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Biomedical subjects

M W Clark

Publications and source records attributed to M W Clark.

At least 55 records · Page 3Linked to original sources

Saccharomyces cerevisiae SSB1 protein and its relationship to nucleolar RNA-binding proteins.

To better define the function of Saccharomyces cerevisiae SSB1, an abundant single-stranded nucleic acid-binding protein, we determined the nucleotide sequence of the SSB1 gene and compared it with those of other proteins of known function. The amino acid sequence contains 293 amino acid residues and has an Mr of 32,853. There are several stretches of sequence characteristic of other eucaryotic single-stranded nucleic acid-binding proteins. At the amino terminus, residues 39 to 54 are highly homologous to a peptide in calf thymus UP1 and UP2 and a human heterogeneous nuclear ribonucleoprotein. Residues 125 to 162 constitute a fivefold tandem repeat of the sequence RGGFRG, the composition of which suggests a nucleic acid-binding site. Near the C terminus, residues 233 to 245 are homologous to several RNA-binding proteins. Of 18 C-terminal residues, 10 are acidic, a characteristic of the procaryotic single-stranded DNA-binding proteins and eucaryotic DNA- and RNA-binding proteins. In addition, examination of the subcellular distribution of SSB1 by immunofluorescence microscopy indicated that SSB1 is a nuclear protein, predominantly located in the nucleolus. Sequence homologies and the nucleolar localization make it likely that SSB1 functions in RNA metabolism in vivo, although an additional role in DNA metabolism cannot be excluded.

Amino Acid Sequence↗

DNA hybridization electron microscopy: ribosomal RNA nucleotides 1392-1407 are exposed in the cleft of the small subunit.

The ribosomal sequence corresponding to Escherichia coli 16S rRNA nucleotides 1392-1407 (the "1400 region") is phylogenetically conserved and is in a functionally important region of the subunit. Using the technique of DNA hybridization electron microscopy, we have mapped this sequence on the surface of the small ribosomal subunit. In this procedure a synthetic oligodeoxynucleotide probe, complementary to a specific rRNA sequence and carrying an attached marker molecule, is hybridized to ribosomal subunits in order to determine the dimensional site of attachment. In the E. coli ribosome, the 1400 region is located at the level of the neck, near the cleft and most likely on the head of the small subunit. The related sequence in yeast 18S rRNA, nucleotides 1618-1633, is located in the topological equivalent of the E. coli site. The location of this region, which has been crosslinked to the anticodon of a peptidyl-site-bound tRNA, indicates that this part of the cleft of the small subunit has a similar three-dimensional organization in phylogenetically diverse organisms and suggests that it is the site of the codon-anticodon interaction.

Avidin↗

Stress in families of children with myelomeningocele.

Three aspects of stress were investigated in 56 families with a child with myelomeningocele and in 53 matched comparison families. Children with myelomeningocele were found to have lower self-concepts than the comparison children, but this did not apply to the siblings in the two groups. Severity of handicap was related to marital satisfaction, in that parents of more severely handicapped children had higher levels of marital satisfaction than parents of less severely involved children. The findings imply that ways should be found of improving the self-concepts of children with myelomeningocele, and of examining interrelationships between the child's self-concept and patterns of family interaction.

Adolescent↗

Eubacteria, halobacteria, and the origin of photosynthesis: the photocytes.

The halobacteria and the photosynthetic members of the eubacteria have previously been classified in two separate urkingdoms--the archaebacteria and the eubacteria, respectively. They were thought to be no more closely related to each other than they each were to the eukaryotes. In accord with this earlier classification, photosynthesis was thought to have originated twice by independent events--once within the eubacteria and once within the archaebacteria. In this paper, however, using three-dimensional ribosome structure as a probe of evolutionary divergences, we show that the eubacteria and the halobacteria are more closely related to each other than they are to any other known organisms. The simplest interpretation of our data is that all extant photosynthetic cells are descended from a single common ancestor that possessed a primeval photosynthetic mechanism. Numerous data on the occurrence of related biochemical processes in halobacteria and eubacteria support this theory. Essential components of the photosynthetic apparatus, such as carotenoids, are present in both halobacteria and in eubacteria, including the nonphotosynthetic eubacteria, suggesting that photosynthesis could be a primitive property of both groups. Our data indicate that together the eubacteria and the halobacteria form a monophyletic group for which we propose the name "photocytes." If other techniques of phylogenetic analysis confirm this evolutionary tree, we propose that the photocytes be given urkingdom status.

Biological Evolution↗

A new ribosome structure.

Ribosomes derived from the sulfur-dependent archaebacteria are structurally distinct from those types found in ribosomes from eubacteria, eukaryotes, and other archaebacteria. All four ribosome types share a common structural core, but each type also has additional independent structural features. In the smaller subunit derived from sulfur-dependent archaebacteria ("eocytes"), lobes, similar to those found at the base of the eukaryotic small subunits, and an archaebacterial bill, similar to those found on the smaller subunit of archaebacteria and eukaryotes, are present. On the larger subunit from sulfur-dependent archaebacteria, an eocytic lobe, eocytic gap, and eocytic bulge are present. These features, with the exception of the eocytic gap, are found in a slightly modified form on eukaryotic large subunits. These novel ribosomal properties are in general consistent with other molecular biological properties peculiar to these organisms.

Archaea↗

Radionuclide thyroid angiography and surgical correlation. A five-year study.

Only 15% to 25% of cold nodules on conventional static thyroid scans are malignant. Radionuclide angiography of the thyroid and conventional static scans using sodium pertechnetate Tc 99m were performed on 114 patients who underwent thyroid surgery within a five-year period. The combined use of radionuclide angiography and conventional static scans increased the specificity for the diagnosis of thyroid carcinoma from 42% to 79% over static scans alone. The incidence of carcinoma in solitary cold nodules in our population was increased from 26% on static scans to 60% if the lesion was hypervascular on radionuclide angiography. Eighty-seven percent of hypervascular solitary cold nodules were neoplasms (carcinomas and adenomas). Hypervascularity as demonstrated by radionuclide angiography is predictive of thyroid neoplasia. The finding of a hypervascular, solitary cold nodule makes a recommendation for surgery predictive and reasonable.

Adenocarcinoma↗

Eocytes: a new ribosome structure indicates a kingdom with a close relationship to eukaryotes.

Ribosomal large and small subunits are organized in four general structural patterns. The four types are found in ribosomes from eubacteria, archaebacteria, eukaryotes, and a group of sulfur-dependent bacteria ( eocytes ), respectively. All four ribosomal types share a common structural core, but each type also has additional independent structural features. The independent features include the eukaryotic lobes and the archaebacterial bill on the smaller subunit. On the larger subunit, they include the eocytic lobe, eocytic gap, and eocytic bulge and a modified central protuberance. These data are most parsimoniously fit by a single unrooted evolutionary tree. In this tree eocytes are closely related to eukaryotes, while archaebacteria and eubacteria are closest neighbors. The tree is consistent with currently known molecular biological properties and indicates that eocytes have a phylogenetic importance equal to that of the three known kingdoms. When other properties and molecular mechanisms of these organisms are better defined, we suggest that an appropriate kingdom name for this group would be the Eocyta .

Animals↗

Unusual rRNA-linked complex of 50S ribosomal subunits isolated from an Escherichia coli RNase III mutant.

We have isolated and characterized complexes of ribosomal subunits from Escherichia coli mutant AB301-105 connected by strands of unprocessed RNA. By electron microscopy of these complexes, the location of the 5' end of 5S RNA was established and the location of the 3' end of 23S RNA was confirmed. We also note that in these complexes insertion of 5S rRNA can proceed without the 23S-5S spacer having been processed.

Endoribonucleases↗

Ribosomal crystalline arrays of large subunits from Escherichia coli.

Crystalline sheets of the 50S ribosomal subunits of Escherichia coli have been formed in vitro. Electron micrographs of these arrays diffract to 35-angstrom resolution. The lattice parameters of the crystals are a = 330 +/- 20 angstroms, b = 330 +/- 30 angstroms, and alpha = 123 degrees +/- 5 degrees, and the space group is most likely p21. These arrays of ribosomal subunits are sufficiently ordered to resolve such known features of the large ribosomal subunit as the L7/L12 stalk and the central protuberance.

Crystallography↗

Mapping evolution with ribosome structure: intralineage constancy and interlineage variation.

Ribosomal small subunits are organized in three general structural patterns that correspond to the eubacterial, archaebacterial, and eukaryotic lineages. Within each of these lineages, ribosomal structure is highly conserved. Small subunits from all three lineages share a common overall structure except for the following differences: (i) small subunits from archaebacteria and from the cytoplasmic component of eukaryotes both contain a feature on the head of the subunit, the archaebacterial bill, that is absent in eubacteria, and (ii) eukaryotic small subunits contain additional regions of density at the base of the subunit, the eukaryotic lobes, that are absent in archaebacteria and in eubacteria. We interpret the intralineage conservation of ribosomal three-dimensional structure as forming a phylogenetic basis for regarding archaebacteria, eubacteria, and eukaryotes as primitive lines. Although our data are separate and independent from those of Woese and Fox, they lend further support to their proposal [Woese, C. R. & Fox, G. E. (1977) Proc. Natl. Acad. Sci. USA 74, 5088-5090]. These data also provide a simple, rapid, and accurate method for classifying organisms and for identifying new lineages. Finally, interlineage variation of ribosomal structure is used to establish a rigorous framework for considering the evolution of these three lines.

Animals↗

Bone stress: a radionuclide imaging perspective.

Thirty-five college athletes with lower leg pain underwent radiography and radionuclide studies to rule out a stress fracture. Their asymptomatic extremities and 13 pain-free athletes served as controls. Four main patterns were observed: (a) sharply marginated scintigraphic abnormalities and positive radiographs; (b) sharply marginated scintigraphic abnormalities and negative radiographs; (c) ill-defined scintigraphic abnormalities and negative radiographs; and (d) negative radionuclide images and negative radiographs. Since the patients with the first two patterns were otherwise identical medically, the authors feel that this scintigraphic appearance is characteristic of bone stress in the appropriate clinical setting, regardless of the radiographic findings. A schema is proposed to explain the occurrence of positive radionuclide images and negative radiographs in the same patient, using a broad conceptual approach to the problem of bone stress.

Adolescent↗

Musculoskeletal problems in blind children.

At a regional school for the blind, 157 children were examined for musculoskeletal abnormalities. The incidence of scoliosis was 9.5 per cent; of foot deformity, 53.5 percent; and of ligament laxity, 25 per cent. Thirty-six children (23 per cent) had evidence of spastic, flaccid, or athetoid cerebral palsy or other disorders of the central nervous system. The orthopaedist should evaluate blind children carefully and repeatedly for evidence of occult cerebral palsy and progressive deformity of the spine or foot.

Abnormalities, Multiple↗

Congenital vertical talus: treatment by open reduction and navicular excision.

Twelve patients with sixteen feet showing true congenital vertical talus were treated at Children's Hospital of Pittsburgh by excision of the navicular as an adjunct to open reduction. When these children were evaluated two to fifteen years after naviculectomy, all were asymptomatic and fully active. Except for one Achilles-tendon lengthening (three months after naviculectomy), none had required further surgical procedures. Fifteen feet were examined in detail. Assessed on an anatomical basis, three of the feet were excellent; seven, good; four, fair; and one, poor. The best results were obtained in the patients who were eighteen months old or younger at the time of operation.

Achilles Tendon↗

Autosomal dominant inheritance of tibial meromelia. Report of a kindred.

Three generations of a family demonstrated an autosomal dominant transmission of congenital absence of the tibia. Nine family members were affected, six in the first generation. Male-to-male, male-to-female, and female-to-female transmission occurred. This is the fourteenth case reported to document familial occurrence of tibial meromelia, and the first to document this mode of inheritance.

Ectromelia↗

Avascular necrosis after treatment of DDH: the protective influence of the ossific nucleus.

We retrospectively reviewed the results of open or closed reduction for developmental dysplasia of the hip (DDH) in 49 children younger than 12 months old, who had 57 hip dislocations. Group A (18 hips) developed partial or complete avascular necrosis (AVN), and group B (39 hips) did not develop AVN. Thirty-eight hips were treated by closed reduction, and 17 had open reduction. One patient with bilateral hip dislocation initially had closed reductions followed by bilateral open reduction 3 months later. With the numbers available for study, there was no significant difference in the occurrence of AVN with respect to variables such as preliminary traction, closed versus open reduction, Pavlik harness use, and age at the time of operative intervention. However, the presence of the ossific nucleus before reduction, detected either by radiographs (p < 0.001) or ultrasonography (p = 0.033) was statistically significant in predicting AVN. Only one (4%) of 25 hips with an ossific nucleus developed AVN, whereas 17 (53%) of 32 hips without an ossific nucleus before reduction developed AVN. Our results suggest that the presence of the ossific nucleus before closed or open reduction for DDH may decrease the risk of AVN.

Female↗

Competitive sports for the disabled.

A full life experience for people with and without physical disabilities usually includes some form of recreation or sport. Competition adds to enjoyment of sport for many people and can improve morale. This paper reviews some of the competitive opportunities available for people with a physical disability. These include competition within existing "able-bodied" organizations with or without adaptive devices and competition in separate organizations for those with disabilities. The latter include the National Wheelchair Basketball Association and the National Wheelchair Athletic Association.

Competitive Behavior↗