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Biomedical subjects

J W Grant

Publications and source records attributed to J W Grant.

At least 19 recordsLinked to original sources
PubMed1995

Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells.

Gliosarcomas are morphologically heterogeneous tumors of the central nervous system composed of gliomatous and sarcomatous components. The histogenesis of the latter is still a matter of debate. As mutations of the p53 tumor suppressor gene represent an early event in the development of gliomas, we attempted to determine whether both components of gliosarcomas share identical alterations of the p53 gene. Using single-strand conformation analysis (SSCA) and direct DNA sequencing of the p53 gene, we analyzed dissected gliomatous and sarcomatous parts of 12 formalin-fixed, paraffin-embedded gliosarcomas. The two tumors that contained a p53 alteration were found to carry the identical mutation (exon 5; codon 151, CCC-->TCC; codon 173, GTG-->GTA) in the gliomatous and the sarcomatous components. These findings suggest a common origin of the two cellular components from neoplastic glial cells.

Adult↗
PubMed1995

The genetic basis of paediatric heart disease.

This review focuses on recent advances in understanding the pathogenesis of paediatric heart disease and on the known single gene defects responsible for these diseases. Many paediatric cardiovascular diseases are heritable, have clinical manifestations in adult ages, are frequent in occurrence, and can have significant social and economic impact. Specific gene defects have been identified for hypertrophic and dilated cardiomyopathies, mitochondrial cardiomyopathies, Marfan's syndrome, Williams syndrome, familial supravalvar aortic stenosis, CATCH-22 syndrome and atrioventricular canal. Limited phenotypic response of the developing heart accounts for similar cardiovascular defects from differing gene defects. Although environmental factors affect expression of many of these genes, it is clear that single gene defects can be identified which cause paediatric cardiovascular disease. Interactions among cardiologists, cardiovascular surgeons, geneticists and basic scientists are vitally important in understanding the genetic basis of paediatric heart disease, its diagnosis and its therapy.

Abnormalities, Multiple↗
PubMed1995

O'Brien's actinic granuloma: response to isotretinoin.

We describe a 75-year-old man demonstrating the florid clinical features of actinic granuloma of O'Brien. This rare disfiguring condition is believed to result from a granulomatous reaction of the dermis to solar-induced elastosis and is poorly responsive to topical steroids. Twelve weeks' treatment with isotretinoin prevented the development of new granulomata and produced almost complete resolution of established lesions.

Aged↗
PubMed1992

Genetic counselling in X-linked ocular albinism: clinical features of the carrier state.

Forty-nine obligate heterozygotes and 64 at risk females were assessed from 17 families affected by X-linked ocular albinism to determine the relative values of clinical examination and skin biopsy in carrier detection. 92% of obligate heterozygotes had a mud-splattered appearance of the fundus with hyperpigmented streaks and in 74% this was associated with marked iris translucency. Skin histology showed macromelanosomes in 84%. 27 of 64 (42%) at risk females had definite features of the carrier state and 19 (30%) were unequivocally normal but a further 18 (28%) had mild RPE abnormalities, often with iris transillumination defects, of uncertain significance. Fundus examination will detect most carrier females but will not allow reliable genetic counselling for all at risk females, even when supplemented by skin biopsy.

Albinism, Ocular↗
PubMed1992

Adenomatoid tumours: a mucin histochemical and immunohistochemical study.

We have examined 16 cases of adenomatoid tumour using a panel of monoclonal and polyclonal antibodies and also stained them for the presence of hyaluronidase-sensitive alcianophilic material. Fourteen cases expressed cytokeratins and a proportion of these also expressed S-100 protein, neuron-specific enolase, vimentin, and human milk fat globule protein 2. The same 14 cases also showed hyaluronidase-sensitive staining with alcian blue. No expression of factor VIII-related antigen was seen in these cases. We conclude that this provides further evidence of a mesothelial origin of these tumours. The remaining two cases did not express cytokeratins and no hyaluronidase-sensitive staining with alcian blue was seen. They did however express factor VIII-related antigen. Although they were morphologically indistinguishable from the other 14 cases, we suggest that they should be more properly regarded as angiomas.

Female↗
PubMed1992

Primary central nervous system lymphoma.

Primary central nervous system lymphomas (PCNSL) are uncommon neoplasms accounting for less than 2% of brain tumours. Their incidence appears to be increasing across a wide age range, in both immunocompetent and immunosuppressed populations. Particular risk groups include those with congenital and acquired immunodeficiencies and transplant recipients. The spread of the AIDS epidemic has seen large numbers of complicating PCNSL develop. Epstein-Barr virus infection appears to play a role in the development of these lymphomas in the immunosuppressed population. The aetiology of these tumours in the immunocompetent is uncertain. Their tendency to remain within the nervous system is not well understood but may be a function of CNS binding molecules carried by lymphocytes. Clinically PCNSL may present with a wide variety of signs and symptoms and has a capacity to mimic many other neurological conditions. Radiologically they appear as hyperdense homogenous deposits in subcortical white matter. Although most lesions are intermediate or high grade B cell lymphomas, T cell lymphomas are being recognised with increasing frequency. Immunohistochemistry and genotypic analysis have an important role in accurately characterising PCNSL, particularly in stereotactic biopsies. Involvement of multiple areas of the neuraxis, the eye and multiple intracranial sites can occur in the absence of obvious systemic lymphoma. The role of surgery in their treatment is uncertain. A combination of radiotherapy and chemotherapy can increase the length of survival. The prognosis, however, remains poor in comparison with nodal lymphomas, and particularly so in those with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Complete repair of total anomalous pulmonary venous connection in infancy.

From 1983 to 1990, 20 infants underwent complete repair of isolated total anomalous pulmonary venous connection. Twelve were male; ages ranged from 1 day to 240 days (mean 32 days). The abnormal anatomic connection was supracardiac in nine, cardiac in four, mixed in five, and infradiaphragmatic in two. In seven patients the pulmonary venous drainage was obstructed. Corrective operations were performed 2.4 days after admission; after medical stabilization, seven patients underwent emergency operations, including extracorporeal membrane oxygenation in one. All operations were performed with the use of circulatory arrest (mean 33 minutes) and cardiopulmonary bypass (mean 54 minutes). There was one hospital death, which occurred in a premature infant (1.5 kg) who had supracardiac drainage. No preoperative risk factors correlated with a poor surgical outcome. Pulmonary hypertensive episodes were expectantly managed after the operation with 100% oxygen, sedation, and hyperventilation. Postoperative arrhythmias occurred predominantly in patients with intracardiac drainage. All survivors (mean follow-up of 42 months) are in sinus rhythm, receiving no medications, and are growing and developing normally. Surgical correction of total anomalous pulmonary venous connection in infancy can be performed at low risk with good results after aggressive preoperative stabilization and postoperative management.

Cardiopulmonary Bypass↗
PubMed1991

Father and two children with total anomalous pulmonary venous connection.

Total anomalous pulmonary venous connection (TAPVC) is a rare form of cyanotic congenital heart disease which, without surgical treatment, has a high mortality in the first year of life. Reports of familial recurrence of TAPVC have involved sibs, first cousins, and twins. This is the first report of TAPVC in a father and his 2 children. The implications for genetic counseling to families with this anomaly and individuals reaching adulthood after repair of TAPVC are considered.

Adult↗
PubMed1991

Epithelioid sarcoma mimicking angiosarcoma: the value of immunohistochemistry in the differential diagnosis.

Epithelioid sarcoma (ES) is a rare malignant tumour of young adults, usually presenting as a skin ulcer or subcutaneous nodule in the distal portion of the upper limb. Multiple recurrences and late metastases are typical, leading to fatality in a third to one-half of all cases. The slow evolution of the tumour is one reason for its delayed recognition. The other is its frequent histological misinterpretation, in particular, as a peculiar granulomatous reaction. In our case, the primary tumour presented a variant morphological pattern so closely mimicking a cavernous angiosarcoma as to mislead several reputable opinions. Later recurrences and metastases were typical of ES, while a focal angiomatoid pattern was maintained. The morphology and immunoreactivity to a wide spectrum of tumour markers is compared with that of six file cases of classical ES. Retrospectively, all neoplastic lesions in our patient were ES. In young adults, lesions of the upper extremity, even when angiomatoid or haemorrhagic, should raise a suspicion of ES. Once epithelioid sarcoma is suspected, the differential diagnosis can be elucidated on immunohistochemical grounds. Early diagnosis provides the best opportunity for radical surgery at a stage when the tumour has not spread locally or disseminated systemically.

Adult↗
PubMed1991

Comparison of commercially available cytokeratin antibodies in normal and neoplastic adult epithelial and non-epithelial tissues.

Five commercially available cytokeratin antibodies (lu-5, AE1/AE3, CAM 5.2, MFN116 and anti-cytokeratin 18) were used to stain a wide range of normal and neoplastic epithelial and non-epithelial tissues to assess their potential value in diagnostic histopathology. All five showed good specificity, with some cross-reactivity in smooth muscle cells. The wider reactivity of AE1/AE3, lu-5, and MFN 116, which includes cytokeratins 8,18 (Moll's catalogue) expressed in simple epithelia and their tumours, as well as cytokeratins expressed in complex stratified squamous epithelia, permits identification of a wider range of epithelial derived tumours. This wider spectrum of reactivity may allow these antibodies to be used in a diagnostic panel for the identification of poorly differentiated tumours.

Antibodies, Monoclonal↗
PubMed1990

Mammalian nonsarcomeric myosin regulatory light chains are encoded by two differentially regulated and linked genes.

The myosin 20,000-D regulatory light chain (RLC) has a central role in smooth muscle contraction. Previous work has suggested either the presence of two RLC isoforms, one specific for nonmuscle and one specific for smooth muscle, or the absence of a true smooth muscle-specific isoform, in which instance smooth muscle cells would use nonmuscle isoforms. To address this issue directly, we have isolated rat RLC cDNAs and corresponding genomic sequences of two smooth muscle RLC based on homology to the amino acid sequence of the chicken gizzard RLC. These cDNAs are highly homologous in their amino acid coding regions and contain unique 3'-untranslated regions. RNA analyses of rat tissue using these unique 3'-untranslated regions revealed that their expression is differentially regulated. However, one cDNA (RLC-B), predominantly a nonmuscle isoform, based on abundant expression in nonmuscle tissues including brain, spleen, and lung, is easily detected in smooth muscle tissues. The other cDNA (RLC-A; see Taubman, M., J. W. Grant, and B. Nadal-Ginard. 1987. J. Cell Biol. 104:1505-1513) was detected in a variety of nonmuscle, smooth muscle, and sarcomeric tissues. RNA analyses comparing expression of both RLC genes with the actin gene family and smooth muscle specific alpha-tropomyosin demonstrated that neither RLC gene was strictly smooth muscle specific. RNA analyses of cell lines demonstrated that both of the RLC genes are expressed in a variety of cell types. The complete genomic structure of RLC-A and close linkage to RLC-B is described.

Amino Acid Sequence↗
PubMed1990

Rotational strength of double-pinning techniques in repair of transverse fractures in femurs of dogs.

Transverse midshaft fractures of femurs from freshly euthanatized dogs were stabilized by means of 6 methods: (1) 3.5-mm bone plate and screws, (2) single intramedullary pin, (3) double intramedullary pins retrograded proximally and driven distally to the level of the femoral trochlea, (4) double intramedullary pins retrograded distally and driven proximally into the trochanteric region, (5) double intramedullary pinning in Rush pin fashion, and (6) multiple intramedullary pinning that filled the medullary cavity at the fracture site. All bones were subjected to torsional stress. The measured strain was converted to forces of torque and correlated with bone diameter to normalize the data. The forces of torque from each fixation technique were compared with each other and with the mean torque force necessary to fracture intact femurs. Torsional shear applied to plated femurs resulted in failure at a mean level of 33.8% of the calculated theoretic moment. Torsional forces were concentrated at one end of the plate and catastrophically failed at that point, whereas the fracture site remained rigidly fixed. There was no significant difference in the initial moment of torsional failure between the single intramedullary pin technique (0.05 Nm) and the double-pinning techniques (0.03 to 0.04 Nm). The multiple-pinning technique was 1.8 to 3 times as effective in resisting rotational forces, compared with the other pinning techniques, but not significantly so.

Animals↗
PubMed1990

Primary T-cell lymphoma of the central nervous system.

We describe a 64-year-old man who presented with a 9-month history of a progressive neurologic disturbance affecting principally his short-term memory, eye movements, and sense of balance. Computed tomography and magnetic resonance imaging showed a 3-cm mass in the left cerebellar hemisphere. This was removed at craniotomy and proved histologically to be a diffuse non-Hodgkin's lymphoma. Further investigation showed no evidence of lymphoma elsewhere in the body. Immunohistochemical studies with an extensive panel of monoclonal antibodies showed the tumor cells to be T cells staining with the markers UCHL1, MT1, OKT3, and OKT11. Cells of the helper phenotype predominated. A small admixed reactive population of polyclonal B cells and macrophages was also present. The proliferation count as judged with the antibody Ki67 was about 15%. Primary cerebral lymphoma is in itself a rare entity with most cases being of B-cell origin. Primary cerebral T-cell lymphoma is extremely rare and the few previously reported cases are reviewed.

Adult↗
PubMed1989

Gliosarcoma: an immunohistochemical study.

Gliosarcomas contain both neuro-ectodermal and mesenchymal elements. Its histogenesis has been much debated and endothelial and adventitial fibroblast origins have been suggested, as has a "histiocytic" origin following the demonstration of antiprotease activity. Eight gliosarcomas have been examined with a panel of ten monoclonal and polyclonal antibodies to investigate the origin of the sarcomatous element. Glial fibrillary acid protein expression showed a sharp distinction between gliomatous and sarcomatous tumour components. Contrary to some previous reports factor 8-related antigen and Ulex europeus agglutinin stained vascular luminal endothelium but no tumour cells. Vimentin and fibronectin expression was extensive and confined largely to sarcomatous areas. Desmin and neurofilament protein could not be demonstrated in any of the cases. Numerous cells, particularly in the sarcoma areas, expressed alpha-1-antitrypsin and -chymotrypsin. A proportion of these stained for the monocyte/macrophage marker MAC 387. Four cases focally exhibited a true storiform pattern and this and the immunohistochemical results suggest analogies with the fibrous histiocytomas. These tumours contain reactive histiocytes but are now thought to be derived from fibroblasts or from pluripotent mesenchymal cells in perivascular adventitia. This resembles the pattern exhibited in the sarcomatous component of gliosarcomas.

Adult↗