of restriction endonuclease BamHI at 1.95 A resolution. The structure was solved by combining phase information derived from multi-wavelength X-ray data by algebraic and maximum likelihood methods. The BamHI subunit consists of a central beta-sheet with alpha-helices on both sides. The dimer configuration reveals a large cleft which could accommodate B-form DNA. Mutants of the enzyme that are deficient in cleavage are located at or near the putative DNA-binding cleft. BamHI and endonuclease EcoRI share a common core motif (CCM) consisting of five beta-strands and two helices. It remains to be determined if other restriction enzymes also contain the CCM. CONCLUSIONS: The structure of BamHI provides the first clear evidence that there may be substantial structural homology amongst restriction enzymes, even though it is undetectable at the sequence level.

Amino Acid Sequence↗
PubMed1994

Structure of restriction endonuclease BamHI and its relationship to EcoRI.

Type II restriction endonucleases are characterized by the remarkable specificity with which they cleave specific DNA sequences. Surprisingly, their protein sequences are in most cases unrelated, and no recurring structural motif has yet been identified. We have determined the structure of restriction endonuclease BamHI at 1.95 A resolution. BamHI shows striking resemblance to the structure of endonuclease EcoRI (refs 3, 4), despite the lack of sequence similarity between them. We also observe some curious differences between the two structures, and propose an evolutionary scheme that may explain them. The active site of BamHI is structurally similar to the active sites of EcoRI and EcoRV (ref. 5), but the mechanism by which BamHI activates a water molecule for nucleophilic attack may be different.

Binding Sites↗
PubMed1994

Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8+ CTL in vivo with peptide vaccine constructs.

CTL are a critical component of protective immunity against viral infections, but requirements for in vivo priming of CTL are not completely understood. Covalent linkage of a helper determinant to a CTL determinant, analogous to that required for cognate help for antibody production, does not appear to be necessary in vitro, but its necessity has not been extensively explored in vivo, especially at a molecular level. We previously defined peptides encompassing multideterminant regions of HIV-1 gp160 (cluster peptides) recognized by Th from mice and humans of multiple MHC types. To investigate the requirement for Th in the development of CTL in vivo, in the context of developing a synthetic peptide vaccine for HIV active in multiple strains of mice, we immunized with compound peptides representing an immunodominant CTL epitope, P18, of gp160, co-linearly synthesized at the C-terminus of three cluster peptides. Spleen cells from compound-peptide-immunized mice of three MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules exhibited enhanced gp160-specific CD8+ CTL activity and CD4+ Th. In contrast, immunization with P18 alone or a mixture of cluster peptide and P18 elicited only marginal CTL activity. These results imply a requirement for determinant linkage in CTL induction in vivo similar to that already well recognized for cognate help for antibody induction. The results also define promising peptide HIV vaccine candidates for induction of CTL, as well as neutralizing antibodies, in diverse MHC types.

AIDS Vaccines↗
PubMed1994

Triplet repeats in clinical subtypes of schizophrenia: variation at the DRPLA (B 37 CAG repeat) locus is not associated with periodic catatonia.

Clinical evidence for a dominant mode of inheritance and anticipation in periodic catatonia, a distinct subtype of schizophrenia, indicates that genes with triplet repeat expansions or other unstable repetitive elements affecting gene expression may be involved in the etiology of this disorder. Because patients affected with dentatorubral-pallidoluysian atrophy (DRPLA) may present with "schizophrenic" symptoms, we have investigated the DRPLA (B 37 CAG repeat) locus on chromosome 12 in 41 patients with periodic catatonia. The B 37 CAG repeat locus was highly polymorphic but all alleles in both the patient and control group had repeat sizes within the normal range. We conclude that variation at the DRPLA locus is unlikely to be associated with periodic catatonia. The evidence for dominant inheritance and anticipation as well as the high prevalence of human brain genes containing trinucleotide repeats justifies further screening for triplet repeat expansions in periodic catatonia.

Adult↗
PubMed1994

Bacterial meningitis in children in southern Ghana.

One hundred and three children (1% of seriously ill children referred to the Korle Bu Teaching Hospital in Accra) were admitted with bacterial meningitis over a 17 month period. 43 of these children had been ill for more than 4 days before arrival at our centre. The main causative organisms were S. pneumoniae (47.9%), Neisseria meningitides (38.4%) and Haemophilus influenzae (9.6%). All bacterial isolates were highly sensitive to ceftriaxone. Resistance to penicillin and chloramphenicol was however present in 5-17% of isolates. All cerebrospinal fluid samples were sterilised within 48 hours of antibiotic treatment. Case fatality rate was 22% with the majority of deaths occurring within hours of admission and closely related to S. pneumoniae infection. Neurological complications occurred in 22%; mild diarrhoea in 33% and secondary fever in 14.8% of survivors. No significant difference was noted among the three treatment regimens of ceftriaxone alone, penicillin plus chloramphenicol, and ceftriaxone alone for 48 hours followed by penicillin/chloramphenicol combination. Our overall outcome would have been better if patients had been started on appropriate antibiotic treatment within the earlier hours of the infection. Furthermore, the latter generation cephalosporins, including ceftriaxone, must be given consideration as antibiotics of first choice world wide.

Anti-Bacterial Agents↗
PubMed1993

X-ray analyses of aspartic proteinases. V. Structure and refinement at 2.0 A resolution of the aspartic proteinase from Mucor pusillus.

The structure of mucor pusillus pepsin (EC 3.4.23.6), the aspartic proteinase from Mucor pusillus, has been refined to a crystallographic R-factor of 16.2% at 2.0 A resolution. The positions of 2638 protein atoms, 221 solvent atoms and a sulphate ion have been determined with an estimated root-mean-square (r.m.s.) error of 0.15 to 0.20 A. In the final model, the r.m.s. deviation from ideality for bond distances is 0.022 A, and for angle distances it is 0.050 A. Comparison of the overall three-dimensional structure with other aspartic proteinases shows that mucor pusillus pepsin is as distant from the other fungal enzymes as it is from those of mammalian origin. Analysis of a rigid body shift of residues 190 to 302 shows that mucor pusillus pepsin displays one of the largest shifts relative to other aspartic proteinases (14.4 degrees relative to endothiapepsin) and that changes have occurred at the interface between the two rigid bodies to accommodate this large shift. A new sequence alignment has been obtained on the basis of the three-dimensional structure, enabling the positions of large insertions to be identified. Analysis of secondary structure shows the beta-sheet to be well conserved whereas alpha-helical elements are more variable. A new alpha-helix hN4 is formed by a six-residue insertion between positions 131 and 132. Most insertions occur in loop regions: -5 to 1 (five residues relative to porcine pepsin): 115 to 116 (six residues); 186 to 187 (four residues); 263 to 264 (seven residues); 278 to 279 (four residues); and 326 to 332 (six residues). The active site residues are highly conserved in mucor pusillus pepsin; r.m.s. difference with rhizopuspepsin is 0.37 A for 25 C alpha atom pairs. However, residue 303, which is generally conserved as an aspartate, is changed to an asparagine in mucor pusillus pepsin, possibly influencing pH optimum. Substantial changes have occurred in the substrate binding cleft in the region of S1 and S3 due to the insertion between 115 and 116 and the rearrangement of loop 9-13. Residue Asn219 necessitates a shift in position of substrate main-chain atoms to maintain hydrogen bonding pattern. Invariant residues Asp11 and Tyr14 have undergone a major change in conformation apparently due to localized changes in molecular structure. Both these residues have been implicated in zymogen stability and activation.

Amino Acid Sequence↗
PubMed1993

Psychiatric consultation for women undergoing rehabilitation for upper-extremity lymphedema following breast cancer treatment.

Breast cancer presently affects one in nine women in the United States. Women receiving radiation and surgical resection of axial lymph nodes are at risk for development of lymphedema of the ipsilateral upper extremity. Mental health consultation and intervention can be an important part of rehabilitative efforts aimed at improving both lymphedema itself and the overall psychosocial adjustment of the patient. Such consultation begins with a careful consideration of possible psychiatric diagnosis but must necessarily depart from standard psychiatric considerations to include an assessment of psychosexual and social factors. Additionally, the consultant must gauge the degree of success the patient has had in adjustment to lifestyle changes brought on by lymphedema. This paper discusses the psychological problems posed by lymphedema and offers case examples. These cases illustrate the nature of psychiatric and psychological factors encountered in this population and the interventions that can help improve both compliance with rehabilitative efforts and psychological adjustment.

Adult↗
PubMed1993

Pro: midazolam is the sedative of choice to supplement narcotic anesthesia.

Having examined the options for adjuvant drug use during cardiac anesthesia, it becomes increasingly apparent that midazolam is "the drug" of choice and that supplementation with an opioid is an ideal adjuvant. In the hands of experienced cardiac anesthesiologists, the majority of the drugs discussed could provide adequate anesthesia with outcomes that would be difficult to distinguish, with the exception of awakening and time to extubation. Regardless of the inability to differentiate overall outcome, when comparing ease of providing complete "balanced" anesthesia, minimal cost increase, ease of use, hemodynamic stability, reliability of amnesia and ability to decrease narcotic requirement and allow early extubation, midazolam is a clear winner. Given as a continuous infusion or a bolus, potent opioids such as alfentanil, fentanyl or sufentanil enhance the amnestic and hypnotic effect of midazolam, decreasing the required dose. In addition, the combination of midazolam and narcotics decreases the catecholamine response that either one alone would produce. This removes the necessity of marked narcotic overdose required when narcotics alone are used. The result of this anesthetic combination is a technique that can be used in the majority of cardiac patients regardless of their ventricular performance, allowing options for earlier awakening, earlier extubation and decreased ICU stay. The goal of complete "balanced" anesthesia is best achieved with continuous infusions of midazolam and opioids. Accepting recall of intraoperative events as a necessary evil is unacceptable in the stable cardiac surgery patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗