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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 271 records · Page 15Linked to original sources
PubMed1995

Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity.

Staphylococcus aureus infections are associated with rapid bone destruction in conditions such as osteomyelitis, bacterial arthritis, and infected orthopedic implant failure. How this bacterium induces bone destruction has not been defined. In studies of the role of oral Gram-negative bacteria in periodontal pathology, we have established that cell surface-associated proteins (SAPs) are potent stimulators of bone resorption. The surface-associated components from S. aureus have now been isolated and demonstrated to be extremely potent stimulators of bone resorption in the murine calvarial bone resorption assay. Bone resorption appears to be due to proteins, is not the result of contamination with lipoteichoic acid or muramyl dipeptide, and is potently inhibited by indomethacin and can be completely blocked by high concentrations of interleukin-1 receptor antagonist or TN3-19.12, a neutralizing monoclonal antibody to murine TNF. The SAP fraction can stimulate fibroblasts or monocytes to release osteolytic cytokines, but only at high concentrations. Fractionation of the SAPs by high performance liquid chromatography demonstrated that a number of fractions were osteolytically active. The most active contained a heterodimeric protein of molecular weight 32-36 kD. The presence of this osteolytically active surface-associated fraction may account for the bone resorption associated with local infection with S. aureus.

Animals↗
PubMed1995

Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds.

Naphthoquinone vitamins (vitamins K) are widely recognized for their role in the gamma-carboxylation of specific glutamyl residues in coagulation, anti-coagulation and extra-hepatic proteins. Recently, however, there have been reports that these compounds can exert actions other than those normally associated with protein gamma-carboxylation. These observations suggest that naphthoquinones may have effects on the production of inflammatory mediators including cytokines. Fibroblasts are now recognized as a rich source of cytokines and we have examined the effect of various naphthoquinones on the production of interleukin 6 (IL-6) by lipopolysaccharide-stimulated human gingival fibroblasts. Compounds examined in this study include: phylloquinone (K1), menaquinone-4 (K2), menadione (K3), 2,3-dimethoxy-1,4-naphthoquinone (DMK) and a synthetic product of vitamin K catabolism, 2-methyl, 3-(2'methyl)-hexanoic acid-1,4-naphthoquinone (KCAT). All of these compounds are capable of inhibiting IL-6 production with a rank order of potency: KCAT > K3 > DMK > K2 > K1. The most potent compound, KCAT, inhibited IL-6 production with an IC50 of 3 x 10(-7)M. The mechanism of action of these naphthoquinones on fibroblast IL-6 production is unknown. Given that K3 and KCAT are inactive in the gamma-carboxylation reaction, we suggest that this activity is not essential for the inhibition of IL-6 production and that activity may be related to the redox capacity of these naphthoquinones.

Cells, Cultured↗
PubMed1995

Neurotropic desmoplastic melanoma: a rare vulvar malignancy.

Melanoma represents the second most frequent vulvar malignancy, and yet is still considered to be an uncommon neoplasm. Several varieties of melanoma exist. A patient who was diagnosed with a rare subtype of melanoma as a primary vulvar process is presented here. To date, there is only one other reported case of neurotropic desmoplastic melanoma as a primary vulvar lesion. Our management included wide local excision of the primary lesion with clinical follow-up. Microstaging of this lesion showed it to fall into the poor prognosis category as per Breslow's technique, with a thickness of 6.5 mm. Clinical follow-up has been greater than 30 months without evidence of recurrence.

Aged↗
PubMed1995

In vivo hepatic 31P magnetic resonance spectroscopy in chronic alcohol abusers.

BACKGROUND/AIMS: In vivo hepatic 31P magnetic resonance spectroscopy (MRS) can provide information on hepatic energy metabolism, phospholipid substrates, and hepatocyte lipid bilayers. The aim of this study was to ascertain the effects of alcohol ingestion on hepatic 31P spectral variables. METHODS: Twenty-six chronic alcohol abusers underwent hepatic 31P MRS 6-12 hours after their last alcoholic drink; studies were repeated in 17 individuals following abstinence from alcohol. The reference population comprised 16 healthy volunteers. Ratios of phosphomonoesters (PME), inorganic phosphate, and phosphodiesters (PDE) relative to beta-adenosine triphosphate (ATP) were measured. RESULTS: In patients with minimal liver injury, recent drinking was associated with a significant elevation in the mean PDE/ATP ratio (P < 0.0001) and an increase in mean PME/ATP, which was not significant; abstinence was associated with reductions in both metabolite ratios. In patients with alcoholic cirrhosis, recent drinking was associated with an elevation in mean PME/ATP (P < 0.05) and an increase in mean PDE/ATP, which was not significant; abstinence was associated with no significant change in PME/ATP but with a reduction in PDE/ATP. CONCLUSIONS: In the absence of significant liver injury, chronic alcohol abuse is associated with the elevation of PME/ATP, possibly reflecting changes in hepatic redox potential, and of PDE/ATP, most likely reflecting the induction of hepatocyte endoplasmic reticulum. In the presence of cirrhosis, these changes are attenuated and modified.

Adenosine Triphosphate↗
PubMed1995

Third molar surgery: an audit of the indications for surgery, post-operative complaints and patient satisfaction.

A prospective investigation was undertaken of 522 patients undergoing third molar surgery. Data relating to indications for surgery and quality of care were collected on both pre- and post-operative proformas. This investigation showed that over half of the patients did not have clinically sound indications for surgery. The incidence of post-operative complications was approximately the same as other studies on third molar surgery. Patient satisfaction was at a high level, although this study revealed that a percentage of symptom-free patients undergoing third molar surgery sustained nerve damage some of which remains unreported. Clear and well defined indications for third molar surgery do exist and should be adhered to. Operating on patients without good reason involves unnecessary expenditure to purchasing authorities, cost to the patient in both time off work and post-operative complications and further, may result in potentially avoidable legal problems for practitioners. A reappraisal of the impacted third molar is indicated prior to committing the patient to surgery, such that the indications for surgery are compatible with current views on quality assurance, health service economics and medico-legal common sense.

Cost of Illness↗
PubMed1995

The role of the occlusal wafer in orthognathic surgery; a comparison of thick and thin intermediate osteotomy wafers.

The aim of this study was to compare two types of osteotomy wafers, derived from model surgery on a semi-adjustable anatomical articulator. The thick wafer was fabricated before autorotation of the mandibular cast and the thin after the autorotation. Twenty-five patients, 19 female and 6 male, who had osteotomies with a maxillary impaction as part of a bimaxillary correction were included in this study. Thick and thin wafers were fabricated and the surgeons were requested to compare both wafers, intra-operatively. Valid results were received for 19 cases, in 14 (74%) the surgeons concluded that both wafers located the maxilla in the same position. In 5 cases (26%) there was up to 2 mm difference in the maxillary position. These were cases when the impaction was > 6 mm, however, chi 2 and Fisher's exact test showed that the difference in impaction between the two groups was not significant (p = 0.06).

Centric Relation↗
PubMed1995

Is early separation anxiety a specific precursor of panic disorder-agoraphobia? A community study.

The present study aimed to examine memories of early separation anxiety symptoms in a community sample of women at heightened risk to neurotic disorder. The chief finding was that subjects with a lifetime history of panic disorder-agoraphobia (PD-Ag) returned statistically higher scores on a retrospective measure of early separation anxiety compared to subjects with either generalized anxiety or other phobic disorders, a result which was not accounted for by differences in neuroticism or General Health Questionnaire scores. Although limited by its retrospective design and the problem of co-morbidity in subclassifying the anxiety disorders, the present study does provide added support for the hypothesis--endorsed by DSM-III-R--that there is a developmental link between early separation anxiety and panic disorder.

Adult↗
PubMed1995

Symmetries and asymmetries in early lexical comprehension and production.

Six children were visited in their homes every two weeks for 18 months from the age of six months in order to observe their developing comprehension and production of words. Controlled testing of the children's developing vocabulary was also carried out to provide a more detailed picture of the precise context in which a word was understood or produced. The results showed both similarities and individual differences among the children in patterns of early comprehension. For all six children there was a very close relationship between early production and comprehension of words: words that were contextually flexible in production tended also to be so in comprehension and words that were context-bound also tended to be so in both modalities although there was some evidence that the two types of word differed in the extent to which comprehension preceded production. All children were also similar in showing evidence of contextually flexible comprehension very early on. However, there were individual differences both in the rate at which comprehension developed and in the lag between comprehension and production. The significance of this pattern of development for accounts of lexical development is explored.

Child Language↗
PubMed1995

Episodically homeless women with serious mental illness: prevalence of physical and sexual assault.

Three aspects of physical and sexual assault in the histories of 99 episodically homeless, seriously mentally ill women were assessed: lifetime prevalence; severity, co-occurrence, and recency; and associations between levels of this victimization and specific characteristics of the women. Results indicate that the life-time risk for violent victimization was so high (97%) as to amount to normative experiences for this population.

Adult↗
PubMed1995

Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma.

Temozolomide, an imidazotetrazine derivative, was given to 18 patients with low-grade non-Hodgkin's lymphoma (NHL) at a dose of 750 mg m-2 orally, divided over five consecutive days, escalated to 1000 mg m-2 over 5 days (i.e. 200 mg m-2 day-1) if no significant myelosuppression was noted at day 22 of the 28 day cycle. Fifty-six treatment cycles were given to 18 patients. The drug was well tolerated. Only one partial tumour response was documented. The patients were heavily pretreated but had chemoresponsive disease, as shown by a response rate of 69% among 13 patients who went on to receive alternative cytotoxic regimens. We conclude that temozolomide given in this schedule is inactive in previously treated low-grade NHL.

Adult↗
PubMed1995

Treatment and survival of lymphoid malignancy in the north-west of England: a population-based study.

Classification of lymphoid malignancy has changed markedly in recent years and advances have been made in therapy. This study investigated the variations in treatment and survival of 1622 patients in a population-based registry. A total of 1009 cases of malignant lymphoma (ML) were classified according to the Kiel classification. Pathology review resulted in major diagnostic changes for 24% of cases. Of the ML cases, 39% had not had full staging procedures. Younger patients were more likely to have been treated with multiagent chemotherapy regimens, as were patients with B symptoms. Median survival for ML patients was 12 months for high-grade patients and more than 60 months for low-grade patients. Significant factors affecting the survival of ML patients were performance status, whether treatment had followed a recognised protocol, whether treatment had been carried out at a specialist oncology centre (SOC), grade of disease, stage, gender and age. The same factors had a significant effect on survival of the leukaemia patients, except for treatment at an SOC, which had a significant favourable effect on survival of acute lymphoblastic leukaemia (ALL) patients only. Median survival for patients with chronic lymphocytic leukaemia was 43 months and 7 months for ALL patients.

Adolescent↗
PubMed1995

Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation.

Four biomarkers of neuronal protein oxidation [W/S ratio of MAL-6 spin-labeled synaptosomes, phenylhydrazine-reactive protein carbonyl content, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), and hippocampus (HIP)] of Alzheimer's disease (AD)-demented and age-matched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The W/S ratios of AD hippocampal and inferior parietal synaptosomes are 30 and 46% lower, respectively, than corresponding values of tissue isolated from control brain; however, the difference between the W/S ratios of AD and control cerebellar synaptosomes is not significant. Protein carbonyl content is increased 42 and 37% in the Alzheimer's HIP and IPL regions, respectively, relative to AD cerebellum, whereas carbonyl content in control HIP and IPL is similar to that of control cerebellum. GS activity decreases an average of 27% in the AD brain; CK activity declines by 80%. The brain regional variation of these oxidation-sensitive biomarkers corresponds to established histopathological features of AD (senile plaque and neurofibrillary tangle densities) and is paralleled by an increase in immunoreactive microglia. These data indicate that senile plaque-dense regions of the AD brain may represent environments of elevated oxidative stress.

Aged↗
PubMed1995

The human immunodeficiency virus type 1 Nef protein functions as a protein kinase C substrate in vitro.

The human immunodeficiency virus type 1 Nef protein was expressed in Escherichia coli as a C-terminal fusion with glutathione S-transferase (GST). The ability of GST-Nef to act as a substrate for cellular kinases in vitro was examined by incubation of purified GST-Nef fusion proteins, immobilized on glutathione-agarose beads, with cytoplasmic extracts from a number of human cell lines. In the presence of [gamma32P]ATP, phosphorylation of Nef occurred predominantly on serine residues. Studies with protein kinase inhibitors suggested that protein kinase C (PKC) was involved in Nef phosphorylation. This was supported further by the demonstration that purified PKC was also able to phosphorylate Nef in the absence of cell extract. Serine/threonine phosphorylation of Nef was also observed in vivo when Nef was expressed with a C-terminal GST or 6-histidine tag in Spodoptera frugiperda insect cells by recombinant baculoviruses. In extracts from Jurkat T cells and U937 monocyte/macrophages Nef also associated with a 57 kDa cellular protein that was itself phosphorylated in vitro. Phosphorylation of this Nef-associated protein was inhibited by heparin and is thus likely to be mediated by casein kinase II. The observation that PKC can phosphorylate Nef in vitro raises the possibility that PKC might play a role in regulating both Nef function and the physical interactions between Nef and cellular components.

Animals↗