PubMed Health⌕ Search

Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 37 records · Page 2Linked to original sources
PubMed1992

Molecular biology of African trypanosomes: development of new strategies to combat an old disease.

African trypanosomes are protozoan parasites that cause a number of diseases of man and domesticated animals in large regions of sub-Saharan Africa. The diseases have proven to be particularly difficult to prevent or to effectively treat due to features of both the trypanosome and the insect vector, the tsetse fly. The habitat of the tsetse and its resistance to insecticides have rendered vector control efforts ineffective. Attempts to develop a vaccine against the African trypanosomes has been dwarfed by the parasite's ability to change the composition of its exposed surface antigens. This process of antigenic variation allows the parasite to avoid the host's immune response and presents the host with a seemingly endless antigenic repertoire. Since conventional approaches to the control of African trypanosomiasis have largely met with failure, there has been a renewed interest in identifying novel aspects of the biology, biochemistry, and molecular biology of trypanosomes that might be exploited to develop new targets for vaccines or chemotherapy. Importantly, this research has opened a virtual Pandora's box of exciting biochemical and molecular surprises, which makes the African trypanosomes not only important medical pathogens but also an exciting experimental system for the basic scientist. In this review, the authors will describe some of the most recent and intriguing developments in the field of molecular parasitology.

Animals↗
PubMed1992

Pseudoangiosarcomatous carcinoma: a clinicopathological study of seven cases.

Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII-related antigen and CD 34 (QB-END/10). Two breast tumours showed binding of UEA-1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication.

Aged↗
PubMed1992

A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.

The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.

Child, Preschool↗
PubMed1992

Enzyme immunoassay for detection of immunoglobulin G (IgG), IgM, and IgA antibodies against type 6B pneumococcal capsular polysaccharide and cell wall C polysaccharide in chinchilla serum.

Conjugation of the capsular polysaccharides of Streptococcus pneumoniae to protein carriers has introduced a new generation of pneumococcal vaccines which may be efficacious in preventing pneumococcal otitis media during infancy. The chinchilla model has been used extensively for studying the pathogenesis of pneumococcal otitis media and for testing the efficacy of early pneumococcal capsular polysaccharide (PCP) vaccines, but immunologic studies in the chinchilla have been limited by the lack of antibodies against specific immunoglobulin isotypes. By using affinity-purified rabbit immunoglobulin G (IgG) anti-chinchilla IgG, IgM, and IgA, we developed a sensitive enzyme immunoassay that is highly specific for IgG, IgM, and IgA antibodies against type 6B PCP (anti-6B) and against C polysaccharide in chinchilla serum. Antibody titers increased in serum from five chinchillas immunized with a type 6B outer membrane protein complex vaccine. Increases of anti-6B IgG and IgM antibody titers were more striking than increases of anti-6B IgA or anti-C polysaccharide IgG, IgM, or IgA titers were.

Animals↗
PubMed1992

Specific cleavage of pre-edited mRNAs in trypanosome mitochondrial extracts.

RNA editing in Trypanosoma brucei is a posttranscriptional processing event that results in the addition and deletion of uridine residues within several mitochondrial mRNAs. We have examined reactions involving pre-edited precursor RNAs in vitro. In this study, we report specific cleavage of pre-edited cytochrome b (CYb), cytochrome oxidase subunit II (COII), and cytochrome oxidase subunit III (COIII) mRNAs when incubated with T. brucei mitochondrial extracts. The pre-edited CYb RNA was cleaved near the 3'-most uridine addition sites, within the region where editing would be expected to commence. Pre-edited COII mRNA was similarly cleaved adjacent to its small editing domain, while pre-edited COIII RNA was cleaved at multiple sites in the region where uridine addition and deletion occurs in vivo. In contrast, edited versions of CYb, COII, and COIII RNAs were not cleaved within the editing domains. Such differential cleavage of the edited and pre-edited forms of these mRNAs suggests either a direct involvement in RNA editing or involvement in another aspect of mitochondrial gene expression requiring cleavage of pre-edited RNAs.

Animals↗
PubMed1992

Audit of bone marrow trephines.

AIMS: To establish criteria of adequacy for bone marrow trephine biopsy specimens and to audit the quality of trephines performed at the Christie Hospital, Manchester. METHODS: Trephines (n = 767) performed over 12 months were reviewed. Their lengths, and the lengths of their constituent parts (soft tissue, cortex, crushed marrow and interpretable marrow) were measured. The mean performance of each operator was calculated. Criteria of adequacy were established by a review of the published findings and an analysis of the relation between trephine length and the rate of infiltration by tumour. RESULTS: Before processing, the average trephine was 1.59 cm long. Trephines shrunk by 25% during processing. In histological sections the average length was 1.15 cm, consisting of 0.09 cm of soft tissue, 0.04 cm of cortex, 0.26 cm of disrupted marrow and 0.74 cm of interpretable marrow. A large number of operators were taking trephine biopsy specimens and their performance varied considerably. Review of the published findings suggested that the minimum adequate length is in the range 1.5 cm to 2.0 cm. The analysis of the relation between length of trephine and the rate of positivity for neoplasia yielded a minimum adequate length of 1.2 cm in section (1.6 cm before processing). Fifty eight per cent of the trephines were inadequate by this criterion. There was a tendency for the Jamshidi needle to produce a longer trephine than the Islam needle. CONCLUSION: According to objective criteria, at the Christie Hospital, many operators are producing a high proportion of inadequate bone marrow trephines.

Biopsy, Needle↗
PubMed1992

Fungal infections of the small and large intestine.

AIMS: To study the pathological features of fungal infections affecting the lower intestinal tract (duodenum, small and large bowels). METHODS: Between mid-1981 and mid-1991, 14 cases of deep mycotic infections affecting the lower intestinal tract were found among 890 consecutive necropsies on patients with malignant disease treated in a regional cancer centre (incidence 1.6%). These 14 cases accounted for 54% of all gastrointestinal fungal infection detected. The relevant clinical, necropsy, histological and microbiological data were reviewed. RESULTS: Candida spp and Aspergillus spp accounted for all infections. The macroscopic appearances included ulcers of varying configuration, mucosal flecks, sloughed mucous membranes, polypoid masses and segmental lesions. Either organism could produce this range of lesions, but Candida tended to have a mucosal location and Aspergillus was associated with transmural invasion. Combined infections showed Candida in the surface mucosa and Aspergillus hyphae in submucosal vessels with spread into the bowel wall in a radiating pattern. During the final illness, gastrointestinal symptoms and signs were often slight and microbiological investigations were unhelpful. CONCLUSIONS: Variable gross appearances are relevant for endoscopists, particularly lesions which resemble pseudomembranous colitis. Endoscopic biopsy specimens may have a role in antemortem diagnosis. Failure to diagnose these infections during life emphasises the importance of necropsy in the clinicopathological audit of deaths in this group of patients.

Adolescent↗
PubMed1992

Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study.

PURPOSE: Using the technique of recursive partitioning and amalgamation analysis with verification, the Pediatric Oncology Group (POG) investigated the independent prognostic significance of previously published prognostic factors significantly associated with event-free survival (EFS) in B-progenitor cell acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Age, leukocyte count, sex, immunophenotype (expression of cytoplasmic immunoglobulin [Ig] and of surface antigens CD10 and CD34), and DNA index (ratio of the flow cytometry-determined DNA content of leukemia cells to that of normal diploid cells) were the variables used in the evaluation of four antimetabolite-based chemotherapy regimens in 1,535 children with the newly diagnosed B-progenitor cell ALL between February 1986 and May 1990. RESULTS: There were three subgroups at widely different risks of treatment failure. A DNA index greater than 1.16 was the most prognostic feature. The final prognostic subgrouping was as follows: (1) DNA index greater than 1.16; (2) DNA index less than or equal to 1.16, age less than 11.0 years, and leukocyte count less than 50 x 10(9)/L; and (3) DNA index less than or equal to 1.16, (age greater than 11.0 years, and/or leukocyte count greater than 50 x 10(9)/L). These groups made up 20%, 53%, and 27% of the patients and had 4-year EFS rates (SE) of 90.1% (6.3%), 80.5% (5.1%), and 50.4% (7.6%), respectively. CONCLUSIONS: Use of the DNA index, leukocyte count, and age--data that are relatively inexpensive and simple to obtain--may be sufficient to stratify patients with B-progenitor cell ALL for risk-directed therapy. Patients at an extremely low risk of failing therapy (approximately 20% of cases in this study) can thus be identified and spared the toxic short-term and late effects of more intensive therapies that may be needed for children with less favorable clinical and biologic features.

Adolescent↗
PubMed1992

Outpatient treatment of the mentally ill chemical abuser: an overview of problems and treatment strategies.

Patients who suffer from the effects of mental illness as well as chemical dependency have fared poorly in traditional mental health and substance abuse treatment. Presenting themselves in increasing numbers at both types of settings, they create challenges for clinicians. This article defines the scope of the problem and reviews treatment philosophies for the development of new approaches to care. Social workers can play a leadership role in integrating treatment theory and developing new clinical models in response to the challenges this patient population presents.

Adult↗
PubMed1992

Computer-generated titanium cranioplasty: report of a new technique for repairing skull defects.

A review of 40 cases of titanium cranioplasty fabricated from impressions taken of the defect through the patient's scalp in the conventional way showed that 23% were ill-fitting and 41% of frontal plates had a poor aesthetic result. Attributable factors were difficulty in defining the defect border accurately and limited information of the surrounding tissue architecture which led to strains produced during insertion. Inadequate communication between surgeon and prosthetist compounded these difficulties. A prospective study of six cases fabricated from CT computer-generated models of challenging cranial defects appears to show significant improvements in plate design, resulting in better plate adaptation, stability and aesthetic contour. Plate insertion was rapid (mean time 27 min) thereby minimizing operating time. This paper also discusses the advantages of the enhanced information derived from CT and describes the potential for pre-craniotomy template and matching cranioplasty, thereby permitting a one-stage procedure.

Computer Graphics↗
PubMed1992

Myofibrosarcoma of subcutaneous soft tissue of the cheek.

A low grade soft tissue sarcoma from the naso-labial fold and designated as myofibrosarcoma (sarcoma of myofibroblasts) is described using standard light microscopy techniques, immunohistochemistry and electron microscopy. Pink fibrillated cytoplasm, regarded as one of the typical histological features of leiomyosarcoma, was not obvious but immunostaining for alpha-smooth muscle actin was positive suggesting smooth muscle differentiation. By electron microscopy, tumour cells contained abundant rough endoplasmic reticulum cisternae and a large Golgi body; there were modest but numerous bundles of fine filaments with focal densities. A conventional lamina was lacking but the cell surface was characterised by fibronexus junctions in which there was a conspicuous extracellular, fibronectin-containing fibril, apparently mediating contact between cell and matrix. The tumour cells therefore showed myofibroblastic differentiation. The cell surfaces showed strong immunoreactivity with an anti-fibronectin antibody. Myofibrosarcoma is not a widely recognised entity and this case is only the 7th example to be documented in detail by means of both immunohistochemistry and ultrastructure. The combination of electron microscopy for detecting the fibronexus junction and immunostaining for fibronectin at the cell periphery is suggested as potentially useful for distinguishing myofibrosarcoma from leiomyosarcoma.

Actins↗
PubMed1992

Skin infections in Tanna, Vanuatu in 1989.

Skin infections are an important health problem in Vanuatu and other Pacific island countries. In this study, 18,223 people, representing 90% of the population of the southern island of Tanna in Vanuatu, were examined. Scabies was found in 16% of those screened, with 24% of children under 10 years affected. Other skin infections were predominantly furuncles, abscesses, impetigo and cellulitis and were found in 12% overall and in 16% of children under 10 years of age. These infections were found to be more common in larger households and in the vicinity of the volcano Yasur. Strategies for prevention and management of skin infections in Vanuatu are discussed.

Adolescent↗
PubMed1991

p53 germline mutations in Li-Fraumeni syndrome.

Germline mutations within a defined region of the p53 gene have recently been found in families with the Li-Fraumeni syndrome (LFS). In the present study this region of p53 was sequenced in affected individuals from 8 families with LFS. In only 2 of them were such mutations detected. Our findings suggest that the p53 mutation could be the primary lesion in some but not all families with LFS, and confirm that there is a "hot spot" for these mutations at the CpG dinucleotide moiety of codon 248. Assigning risks and counselling families on the basis of presence of p53 mutations should be approached with caution.

Adolescent↗
PubMed1991

Evidence for the mechanism of action of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decrease of nuclear estrogen receptor levels in wild-type and mutant mouse Hepa 1c1c7 cells.

Treatment of wild-type Hepa 1c1c7 cells with 1 nM [3H]-17 beta-estradiol resulted in the rapid accumulation of the nuclear estrogen receptor complex whose levels were maximized within 1 hr. Cotreatment of the cells with 10 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and [3H]-17 beta-estradiol did not affect the nuclear estrogen receptor levels 1 hr after addition of the radioligand; however, pretreatment of the cells for 1, 6, 24 or 42 hr with 10 nM TCDD prior to the addition of the radiolabeled hormone caused a greater than 50% decrease in nuclear estrogen receptor levels (determined by velocity sedimentation analysis) 1 hr after the addition of [3H]-17 beta-estradiol. In parallel experiments in which 10 nM TCDD was added 6 hr prior to the radiolabeled hormone, TCDD caused a 63 and 74% decrease in immunodetectable cytosolic and nuclear estrogen receptor protein levels, respectively, in the wild-type Hepa 1c1c7 cells. The nuclear estrogen receptor was also detected in two Hepa 1c1c7 mutant (class 1 and class 2) cell lines which have been characterized previously as TCDD non-responsive due to either decreased aryl hydrocarbon (Ah) receptor levels or a defect in the accumulation of transcriptionally active nuclear Ah receptor complexes, respectively. Treatment of these mutant cell lines with TCDD and [3H]-17 beta-estradiol (as described above) caused only a minimum (class 1) or non-detectable (class 2) decrease in nuclear estrogen receptor binding activity or immunodetectable protein levels. These results, coupled with the structure-dependent differences in the activities of TCDD (a strong Ah receptor agonist) and 2,8-dichlordibenzo-p-dioxin (a weak Ah receptor agonist) in this assay system, support a role for the Ah receptor in the TCDD-mediated decrease of the nuclear estrogen receptor in mouse Hepa 1c1c7 cells. In addition, actinomycin D and cycloheximide both inhibited the TCDD-mediated decrease of nuclear estrogen receptor levels in the Hepa 1c1c7 wild-type cells, and these results suggest that TCDD may induce specific gene products which are involved in this process.

Animals↗