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R W Nelson

Publications and source records attributed to R W Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Protein determinants for specific polysialylation of the neural cell adhesion molecule.

Expression of polysialic acid (PSA) involves its specific attachment to the neural cell adhesion molecule (NCAM). Here we identify the amino acid residues within NCAM that are polysialylated and structural domains of the NCAM polypeptide that are required for addition of PSA in cells. Chicken NCAM cDNAs containing amino acid mutations, domain deletions, and domain substitutions were expressed in the F11 rat/mouse hybrid cell line, which can produce polysialylated NCAM. Polysialylation of the chicken NCAM was evaluated by immunopurification and electrophoresis. Mutation of all three potential N-glycosylation sites within the fifth immunoglobulin domain (Ig5) abrogated polysialylation. Analysis of paired mutations revealed that Asn-459 is heavily polysialylated, Asn-430 has a lower level of substitution, and Asn-404 receives little or no PSA. Analysis of domain deletions established that the intracellular domain, Ig domains 1-3, and the COOH-terminal fibronectin-type III (FNIII) repeat are not required for polysialylation, but that deletion of either the adjacent Ig4 or FNIII-type domain prevented addition of PSA. Accordingly, a minimal polypeptide for polysialylation was found to contain Ig domains 4 and 5, the adjacent FNIII repeat, plus a membrane attachment. These results suggest that although all PSA is located within Ig5, regions outside Ig5 also play a role in PSA addition to NCAM. Furthermore, molecular modeling indicates spatial proximity of Asn-430 and Asn-459 and a tight-locking arrangement between Ig4, Ig5, and FNIII#1 that would be consistent with their formation of a spatially discrete enzyme recognition site for polysialylation.

Amino Acid Sequence↗
PubMed1995

Effect of lente insulin for treatment of diabetes mellitus in 12 cats.

Ultralente insulin has replaced protamine zinc insulin as the treatment of choice in treatment of diabetes mellitus in cats. There is variability in effectiveness of ultralente insulin and problems with glycemic control develop in some cats. Alternative insulin preparations are sought when ultralente insulin is ineffective. Twelve cats with insulin-dependent diabetes mellitus were treated with lente insulin. Clinical signs improved in 8 cats given lente insulin every 12 hours. Lente insulin was ineffective in 4 cats. Three of these cats were subsequently found to have an insulin resistant disorder. In 1 cat, lente insulin was ineffective because of short duration of action. Lente insulin is a viable treatment alternative when ultralente insulin is ineffective in achieving glycemic control. Ultralente insulin is still the insulin of choice for the initial treatment of diabetes in cats, because of the potential to establish glycemic control with once-a-day treatment.

Animals↗
PubMed1995

Mass spectrometric immunoassay.

A new, general method of immunoassay is demonstrated. The approach is based on the microscale immunoaffinity capture of target antigens followed by mass-specific identification and quantitation using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Immunoaffinity capture of antigens effectively overcomes signal suppression effects typically encountered during traditional matrix-assisted laser desorption/ionization analysis of complex biological mixtures while simultaneously concentrating the analyte into a small volume. Mass spectrometric detection of antigens is unambiguous, as antigen signals are observed at characteristic mass-to-charge values in the mass spectrum, offering a high level of immunity to artifacts due to nonbiospecific retention of mixture components. However, the most important aspect of such mass-specific detection is the ability to use a single assay to screen biological systems for the presence of multiple, mass-resolved antigens. Analyte quantitation is possible by using a single antibody to capture both the antigen and an antigen variant which has been chemically modified to have a different mass. With proper calibration, the relative signal intensities of the two species in the mass spectrum can be used to determine the antigen concentration. Sample incubation and processing methods were such that a typical analysis could be performed in less than 1 h while subnanomolar sensitivities were maintained. The technique has been used for the rapid, selective, and quantitative screening of human blood for the presence of myotoxin a, and Mojave toxin form the venoms of the prairie rattlesnakes, Crotalus viridis viridis, and and the Mojave rattlesnake, Crotalus scutulatus scutulatus.

Animals↗
PubMed1995

Magnetic resonance imaging of the brain in dogs with recently diagnosed but untreated pituitary-dependent hyperadrenocorticism.

Magnetic resonance imaging was used to determine the prevalence of visible pituitary masses in 21 dogs with recently diagnosed and untreated pituitary-dependent hyperadrenocorticism. All dogs had clinical signs and routine database values (CBC, serum biochemical panel, and urinalysis) consistent with a diagnosis of hyperadrenocorticism, and none had clinical signs suggestive of an intracranial mass. Each dog had plasma cortisol concentrations after adrenocorticotropic hormone administration or low-dose dexamethasone administration consistent with hyperadrenocorticism. Pituitary-dependent hyperadrenocorticism was confirmed by the finding of 2 equal-size adrenal glands on abdominal ultrasonography and by results of plasma endogenous adrenocorticotropic hormone concentration and high-dose dexamethasone suppression testing. Sagittal and transverse T1-weighted magnetic resonance images of the brain were obtained before and after IV administration of gadopentenate dimeglumine. Eleven dogs had visible masses, ranging in size from 4 to 12 mm at greatest vertical height. Mean age and body weight of dogs with a visible pituitary mass was not significantly different from dogs without a visible mass. There was no significant difference in endocrine test results when comparing dogs with a visible pituitary mass to dogs without. The prevalence of visible pituitary masses in dogs with pituitary-dependent hyperadrenocorticism was greater than suggested by the prevalence of clinical neurologic signs.

Adrenal Cortex Diseases↗
PubMed1995

Magnetic resonance imaging for diagnosis of pituitary macrotumors in dogs.

The value of magnetic resonance imaging (MRI) for the evaluation of dogs with pituitary-dependent hyperadrenocorticism (PDH) and CNS signs was assessed. Magnetic resonance imaging of the brain was performed in 13 dogs with PDH and neurologic signs. The diagnosis of PDH was made on the basis of results of adrenocortical function tests and abdominal ultrasonography, in conjunction with appropriate history, clinical signs, and clinicopathologic alterations. Eight dogs had been treated with the adrenocorticolytic agent, mitotane, for 1 to 30 months before the development of neurologic signs. Prior to MRI, each dog had progressive neurologic signs that could not be attributed to hypocortisolism or mitotane toxicosis. The neurologic signs most frequently detected were disorientation and ataxia. Mean age of dogs at the time neurologic signs developed was 9.5 years. Sex predilection was not detected; however, most were large-breed dogs, with 11 of the 13 dogs weighing more than 20 kg. A large mass in the pituitary gland, suprasellar region, or both was easily identified on the magnetic resonance images of each dog. The masses ranged from 8 to 24 mm in size. Expansion of tumors into the suprasellar region and compression of structures adjacent to the pituitary gland were readily detected by MRI. Contrast enhancement did not improve tumor identification, but did enable better delineation between tumor and surrounding structures. After the diagnosis of a macrotumor was made by MRI, radiotherapy was initiated in 9 dogs and was successfully completed in 6. Three dogs had a relapse of neurologic signs 8, 11, and 26 months after radiotherapy was completed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Peptide characterization using bioreactive mass spectrometer probe tips.

A method has been developed for the rapid and sensitive mass spectrometric characterization of peptides. The approach uses bioreactive mass spectrometer probe tips, incorporating covalently bound enzymes, which are capable of modifying biomolecules for analytical purposes. In the demonstrated cases, enzymatic proteolysis is initiated upon application of analyte to the probe tips, time is allowed for digestion, and the products are analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The probe tips have been used for proteolytic mapping and partial sequence determination of picomole quantities of peptide. Analysis times were approximately 30 min. Two methods of database search were utilized. The first used limited peptide sequence information and parent molecular weight, while the second used exclusively the molecular weights of a number of endoproteolytic fragments. A simple method of comparing the match of experimental data for a tryptic digest with the results of a search is described.

Amino Acid Sequence↗
PubMed1994

Mass determination of human immunoglobulin IgM using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Monoclonal human immunoglobulin IgM has been analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Using a matrix of sinapinic acid with a laser wavelength of 355 nm, positive ions with 2 to 6 charges were observed in the mass spectra. Two major molecular species were present. The molecular weights estimated from the multiply-charged signals were found to decrease systematically with decrease in the charge state of the ion. This effect was determined to stem from the non-linear influence of the initial kinetic energy of desorption on the final kinetic energy of the multiply-charged species. A method of successive approximations, with the molecular weights and desorption velocities of the analytes as variables, was used to correct for these non-linearities. Mean molecular weights for the two IgM species were found to be 939,000 +/- 2000 and 982,000 +/- 2000 Da. An initial desorption velocity of 565 +/- 10 ms/s was determined for both.

Humans↗
PubMed1994

Comparative aspects of Cushing's syndrome in dogs and cats.

Naturally occurring hyperadrenocorticism (Cushing's syndrome) is extremely common in dogs, with an incidence far greater than that in humans. The incidence of the syndrome in cats, much less frequently diagnosed than in dogs, probably is similar to that in humans. Many features of canine hyperadrenocorticism are strikingly similar to those in humans; however, several alterations in dogs are unique and not observed in other species. Clinical features and hospital testing abnormalities are reviewed in this article.

Adrenal Cortex Diseases↗
PubMed1994

Nonoperative management of upper thoracic spine fractures.

We attempted to determine if nonsurgical treatment could be successful in treating instability of upper thoracic spine fractures, which may receive some stabilization and splinting from the ribs. From 1966 to 1989, the records of all patients treated at Rancho Los Amigos Medical Center for fractures from T-1 to T-8 were reviewed. Penetrating injuries and malignant lesions were excluded. A total of 118 patients were admitted during this period; 49 patients had nonsurgical treatment. Complications included 1 patient with neurologic worsening, brace-related skin necrosis in 8 cases, and deep venous thrombosis in 12 patients. No failure of arthrodesis was noted. Rib fractures did not adversely affect late stability. We conclude that orthotic treatment of thoracic spine instability from T-1 to T-8 can be successful, especially in cases where early surgery is not possible.

Adult↗
PubMed1994

Cervical spine fusions for trauma. A long-term radiographic and clinical evaluation.

Ninety-six successful cervical spine fusions performed for trauma, with a minimum of 5 years' follow-up, were retrospectively reviewed. Radiographic degenerative changes adjacent to fusion masses were assessed and correlated with clinical symptoms. The type of fusion, fusion extension, and final kyphosis of the involved segments were also analyzed. Twenty-eight patients had fusion masses aligned in 20 degrees or more of kyphosis. There was a significant increase in complaints of cervical pain in patients with neck fusions equal to or exceeding 20 degrees of kyphosis (P < 0.01). Evidence of mild degenerative changes adjacent to fusion masses was common, but did not correlate with symptoms.

Adult↗
PubMed1993

Effect of an orally administered sulfonylurea, glipizide, for treatment of diabetes mellitus in cats.

An orally administered sulfonylurea drug, glipizide, was evaluated for treatment of diabetes mellitus. Confirmation of diabetes was based on evidence of appropriate clinical signs, persistent hyperglycemia, and glucosuria. Glipizide (5 mg, PO, q 12 h) was administered to each cat. Sixteen cats were fed a commercial high-fiber diet and 4 cats were fed a commercial low-fiber diet. Insulin was not administered to any cat during the study. Each cat was evaluated 2, 4, 8, and 12 weeks after initiation of treatment. Three clinical responses to glipizide treatment were identified. Mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period decreased to < 200 mg/dl in 5 of 20 (25%) cats. In these 5 cats, glucosuria was no longer detected and clinical signs resolved by the 4-week reevaluation. Euglycemia was maintained after discontinuing glipizide treatment in 2 of these 5 cats. Glycemic control has been maintained in 2 of 5 of the responding cats for 5 and 7 months of glipizide treatment. One of 5 of the responding cats developed insulin-requiring diabetes mellitus after 6 months of glipizide treatment. Seven of 20 (35%) cats failed to respond to treatment. Mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period did not change from pretreatment values after 2 +/- 1 months; glucosuria persisted and clinical signs progressively worsened. Insulin treatment was required to establish glycemic control in these 7 cats. Eight of 20 (40%) cats partially responded to glipizide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Prostaglandin induction of abortion in pregnant bitches after misalliance.

Of 48 privately-owned bitches evaluated 30 to 35 days after a single, unplanned breeding, 30 (62%) dogs were determined not to be pregnant by abdominal ultrasonography and 18 dogs were confirmed to be pregnant. Each pregnant dog was hospitalized, allotted to a treatment group, and given prostaglandin F2 alpha, SC, at 1 of 3 dosages: group 1, 0.1 mg/kg of body weight, every 8 hours; group 2, 0.25 mg/kg, every 12 hours; and group 3, 0.1 mg/kg, every 8 hours for 2 days and then 0.2 mg/kg every 8 hours thereafter. Plasma from each dog was assayed for progesterone concentration before treatment and daily until abortion was completed. Physical examinations and abdominal ultrasonography were performed every 12 and 48 hours, respectively. Treatment was continued until abortion was complete as determined by results of abdominal ultrasonography. Ultrasonography was performed earlier than the scheduled 48 hours if abdominal contractions, fetuses, or bloody or dark colored vaginal discharge was observed. Dogs of 14 breeds were treated; body weight ranged from 5.4 to 37.7 kg. All dogs aborted all fetuses within 9 days of beginning treatment. Abdominal palpation was not satisfactory in confirming whether the abortion process had been completed; however, results of ultrasonography were a reliable indicator. Plasma progesterone concentrations prior to treatment were typical of the middle phase of gestation, with all concentrations > 6.0 ng/ml. The plasma progesterone concentration decreased significantly in each dog after the first 48 hours of therapy. None of the bitches aborted any fetal material until at least 24 hours after the plasma progesterone concentration was < 2.0 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1993

Insulin resistance in three dogs with hypothyroidism and diabetes mellitus.

Insulin resistance resolved in 3 dogs with hypothyroidism and diabetes mellitus after treatment with sodium levothyroxine. A thorough diagnostic evaluation failed to identify any other cause of insulin resistance in these dogs. Hypothyroidism was diagnosed in each dog on the basis of clinical signs, physical findings, hyperlipidemia, and results of thyrotropin or thyrotropin-releasing hormone stimulation test. Hypoglycemia was documented in each dog within 2 weeks of starting sodium levothyroxine administration. The insulin dosage was decreased by 60 to 62% during the ensuing months and good glycemic control was obtained at these lower insulin dosages in all dogs. These findings would suggest hypothyroidism-induced insulin resistance in these dogs.

Animals↗
PubMed1993

Primary parathyroid gland hyperplasia in dogs: six cases (1982-1991).

Persistent hypercalcemia attributable to parathyroid gland hyperplasia was identified in 6 dogs with primary hyperparathyroidism. Clinical signs included polydipsia (n = 4), polyuria (n = 4), and signs caused by cystic calculi (n = 3). Abnormal clinical pathologic findings included hypercalcemia (mean, 13.6 mg/dl; range, 12.6 to 14.7 mg/dl; n = 6), hypophosphatemia (mean, 2.2 mg/dl; range, 1.4 to 2.9 mg/dl; n = 6), high serum alkaline phosphatase activity (mean, 222 IU/L; range, 161 to 286 IU/L; n = 3), and isosthenuria (mean, 1.012; range, 1.006 to 1.017; n = 6). Serum parathyroid hormone concentration was within the reference range or high (mean, 23 pmol/L; range, 7 to 119 pmol/L; reference range, 1.5 to 13 pmol/L) in all dogs. At surgery, the number of large parathyroid glands was variable, being limited to 1 gland in 3 dogs, 2 glands in 2 dogs, and 4 glands in 1 dog. All visibly large parathyroid glands were surgically removed from each dog. Serum calcium concentration decreased into or below the reference range within 72 hours of surgery in all dogs, confirming the diagnosis of primary parathyroid disease. Multiple nodules of adenomatous hyperplasia were identified in each dog. All 6 dogs were treated with vitamin D and calcium carbonate following surgery. The dog from which all 4 parathyroid glands were removed has remained eucalcemic for more than 1 year with vitamin D supplementation. Vitamin D and calcium administration was discontinued within 4 to 12 weeks of surgery in the remaining 5 dogs. These dogs remained eucalcemic without vitamin D supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

Hyperadrenocorticism caused by bilateral adrenocortical neoplasia in dogs: four cases (1983-1988).

Hyperadrenocorticism caused by bilateral adrenocortical neoplasia was diagnosed in 4 dogs. Three dogs had bilateral adrenocortical adenomas, and 1 dog had bilateral adrenocortical carcinomas. The history, physical findings, clinicopathologic abnormalities, and results of ACTH stimulation and low-dose dexamethasone suppression tests were compatible with diagnosis of hyperadrenocorticism. Adrenocortical neoplasia was differentiated from pituitary-dependent hyperadrenocorticism on the basis of a combination of test results, including lack of suppression of plasma cortisol after being given a high dose dexamethasone (n = 4), undetectable (< 20 pg/ml) plasma endogenous ACTH concentration (n = 4), identification of a single mineralized adrenal mass by abdominal radiography (n = 2) and abdominal ultrasonography (n = 1), and identification of bilateral nonmineralized adrenal masses by ultrasonography (n = 1). A left adrenal mass was excised from 1 dog. Clinical signs persisted and administration of mitotane was initiated. One dog was treated only with mitotane. Treatment with ketoconazole was attempted in 2 dogs. All dogs died or were euthanatized because of persistent hyperadrenocorticism. Necropsy and histologic evaluation of the pituitary and adrenal tissue confirmed bilateral adrenocortical neoplasia in all dogs. Bilateral adrenocortical neoplasia should be considered as an uncommon, but possible, cause of bilaterally large adrenal glands in dogs with hyperadrenocorticism.

Adenoma↗
PubMed1993

Efficacy of microcrystalline desoxycorticosterone pivalate for treatment of hypoadrenocorticism in dogs. DOCP Clinical Study Group.

The efficacy of microcrystalline desoxycorticosterone pivalate (DOCP) therapy was evaluated in 60 dogs with hypoadrenocorticism. Fifty-one of the dogs were being treated with either DOCP or fludrocortisone acetate prior to entering the study. The disease had been recently diagnosed in 9 dogs that were not under maintenance treatment prior to entering the study. Desoxycorticosterone pivalate (2.2 mg/kg of body weight, IM) was administered on days 0, 25, and 50. Physical examination was performed, and blood samples were obtained for serum biochemical analysis (Na+, K+, and BUN concentrations) on days 0, 14, 25, 39, 50, 64, and 75. On day 75 of the study, a final physical examination was performed and the course of treatment was evaluated. Sixty-eight percent (41/60) of the dogs had normal physical findings on day 0 vs 87% (52/60) on day 75. Mean (+/- SD) body weight increased from 24.8 +/- 12.7 kg on day 0 to 26.2 +/- 13.7 kg on day 75. Mean serum Na+ (137.7 +/- 8.5 mEq/L) and K+ (5.6 1.0 mEq/L) concentrations and Na(+)-to-K+ ratio (25.4 +/- 5.0:1) were outside normal reference limits on day 0. By day 75, serum Na+ (144.3 +/- 4.8 mEq/L) and K+ (4.9 +/- 0.8 mEq/L) concentrations and Na(+)-to-K+ ratio (30.4 +/- 5.1:1) were normal and were significantly (P < 0.01) improved, compared with the corresponding values on day 0. Of the 60 dogs, 58 (97%) regained the loss in body weight, appetite, and muscular strength while given DOCP; once achieved, these improvements were maintained. These 58 dogs did not vomit or have diarrhea, common problems in dogs with hypoadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Insufficiency↗
PubMed1993

Origin of the isoelectric heterogeneity of monoclonal immunoglobulin h1B4.

The origin of the microheterogeneity of a highly purified antiinflammatory humanized monoclonal antibody prepared in mammalian cell culture has been investigated. This antibody is an IgG directed toward human CD18 (a subunit of leukocyte integrins). When the IgG preparation is subjected to isoelectric focusing, it is found to contain four major species with pI values ranging from 6 to 7. Although the relative amounts of each form differ and some species are present only in small quantities, each has been isolated by a combination of high-resolution anion-exchange chromatography and isoelectric focusing. Comparative studies reveal no detectable differences in overall secondary (far UV circular dichroism) or tertiary (intrinsic fluorescence) structure, molecular weight (laser-desorption mass spectroscopy), or antigen binding activity. When each of the isolated species is incubated under conditions which favor deamidation, it is converted to forms of lower pI which appear to correspond to naturally observed species. While the isolated light chain is relatively homogeneous, the heavy chain exhibits a pattern of isoelectric focusing bands similar to that of the intact immunoglobulin. These results suggest that in this case, charge microheterogeneity is due to the sequential deamidation of the immunoglobulin heavy chain.

Antibodies, Monoclonal↗