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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 397 records · Page 22Linked to original sources

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↗

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↗

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↗

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↗

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↗

Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonists: characterization of 6-[125I]methyl-8-iodo-1,3-dichlorodibenzofuran-Ah receptor complexes.

6-Methyl-8-iodo-1,3,-dichlorodibenzofuran (I-MCDF) and its radiolabeled analog [125I]MCDF have been synthesized and used to investigate the mechanism of action of 1,3,6,8-substituted dibenzofurans as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) antagonists. Like 6-methyl-1,3,8-trichlorodibenzofuran (MCDF), I-MCDF partially antagonized the induction by TCDD of microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities in rat hepatoma H-4-II E cells and male Long-Evans rat liver. Incubation of rat liver cytosol with [125I]MCDF followed by velocity sedimentation analysis on sucrose gradients gave a specifically bound peak which sedimented at 9.6 S. This radioactive peak was displaced by coincubation with a 200-fold excess of unlabeled I-MCDF, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and benzo [a]pyrene. Based on the velocity sedimentation results and the elution profile from a Sephacryl S-300 gel permeation column, the Stokes radius and apparent molecular weights of the cytosolic [125I]MCDF-Ah receptor complex were 6.5 nm and 259,200, respectively. In addition, the nuclear [125I]MCDF-receptor complex eluted at a salt concentration of 0.29 M KCl from a DNA-Sepharose column. Velocity sediment analysis of the nuclear [125I]MCDF-Ah receptor complex from rat hepatoma H-4-II E cells gave a specifically bound peak at 5.6 +/- 0.8 S. All of these properties were similar to those observed using [3H]TCDD as the radioligand. In addition, there were several ligand-dependent differences observed in the properties of the I-MCDF and TCDD receptor complexes; for example, the [125I]MCDF rat cytosolic receptor complex was unstable in high salt buffer and was poorly transformed into a form with increased binding affinity on DNA-Sepharose columns; Scatchard plot analysis of the saturation binding of [3H]TCDD and [125I]MCDF with rat hepatic cytosol gave KD values of 1.07 and 0.13 nM and Bmax values of 137 and 2.05 fmol/mg protein, respectively. The nuclear extract from rat hepatoma H-4-II E cells treated with I-MCDF or TCDD interacted with a dioxin-responsive element in a gel retardation assay. These results suggest that the mechanism of antagonism may be associated with competition of the antagonist receptor complex for nuclear binding sites.

Animals↗

Early lexical development and maternal speech: a comparison of children's initial and subsequent uses of words.

In Harris, Barrett, Jones & Brookes (1988), we reported the results of a detailed analysis of the initial uses of the first 10 words which were produced by four children. The present paper reports the results of an analysis of the subsequent uses of these 40 words. This analysis reveals that seven qualitatively different patterns of change occurred between the children's initial and subsequent uses of these words; the particular patterns of change which occurred support Barrett's (1986) model of early lexical development. In addition, it was found that, although there was a strong relationship between maternal speech and the children's initial word uses, the relationship between maternal speech and the children's subsequent word uses was very much weaker. These findings indicate that the role of linguistic input in early lexical development may decline quite sharply once the child has established initial uses for words.

Child Language↗

Sarcomas in north west England: I. Histopathological peer review.

A total of 468 cases of bone, soft tissue and visceral sarcomas (and certain other tumours) diagnosed during the years 1982-84 in North West England were entered in a study of histopathological peer review, incidence and survival. This paper describes the effects of peer review. Material was reviewed by a panel of five pathologists for 413 of the 450 cases originally registered as sarcomas with the Regional Cancer Registry. The diagnosis of sarcomas was confirmed in 76% cases and and there was agreement on sub-type for 53% cases. Measures of agreement were lowest for the two sub-types most commonly diagnosed i.e. malignant fibrous histiocytoma and leiomyosarcoma. Degree of agreement between individual pathologists and final panel diagnosis was also very variable but never less than 65%. It is concluded that second opinion is essential in cases of presumed sarcomas for studies of incidence and aetiology and to ensure that appropriate treatment is selected.

Bone Neoplasms↗

Sarcomas in north west England: II. Incidence.

Incidence data on a population-based series of bone, soft tissue and visceral sarcomas from the North West of England are presented. The data are derived mainly from a total of 429 cases registered with the North Western Regional Cancer Registry and diagnosed during the period 1982-84, 76% of which were confirmed as sarcomas by a panel of five pathologists. Overall incidence of confirmed sarcomas per million person years was slightly higher in females (26.81) than in males (24.71) but there was no sex difference when 38 non-reviewed cases were taken into consideration (females 29.07, males (28.83). After exclusion of tumours of female genital tract, incidence of soft tissue tumours was very similar in both sexes (females 18.25, males 18.70). Bone tumours were almost twice as frequent in males (6.01) as in females (3.55).

Age Factors↗

How representative are patients in general practice morbidity surveys?

This study examined differences arising from the sampling of patients from general practice and household surveys. When 25 general practitioners, who agreed to participate in one week morbidity survey in inner western Sydney, were compared with all general practitioners (192) identified in the area, they were not significantly different in terms of socio-demographic variables and practice details. When the demographic characteristics of a sample of patients at 539 encounters with the 25 participating general practitioners were compared with those of a sample of 500 patients identified from a household survey who had consulted with any general practitioner within 2 weeks of the interview, few differences were found. Few significant differences were found in the reasons for encounter and diagnoses treated as recalled by the patients of the two groups. No differences were found in management--specifically prescription, investigations and referral--or with respect to health status. This study suggests that sampling of patients from randomly selected general practitioners can produce useful representative samples for studies of morbidity even when doctor participation rates are as low as 29%.

Adult↗