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D L Cooper

Publications and source records attributed to D L Cooper.

At least 91 records · Page 5Linked to original sources

Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells.

In addition to the 85-95 kD CD44 species found on most hemopoietic cell types, the human myelomonocytic cell line KG1a expresses proteins of approximately 115 kD and 130 kD that react with monoclonal antibodies belonging to CD44. The possibility that these higher molecular weight species may represent novel CD44 isoforms containing additional protein sequence was investigated. CD44 cDNA clones were isolated from a plasmid-based expression library prepared from KG1a mRNA. One of the three clones obtained (clone 2.3) was found to encode a CD44 molecule of approximately 130 kD in transfected COS cells. Sequences analysis indicated that the molecule encoded by this cDNA clone, designated CD44R1, was essentially identical to CD44 except for the presence of an additional 132 amino acids inserted into the extracellular domain. This inserted region is rich in serine and threonine residues that may serve as sites of O-linked glycosylation, and contains a potential site of N-linked glycosylation and a potential site of chondroitin sulphate attachment. PCR analysis using primers that flank the inserted region present within CD44R1 identified an additional CD44 isoform, designated CD44R2, that contains only the last 69 amino acids present within the unique region of CD44R1. Peripheral blood mononuclear cells and granulocytes from normal individuals and patients with chronic myelogenous leukemia, polycythemia vera, or acute myelomonocytic leukemia, express both CD44R1 and CD44R2. In contrast, CD44R1 and CD44R2 appear to be differentially expressed in various CD44-positive cell lines. Thus KG1a, and the Epstein-Barr Virus-transformed B cell lines WalkDR4 and Way-1 express both CD44 and the CD44 isoforms CD44R1 and CD44R2, while the myeloid cell lines HL60 and U937 express high levels of CD44, but only very low levels of CD44R1 and CD44R2. The CD44-negative cell lines DHL-4, DHL-10, Jurkat, and K562 are also negative for CD44R1 and CD44R2.

Amino Acid Sequence↗

Inhibition of poly(adenosine diphosphate-ribose) polymerase by thymidine and thymidine analogues in L1210 cells and its relationship to the potentiation of the antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea but not of 3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine.

The coadministration of thymidine (dThd) with either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine (3'-CTNU) to L1210-bearing mice significantly enhanced the antitumor activity of both nitrosoureas (T-S. Lin and W. H. Prusoff, Cancer Res., 47:394-397, 1987, and T-S. Lin, P.H. Fischer, J. C. Marsh, and W. H. Prusoff, Cancer Res., 42:1624-1629, 1982). As a possible mechanism for this observed enhancement, we have investigated the role of dThd as an inhibitor of poly(ADP-ribose) polymerase (ADPRP), an enzyme which is activated in response to DNA damage. Exposure of L1210 cells in culture to 50 microM BCNU resulted in a greater than 10-fold increase in ADPRP activity within 3-4 h. The polymerase activity increased with increasing BCNU concentration after a 4-h exposure, reaching apparent saturation at 50 microM BCNU. However, this activation was abolished by 2 mM dThd. Median inhibition of the ADPRP activity elicited by 30 and 75 microM BCNU occurred at 38 and 135 microM dThd, respectively. When BCNU was replaced by 3'-CTNU, no activation of ADPRP was observed, even at or above concentration of 3'-CTNU previously shown to cause DNA damage. 3'-Amino-3'-deoxythymidine, the principal hydrolysis product of 3'-CTNU, was found to be an inhibitor of BCNU-stimulated ADPRP activity with potency similar to dThd. Furthermore, intact 3'-CTNU was found to inhibit BCNU-stimulated ADPRP activity. Although 3'-CTNU should be capable of activating ADPRP by causing DNA damage, our results suggest that no net activation is observed due to inhibition by the various thymidine species present. Thus, inhibition of ADPRP by dThd following DNA damage by BCNU is consistent with the potentiation of antitumor activity previously reported. However, the observed potentiation of 3'-CTNU activity by dThd does not appear to result from such a mechanism.

Animals↗

Bovine corneal protein 54K (BCP54) is a homologue of the tumor-associated (class 3) rat aldehyde dehydrogenase (RATALD).

Amino acid (aa) sequence data from Staphylococcus areas V8 protease-digested bovine corneal 54-kDa protein (BCP54) fragments were utilized to derive mixed oligodeoxyribonucleotide (oligo) primers complementary to the reverse translation products of these sequences. These degenerate oligo primers were used to prime the amplification of BCP54 sequence from bovine corneal epithelial cell cDNA. The cDNA probe generated by this mixed oligo-primed amplification of cDNA was cloned and dideoxy-sequenced. A search of the GenBank database (version 63.0) revealed extensive sequence similarity to the cDNA encoding tumor-associated rat liver (class 3) aldehyde dehydrogenase (RATALD). Nucleotide (nt) and aa sequence alignment of the BCP54 translation product reveals it is 78% and 84% homologous with RATALD at the nt and aa levels, respectively. Conservation of aa sequence elements common to the aldehyde dehydrogenase family thought to be of structural/functional significance is further substantiated by this analysis. Included in the discussion is the likelihood that gene sharing (genes encoding metabolic enzymes and other stable proteins) may extend to the cornea.

Aldehyde Dehydrogenase↗

Multidisciplinary approach to the differential diagnosis of facial, head and neck pain.

Pain in the region of the head and neck is one of the most common complaints that bring patients to the dentist. Because of the complexity of the anatomy as well as the vagueness of presenting symptoms, head and neck pain often is a diagnostic problem. Many different specialists may ultimately be consulted to make a comprehensive diagnosis and institute effective therapy. It is up to the one who coordinates the diagnostic sequence to have an understanding of the various pathologic conditions that can be manifested as pain in the head and neck. Although a comprehensive knowledge of all disciplines is not necessary, an overall understanding of the various disciplines of medicine as they relate to head and neck pain is valuable. The primary provider should establish a group of specialists to whom patients can be referred for further diagnosis and treatment when necessary to provide optimum care.

Cervical Vertebrae↗

The response of parathyroid hormone to specific changes in either ionized calcium, ionized magnesium, or protein-bound calcium in humans.

Because the effects of specific changes in magnesium or protein-bound calcium on biologic processes in humans have not been clearly defined, we developed an experimental system to specifically lower either ionized calcium, protein-bound calcium, or ionized magnesium. As an indicator of the biological effect of these changes, we measured parathyroid hormone (PTH) in blood. To selectively dilute only one constituent, we infused one of four specially prepared solutions into each of six healthy blood donors following ordinary blood donation. Each donor received at random 450 mL of a different solution at four different blood donations. The respective concentrations of ionized calcium (mmol/L), total magnesium (mmol/L), and albumin (g/L) in these fluids were as follows: control fluid, 1.25, 1.20, 40; no calcium fluid, 0, 1.20, 40; no magnesium fluid, 1.25, 0, 40; no albumin fluid, 1.25, 1.00, 0. Using selective in vivo dilution of the volunteers' blood, we specifically lowered either (1) ionized calcium by 0.07 mmol/L (5.5%), (2) protein-bound calcium by 0.09 mmol/L (10%), or (3) ultrafiltrable magnesium by 0.03 mmol/L (4.8%). While measurements of intact PTH showed that concentrations of PTH in blood did not respond to either decreased ultrafiltrable magnesium or decreased protein-bound calcium, these measurements showed that PTH increased by 400% within 10 minutes in response to decreased ionized calcium.

Adult↗

Bazex syndrome (acrokeratosis paraneoplastica). An analytic review.

Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions.

Carcinoma, Squamous Cell↗

Degenerate oligonucleotide sequence-directed cross-species PCR cloning of the BCP 54/ALDH 3 cDNA: priming from inverted repeats and formation of tandem primer arrays.

Bovine corneal protein 54 (BCP 54) is the major soluble protein of the bovine cornea, and immunoreactive forms of this protein have been described in a wide range of mammals. Dideoxy sequence determination of a previously synthesized 420-bp cDNA to BCP 54 generated by the novel mixed oligonucleotide primer amplification of cDNA (MOPAC) procedure revealed extensive similarity to the cDNA encoding tumor-associated rat liver (class 3) aldehyde dehydrogenase (RATALD). PCR amplification with additional pairs of degenerate oligonucleotide sequence (DOS) primers derived from both BCP 54-amino-acid sequence and amino acid and nucleotide sequence data from RATALD produced three PCR products that were cloned and subsequently sequenced. The major product was 716-bp BCP 54 cDNA clone encompassing the BCP 54 carboxy-terminal amino acid sequence for which the DOS pair was designed. Sequence alignment of the BCP 54 cDNA and its translation product with RATALD demonstrated 81% and 85% identity at the nucleotide and amino acid levels, respectively. Analysis of the additional two clones established that they were the results of PCR artifactual processes. The first of these was a 552-bp product occurring at elevated primer concentrations that formed through bidirectional amplification from a single DOS annealing to an inverted repeat located in the BCP 54 coding sequence. The second artifactual product was a 212-bp sequence that contained several unreported amplification anomalies, including the formation of a tandem primer array.

Aldehyde Dehydrogenase↗

Electromyography of masticatory muscles in craniomandibular disorders.

Patients presenting to the otolaryngologist with complaints such as otalgia, dizziness, tinnitus, or fullness in the ear may be experiencing the effects of craniomandibular disorders. These disorders can involve dysfunction in the delicate interrelationship of the skull, mandible, cervical vertebrae, and neuromuscular apparatus and can present as myofacial pain. Electromyographic recordings using surface electrodes were made bilaterally on the masseter, anterior temporalis, and digastric muscles in 641 craniomandibular patients, before and after transcutaneous electrical neural stimulation, at their initial presentation and following the insertion of mandibular orthopedic appliances. In the presenting patient, muscle-resting levels significantly decreased from hyperactive levels with transcutaneous electrical neural stimulation therapy. The creation of a new occlusal position with an orthotic appliance was found to correlate with a significant reduction in otolaryngologic symptoms as well as an increase in maximum muscle activity in function and coordination of muscle groups during mandibular movement. Thus, clinical electromyographic studies are an important aid in the treatment of craniomandibular disorders.

Electromyography↗

Screening recombinant DNA libraries: a rapid and efficient method for isolating cDNA clones utilizing the PCR.

We describe an expeditious method for the isolation of cDNA clones utilizing PCR-based amplification of target sequences from cDNA libraries. This method is rapid, less labor-intensive and inexpensive when compared with screening libraries with radiolabeled probes. This method can be applied to isolate multiple members of a protein family as well as homologous genes in different species by designing appropriate primers to amplify the most conserved regions. Utilizing this method, a novel reticulocyte CD44 transcript was isolated.

Bacteriophage lambda↗

Year 2000 fitness objectives for the nation. The physician's role.

Physicians and other health care professionals can play an integral role in encouraging individuals to exercise. This article presents a general philosophical approach to the exercise prescription as well as the Year 2000 Physical Activity and Fitness Objectives for the Nation, which call for greater physician involvement in this area.

Health Promotion↗

Partial amino acid sequence determination of bovine corneal protein 54 K (BCP 54)

The most abundant soluble protein of bovine cornea, BCP 54 (Bovine Corneal Protein, molecular weight 54 kD) was isolated and digested under both limited and complete digestion conditions with Staphylococcus aureus V8 protease. The fragments resulting from limited digestion were separated by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred to a polyvinylidene difluoride membrane, visualized by Coomassie Blue staining, cut out, and submitted to N-terminal protein sequence analysis. Complete digestion fragments were separated on a Vydac C18 reverse-phase HPLC, collected, and concentrated prior to sequencing. Using this method, we obtained amino acid sequence data from three internal V8 protease derived fragments of BCP 54 and a number of HPLC fragments. Comparison of these amino acid sequences, corresponding to 30% of the BCP 54 molecule, to those sequences contained within release 22 of the National Biomedical Research Foundation Protein Identification Resource revealed no extended sequence similarity of known proteins to BCP54.

Aldehyde Dehydrogenase↗

Full-length cDNA cloning utilizing the polymerase chain reaction, a degenerate oligonucleotide sequence and a universal mRNA primer.

A full-length cDNA was selectively amplified by the polymerase chain reaction (PCR) utilizing a primer pair consisting of a "universal" 21-base synthetic deoxyoligonucleotide (oligo dT 17GGCC) and a specific degenerate deoxyoligonucleotide sequence (DOS) derived from the N-terminal amino acid sequence. This double-stranded amplified cDNA was uni-directionally cloned into M13mp19 utilizing two restriction sites that had been previously incorporated into the termini of the universal and specific DOS primers. Cloning of the specific cDNA via this PCR amplification with the universal/specific DOS primer pair approach was confirmed by screening with a second DOS contiguous with the DOS employed to prime second (sense)-strand cDNA synthesis. This technique allows for the selective full-length cDNA cloning of low-abundance mRNAs from a single-protein sequence determination.

Amino Acid Sequence↗

A novel approach to molecular similarity.

We review briefly the general problem of assessing the similarity between one molecule and another. We propose a novel approach to the quantitative estimation of the similarity of two electron distributions. The procedure is based on momentum space concepts, and avoids many of the difficulties associated with the usual position space definitions. Results are presented for the model systems CH3CH2CH3, CH3OCH3, CH3SCH3, H2O and H2S.

Drug Design↗

Nabumetone pharmacokinetics in patients with varying degrees of renal impairment.

The pharmacokinetics of 1 g of oral nabumetone were studied in 20 patients divided into three groups according to the creatinine clearance rate of each. Pharmacokinetic assessment was made on the presence of the major and active metabolite found in the plasma, 6-methoxy-2-naphthylacetic acid, BRL 10720. Although the differences in the kinetic parameters measured in the three groups of patients were not statistically significant, that the drug should be used with care in patients with impaired renal function until additional data are available.

Adult↗

Restriction-fragment-length polymorphisms of 5'-flanking region of insulin I gene in BB and other rat strains. Absence of association with IDDM.

Because the 5'-flanking hypervariable region of the human insulin gene may be associated with insulin-dependent diabetes mellitus (IDDM), we examined the spontaneously diabetic BB rat and other rat strains for polymorphisms of the two rat insulin genes, the localization of such polymorphisms, and their possible association with IDDM. By use of restriction-fragment-length polymorphism analysis, we found that the transcribed portion of the insulin I gene, its 3'-flanking region, and the insulin II gene were not polymorphic. However, four alleles of the insulin I gene were identified, two of which (IA and IB) were found in BB rats. Alleles IA and IB varied in their 5'-flanking regions, yet neither was associated with IDDM in the BB rat.

Alleles↗

Degradation rates of acetylcholine receptors can be modified in the postjunctional plasma membrane of the vertebrate neuromuscular junction.

Denervation of vertebrate muscle causes an acceleration of acetylcholine receptor turnover at the neuromuscular junction. This acceleration reflects the composite behavior of two populations of receptors: "original receptors" present at the junction at the time of denervation, and "new receptors" inserted into the denervated junction to replace the original receptors as they are degraded (Levitt, T. A., and M. M. Salpeter, 1981, Nature (Lond.), 291:239-241). The present study examined the degradation rate of original receptors to determine whether reinnervation could reverse the effect of denervation. Sternomastoid muscles in adult mice were denervated by either cutting or crushing the nerve, and the nerves either allowed to regenerate or ligated to prevent regeneration. The original receptors were labeled with 125I-alpha-bungarotoxin at the time of denervation, and their degradation rate followed by gamma counting. We found that when the nerve was not allowed to regenerate, the degradation decreased from a t1/2 of approximately 8-10 d to one of approximately 3 d (as reported earlier for denervated original receptors) and remained at that half-life throughout the experiment (approximately 36 d). If the axons were allowed to regenerate (which occurred asynchronously between day 14 and day 30 after nerve cut and between day 7 and 13 after nerve crush), the accelerated degradation rate of the original receptors reverted to a t1/2 of approximately 8 d. Our data lead us to conclude that the effect of denervation on the degradation rate of original receptors can be reversed by reinnervating. The nerve can thus slow the degradation rate of receptors previously inserted into the postsynaptic membrane.

Animals↗