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Biomedical subjects

D L Johnson

Publications and source records attributed to D L Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy.

The atomic structure of glycinamide ribonucleotide transformylase, an essential enzyme in purine biosynthesis, has been determined at 3.0 A resolution. The last three C-terminal residues and a sequence stretch of 18 residues (residues 113 to 130) are not visible in the electron density map. The enzyme forms a dimer in the crystal structure. Each monomer is divided into two domains, which are connected by a central mainly parallel seven-stranded beta-sheet. The N-terminal domain contains a Rossmann type mononucleotide fold with a phosphate ion bound to the C-terminal end of the first beta-strand. A long narrow cleft stretches from the phosphate to a conserved aspartic acid, Asp144, which has been suggested as an active-site residue. The cleft is lined by a cluster of residues, which are conserved between bacterial, yeast, avian and human enzymes, and likely represents the binding pocket and active site of the enzyme. GAR Tfase binds a reduced folate cofactor and glycinamide ribonucleotide for the catalysis of one of the initial steps in purine biosynthesis. Folate analogs and multi-substrate inhibitors of the enzyme have antineoplastic effects and the structure determination of the unliganded enzyme and enzyme-inhibitor complexes will aid the development of anti-cancer drugs.

Acyltransferases↗
PubMed1992

Cystine-containing urinary calculi in dogs: 102 cases (1981-1989).

One hundred and seven cystine-containing urinary calculi from 1 female and 101 male dogs were analyzed. Cystine-containing calculi accounted for 2% (107 of 5,375) of all canine urinary calculi submitted to the urinary stone analysis laboratory from July 1981 through December 1989. Male dogs that formed cystine calculi were compared with 3 other canine populations to determine whether certain breeds were apparently at increased or decreased risk for cystine calculus formation. In one or more of 3 population comparisons, significantly increased risk of cystine calculus formation was found in Mastiffs, Australian Cattle Dogs, English Bulldogs, Chihuahuas, Bullmastiffs, Newfoundlands, Dachshunds, Basenjis, Australian Shepherd Dogs, Scottish Deerhounds, Staffordshire Terriers, Miniature Pinschers, pitbull terriers, Welsh Corgis, Silky Terriers, and Bichon Frises. Significantly low risk of cystine calculus formation was found in German Shepherd Dogs, Poodles, Schnauzers, and mixed-breed dogs.

Animals↗
PubMed1992

Selective uptake of the somatostatin analog RC-160 across the blood-brain tumor barrier of mice with KHT sarcomas.

The development of somatostatin analogs with anti-tumor effects has raised hopes for their use in various cancers and tumors of the central nervous system. However, for many therapeutic agents, access to normal brain is retarded by the blood-brain barrier (BBB) and to tumor tissues by a blood-brain tumor barrier (BBTB). We examined the ability of RC-160, a somatostatin analog with known anti-tumor activity, to cross the normal BBB and the BBTB in mice with brain sarcomas. In comparison with the normal BBB, the BBTB was about 10 times more permeable to the vascular marker albumin (radioactively labeled with 99mTc), but the BBTB still represents a substantial barrier. By contrast, the entry rate of RC-160, radioactively labeled with 125I, into brain sarcomas was 60 times higher than into normal brain tissue; more than 1% of the RC-160 injected i.v. was taken up by each gram of brain tumor. These results show that a brain tumor can selectively accumulate the potentially therapeutic agent RC-160.

Amino Acid Sequence↗
PubMed1992

Epidural lipomatosis in steroid-treated patients.

Epidural lipomatosis is a condition in which excess adipose tissue is deposited circumferentially about the spinal cord in the epidural space. It is most frequently seen in patients on chronic steroid treatment for a variety of medical problems and can present as nonspecific back pain, radiculopathy, or frank spinal cord compression. Diagnosis and treatment have generally relied on multi-level decompressive laminectomy after myelography and computed tomography. The immunocompromised state and the reported postoperative mortality (22%) of these patients, however, suggests that nonoperative therapy may be preferable whenever possible. Five cases of epidural lipomatosis are reported, and previous literature is reviewed for presentation, evaluation, and treatment of this condition.

Adult↗
PubMed1992

Retention for a removable partial denture.

This article addresses the complex nature of retention in a removable partial denture. Retentive features range from magnets and springs to clips, clasps, and interfacial surface tension. The retentive quality of an extracoronal clasp varies with the alloy, physical form, location on the abutment, and positional relationship to other elements. Surveying to identify both occlusogingival and mesiodistal undercuts when the path of random dislodging forces are not definitely controlled is needed for effective retention. Augmentation of ineffective retention in existing clasps should concentrate on methods of deepening the undercut or increasing the suprabulge. Tightening of clasps already in contact with a tooth frequently produces adverse changes.

Dental Abutments↗
PubMed1992

Differential expression of oocyte-type class III genes with fraction TFIIIC from immature or mature oocytes.

The Xenopus OAX genes can be expressed in oocytes but are virtually inactive in somatic tissues. The tRNA(Met1) (tMET) genes also appear to be developmentally regulated. We have examined the reason for the differential expression of these class III genes. Analysis of the transcriptional activities of extracts derived from immature and mature oocytes revealed that the developmental regulation of these genes can be reproduced in vitro. We have partially purified the required transcription factors B and C from these extracts to ascertain the components responsible for this differential activity. The immature oocyte C fraction activates the tMET and OAX genes when reconstituted with either the immature or mature oocyte-derived B fraction. In contrast, the mature oocyte C fraction fails to activate these genes regardless of which B fraction is used. Both C fractions activated the somatic 5S gene. Purification of the oocyte C fractions by phosphocellulose or B box DNA affinity chromatography failed to separate additional activities responsible for the differential expression of OAX or tMET. By using template exclusion assays, the inability of the mature oocyte C fraction to activate transcription was correlated with an inability to form stable transcription complexes with the tMET or OAX gene.

Animals↗
PubMed1992

The role of immediate operative intervention in severely head-injured children with a Glasgow Coma Scale score of 3.

In an attempt to improve and expedite the care of head-injured children, data have been published recommending burr hole exploration in lieu of computed tomography for children with signs of brain stem compression or with a Glasgow Coma Scale score of 3. Exploratory burr holes revealed a high incidence of subdural hematomas, and removal of the hematomas improved survival. We are reporting 19 consecutive children with Glasgow Coma Scale scores of 3. Coma score evaluation was confounded by intubation, sedation, pharmacological paralysis, and posttraumatic seizures. We found no radiographical or postmortem pathological evidence of intracranial hemorrhage, which would warrant operative intervention. A high incidence of multisystem injuries and high cervical spine injuries would have made early intervention both dangerous and inappropriate. Although there is a definite role for emergency trephination, routine exploratory burr holes for children with a Coma score of 3 is not justified.

Accidents, Traffic↗
PubMed1992

Brainstem gliomas.

Brainstem gliomas, a relatively common form of childhood brain tumor, are highly resistant to therapy. With computed tomography and magnetic resonance imaging, these lesions can be diagnosed with a high degree of reliability. The indications for surgery are unclear. Focal lesions may be amenable to partial resections. Stereotactic approaches can be used for diffuse lesions, but it has not been shown that the information obtained changes the approach to treatment or outcome. Higher dose radiotherapy has been recently used but has not improved survival for most patients. Patients with brainstem gliomas must be stratified into risk groups, and new means of treatment are needed.

Brain Neoplasms↗
PubMed1992

Compression plating for non-union after failed external fixation of open tibial fractures.

Fifty non-unions of the tibia that were present in forty-nine patients after external fixation and immobilization in a cast for a high-energy fracture were subsequently treated by compression plating. Initially, there were forty-six open fractures and four closed fractures with a compartment syndrome. Twenty-two non-unions (44 per cent) had early soft-tissue reconstruction (thirteen rotational and nine free flaps). The duration of external fixation averaged ten weeks, and the mean time from injury to plating was eight months. None of the non-unions were infected at the time of plating. The average preoperative deformity in the sagittal (anterior-posterior) plane was 8 degrees and in the frontal (medial-lateral) plane, 9 degrees; after plate fixation, the residual angulation averaged 3 and 2 degrees. Autogenous bone graft was used in thirty-nine of the fifty non-unions. The patients were followed for an average of twenty-four months. Forty-six (92 per cent) of the non-unions united, in an average of seven months, without further intervention. In four patients (8 per cent), the plate broke, necessitating re-plating in three and external fixation in one (the latter patient had an infected non-union). A deep infection developed in three patients (6 per cent). Ultimately, forty-eight non-unions (96 per cent) healed without evidence of infection. Plate osteosynthesis is an effective method of treatment for patients who have had an open fracture of the tibia that has failed to unite after external fixation and immobilization in a cast.

Adolescent↗
PubMed1992

Atlantoaxial instability in Down's syndrome: a case report and review.

Down's syndrome is the most common autosomal chromosomal abnormality in humans and is associated with a number of well known clinical findings. Atlantoaxial instability is a less recognized, yet potentially significant, manifestation of Down's that has gained importance because of the widespread participation of Down's syndrome individuals in athletic events. Early recognition and appropriate management of patients with atlantoaxial instability can significantly reduce the morbidity and mortality associated with this condition and guide patients and their parents toward continued safe participation in athletics.

Adolescent↗
PubMed1992

Leigh's disease presenting as an intramedullary mass lesion.

An unusual presentation of Leigh's disease consisting of rapid progression of leg weakness in a young child is discussed. Magnetic resonance imaging revealed an intramedullary mass lesion of the conus medullaris. Surgical exploration revealed only necrosis and inflammation. Subsequent studies revealed pathology in the cerebrum as well as the spinal cord. Metabolic abnormalities confirmed the diagnosis of Leigh's disease. The differential diagnosis of intramedullary mass lesions demonstrated by magnetic resonance imaging should include metabolic, inflammatory, and ischemic processes as well as neoplastic disease.

Adult↗
PubMed1991

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, induces specific transcription by RNA polymerase III in Drosophila Schneider cells.

We have examined the ability of the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to regulate RNA polymerase III gene expression in Drosophila. Using nuclear run-on assays, we detected a 3-5-fold increase in tRNA synthesis following treatment of Drosophila Schneider S2 cells with TPA, whereas transcription from the actin 5C, fos-, and jun-related antigen promoters was unaffected. This response is rapid and transient, peaking at about a 45-min exposure of the cells to TPA, and dissipating after 60 min. We have reproduced this stimulation in vitro. Extracts prepared from cells treated with TPA show an approximate 10-fold increase in specific transcription using a 5 S RNA and various tRNA gene templates. The nonspecific transcription by RNA polymerase III in these extracts, however, is essentially unchanged. Mixing the extracts derived from uninduced and induced cells suggests that the TPA stimulation observed may be due to the increase of a positive-acting factor. These results are the first to demonstrate that a phorbol ester can induce RNA polymerase III gene expression. The ability to reproduce this activation in vitro will now allow us to assess the role of the transcription components in this regulatory event, and the biochemical consequence of this signaling pathway.

Actins↗
PubMed1991

Analysis of the molecular mechanisms for the species-specific transcription of Drosophila and human tRNA gene transcription components.

The transcription of eucaryotic tRNA genes requires two factors IIIB and IIIC, in addition to RNA polymerase III, to reconstitute this process in vitro. We have examined the functional exchangeability of these components from Drosophila and human systems. The reconstitution of heterologous IIIB and IIIC components demonstrated that neither factor will functionally substitute for the homologous components to activate tRNA gene transcription. The addition of the heterologous Drosophila factors to HeLa transcription assays causes an inhibition of RNA synthesis that is dependent upon the order of addition of these proteins to the DNA template. Thus, it appears that tRNA gene transcription in these systems is species-specific. We have further analyzed the reason for the apparent incompatibilities of these components by the use of stable complex formation assays. We find that human HeLa IIIB and Drosophila IIIC are unable to form stably associated complexes with a tRNA gene template, whereas the Drosophila IIIB and HeLa IIIC do form stable but nonproductive complexes. These results demonstrate that specific IIIC-IIIB interactions are critical in the formation of productive transcription complexes and are responsible for the observed species specificity of Drosophila and human tRNA gene transcription.

Animals↗
PubMed1991

Xanthine-containing urinary calculi in dogs given allopurinol.

Clinical features and laboratory findings were evaluated in 10 dogs that formed xanthine-containing urinary calculi during the period that they were given allopurinol (9 to 38 mg/kg of body weight/d). Duration of allopurinol treatment was 5 weeks to 6 years. Of the 10 dogs, 9 (all Dalmatians) had formed uric acid-containing calculi at least once before allopurinol treatment was initiated. It was not possible to recognize xanthine as a crystalline component of the calculi by use of a chemical colorimetric method or by polarized light microscopy. We concluded that the best diagnostic method for recognition of xanthine-containing calculi was high-pressure liquid chromatography because it is quantitative, sensitive, and accurate, and can be conducted on a small amount (1 to 2 mg) of crystalline material.

Allopurinol↗
PubMed1991

Field studies: industrial exposures.

The databases and models for the prediction of noise-induced permanent threshold shift (NIPTS) from industrial noise exposures are reviewed. Models available in 1973, compared with later models and data, are shown still to be reasonable. The effect of hearing conservation procedures on the acquisition of new data is discussed. Because of the impact of hearing conservation, new research focus is recommended in three areas: sex differences, newly hired individuals exposed for the first time in occupational noise, and the contribution of nonoccupational noise through the use of questionnaires and dosimetry.

Auditory Fatigue↗
PubMed1991

Genetic and environmental effects on carcass characteristics of Southdown x Romney lambs: I. Growth rate, sex, and rearing effects.

Carcass data from more than 4,400 Southdown x Romney ewe and wether lambs collected over a 16-yr period were analyzed for the effects of sex, rearing status, and growth rate. Ewe lambs grew more slowly than wethers and had .78 kg less carcass weight at the same age. The carcass weight advantage for wethers was nearly all caused by heavier fat-free weight. Based on fat depths, the fat on ewe lambs was distributed in more anterior and ventral parts of the carcass relative to wether lambs. Lambs reared as twins had 1.73 kg less carcass weight and correspondingly reduced carcass measurements compared with lambs reared as singles. Sex and rearing status interacted for some traits. However, in no case was a significant sex difference reversed in single- and twin-related lambs. Growth rate effects were determined by regressing average change in carcass measurements on average carcass weight gain over a 5-wk period. When carcass weight remained constant over a 5-wk period, fat weight increased by .12 kg, fat-free weight and muscle measurements decreased, and bone lengths increased. For each kilogram of increase in 5-wk carcass weight gain, the marginal increase in fat weight was .41 kg and that of fat-free weight was .59 kg. At the average 5-wk carcass weight gain of 1.4 kg, fat and fat-free gains were As carcass weight gain increased above 1.4 kg, fat-free gain exceeded fat gain.

Adipose Tissue↗
PubMed1991

Genetic and environmental effects on carcass characteristics of Southdown x Romney lambs: II. Genetic and phenotypic variation.

Approximately 4,400 crossbred lambs from Southdown sires and Romney ewes were slaughtered at approximately 18, 23, and 28 wk of age over a 16-yr period. Live weights, carcass measurements, and chemical percentages were analyzed to estimate genetic and phenotypic parameters. Heritabilities of postweaning weights and gains were about .20. Heritabilities of fat and water percentages were about .35 adjusted for age. Heritability of kidney fat percentage was .53. Heritabilities of fat depth and muscle measurements ranged from .21 to .37. Crutch depth (h2 = .73) and cannon bone length (h2 = .74) were the most highly heritable carcass measurements. The genetic correlation between carcass fat and fat-free weight was .47 when lambs were slaughtered at a constant age. Fat-free weight was nearly uncorrelated with percentages of fat, water, and protein when lambs were slaughtered at the same age. Carcass measurements increased accuracy of selection for fat-free weight at a constant age very little compared with using only carcass weight. However, this does not mean that additional measurements are useless. The addition of carcass measurements to the selection criteria would result in correlated responses in chemical composition that more closely resembled direct selection for fat-free weight. Carcass weight would be of little value when used by itself to reduce fat weight adjusted for carcass weight. Direct measurement of carcass composition resulted in 1.6 to 2.6 times more predicted response for reduced fat weight than any combination of carcass weight and one fat depth measurement.

Adipose Tissue↗