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Biomedical subjects

M M Collins

Publications and source records attributed to M M Collins.

12 recordsLinked to original sources

The human complement C4B/steroid 21-hydroxylase (CYP21) and complement C4A/21-hydroxylase pseudogene (CYP21P) intergenic sequences: comparison and identification of possible regulatory elements.

We determined the 1.8 kb intergenic sequences between the human complement C4B gene and the active steroid 21-hydroxylase gene in two subjects, and between the C4A gene and the steroid 21-hydroxylase pseudogene in one subject. Comparison of these sequences with each other and with published homologues revealed no differences which were unique to either intergenic region. Sequence analysis revealed two copies of an AGGTCA motif in all sequences. This motif is common to steroidogenic enzyme gene promoters and to the response elements for nuclear hormone receptors. Similarities with human enhancers were also found.

Bacteriophage lambda

Ultrasound scattering from spherical tumours.

The interaction of biomedical ultrasound with spherical tumours in the human body is investigated using analytic methods which predict the angular distribution of the ultrasound scattered by the tumour. Both the tumour and the surrounding tissue are considered to be lossy elastic media, which support shear-wave modes in addition to the familiar compressional-wave acoustic modes. Exact expressions for the angular distribution of the ultrasonic energy scattered by the tumour are used to illustrate graphically the behaviour of plane ultrasound wave interactions.

Humans

Exon 7 Ncol restriction site within CYP21B (steroid 21-hydroxylase) is a normal polymorphism.

A point mutation within exon 7 producing an amino acid coding change and a recognition site for the endonuclease Ncol has been reported in the HLA-Bw47-linked CYP21A pseudogene and some mutant CYP21B (steroid 21-hydroxylase) genes of patients with congenital adrenal hyperplasia (CAH). Whether this mutation is deleterious was not demonstrated. We analyzed DNA from various subjects for the presence of the exon 7 Ncol site: group 1, 10 normal subjects; group 2, 11 patients with salt-losing CAH; and group 3, 18 members of an Amish pedigree in which 10 expressed HLA-Bw47 not linked to CAH. Southern blots of Ncol-digested genomic DNA which were hybridized with CYP21 cDNA showed that four subjects of group 1 had a heterozygous Ncol pattern. In group 2, seven patients had the Ncol site; two of them were homozygous for the site and had deletions of both CYP21B genes. The other five were heterozygous for the Ncol site, which was linked to a CYP21B deletion and a HLA-Bw47 haplotype. In group 3, no one exhibited the exon 7 Ncol site. To map the Ncol sites to CYP21A or CYP21B in the normal subjects, DNA from the four Ncol heterozygous subjects was double digested with Ncol and Mbol and hybridized with CYP21 cDNA. Ncol-Mbol fragments unique to CYP21A were identified in all four, but the smaller CYP21B-specific fragments were not detected. Their genomic DNA in the region of exon 7 (bases +1167 to +2058) was then amplified, cloned, and sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Hyperplasia, Congenital

Association of DNA content and proliferative activity with clinical outcome in patients with diffuse mixed cell and large cell non-Hodgkin's lymphoma.

Formalin-fixed and paraffin-embedded lymph node biopsy specimens from 52 untreated patients with newly diagnosed diffuse large cell (n = 48) or mixed cell (n = 4) non-Hodgkin's lymphoma (NHL) were analyzed for DNA content and proliferative activity (PA) by flow cytometry. The results obtained by flow cytometry were compared with the results of cytogenetic studies performed on 28 of the specimens. The median age of the patients was 65 years (range, 15-84 years) and the male to female ratio was 3 to 2. All patients were uniformly staged and uniformly treated with cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The flow cytometric results were compared statistically by univariate analysis with the rate and duration of complete remission and survival. Tumors with low PA (greater than or equal to 80% of cells in G0/G1 phase) were found in 65% of the patients; 74% of those with low PA versus only 44% of those with high PA achieved an initial complete remission (P less than 0.02). DNA aneuploidy was detected in tumors of 56% of the patients and was associated with a significantly longer duration of complete remission (P less than 0.01). Both low PA and aneuploidy independently predicted longer survival. The predicted 2-year actuarial survival for patients with tumors with low PA was 68% versus 10% for those with high PA (P less than 0.01). Similarly, the 2-year survival of patients with aneuploid tumors was 60% versus 36% for those with diploid tumors (P less than 0.01). The combination of PA and DNA content categorized the patients into four groups with decreasing 2-year survivals: low PA/aneuploid (n = 20), 77%; low PA/diploid (n = 14), 57%; high PA/aneuploid (n = 9), 32%; high PA/diploid (n = 9), 0%. The flow cytometric results correlated well with those of the cytogenetic studies. We conclude that low PA and DNA aneuploidy, both separately and in combination, predict a favorable clinical outcome for patients with diffuse mixed cell and large cell NHL.

Adolescent

Low rate of NADPH/ADP-iron dependent lipid peroxidation in hepatic microsomes of DBA/2 mice.

Hepatic microsomal lipid peroxidation has been studied in 4 inbred strains of mice: C57BL/6, BALB/c, AKR and DBA/2. The rates of lipid peroxidation stimulated in vitro by carbon tetrachloride, ascorbate-iron and cumene hydroperoxide were similar in all 4 strains. Lipid peroxidation induced by NADPH/ADP-iron, however, proceeded at a substantially lower rate in the hepatic microsomes of DBA/2 mice. It is suggested that this low rate of enzymic iron-induced lipid peroxidation is a factor that may be involved in the resistance of this strain of mice to experimental hepatic porphyria induced by polyhalogenated aromatic hydrocarbons.

Adenosine Diphosphate

A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity.

The oestrogenic and antioestrogenic properties of tamoxifen and its monohydroxylated (monohydroxytamoxifen) and dihydroxylated (dihydroxytamoxifen) metabolites have been investigated in the immature rat. Whether administered orally or subcutaneously, monohydroxytamoxifen was more active than tamoxifen as an antioestrogen. Dihydroxytamoxifen was less active than tamoxifen as an antioestrogen, but this derivative alone was unable to induce a uterotrophic response. Both metabolites of tamoxifen were potent inhibitors of the binding of [3H]oestradiol to oestrogen receptors in vitro. It is possible that the metabolites play a supportive role in the antioestrogenic activity of tamoxifen. The potent activity of monohydroxytamoxifen in vivo and in vitro suggests that this compound could be an important new tool for the subcellular investigation of oestrogenic and antioestrogenic events.

Animals

The surface properties of the lung in rats with alveolar lipo-proteinosis.

The physical behaviour of the intact lungs and of lung extracts from rats affected by alveolar lipo-proteinsosis as a consequence of silica inhalation, was studied by means of pressure volume relations and surface tension area loops. Air inflation of diseased lungs occurred at a lower pressure and collapse was less on deflation than in control specimens, although there appeared to be little change in elastic forces. When saline was used dusted rat lungs showed at higher lung volumes a peculiar hysteresis effect which is attributable to consolidation of alveoli by the lipid material. Extracts from affected lungs showed differences from controls in respect of maximum and minimum surface tensions and stability index but all the values fell within the accepted limits of normal. However, with extracts from pathological lungs the area of the hysteresis loop increased, the shape of the surface tension area curve was abnormal and the percentage compression required to reduce the surface tension to 120 muN/cm fell. Extracts from diseased lungs depressed the maximum surface tension of normal lung extracts and increased the hysteresis area but had little effect on the minimum tension, the stability index or the % compression to achieve 120 muN/cm. The response was thus mainly that of an extract from a dusted rat. The surface activity of phospholipids may be affected by neutral lipid, cholesterol and the products of cell breakdown, all of which occur in the alveolar material. The occurrence within the same lung of compunds which reduce surface tension and others which modify the same lung of compounds which reduce surface tension and others which modify this property suggests that their relative concentrations may determine the overall effectiveness of the lung lining.

Animals