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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 433 records · Page 24Linked to original sources

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds on the occupied nuclear estrogen receptor in MCF-7 human breast cancer cells.

Treatment of MCF-7 human breast cancer cells with 17 beta-[3H]estradiol resulted in a rapid accumulation of occupied nuclear estrogen receptor complex in which levels were maximized within 1 h and decreased after 3 h. Pretreatment of the cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 6 or 12 h prior to the addition of the radiolabeled hormone resulted in a 38 and 63% reduction in the levels of the occupied nuclear estrogen receptor, respectively, whereas addition of TCDD 1 h prior to the radioligand did not cause any significant change in the levels of the occupied nuclear receptor using velocity sedimentation analysis. Moreover, it was also shown with estrogen receptor antibodies that the TCDD-mediated dose-dependent decrease in occupied nuclear receptor levels was paralleled by a comparable decrease in immunoreactive protein at concentrations of 10(-8) to 10(-11) M TCDD. The reduction in levels of the occupied nuclear estrogen receptor was not due to increased estradiol metabolism since a significant reduction was observed at TCDD concentrations (10(-11) to 10(-13) M) which do not induce cytochrome P-450-dependent monooxygenase enzyme activities in MCF-7 cells. Treatment of the MCF-7 cells with actinomycin D or cycloheximide resulted in a greater than 2-fold increase in levels of the occupied nuclear estrogen receptor, and cotreatment of the cells with both TCDD and these inhibitors significantly decreased levels of the nuclear estrogen receptor complex. The structure-activity relationships for TCDD and several congeners were similar for both the reduction of occupied nuclear estrogen receptor levels and several aryl hydrocarbon (Ah) receptor agonist activities, and these results support a role of the Ah receptor in these processes.

Breast Neoplasms↗

Epidemiological and familial aspects of hepatoblastoma.

Data on the 20 cases of hepatoblastoma registered with the Manchester Children's Tumour Registry between 1954 and 1988 are presented. The cases represent about 0.6% of childhood malignancies and show a male:female ratio of 2.3:1. Age at presentation was almost always under 2 1/2 years. Cancer rates in close relatives were not significantly different from those expected. One family was confirmed as having Gardner syndrome, but the presence of other syndromes e.g., Beckwith-Wiedemann, could not be reliably detected in this retrospective series. The need to take an extensive pedigree and for clinical examination of other family members at the time of the child's diagnosis is emphasized.

Adult↗

Developmental toxicity of orally administered 2',3'-dideoxycytidine in mice.

2',3'-Dideoxycytidine (DDC), a potent inhibitor of human immunodeficiency virus (HIV), is presently undergoing clinical trials as a promising anti-AIDS drug. Since there are very limited published animal toxicity data available, and nucleoside analogues are being considered for treatment of HIV-infected pregnant women, a study was conducted in mice to investigate the potential adverse developmental effects of this drug. DDC, suspended in 0.5% methyl cellulose, was administered via gavage twice per day during gestation days (gd) 6 through 15 to C57Bl/6N mice in a total dose of 0, 200, 400, 1,000, or 2,000 mg/kg/day. Maternal weight gain during the gestation and treatment period, as well as gravid uterine weight, decreased significantly in the 2,000 mg group, but weight gain, corrected for gravid uterine weight, was not affected by DDC. The percent resorptions per litter increased significantly in the highest dose group, and there were fewer live litters because of complete litter resorption in six dams. Among litters with live fetuses, the mean litter size was significantly reduced in the 2,000 mg group. Average fetal body weight per litter decreased significantly in the 1,000 and 2,000 mg groups. The number of fetuses with any malformation, the number of litters with one or more malformed fetuses and the percent of malformed fetuses per litter increased significantly in the 1,000 and 2,000 mg groups. There was an increase in malformations at 400 mg/kg/day; however, it was not statistically significant. In conclusion, DDC produced developmental toxicity (malformations, reduced fetal body weight, and resorptions) in the absence of overt maternal toxicity except for body weight changes due to resorptions and reduced fetal weights.

Animals↗

The ultrastructure of signet-ring cell non-Hodgkin's lymphoma.

New ultrastructural findings are reported from two lymphomas of vacuolar signet-ring cell morphology (SR+), one of B cell and one of T cell lineage. When these lymphomas were compared ultrastructurally a difference in the relationship of the endoplasmic reticulum (ER) to the vacuole was noted, although the fine structure of the vacuoles themselves was similar and they were interpreted as giant multivesicular bodies (mvbs). Smooth ER was found near the vacuoles in both cases. Dark mvbs with a complex, reticulate form are emphasised as readily identified but hitherto unreported cell components in these tumours. A further B cell lymphoma of centroblastic/centrocytic type which was SR- was found to be rich in mvbs and may be a transitional form between SR- and SR+ lymphomas. In addition, the occurrence of mvbs has been studied quantitatively in a number of other lymphomas and in B and T lymphocytes in reactive nodes. Although increased numbers of mvbs were found in neoplastic compared with reactive lymphocytes, and in T compared with B cell lymphomas, these differences were not statistically significant. The possible roles of endoplasmic reticulum and mvbs in the generation of SR+ change are discussed.

Adult↗

Mandibular reconstruction using vascularised fibula.

The osteocutaneous fibula flap has been used to reconstruct large segments of mandible in cases following ablation for cancer or radionecrosis. The bone can be cut to the appropriate shape and the fasciocutaneous flap may be used simultaneously to provide oral cavity lining or skin cover. The technique is described and its successful use in seven patients is reported with details of the complications encountered.

Adult↗

Sequence and developmental expression of the mRNA encoding the seleno-protein of the sperm mitochondrial capsule in the mouse.

We have characterized cDNA clones encoding the selenium-containing polypeptide of the keratinous mitochondrial capsule in mouse sperm. The longest open reading frame encodes a polypeptide 143 amino acids long which contains 21% cysteine and 27% proline and closely resembles the size and amino acid composition of bull mitochondrial capsule seleno-protein (V. Pallini, B. Baccetti, and A. G. Burrini, 1979, in "The Spermatozoon," D. W. Fawcett and J. M. Bedford, Eds., pp. 141-151, Urban & Schwartzenberg, Baltimore/Munich). The reading frame encoding the mitochondrial capsule seleno-protein ends with an amber stop codon suggesting that selenium is not incorporated cotranslationally into the protein by an opal suppressor selenocysteyl-tRNA as has been found for several eukaryotic and bacterial proteins. Northern blots using RNA extracted from purified spermatogenic cells and staged prepuberal mice suggest that the mitochondrial capsule seleno-protein mRNA is first transcribed in late meiotic cells and that the levels of the mRNA increase after meiosis in early haploid cells. Southern blots demonstrate that there is one copy of the gene in the mouse genome. The identification of this cDNA clone, in combination with previous work (K. C. Kleene, 1989, Development 106, 367-373) demonstrates that the mRNA for the mitochondrial capsule seleno-protein is translationally repressed with long homogenous poly(A) tracts in round spermatids and translationally active with shortened heterogenous poly(A) tracts in elongating spermatids.

Amino Acid Sequence↗

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on I-compounds in hepatic DNA of Sprague-Dawley rats: sex-specific effects and structure-activity relationships.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds on the specific patterns of age-dependent I-compound DNA adducts in the liver of male and female Sprague-Dawley rats were determined by the 32P-postlabeling assay. In female rats, TCDD causes a dose-dependent decrease of several individual and total hepatic I-compound levels after administration of 1 and 5 micrograms/kg per week for 4 weeks. In contrast, no such effects were observed in male Sprague-Dawley rats treated with the 5 micrograms/kg dose level of TCDD. The relative effects of TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) and 1,2,4,7,8-PCDD on hepatic I-compound levels in the susceptible female Sprague-Dawley rats were determined using a dose of 5 micrograms/kg per week for 4 weeks. The two compounds which are substituted in all four lateral positions, namely TCDD and 1,2,3,7,8-PCDD, caused a significant decrease in hepatic I-compound levels, whereas 1,2,4,7,8-PCDD which is substituted in only three lateral positions was inactive. The structure-activity relationships observed for the effects of these compounds on hepatic I-compounds correlated with their corresponding structure-Ah receptor binding and structure-toxicity relationships. The results are therefore consistent with a role for the Ah receptor in the TCDD-mediated reduction in hepatic I-compound levels in female Sprague-Dawley rats. These results and data from previous studies demonstrate a correlation between the susceptibility of an organ/species to the carcinogenic effects of TCDD and the reduction of I-compound levels. The significance of this correlation in the development of TCDD-induced carcinogenesis has not been delineated.

Age Factors↗

Sarcomas in three generations of a family with neurofibromatosis.

The development of sarcomas in three generations of a family with neurofibromatosis (NF) is described. A 7-month-old boy developed a prostatic rhabdomyosarcoma. Family history revealed that his maternal grandmother had died of a malignant peripheral nerve sheath tumor at age 37 years and had been affected with neurofibromatosis. His mother (aged 36 years) has also developed a malignant peripheral nerve sheath tumor and NF has been confirmed in both mother and son. This family illustrates a cluster of sarcomas associated with NF and shows the importance of thorough investigation of reported family illnesses.

Adult↗

Model surgery for orthognathic planning.

A modification of a popular North American model surgery technique is described, with a brief comparison with the key-spacer planning system of Lockwood. This technique enables bimaxillary movements to be planned with greater accuracy than with the Lockwood system.

Dental Articulators↗

Arthrotomography and the surgical correction of temporomandibular joint disorders.

Over a 2-year-period, 321 new patients were seen at one clinic with temporomandibular joint dysfunction and pain. Sixty-seven (21%) of these who did not respond to 12 weeks medical therapy, had arthrotomography performed and 24 patients (7.5%) underwent surgery to the joint. Eighteen (75%) of these patients were free of pain 1 year later, although this success was not always sustained without medical therapy. Meniscus adhesions were under-estimated on arthrotomography compared to surgical findings and meniscus perforations were over diagnosed. However, increased accuracy in preoperative diagnosis was seen with experience. There was only one false positive result which lead to unnecessary surgery.

Adult↗

The investigation of osteoradionecrosis of the mandible by 99mTc-methylene diphosphonate radionuclide bone scans.

The need for a reliable non-invasive investigation in osteoradionecrosis (ORN) of the mandible is discussed. The results of 99mTc-methylene diphosphonate bone scans using single photon emission tomography, and measuring dynamic uptake in 13 patients are presented. These suggest that sites of osteoradionecrosis may be defined by a paradoxically increased uptake of 99mTc-methylene diphosphonate.

Gamma Cameras↗

The investigation of osteoradionecrosis of the mandible by near infrared spectroscopy.

The results of near infrared spectroscopy in eight patients with osteoradionecrosis of the mandible are presented. These suggest that sites of osteoradionecrosis may be marked by decreased amounts of deoxygenated haemoglobin. The advantages and potential of near infrared spectroscopy are discussed but the technique requires further refinement.

Adult↗

Conservation of the breast using two different radiotherapy techniques: interim report of a clinical trial.

Patients with a clinically palpable breast carcinoma, 4 cm or less in diameter, and with no palpable nodes in the axilla were prospectively entered into a randomized clinical trial. A total of 713 patients were registered between November 1982 and December 1987, of whom 708 are evaluable at a median follow-up of 37 months. Following excision of the primary tumour, patients were randomly allocated either to have radiotherapy to the affected quadrant only (LF group) or to the whole breast and regional lymph node areas (WF group). No adjuvant hormone or chemotherapy was prescribed. The primary tumour was reported as completely excised histologically in 80% of cases, incompletely excised in 10%, and no estimate was possible in 10%. At six years from first randomization, 96% of the WF group and 92% of the LF group have remained free of breast recurrence (94% and 87% actuarial breast recurrence-free survival at 5 years). Part of the difference may be explained by the 20% recurrence rate in the breast for lobular carcinomas treated within the LF group. Of the WF group 14 patients (4%) developed recurrent disease in the axilla, compared to 50 patients (14%) in the LF group (95% and 86% actuarial axillary recurrent-free survival at 5 years). Patients with primary tumours histologically 1 cm or less in diameter had a 98% actuarial 5-year survival compared with 74% for those with tumours measuring 2 cm or more in diameter (P = 0.003). Continued follow-up of these patients will provide further information on the factors governing local/regional recurrence.

Breast Neoplasms↗

Comprehension of reversible sentences in specifically language-impaired children.

This study investigated comprehension of reversible sentences in specifically language-impaired (SLI) children. Two experiments, using different paradigms, were undertaken. In Experiment 1, 14 SLI children (aged 4:10-7:10) were compared with children matched on chronological age and language age (LA). Subjects acted out 36 semantically reversible sentences that varied in thematic content (transitives, locatives, and datives) and in the order of thematic roles (canonical and noncanonical). The SLI children performed at a significantly lower level than both control groups. In Experiment 2, the same sentences were presented using a picture-pointing task. A single word vocabulary test preceded the test sentences to assess semantic knowledge of the predicates. Sixteen SLI children were compared with language age controls. No significant differences were found between the performance of the two groups on the vocabulary test, and in general, the results of Experiment 2 supported those of Experiment 1. Analysis of individual children's error patterns identified qualitative differences between the SLI children and the LA controls. The majority of SLI children had a very high proportion of word order errors. The proportion of word order errors of the SLI children, unlike those of the LA controls, was unrelated to language age. These findings are considered in relation to the processes involved in sentence comprehension.

Child↗

Autoimmune cytopenias in Castleman's disease.

The authors report a case of Castleman's disease in which the major clinical problems have been caused by severe thrombocytopenia and neutropenia. The cytopenias were caused by autoimmune destruction of mature cells as demonstrated by bone marrow findings and cell-specific antibody assays. There also was evidence of red cell autoantibody production but no overt hemolysis. The thrombocytopenia currently is controlled by intermittent vincristine, having proved refractory to steroids, splenectomy, and danazol and only partially responsive to high dose intravenous immunoglobulin. The neutropenia showed temporary improvement with immunoglobulin but has been resistant to all other therapy. This case provides further evidence for disordered immune regulation in Castleman's disease.

Adolescent↗

Conservative treatment of cutis aplasia.

Three cases of cutis aplasia are presented. The defects involved include full-thickness defects of scalp and cranium as well as full-thickness skin defects of the abdomen and thigh. All patients were treated conservatively with the use of Silvadene cream dressings. Healing was obtained in all patients.

Bandages↗