Search PubMed⌕ Search

Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 253 records · Page 14Linked to original sources

Characteristics of 3-O-methylfluorescein phosphate hydrolysis by the (Na+ + K+)-ATPase.

With 3-O-methylfluorescein phosphate (3-OMFP) as substrate for the phosphatase reaction catalyzed by the (Na+ + K+)-ATPase, a number of properties of that reaction differ from those with the common substrate p-nitrophenyl phosphate (NPP): the Km is 2 orders of magnitude less and the Vmax is two times greater, and dimethyl sulfoxide (Me2SO) inhibits rather than stimulates. In addition, reducing the incubation pH decreases both the Km and Vmax for K+-activated 3-OMFP hydrolysis as well as the K0.5 for K+ activation. However, reducing the incubation pH increases inhibition by Pi and the Vmax for 3-OMFP hydrolysis in the absence of K+. When choline chloride is varied reciprocally with NaCl to maintain the ionic strength constant, NaCl inhibits K+-activated 3-OMFP hydrolysis modestly with 10 mM KCl, but stimulates (in the range 5-30 mM NaCl) with suboptimal (0.35 mM) KCl. In the absence of K+, however, NaCl stimulates increasingly over the range 5-100 mM when the ionic strength is held constant. These observations are interpreted in terms of (a) differential effects of the ligands on enzyme conformations; (b) alternative reaction pathways in the absence of Na+, with a faster, phosphorylating pathway more readily available to 3-OMFP than to NPP; and (c) a (Na+ + K+)-phosphatase pathway, most apparent at suboptimal K+ concentrations, that is also more readily available to 3-OMFP.

Animals↗

Pituitary adenomas in Cushing's disease: do they arise from the intermediate lobe?

Pituitary adenomas from 15 patients with Cushing's disease were studied histopathologically. The tumors were examined for the presence of neural axons by the Bodian silver impregnation technique and a specific immunohistologic technique based on a monoclonal antibody to axonal neurofilaments. Axons were not seen in any of the surgical specimens. This finding suggests that most, if not all, adrenocorticotropin-secreting pituitary adenomas are of anterior lobe origin.

Adenoma↗

Radiation dose response of normal brain.

Dose response relationships were determined after hemibrain x-irradiation of normal beagle dogs. Radiation doses of 11.5, 13.5, 14.3, and 17 Gy were delivered in a single dose and results were compared to previous studies using doses of 15 and 30 Gy. Brain injury was quantified using computed tomography (CT), with serial studies obtained monthly up to 1 year following irradiation. Quantitative endpoints included low density volume and contrast enhancement. Doses above 14.3 Gy resulted in high lethality 5-8 months following irradiation, and an LD50 of 14.9 Gy was calculated. At these lethal doses, low density volume representing edema, demyelination, and necrosis had a similar response with an ED50 of 14.6 Gy. Radiation-induced decreases in white matter density appeared 5-6 months after sublethal doses (less than or equal to 14.3 Gy) and the volume of tissue characterized by this low density increased with time and dose. This sublethal low density change had an ED50 of 12.8 Gy, and may reflect a loss or generalized atrophy of glial cells and/or myelin. These results show that: (a) the dose response curves obtained after hemibrain x-irradiation are extremely steep; and (b) at least two processes may be involved in the development of late radiation damage, one that is rapid upon onset (a "delayed acute" reaction) and the other which is a slower and more degenerative process.

Animals↗

Radiation therapy for the treatment of non-eight nerve intracranial neurilemmoma.

The records of 19 patients treated for intracranial neurilemmomas, other than of the eighth nerve, at the University of California, San Francisco from 1945 through 1983 were reviewed. One patient who died within 30 days following surgery was excluded from the analysis. The 5th and the 9/10/11th nerve complex were the most common sites of tumor origin. Patients were classified by the extent of surgical resection: total (90-99% resection, NTR), subtotal (less than 90% resection, STR) and biopsy. Five patients had total excision of their tumor without post-operative irradiation and none had recurred. One of the 2 patients who had STR and did not receive post-operative irradiation recurred, while 2 of the 3 patients who received post-operative irradiation following STR recurred. One of the 2 patients who had NTR and did not receive post-operative irradiation recurred, while 1 of the 3 patients who received post-operative irradiation following NTR recurred. Two patients were treated with post-operative irradiation following biopsy and one recurred. One patient was treated with planned preoperative irradiation to reduce tumor vascularity, followed by total resection. Because of the small number of patients, no firm conclusion regarding the efficacy of irradiation for non-eighth nerve intracranial neurilemmoma can be made.

Adolescent↗

Effect of oral activated charcoal on tobramycin clearance.

To evaluate the effect of activated charcoal on aminoglycoside pharmacokinetics, six healthy volunteers received tobramycin intravenously with and without multiple oral doses of activated charcoal. Activated charcoal did not have a statistically significant effect on any pharmacokinetic parameter. We conclude that activated charcoal does not enhance tobramycin clearance in subjects with normal renal function when concentrations in serum are within the therapeutic range.

Administration, Oral↗

Chordomas: MR imaging.

Twenty histologically verified intracranial and upper cervical chordomas were retrospectively studied with both magnetic resonance (MR) imaging and computed tomography (CT), and the advantages of each modality were compared with regard to three criteria: detection of tumor, delineation of extent of tumor, and characterization of tumor. MR imaging and CT were equivalent in permitting the detection of chordomas. MR imaging was considerably better in delineating the full extent of the tumor, which would influence establishment of treatment. MR imaging also provided a degree of histologic specificity that would be useful in prognosis.

Adult↗

Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine.

Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.

Adolescent↗

Prognostic implications of the proliferative potential of low-grade astrocytomas.

The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.

Astrocytoma↗

Expression of a single transfected cDNA converts fibroblasts to myoblasts.

5-azacytidine treatment of mouse C3H10T1/2 embryonic fibroblasts converts them to myoblasts at a frequency suggesting alteration of one or only a few closely linked regulatory loci. Assuming such loci to be differentially expressed as poly(A)+ RNA in proliferating myoblasts, we prepared proliferating myoblast-specific, subtracted cDNA probes to screen a myocyte cDNA library. Based on a number of criteria, three cDNAs were selected and characterized. We show that expression of one of these cDNAs transfected into C3H10T1/2 fibroblasts, where it is not normally expressed, is sufficient to convert them to stable myoblasts. Myogenesis also occurs, but to a lesser extent, when this cDNA is expressed in a number of other cell lines. The major open reading frame encoded by this cDNA contains a short protein segment similar to a sequence present in the myc protein family.

Animals↗

Buffer, pH, and ionic strength effects on the (Na+ + K+)-ATPase.

A dog kidney (Na+ + K+)-ATPase preparation also catalyzes K+-independent and K+-activated phosphatase reactions with p-nitrophenyl phosphate as substrate. K+-independent activity increases with declining pH over the range 7.5 to 5.8, whereas the other two activities decrease. The increased K+-independent activity is similar with imidazole, histidine, and several Good buffers, and is thus attributable to free H+, probably by affecting enzyme conformations rather than by changing affinity for Mg2+ or substrate or by H+ occupying specific K+-sites. The decrease in K+-phosphatase and (Na+ + K+)-ATPase activities with pH also occurs similarly with those buffers, and is not due to changes in apparent affinity for substrate or for cation activators. However, the Good buffers Pipes and ADA inhibit the K+-independent phosphatase reaction strongly, the K+-activated reaction moderately, and the (Na+ + K+)-ATPase reaction little; both contain two acidic groups, unlike the other buffers tested. Inhibition of the phosphatase reaction by Pipes is associated with a decreased apparent affinity for K+ and an increased sensitivity to inhibition by Na+ and ADP, consistent with Pipes hindering conformational transitions to the E2 enzyme forms required for phosphatase hydrolytic activity.

Alkanesulfonates↗

An interchromosomal gene conversion of the Drosophila dunce locus identified with restriction site polymorphisms: a potential involvement of transposable elements in gene conversion.

Females heterozygous for the two alleles dnc2 and dncM14 of the X-linked gene dunce (dnc), and carrying a copy of dnc+ on the second chromosome, have produced a cluster of six dnc+ progeny X-chromosomes from recombination experiments. Restriction site polymorphisms have been used as genetic markers to follow the parentage of dnc locus segments in these chromosomes. All six chromosomes are identical with respect to the spectrum of restriction site markers they carry in the dnc+ chromosomal region. In the progeny chromosomes, this region is comprised of sequences like the dncM14 X-chromosome and the translocation copy of dnc+. Sequences flanking the dnc gene in the progeny chromosomes are like the dncM14 chromosome. Internal to the gene but near the 5' end, is a segment from the dnc+ translocation which has apparently originated from an interchromosomal and premeiotic gene conversion event. In addition, two transposable elements have inserted into the progeny chromosomes, one towards the 5' end of dnc and the other near the 3' end. The insertion of these elements occurred premeiotically since all six chromosomes are structurally identical. The data are interpreted with respect to a potential role of transposable element transposition in the process of gene conversion.

3',5'-Cyclic-AMP Phosphodiesterases↗

A new family of the poly-deoxyadenylated class of Drosophila transposable elements identified by a representative member at the dunce locus.

Two transposable elements have been identified at the dunce locus in chromosomes recovered after a premeiotic and interchromosomal conversion event occurred at this gene. One is approximately 8.2 kb and is inserted near the 5' end of the gene. This element was identified by sequence analysis as a member of the B104 (roo) family of copia-like transposable elements. The second resides near the 3' end of the gene and represents a new family of the class of poly-deoxyadenylated [poly(dA)] transposable elements. It is 0.38 kb in length and has one terminus consisting of a stretch of 29 deoxyadenosine residues with a polyadenylation site like those found in mRNA molecules, located about 20 bp away from the poly(dA) stretch. Fourteen base pairs of genome DNA is duplicated at the target site of this element.

3',5'-Cyclic-AMP Phosphodiesterases↗

Giant axonal neuropathy. A neuropathological study.

Giant axonal neuropathy (GAN) is a disease characterized by a slowly progressive neuropathy and signs of central involvement, manifested by visual impairment, corticospinal tract dysfunction, ataxia, and dementia. Pathological hallmarks of the disease include axonal swellings packed with neurofilaments in both peripheral and central nervous systems, and accumulations of intermediate filaments in Schwann cells, fibroblasts, melanocytes, endothelial, and Langerhans cells. Rosenthal fibers, sometimes appearing in masses and mimicking Alexander's disease, emerge as a conspicuous characteristic in longstanding GAN.

Axons↗

Distribution of extracellular matrix proteins in primary human brain tumours: an immunohistochemical analysis.

Using immunohistochemical techniques, we localized several glycoproteins of the extracellular matrix in paraffin-embedded sections of 4 normal brain and 38 primary intracranial tumour specimens. All specimens were positively immunostained to various degrees by monoclonal antibodies to type IV collagen and procollagen III and by antisera to laminin and fibronectin. Staining was consistently most intense at sites of contact between neuroepithelial and mesenchymal or leptomeningeal elements; there was no demonstrable staining within or between neuroepithelial elements in the neuropil. Tumour cells from meningiomas and from the sarcomatous portion of a gliosarcoma were positively immunostained for fibronectin and laminin. The integrity of the glial limitans externa was demonstrated by the positive linear reaction product produced by immunostains for type IV collagen and laminin, even in the most malignant gliomas. The deposition of extracellular matrix glycoproteins at the glial-mesenchymal interface observed in this study of primary human brain tumours is a manifestation of one of the interactions between tumour and stromal cells in the central nervous system. A loss of coordination and an alteration in the interactions between epithelial cells and stromal cells across extracellular matrices such as basement membranes are thought to be fundamental steps in the development and progression of cancer. Further characterization studies focusing on other markers of the extracellular matrix are needed to elucidate completely the function of this structure in the central nervous system.

Antibodies, Monoclonal↗

Effect of orally administered activated charcoal on vancomycin clearance.

Vancomycin is a narrow-spectrum antibiotic that has concentration-dependent efficacy and toxicity. Recent literature indicates that orally administered activated charcoal can enhance the clearance of intravenously administered drugs. To evaluate the effects of activated charcoal on vancomycin clearance, six healthy male volunteers received vancomycin (1 g) intravenously with and without activated charcoal coadministration. In a randomized crossover sequence, subjects were given 50 g of activated charcoal immediately before the vancomycin infusion was begun and 15 g at 2, 4, 6, and 8 h afterwards, or an equal volume of water. Multiple doses of charcoal did not have a statistically significant effect on any pharmacokinetic parameter for vancomycin. Mean control values +/- standard deviation for vancomycin clearance, elimination half-life, and 24-h urinary recovery were 6.4 +/- 1.0 liters/h, 6.6 +/- 1.5 h, and 856 +/- 116 mg, respectively. Mean values for the same parameters were 6.4 +/- 1.0 liters/h, 6.0 +/- 0.9 h, and 897 +/- 130 mg when activated charcoal was given. We conclude that multiple doses of orally administered activated charcoal do not enhance vancomycin clearance in subjects with normal renal function when serum concentrations are within the therapeutic range. The results of this investigation cannot be extrapolated to patients with toxic vancomycin concentrations or renal dysfunction. The use of activated charcoal in these populations warrants further study.

Administration, Oral↗