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Biomedical subjects

D M Parry

Publications and source records attributed to D M Parry.

At least 73 records · Page 4Linked to original sources
PubMed1987

Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene.

von Recklinghausen neurofibromatosis (VRNF) is one of the most common inherited disorders affecting the human nervous system. VRNF is transmitted as an autosomal dominant defect with high penetrance but variable expressivity. The disorder is characterized clinically by hyperpigmented patches of skin (café au lait macules, axillary freckles) and by multiple tumors of peripheral nerve, spinal nerve roots, and brain (neurofibromas, optic gliomas). These tumors can cause disfigurement, paralysis, blindness, and death. We have determined the chromosomal location of the VRNF gene by genetic linkage analysis using DNA markers. The VRNF gene is genetically linked to the locus encoding nerve growth factor receptor, located on the long arm of chromosome 17 in the region 17q12----17q22. However, crossovers with the VRNF locus suggest that a mutation in the nerve growth factor receptor gene itself is unlikely to be the fundamental defect responsible for the VRNF phenotype.

Chromosome Mapping↗
PubMed1987

Baseline and mutagen-induced sister-chromatid exchanges in cultures of human whole blood and purified fresh or frozen lymphocytes.

Baseline and mutagen-induced levels of sister-chromatid exchanges were evaluated in 10 normal individuals. Cultures with whole blood or purified lymphocytes, either freshly isolated or after 1 or 6 months of cryopreservation, were analyzed to determine whether frozen lymphocytes are suitable for SCE studies. Whole blood and freshly isolated lymphocytes were cultured from samples taken at the beginning of the study (Time 0) and 6 months later (Time 6). Cryopreserved lymphocytes were recovered after 1 month (Time 1) and 6 months (Time 6) of cryopreservation and then challenged with mutagens in culture. The mutagens used were mitomycin C, 4-nitroquinoline-1-oxide, and N-methyl-N'-nitro-N-nitrosoguanidine. Purified lymphocytes had consistently and significantly higher baseline SCE frequencies than cells from whole blood cultures and were more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine and 4-nitroquinoline-1-oxide. The response to mitomycin C was similar in all culture types. There was, overall, no consistent effect of freezing on baseline or induced sister-chromatid exchange frequencies in the purified lymphocytes. This suggests that purification and cryopreservation of human lymphocytes does not alter the baseline or mutagen-induced sister-chromatid exchange response and in certain epidemiological, occupational and monitoring situations may have logistical and technical advantages over the use of fresh whole blood.

4-Nitroquinoline-1-oxide↗
PubMed1987

Linkage analysis in von Recklinghausen neurofibromatosis (NF1) with DNA markers for chromosome 17.

The mutant gene causing von Recklinghausen neurofibromatosis (NF1) was recently shown to map to chromosome 17. We have used additional markers for chromosome 17 to narrow further the location of the gene defect. A preliminary multipoint linkage analysis suggests that the NF1 gene is located on the long arm of chroomsome 17, flanked by D17Z1 and NGFR. Linkage analysis with the human oncogene homolog erbA1, which maps to this region, suggests that this cancer-related gene is not the primary cause of NF1.

Chromosomes, Human, Pair 17↗
PubMed1987

Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma.

A translocation that involves chromosome X (band p11.2) and chromosome 18 (band q11.2) was observed in short-term in vitro cultures of cells from five synovial sarcomas and one malignant fibrous histiocytoma. In four of these tumors, the translocation t(X;18)(p11.2;q11.2) was reciprocal. The two other tumors had complex translocations: t(X;18;21)(p11.2;q11.2;p13) and t(X;15;18)(p11.2;q23;q11.2). A translocation between chromosomes X and 18 was not detected in other histological types of soft tissue sarcoma. The X;18 rearrangement appears to characterize the synovial sarcoma and is the first description of a primary, nonrandom change in the sex chromosome of a human solid tumor.

Adolescent↗
PubMed1987

Genetic linkage studies with neurofibromatosis: the question of heterogeneity.

Three new families are reported for standard gene linkage markers and classical peripheral neurofibromatosis (Von Reckling-hausen disease). Additional data are summarised for the exclusion map. One family gives slight evidence of close linkage with the Gc locus on chromosome 4, raising again the question of possible genetic heterogeneity in NF.

Chromosome Mapping↗
PubMed1986

SC phocomelia syndrome, premature centromere separation, and congenital cranial nerve paralysis in two sisters, one with malignant melanoma.

Two middle age sisters had most manifestations of the SC phocomelia syndrome including postnatal growth retardation, symmetric limb deficiencies with radial aplasia and absent thumbs, facial anomalies with microcephaly, microphthalmia, hypoplastic nasal alae, and borderline to mild mental retardation. Unusual findings included congenital paralysis of some cranial nerves in both patients and malignant melanoma in the proposita. Cultured lymphocytes from both patients, and skin fibroblasts, Epstein Barr virus-transformed lymphocytes, and tumor cells from the proposita demonstrated premature separation of centromeric heterochromatin (PCS) of many chromosomes, a finding noted previously in the SC phocomelia syndrome and the similar but more severe Roberts syndrome. Extensive overlap of the phenotypes of the sisters and 15 other patients with either syndrome and PCS confirms that these are either allelic conditions or the same disease--designated Roberts-SC phocomelia syndrome. The role of PCS in the syndrome(s) remains uncertain since some patients with the characteristic clinical phenotypes are reported to lack it.

Adult↗
PubMed1986

Chromatid repulsion associated with Roberts/SC phocomelia syndrome is reduced in malignant cells and not expressed in interspecies somatic-cell hybrids.

Different cell types from a female patient with Roberts/SC phocomelia syndrome were evaluated quantitatively for the presence of repulsion of heterochromatin and satellite regions of mitotic chromosomes. Whereas EBV-transformed lymphoblasts from an established cell line revealed these phenomena at frequencies equal to those in PHA-stimulated lymphocytes and cultured skin fibroblasts, aneuploid cells from a metastatic melanoma displayed them at 50% lower frequency. Cocultivation of the patient's fibroblasts with either an immortal Chinese hamster cell line or with a human male fibroblast strain carrying a t(4;6)(p14;q21) translocation showed that the phenomenon was not corrected or induced by a diffusible factor or by cell-to-cell contact. In each experiment, only the patient's metaphase spreads revealed chromatid repulsion. In fusion hybrids between the patient's fibroblasts and an established Chinese hamster cell line, the human chromosomes behaved perfectly normally, suggesting that the gene product which is missing or mutant in Roberts/SC phocomelia syndrome is supplied by the Chinese hamster genome.

Adult↗
PubMed1985

Familial Sotos syndrome (cerebral gigantism): craniofacial and psychological characteristics.

Most reported cases of Sotos syndrome are sporadic, but autosomal dominant and recessive inheritance patterns have been suggested. Ascertainment of a two-generation family through a 7-year-old proposita with a learning disability allowed the relatively unbiased study of two affected relatives. Developmental delay was not pronounced in the patient's mother or sister; craniofacial characteristics at variance with the characteristic description included acrocephaly and maxillary prominence. Steepness of the anterior cranial base angle and protrusion of the middle and lower face, shown in all three patients by cephalometric radiographs, deserve further evaluation as diagnostic criteria.

Adult↗
PubMed1984

Intracellular localization of rat kidney hexokinase. Evidence for an association with low density mitochondria.

The subcellular location of hexokinase was investigated in rat kidney. Both soluble and particulate locations are indicated by differential centrifugation. The particulate form is predominant, representing about 80% of the total activity. None of the activity is latent. Density gradient centrifugation followed by marker enzyme analysis reveals the presence of two populations of mitochondria with distinct densities. Hexokinase is associated primarily with the mitochondrial population having the lower density. Association of hexokinase with brush border, plasma membrane, lysosomes, and endoplasmic reticulum is considered unlikely on the basis of density gradient centrifugation and enzyme analysis. About 95% of the hexokinase activity associated with the mitochondrial fraction can be released in soluble form by repeated incubations with glucose 6-phosphate. An incubation time of about 4 min at 30 degrees C is required to achieve a maximal solubilizing effect. Release is accomplished without disrupting the mitochondrial compartments. Hexokinase is released also by treatment of the mitochondrial fraction with increasing concentrations of digitonin. This technique disrupts and differentially releases the mitochondrial compartments. As observed with liver, but in contrast to that observed with tumor (Parry, D. M., and Pedersen, P. L. (1983) J. Biol. Chem. 258, 10904-10912), the release of hexokinase from the mitochondrial fraction of kidney does not correlate with the release of enzymes known to mark the mitochondrial membranes or compartments. These studies provide the first critical evidence about the subcellular location of hexokinase in kidney. They show that in this tissue hexokinase is associated primarily with low density mitochondria, a finding that adds credibility to the existence of this discrete population of mitochondria in vivo. Significantly, this association of hexokinase with kidney mitochondria appears unique in that its release on submitochondrial fractionation does not correlate with the release of known mitochondrial marker enzymes. These results are directly relevant to those cells in the kidney which utilize glucose as an energy source. It is suggested that the enhanced glycolytic capacity of these cells may be due, at least in part, to an association of hexokinase with low density mitochondria.

Animals↗
PubMed1983

Intracellular localization and properties of particulate hexokinase in the Novikoff ascites tumor. Evidence for an outer mitochondrial membrane location.

A detailed investigation concerned with localizing hexokinase in the Novikoff ascites tumor is presented. At least 50% of the total hexokinase activity was shown by differential and density gradient centrifugation techniques to be associated with tumor mitochondria. None of this activity was latent. Fractionation of isolated tumor mitochondria with digitonin revealed an outer membrane location for this enzyme. Treatment of tumor mitochondria with glucose 6-phosphate released about 80 to 85% of the hexokinase activity without disrupting the intermembrane compartment. This suggests that at least this proportion of the activity is bound to the outer surface of the outer membrane. Successive treatments did not remove the remaining hexokinase activity. At 30 degrees C, an incubation time of about 10 min with glucose 6-phosphate was required to achieve maximal release. No solubilization occurred at 0-4 degrees C. The isozymes derived from Novikoff mitochondria were identified by anion exchange chromatography as types I and III. Glucokinase activity was not detectable. Evidence is also presented which indicates that the hexokinase obtained from Novikoff mitochondria binds to the outer membrane of rat liver mitochondria. In contrast, the low endogenous hexokinase activity present in isolated liver mitochondria was found not to fractionate with outer membrane markers, but rather with contaminating microsomal membrane markers. Results described here provide the first direct evidence for the submitochondrial location of hexokinase in a tumor. They reveal an outer membrane location and an involvement of two hexokinase isozymes. Because these findings are characteristic of the hepatoma and not observed in control liver preparations, it is suggested that they may be very relevant to the general property of rapidly growing tumors to catabolize large amounts of glucose.

Animals↗
PubMed1983

Linkage analysis of neurofibromatosis (von Recklinghausen disease).

Linkage analysis of 28 genetic markers was undertaken in 108 subjects from 11 families with well-documented, classic, peripheral neurofibromatosis. Fifty-four persons were affected in one four-generation family, seven three-generation families, and three two-generation families. Lod scores were calculated using the standard LIPED programme for 49 combinations of theta male and theta female from 0.01 to 0.50. Lod scores excluded close linkage with 16 markers, including most tested on chromosome 1 and HLA on chromosome 6, and were inconclusive for 12 markers, including the secretor locus, closely linked to myotonic dystrophy. Analysis of five informative families resulted in a lod score of +2.2 for close linkage with GC on chromosome 4. However, the lod score for GC in the one additional informative family was negative, so that the final interpolated maximum was Z = 0.89 for theta male = 0.03, theta female = 0.28. Further studies are needed to evaluate this suggestion of linkage and possible genetic heterogeneity.

Carrier Proteins↗
PubMed1982

Immunohistochemical localisation of cyclooxygenase in the human uterus.

The distribution in the human uterus of the enzyme cyclooxygenase,, involved in prostaglandin synthesis, was studied using the peroxidase-antiperoxidase immunohistochemical technique. Specific staining was observe only during the luteal phase of the menstrual cycle It was found that cyclooxygenase was localised in the surface and glandular epithelium of the endometrium but could not be demonstrated in the endometrial stroma, myometrium or blood vessels The location of specific staining for cyclooxygenase and its variation during the menstrual cycle was the same regardless of the amount of menstrual blood loss. Tissue samples obtained from early pregnant and postmenopausal patients failed to exhibit any specific staining.

Female↗
PubMed1982

Carotid body tumors in humans: genetics and epidemiology.

Genetic factors in the etiology of carotid body tumors (CBT) were sought in a medical record review of 222 histologically diagnosed cases at 12 U.S. medical centers. Patients in the series, which had a marked female predominance (146 females:76 males), usually developed tumors between the fourth and seventh decades of life (mean, 44.7 yr). In 16 patients who also had other extra-adrenal paragangliomas, suggesting a multiple primary tumor syndrome, CBT were diagnosed significantly earlier (mean, 35.4 yr; P less than 0.01). The occurrence of thyroid cancer in 5 other patients appeared to be excessive. Familial CBT was recognized in 16 patients from 13 affected families, including 9 newly ascertained kindreds. Compared with non-familial lesions, familial CBT tended to develop bilaterally (38% vs. 8% unilaterally) and at slightly earlier ages (41.6 vs. 44.9 yr). CBT was reported to occur in an autosomal dominant pattern in some families and within sibships in others; relatives were not examined for confirmation. The familial findings are generally consistent with a two-step mutation model of the development of hereditary and nonhereditary CBT; apparent deviations from the model might be clarified with additional data on this rare neoplasm.

Adolescent↗