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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 163 records · Page 9Linked to original sources
PubMed1998

Expression of feline recombinant interferon-gamma in baculovirus and demonstration of biological activity.

We have previously reported the cloning of the coding sequence for feline-specific interferon-gamma. Here, we describe the expression of this sequence in a baculovirus system and demonstrate the biological activity of the recombinant protein. The coding sequence for feline interferon was directionally cloned into the baculovirus transfer vector pAcCL29-1. Transfer vector and linearized wild-type AcMNPV (BacPAK6) were used to co-transfect Sf9 cells by calcium phosphate coprecipitation. Subsequently, wild-type and recombinant viruses were separated by plaque assay. Recombinant plaques were expanded and a master stock of virus is produced. Production of biologically active interferon-gamma from infected Sf9 cells was demonstrated using a standard cytopathic effect reduction assay, utilising vesicular stomatitis virus (VSV), and an MHC class II induction assay.

Animals↗
PubMed1998

Genetic heterogeneity of the structure and function of GSTT2 and GSTP1.

In this study new methods for the detection of two polymorphic sites in the GSTP1 coding region have been developed. Both sites are polymorphic in several racial groups and there are significant differences between groups, in the gene frequency at each site. Although previous studies of recombinant GSTP1-1 have suggested that there are significant differences in the specific activity and stability of the I105 or V105 isoforms, no differences in the distribution of GSTP1-1 activities in normal blood donors with different GSTP1 genotypes were detected in this study. These data were obtained with CDNB as a substrate and greater differences may be apparent with different substrates. The structure and organization of the GSTT2 gene was also investigated and a pseudogene that occurs at a polymorphic frequency in European Australians was discovered. This pseudogene can be detected by PCR/RFLP analysis.

Alleles↗
PubMed1998

A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. OBJECTIVE: To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. DESIGN: Double-blind, controlled, randomized trial. SETTING: University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). PATIENTS: Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). INTERVENTION: Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA. RESULTS: Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08). CONCLUSIONS: Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.

Adult↗
PubMed1998

Immunolocalization of cytokines and growth factors in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic fibrotic disease of the oral cavity and oropharynx characterized by fibroelastic change in the mucosa which leads to progressive inability to open the mouth. The inflammatory cells in the lesional tissue consist mainly of T lymphocytes, with a high CD4:CD8 ratio, and major histocompatibility complex (MHC) class II expressing antigen-presenting cells. Cytokines and growth factors produced by inflammatory cells within the lesion may promote fibrosis by inducing proliferation of fibroblasts, upregulating collagen synthesis and downregulating collagenase production. The authors used a three-stage immunoperoxidase technique to investigate the expression of interleukin alpha (IL-1alpha) and beta, IL-6 interferon (IFN)-alpha, beta and gamma, transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in frozen sections of OSF and compared it with that in normal buccal mucosa. The expression of cytokines and growth factors in normal tissues was consistent with their well known distribution and cell of origin, but the intensity and distribution in OSF were all, with the exception of IFN-alpha and gamma, upregulated with strong expression in both the epithelium and underlying connective tissue. IFN-alpha showed a similar pattern of staining in both normal mucosa and OSF. IFN-gamma showed little or no expression in most lesional tissues, suggesting an innate deficiency or downregulation of this cytokine. The general increase in pro-inflammatory cytokines and growth factors, and reduced production of IFN-gamma, may play an important role in the pathogenesis of OSF.

Adolescent↗
PubMed1998

A case of chronic myelomonocytic leukemia with isochromosome 14q.

A 72-year-old man with increased monocytes and eosinophils in the bone marrow was found to have an isochromosome, i(14q), as the sole abnormality on bone-marrow cytogenetics. Follow-up over 12 months with repeat cytogenetic testing of bone marrow specimens on three further occasions showed an additional abnormality consisting of an apparently balanced translocation, t(6;21)(p21.1; q22). This abnormality, together with other features, indicated disease progression. A review of seven reported cases of i(14q) revealed limited follow-up information.

Aged↗
PubMed1998

Ocular psychiatric disorders in maxillofacial injuries. Two case reports and a review of psychogenic ocular symptoms.

Ocular signs and symptoms associated with facial trauma can be a manifestation of an underlying psychiatric disorder which may exist prior to the traumatic incident, or even develop as a result of the stressful traumatic experience in a psychologically vulnerable individual. Two such cases are presented. A brief review of psychogenic ocular symptoms as well as suggestions for evaluation and treatment are discussed.

Adult↗
PubMed1998

Therapeutic ultrasound for osteoradionecrosis: an in vitro comparison between 1 MHz and 45 kHz machines.

Mandibular osteoradionecrosis is a serious chronic complication which may follow radiotherapy. Therapeutic ultrasound is a highly effective, inexpensive and readily available means of promoting revascularisation and healing. 'Long wave' ultrasound increases penetration depth and, therefore, seems to be more appropriate than traditional high frequency ultrasound. The aim of this study was to compare a new treatment using 45 kHz with the current standard 1 MHz machine. A traditional 1 MHz machine, pulsed 1:4, at intensities of 0.1, 0.4, 0.7 and 1.0 W/cm2(SAPA) was compared with a long wave machine, 45 kHz, at intensities of 5, 15, 30 and 50 mW/cm2(SA). The ultrasound was applied to human gingival fibroblasts and mandibular osteoblasts in vitro. Cell proliferation (DNA synthesis) and collagen and non-collagenous protein synthesis assays were performed, using radiolabelled thymidine and proline, respectively. Controls were sham-insonated and all readings were given as a percentage of controls. Fibroblast proliferation increased by 47% at 0.7 W/cm2 (1 MHz) and by 43% at 50 mW/cm2 (45 kHz), and osteoblast proliferation increased by 52% at 1.0 W/cm2 (1 MHz), and by 35% at 30 mW/cm2 (45 kHz). Fibroblast collagen production increased by 48% at 0.1 W/cm2 (1 MHz), and by 44% at 15 mW/cm2 (45 kHz) and osteoblast collagen production increased by 55% at 0.1 W/cm2 (1 MHz) and by 112% at 30 mW/cm2 (45 kHz). Long wave ultrasound was, therefore, capable of inducing a comparable or even higher enhancement of bone formation compared with traditional ultrasound, which, with its greater penetration, may accelerate the healing effect of ultrasound on osteoradionecrosis. The suggested intensity for 45 kHz ultrasound is 30 mW/cm2.

Cell Division↗
PubMed1998

Ligamento-muscular protective reflex in the lumbar spine of the feline.

A ligamento-muscular protective reflex in the lumbar spine was demonstrated in a feline model. Stimulating electrodes were applied to the supraspinous ligament between several lumbar vertebra (L1 to L6) while recording myoelectric discharge from the paraspinal muscles at the L3, L4 and L5, bilaterally. Electromyographic (EMG) activity was present in the paraspinal muscles bilaterally, upon stimulation of the supraspinous ligament, in six preparations. The EMG discharge was strongest in the muscles one level below that of the stimulated ligament, whereas weaker EMG signals were recorded from as far as two levels above and below. The mean time delay between the application of the stimulus to the ligament to the resulting EMG ranged from 2.52 to 2.77 ms at all levels. Stimulation of the supraspinous ligament in the L6 segment resulted in a weak reflex response, and stimulation in the L7 segment did not produce any EMG activity. It was concluded that mechanoreceptors in the supraspinous ligament at the L1/6 levels may initiate sensory signals upon strain of the ligament, during flexion. This, in turn, causes contraction of the paraspinal muscles, bilaterally, to extend the spine and prevent possible damage to the ligament while maintaining stability. The results may add to the understanding of low back pain, and to the formulation of surgical procedures which could spare the neural supply of the ligament, allowing advanced physiotherapeutic modalities to be implemented for post-surgical rehabilitation.

Animals↗
PubMed1998

Genetic and environmental correlations between bone formation and bone mineral density: a twin study.

Bone mineral density (BMD) and bone turnover are both heritable. Although bone turnover affects bone mass, it is not clear whether these parameters are under common genetic or environmental control. The relative contribution of genetic and environmental factors to the determination of an index of bone turnover, bone specific alkaline phosphatase (BSAP), and the extent of common genetic regulation with BMD, were examined in 97 female twin pairs, aged 50 +/- 15 years (mean +/- SD), consisting of 48 monozygotic (MZ) and 49 dizygotic (DZ) pairs. BSAP was analyzed by radioimmunometric assay. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry. Twin resemblance for variable traits was assessed by intraclass correlation coefficients. Estimates of genetic and environmental components of variance were based on univariate and multivariate genetic models. As expected, BSAP in premenopausal women (9.8 +/- 4.3 microg/L) was significantly lower than in postmenopausal women (13.3 +/- 6.6 microg/L, p < 0.001), but similar to the subgroup of postmenopausal women on hormone replacement therapy (10.8 +/- 2.6 microg/L, p = 0.15). Although BSAP and BMD were correlated in a cross-sectional analysis (r = -0.35, p < 0.001 for LS-BMD; r = -0.16, p = 0.03 for FN-BMD), the intrapair difference in BSAP was not significantly correlated with the intrapair difference in BMD for MZ twin pairs. After adjustment for menopausal status, the intraclass correlation for BSAP was significantly higher in MZ than DZ twins (0.60 +/- 0.09 vs. 0.27 +/- 0.13, p = 0.03). Univariate model-fitting analyses indicated a heritability of 63% for BSAP, and 77% and 72% for lumbar spine and femoral neck BMD, respectively. By multivariate analyses, genes specifically influencing BSAP accounted for 16% of the total genetic variance in LS-BMD and 4% of the total genetic variance in FN-BMD. There was no evidence for shared environmental factors affecting BSAP and BMD. These findings indicate that BSAP and BMD are heritable and negatively correlated. However, the genetic loci influencing BSAP and BMD appear to be largely independent as are any environmental factors.

Adult↗
PubMed1998

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease): continuing diagnostic difficulties.

AIMS: To describe the clinicopathological and immunophenotypic features of 25 cases of Kikuchi-Fujimoto disease (K-F), which remains a poorly recognized entity and is still frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist. METHODS AND RESULTS: Haematoxylin and eosin sections of 27 lymph node biopsies were re-examined. Immunostains for B-lymphocytes, T-lymphocytes and macrophages were performed. Clinical and follow-up data were obtained through a questionnaire to the referring pathologist or from the patients' notes where available. The suggested initial diagnoses are discussed. The lymph nodes showed a necrotizing process characterized by patchy or confluent areas of necrosis associated with karyorrhexis and absence or paucity of granulocytes. This was associated with a proliferation of large blastic cells consisting of a mixture of T-lymphocytes and histiocytes. Fragmentation of the biopsy was a frequent feature. The diagnosis of K-F was suggested by the referring pathologist in three cases only. The most common suggested diagnosis was that of a non-Hodgkin's lymphoma. CONCLUSION: This series documents continuing difficulties in the diagnosis of Kikuchi-Fujimoto disease in the UK and emphasizes that cases are still being mistakenly diagnosed as malignant lymphomas. The diagnosis of Kikuchi-Fujimoto disease merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young women presenting with cervical lymphadenopathy.

Adolescent↗
PubMed1998

Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria.

AIMS: To study the clinical and histopathological features of sclerosing epithelioid fibrosarcoma, and to define diagnostic criteria for this uncommon soft-tissue tumour. METHODS AND RESULTS: Standard histological, immunohistochemical and ultrastructural techniques were applied to five tumours from head and neck, chest wall and groin. Tumours consisted of groups of monomorphic rounded/epithelioid cells surrounded by a prominent collagenous stroma. Tumour cells showed positive vimentin staining but were negative for other markers. They contained prominent rough endoplasmic reticulum and a large Golgi apparatus which in one case was producing collagen secretion granules, an ultrastructural marker for collagen production. Three patients had medium to long-term survival (3-7 years). Of these, one was disease-free for 3 years, and two experienced multiple recurrences: one of the latter died of metastatic disease. CONCLUSION: Criteria for diagnosing this uncommon tumour include: small to medium cell size, clear or pale cytoplasm, cellular arrangement in cords and strands, dense collagenous stroma; vimentin staining; rough endoplasmic reticulum and a Golgi apparatus producing, in well preserved examples, collagen secretion granules. The paper emphasizes the value of electron microscopy, supporting an appropriate histological picture and immunophenotype, in identifying these relatively low-grade sarcomas.

Adult↗
PubMed1998

A community survey of children with severe intellectual disability and their families: psychological adjustment, carer distress and the effect of respite care.

The present paper describes a cross-sectional study of the psychosocial adjustment of 143 children with severe disability and their families identified from a regional case register for children with special needs. Thirty-eight per cent of the children had significant psychiatric morbidity. By contrast, the overall level of distress in carers was not that different from probable community prevalence figures. Nevertheless, distress among carers was consistently associated with increased disability in the child. Although respite care is a valuable resource for many carers, its use is indicative of underlying distress in the carer.

Adaptation, Psychological↗
PubMed1998

A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy.

The effects of nevirapine, indinavir, and lamivudine in combination were studied among 22 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < or =50/mm3, whose options for antiretroviral therapy were limited by clinical or laboratory failure or toxicity with previous regimens. Median plasma HIV RNA was 5.16 log10 copies/mL at baseline, decreasing by a median of 3.12 log10 copies/mL at 24 weeks. Median baseline CD4 cell count was 30/mm3, increasing by a median of 95/mm3 at week 24. Adverse reactions led to drug discontinuation in 4 cases. Steady-state pharmacokinetic analysis in 17 patients was consistent with an interaction between nevirapine and indinavir. Nevirapine plasma levels were within the expected range, while indinavir levels were lower than expected. Despite this interaction, the combination of nevirapine, indinavir, and lamivudine was safe and well-tolerated and had substantial antiviral and immunologic effects lasting for the 24-week study.

Anti-HIV Agents↗
PubMed1998

Moderation of lactulose-induced diarrhea by psyllium: effects on motility and fermentation.

Psyllium has been reported to inhibit lactulose-induced colonic mass movements and to benefit patients with irritable bowel syndrome, improving both constipation and diarrhea. Our aim was to define how psyllium modified the whole-gut transit of a radiolabeled lactulose-containing test meal by using gamma scintigraphy. Eight subjects participated in a randomized crossover study comparing gastric emptying and small bowel and colonic transit after consumption of 20 mL lactulose three times daily with or without 3.5 g psyllium three times daily. Psyllium significantly delayed gastric emptying: the time to 50% emptying increased from a control value of 69 +/- 9 to 87 +/- 11 min (mean +/- SEM; P < 0.05, n = 8). Small bowel transit was unaltered. However, progression through the colon was delayed with an increase in the percentage of the dose at 24 h in the ascending (control group: 2 +/- 3%, psyllium group: 11 +/- 8%; P < 0.02) and transverse colon (control group: 5 +/- 12%, psyllium group: 21 +/- 14%) with correspondingly less in the descending colon. Although the time for 50% of the isotope to reach the colon was not significantly different with psyllium, psyllium significantly delayed the rise in breath-hydrogen concentrations, which reached 50% of their peak at 217 +/- 34 min compared with control values of 155 +/- 27 min (P < 0.05). Psyllium delays gastric emptying, probably by increasing meal viscosity, and reduces the acceleration of colon transit, possibly by delaying the production of gaseous fermentation products.

Adult↗
PubMed1998

Implicit phonological awareness and early reading development in prelingually deaf children.

This article reports on a longitudinal study of reading progress in a group of five-year-old deaf children and a group of hearing controls. All children were prereaders at the beginning of the study and the IQ of the two groups were matched. The deaf children varied considerably on a number of measures, including implicit phonological awareness, oral ability, and familiarity with British Sign Language and fingerspelling. Overall, the deaf children made significantly less reading progress than their hearing peers over the first year of schooling, and they also scored significantly lower on the test of rime and onset awareness. However, considerable variation in the reading progress of the deaf children was positively correlated with oral skills, rime/onset awareness, and language comprehension. Language comprehension, itself, was positively correlated with signing and fingerspelling. The deaf children were assessed again one year later, when learning to read continued to be very delayed, and the pattern of correlation was essentially the same. The implications of these findings for the education of deaf children are discussed.

Journal Article↗
PubMed1998

Surface-associated protein from Staphylococcus aureus stimulates osteoclastogenesis: possible role in S. aureus-induced bone pathology.

OBJECTIVE: Staphylococcus aureus is the cause of bone destruction in osteomyelitis, bacterial arthritis and orthopaedic implant failure. We have previously shown that gentle saline extraction of S. aureus has revealed the presence of an extremely potent stimulator of osteoclast activation in both the murine calvarial bone resorption assay and the isolated chick osteoclast resorption assay. In order to investigate the mechanism of action of this surface-associated material (SAM), we have investigated its capacity to recruit osteoclasts. METHODS: The murine bone marrow osteoclast recruitment assay was used. The ability of the recruited cells to resorb dentine slices was also investigated. Results. The SAM from S. aureus dose dependently stimulated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and pit formation on dentine slices. Neutralization of the cytokines tumour necrosis factor alpha and interleukin (IL)-6 totally inhibited, but antagonism of IL-1 only partially blocked, the stimulated maturation of osteoclast-like cells. CONCLUSION: These findings suggest that bone destruction associated with local infection by S. aureus is due to the stimulation of osteoclast formation induced by the action of the easily solubilized SAM, and could explain the large numbers of osteoclasts found in infarcted bone in osteomyelitis.

Acid Phosphatase↗