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Biomedical subjects

R M Howell

Publications and source records attributed to R M Howell.

At least 19 recordsLinked to original sources
PubMed1999

The socioeconomic impact of hepatitis E in Nepal.

Hepatitis E disease is responsible for substantial morbidity in Nepal. A socioeconomic analysis was performed to describe the costs and the effects of hepatitis E disease (HE) on health status in a Nepalese population living in the Kathmandu Valley. A modified health status index was used to quantify healthy days lost associated with HE. One hundred thirty-four individuals recently recovered from HE were interviewed in June 1998. The median age was 22 years and 60% were female. Study participants were sick and bedridden for a median of 22 and 10 days, respectively. The median healthy days lost per individual was 35 (768,000 total per region). The median cost of illness per individual, including direct and indirect, was $37 ($1,238,676 total per region). The percentage of yearly income lost for wage earners totaled 19.4%. Hepatitis E disease is associated with significant costs and loss of healthy days in Nepal. Further research is warranted to understand and limit this common disease.

Adolescent↗
PubMed1997

Expression of hsc 70, but not hsp 70, in human third molar dental pulp.

The constitutive (hsc 70) and inducible (hsp 70) isoforms of heat shock protein 70 are important members of the superfamily of stress related proteins that protect and promote the recovery of cells from physiological and pathologic stress. The goal of this study was to define the baseline expression of hsc 70 and hsp 70 in disease-free, minimally stressed human dental pulp of the adult 3rd molar. Immunolocalization demonstrated moderate to heavy staining intensity for hsc 70 in both the cytoplasm and nucleus of odontoblasts and fibroblasts comprising the human pulp. Endothelial and smooth muscle cells displayed weak to moderate immunoreactivity for hsc 70 in both the cytoplasm and nucleus. Schwann cells demonstrated only weak nuclear staining for hsc 70. No immunoreactivity for hsp 70 was observed in any cell type in human pulp. Western, northern, and RT-PCR analysis of pulp preparations confirmed the expression of hsc 70 mRNA and protein within components of the pulp. These results demonstrate that cells of the human pulp express, under conditions of minimal stimulation, a key component of the stress response protein superfamily. The expression of hsc 70 under conditions of minimal stress may provide pulp components an advantage in resisting cell injury when stress occurs.

Adult↗
PubMed1997

The physiology and technique of skin grafting.

Skin grafting is one of the earliest described surgical procedures. In the age of microsurgery and free-tissue transfer, it remains a utilitarian means of achieving tissue coverage. This article discusses the physiology of skin grafting as well as current grafting techniques.

Body Temperature Regulation↗
PubMed1996

The chicken beta-globin gene promoter forms a novel "cinched" tetrahelical structure.

We have previously shown that the G-rich sequence G16CG(GGT)2GG in the promoter region of the chicken beta-globin gene poses a formidable barrier to DNA synthesis in vitro (Woodford et al., 1994, J. Biol. Chem. 269, 27029-27035). The K+ requirement, template-strand specificity, template concentration independence, and involvement of Hoogsteen bonding suggested that the underlying basis of this new type of DNA synthesis arrest site might be an intrastrand tetrahelical structure. However, the arrest site lacks the four G-rich repeats that are a hallmark of previously described intramolecular tetraplexes and contains a number of noncanonical bases that would be expected to greatly destabilize such a structure. Here we report evidence for an unusual K+-dependent intrastrand "cinched" tetraplex. This structure has several unique features including the incorporation of bases other than guanine into the stem of the tetraplex, interaction between loop bases and bases in the flanking region, and base pairing between bases 3 and 5 of the tetrahelix-forming region to form a molecular "cinch." This finding extends the range of sequences capable of tetraplex formation as well as our appreciation of the conformational complexity of the chicken beta-globin promoter.

Animals↗
PubMed1996

Expression of heat shock protein 27 in adult human third molar dental pulp.

This study is the first to define the expression of hsp 27 in the pulp of the adult human third molar. Using a monoclonal antibody against human hsp 27, immunoreactivity was demonstrated in the odontoblasts, odontoblast processes, pulp fibroblasts, and smooth muscle and endothelial cells of vessel walls. Nerves were negative. Pulp fibroblasts were characterized by cytoplasmic staining and variable nuclear staining. Odontoblasts also displayed consistent cytoplasmic staining and variable nuclear staining. Western, Northern, and RT-PCR analysis confirmed the expression of hsp 27 mRNA and protein. Hsp 27 was also shown to be present in both the unphosphorylated and phosphorylated isoforms. In general, nuclear localization and phosphorylation of hsp 27 has been correlated with cells responding to stress or other stimuli. This study demonstrates that pulp from a single human third molar provides sufficient material to support a detailed molecular analysis of gene expression.

Adult↗
PubMed1995

The effect of lipid peroxidation and lipolysis on the ability of lipoproteins to influence thromboplastin activity.

High, low and very low density lipoproteins and lipoprotein (a) were prepared from porcine serum. The apolipoprotein components of the lipoproteins were then isolated and resuspended in soybean lecithin. Apolipoprotein B was also resuspended in lipids more representative of those found in LDL and VLDL. Lipid peroxidation was induced in samples of all the lipoproteins and reconstituted apolipoproteins by incubation with either Cu2+ ions or hedgehog 15-lipoxygenase. Furthermore, aliquots of the samples were incubated with a mixture of lipases. The effect of native preparations and the treated samples on the procoagulant activity of thromboplastin was examined. Native HDL, apo A-II, native LDL, reconstituted LDL and apo B inhibited thromboplastin activity, whereas native VLDL and reconstituted VLDL enhanced this activity. While the ability of HDL and apolipoprotein A-II to inhibit thromboplastin was unaltered by either Cu2+ oxidation, lipoxygenase oxidation or lipolysis, VLDL and particles resembling VLDL, which acted cooperatively with thromboplastin lost their activating potential. On the other hand, LDL and particles resembling LDL changed from being inhibitory to enhancing the thromboplastin activity following oxidation, but not after lipolysis. Apolipoprotein B fragments obtained by mild digestion of this protein, expressed an inhibitory effect towards thromboplastin, while extensive degradation of the protein reduced its inhibitory potential. It is suggested that modifications of lipoproteins in vivo can lead to a hypercoagulable state by modulation of the cofactor activity of thromboplastin to factor VII.

Animals↗
PubMed1994

A novel K(+)-dependent DNA synthesis arrest site in a commonly occurring sequence motif in eukaryotes.

We have found that a strong DNA synthesis arrest site forms in the chicken beta-globin promoter in vitro under physiological conditions. The arrest site is located in a G+C-rich region in which the guanines are located predominately on the top strand and the pyrimidines on the bottom strand. This region is non-palindromic and has no mirror symmetry. Arrest of DNA synthesis is only observed when the G-rich strand of the promoter is used as the template, and shows an absolute requirement for K+. The sequence G16CG(GGT)3 is necessary and sufficient to arrest DNA synthesis. This arrest is template concentration independent and is eliminated by blocking the N7 positions of the last 4 guanine residues in the arrest site. These observations suggest that the basis of the block to chain extension is the formation of an unusual tetraplex-like structure by the template strand. Sequences able to form intrastrand tetraplexes are ubiquitous in eukaryotes. We show that known intrastrand tetraplex-forming sequences arrest DNA synthesis in vitro, suggesting that this may be a general property of DNA tetraplexes. We suggest that the arrest of DNA synthesis by some of these structures may account for some of the high frequency of recombination associated with these loci, perhaps by promoting strand slippage or providing an opportunity for strand exchange.

Animals↗
PubMed1992

The inhibition of thromboplastin by apolipoprotein-B and the effect of various associated lipids.

Human apolipoprotein B was purified by barium sulphate adsorption, subsequent delipidation and gel filtration. The protein was then reconstituted in soya bean lecithin and its inhibitory effect towards thromboplastin was assayed by incubation with rabbit brain thromboplastin. The use of an antibody against human apolipoprotein B diminished this inhibition. The level of inhibition of thromboplastin by the reconstituted apolipoprotein was found to be dependent on the concentration of the phospholipids with which it was reconstituted, reaching a maximum inhibition at a lipid: protein ratio of 1:1 (w/w). However, higher phospholipid concentrations or inclusion of cholesterol esters or triglycerides diminished and at certain concentrations reversed the inhibitory effect of the apolipoprotein. These results point towards apolipoprotein B as an inhibitor whose activity towards thromboplastin could be dependent on the complexes it forms with the surrounding lipids.

Animals↗
PubMed1992

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine.

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; cross-resistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The Ile-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient.

Acquired Immunodeficiency Syndrome↗
PubMed1991

In vivo prevalence of azidothymidine (AZT) resistance mutations in an AIDS patient before and after AZT therapy.

In order to examine the in vivo prevalence of AZT resistance mutations in AID patients after long-term therapy we amplified, by polymerase chain reaction (PCR), a 654 bp pol gene fragment from peripheral blood mononuclear cell DNA samples from a patient before, and 19 months after, the start of AZT therapy. PCR products from each sample were cloned and 9 clones from each sample were sequenced. Seven of 9 clones from the post-AZT sample, but none from the pre-AZT sample, contained an amino acid substitution (Thr215 to Tyr) requiring two nucleotide changes within the same codon (ACC to TAC). This change had previously been shown by Larder and Kemp (Science, 246:1155-1158, 1989) to correlate with partial AZT resistance of virus isolates. In colony hybridizations using synthetic oligonucleotides corresponding to the mutant and wild-type sequences, 22 of 22 clones from the pre-AZT sample hybridized only to the wild-type probe while 21 of 26 clones from the post-AZT sample hybridized only to the mutant. Clinically, this patient remains well, indicating that while Tyr215 may be the first amino acid substitution leading to resistance, it alone does not appear to have significantly influenced the clinical status of this patient.

Acquired Immunodeficiency Syndrome↗
PubMed1991

In vivo sequence variation of the human immunodeficiency virus type 1 env gene: evidence for recombination among variants found in a single individual.

To assess in vivo sequence heterogeneity of the human immunodeficiency virus type 1 (HIV-1) env gene, we used the polymerase chain reaction to amplify proviral sequences present in peripheral blood mononuclear cell DNA of a patient with acquired immunodeficiency syndrome (AIDS). The amplified env gene fragment (575 bp) contains the first hypervariable region and part of the first conserved region. Eleven and twelve clones were sequenced, respectively, from specimens collected two months apart. Notable heterogeneity was observed among sequences recovered from both specimens. Also, the proviral population recovered from the first specimen varied significantly from that found in the second specimen. Both specimens contained forms with and without an 18 bp duplication. The presence or absence of this duplication, in addition to several point mutations, appear to define two molecular groups evolving in parallel within this patient. Several genotypes which had sequences characteristic of both groups occurred primarily in the second specimen; these can best be explained by multiple recombinational events between representatives of the two groups during reverse transcription. This study demonstrates that recombination may contribute significantly to the generation of diversity among HIV variants within a single individual.

Adult↗
PubMed1989

Maxillary metastasis of transitional cell carcinoma: report of a case.

Metastases to the maxilla are extremely rare, and only 64 cases of histologically proven maxillary metastases can be found in the English-language literature. This article reports the first case of metastatic transitional cell carcinoma of the urinary bladder to the maxilla. The distribution of proven cases of maxillary metastasis and the possible anatomic pathways for this metastasis are discussed.

Aged↗