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Biomedical subjects

D M Clark

Publications and source records attributed to D M Clark.

At least 73 records · Page 4Linked to original sources
PubMed1989

T-cell antigen receptor beta-chain variable region families: a study of their distribution in normal and reactive tissues.

The beta chain of the T-cell antigen receptor is constructed using a variable region gene from one of approximately 20 variable gene families. Antibodies that react with the products of these gene families have been used to demonstrate clonal proliferation of T cells. Here, we describe the expression of two beta-chain variable region families in normal and reactive lymphoid tissues. In all the tissues studied, expression was scattered throughout the T-cell areas, without any clustering of expression.

Antibodies, Monoclonal↗
PubMed1989

pCloDF13-encoded bacteriocin release proteins with shortened carboxyl-terminal segments are lipid modified and processed and function in release of cloacin DF13 and apparent host cell lysis.

By oligonucleotide-directed mutagenesis, stop codon mutations were introduced at various sites in the pCloDF13-derived bacteriocin release protein (BRP) structural gene. The expression, lipid modification (incorporation of [3H]palmitate), and processing (in the presence and absence of globomycin) of the various carboxyl-terminal shortened BRPs were analyzed by a special electrophoresis system and immunoblotting with an antiserum raised against a synthetic BRP peptide, and their functioning with respect to release of cloacin DF13, lethality, and apparent host cell lysis were studied in Sup-, supF, and supP strains of Escherichia coli. All mutant BRPs were stably expressed, lipid modified, and processed by signal peptidase II, albeit with different efficiencies. The BRP signal peptide appeared to be extremely stable and accumulated in induced cells. Full induction of the mutant BRPs, including the shortest containing only 4 amino acid residues of the mature polypeptide, resulted in phospholipase A-dependent and Mg2+-suppressible apparent cell lysis. The extent of this lysis varied with the mutant BRP used. Induction of all mutant BRPs also prevented colony formation, which appeared to be phospholipase A independent. One shortened BRP, containing 20 amino acid residues of the mature polypeptide, was still able to bring about the release of cloacin DF13. The results indicated that the 8-amino-acid carboxyl-terminal segment of the BRP contains a strong antigenic determinant and that a small segment between amino acid residues 17 and 21, located in the carboxyl-terminal half of the BRP, is important for release of cloacin DF13. Either the stable signal peptide or the acylated amino-terminal BRP fragments (or both) are involved in host cell lysis and lethality.

Acylation↗
PubMed1989

Stroke in patients with fusiform vertebrobasilar aneurysms.

We studied seven patients with brainstem infarction and large fusiform vertebrobasilar (VB) aneurysms to clarify the clinical, radiologic, and pathologic features. All presented with pontine infarcts; one also had a cerebellar infarct. VB TIAs preceded brainstem infarction in four patients. Angiography and CT documented VB fusiform aneurysmal dilatation. Four had intraluminal thrombi and one had severe basilar artery stenosis. Two distinct clinical pictures emerged: unilateral pontine infarcts with favorable outcome, presumably related to obstruction of a pontine penetrating artery at its origin from the posterior wall of the aneurysmal basilar artery, and major fatal bilateral pontine infarcts from basilar artery occlusion. Two patients came to autopsy. One had thrombus in the dilated basilar artery and a posterior cerebral artery branch embolus with hemorrhagic occipital infarction; the other had basilar artery thrombus with aneurysmal rupture and subarachnoid hemorrhage. Fusiform VB aneurysms caused brainstem stroke by intraluminal thrombus, local embolism, atherostenosis, and obstruction of paramedian penetrating arteries. Subarachnoid hemorrhage is an uncommon complication.

Adult↗
PubMed1988

An ELISA method for detecting antibodies to the T cell antigen receptor.

An ELISA method for the detection of monoclonal antibodies (MAb) to the T3-T cell antigen receptor (TCR) complex was devised. The T3-TCR complex was solubilised using digitonin and a rat anti-T3 MAb (Campath 3) was used to bind it to an ELISA plate. Normal rat serum was used to block cross-reactivity between the rat MAb and peroxidase-conjugated rabbit anti-mouse immunoglobulins. The assay was tested on four T cell tumour lines and successfully detected MAbs to TCR beta chain variable regions, as well as the anti-T3 MAb UCHT1. Other anti-T3 MAbs were not detected because Campath 3 blocked their binding. None of a panel of MAbs reacting with other T cell surface antigens reacted in the assay.

Antibodies, Monoclonal↗
PubMed1988

Definitive identification of human T cells in formalin fixed paraffin wax embedded tissue.

The use of a new monoclonal antibody, BF1, which reacts in routinely fixed tissues, directed against the beta chain of the T cell antigen receptor was assessed to determine its reactivity in a variety of normal tissues as well as in a number of B and T cell tumours and other lymphoid disorders. It reacted with all five of the unequivocal T cell tumours tested. BF1 will have widespread use in the assessment of lymphoid tissues in patients with the acquired immune deficiency syndrome (AIDS) and the differential diagnosis of tumours.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effect of therapy with vitamin B12 and folic acid on elderly patients with low concentrations of serum vitamin B12 or erythrocyte folate but normal blood counts.

To help understand the haematological significance of the low concentrations of serum vitamin B12 and erythrocyte folate occurring in elderly patients, 17 acute admissions to a geriatric unit with a low concentration of serum vitamin B12 or erythrocyte folate but a normal blood count were treated with vitamin B12 and folic acid for 3 months. Bone marrow deoxyuridine suppression was abnormal in 3 of these 17 patients, 2 of whom also had megaloblastic change in the marrow. With treatment, the MCV fell in 13 of the 17, and the average MCV fell from 90.5 to 87.9 fl (p = 0.007), but the mean Hb did not change. Ten untreated similar patients showed no change in their MCV over the same period, but the mean Hb fell from 14.0 to 13.1 g/dl (p = 0.04). Thus the low concentrations of serum vitamin B12 or erythrocyte folate found in approximately a quarter of acutely admitted elderly patients may indicate true tissue deficiency of these vitamins, even when the blood count is normal.

Blood Cell Count↗
PubMed1987

Unusual forms of T cell gamma mRNA in a human T cell leukemia cell line: implications for gamma gene expression.

The expression and rearrangement of T cell rearranging (TRG) gamma genes in human leukemic cell lines has been examined. The cell line MOLT-17 produces abundant gamma mRNA which is translated into a protein found on the cell surface which is associated with the CD3 molecule. The analysis of the gamma mRNA sequences in MOLT-17, by cDNA cloning, shows transcripts of aberrantly rearranged genes as well as the productively rearranged allele. The productive allele consists of a rearranged V gamma 8 gene joined to J gamma 2. Two forms of aberrant transcript originate from the other rearranged gamma allele. One of these initiates just upstream of the unrearranged J gamma 2 segment, and the other initiates from a V gamma 8 gene segment joined to another J gamma segment, upstream of J gamma 2. An unusual feature of the latter transcript is that polyadenlyation has occurred at the end of the first exon of C gamma 2, where two conserved poly(A) addition signals occur. The MOLT-4 cell line, on the other hand, has productively and nonproductively rearranged gamma alleles, from which relatively little transcription occurs. These results define new J gamma segments in the human TRG gamma locus and suggest that positive activation of the gamma locus is necessary for high level transcription after rearrangement.

Amino Acid Sequence↗
PubMed1987

The use of electrical current in the treatment of nonunions.

The use of electrostimulation in the treatment of nonunions in human beings is gaining in popularity. Increased understanding of the electrophysiology of fracture healing has lead to advances in the utilization of electric currents to stimulate nonunions to heal without resorting to major orthopedic surgery and its attendant risks. Most workers report success rates of 75 to 85 per cent, which are comparable to rates achieved by more routine orthopedic techniques. Brighton suggested that the risk/benefit ratio was lower for direct-current treatment of nonunion than that associated with conventional bone-graft surgery in human beings. Such information is not yet available for the veterinary surgeon. However, some authors have questioned the glowing reports of successful electric stimulation of clinical nonunions, citing poor design of clinical trials, erratic or inappropriate selection of patients, and empiricism in interpretation of results. Although the use of electrotherapy for treatment of nonunions appears promising, much more work is needed to define those patients best able to respond favorably to such techniques. Nonunions in dogs and cats are now only rarely treated with electric current. To date, no major clinical studies have been published concerning such techniques, although much of the basic research in this area was done on animals. It would appear that the totally implantable stimulators have the most potential for use in small animals because minimal cooperation is required of the patient and client. Furthermore, such devices cannot be easily damaged or dislodged. Whether electric stimulation of nonunions in dogs and cats will replace or supplant conventional orthopedic techniques remains to be seen.

Animals↗
PubMed1987

Symbolic play and social participation abilities of language-impaired and normally developing children.

The symbolic play and social participation behaviors of 6 language-impaired and 8 normal language-learning children were compared on three measures of play: (a) the Symbolic Play Test (Lowe & Costello, 1976), (b) the Brown-Lunzer Scale (Brown, Redmond, Bass, Liebergott, & Swope, 1975), and (c) the Scale of Social Participation in Play (Tizard, Philps, & Plewis, 1976). Subject groups were equated for MLU (Brown, 1973), Developmental Sentence Scoring (Lee, 1974), and performance on the Test of Auditory Comprehension of Language (Carrow, 1973). Results indicated that the language-impaired subjects demonstrated significant deficits in symbolic, adaptive, and integrative play behaviors in comparison with the linguistically equivalent normal subjects. The language-impaired group also evidenced significantly more nonplay and significantly less solitary and parallel play than their normal peers. Findings are discussed with respect to the developmental relationship between language and cognition.

Child↗
PubMed1986

Neuroepithelioma in a middle-aged dog.

Paresis progressing to paralysis was caused by a neuroepithelioma located at the level of the L1-L2 interspace in a 7 1/2-year-old Golden Retriever. This tumor has never been reported in a dog more than 3 years old. The possibility of a neuroepithelioma should be considered in the differential diagnosis of paresis/paralysis in older dogs.

Animals↗
PubMed1986

Antibodies to T cell antigen receptor beta chain families detect monoclonal T cell proliferation.

The T cell antigen receptor is constructed from independent gene segments much like those used to assemble immunoglobulin genes. One of the receptor's two protein subunits, the beta chain, uses a limited number of variable region segments. The product of these V region segments can be identified by monoclonal antibodies and can be used to define populations of normal T cells which use the same V beta (V beta) gene segment. These antibodies have been used to define monoclonality or its absence in T cell populations. Twenty-four cases have been studied (twenty with solid T cell lymphomas and four with T cell leukaemias). Two monoclonal antibodies to V beta (anti-HPB-A11 and anti-Jurkat) were tested, and three cases of T cell lymphoma were positive, two to anti-Jurkat and one to anti-HPB. The malignant nature of T cell proliferations can be directly diagnosed in tissue sections and intact cell suspensions. This approach should also make possible the monitoring of changes in malignant populations in response to therapy.

Antibodies, Monoclonal↗
PubMed1986

Dose-response range of encainide for benign and potentially lethal ventricular arrhythmias.

A multicenter, 2-week, double-blind, placebo-controlled, parallel group study was performed to determine the dose-response relation of encainide administered 3 times daily and to determine its onset of action. To be included in the study, patients with benign or potentially lethal ventricular arrhythmias were required to have an average of at least 30 ventricular premature complexes (VPCs) per hour on 48-hour Holter monitoring after a 48-hour washout period without antiarrhythmic drug treatment. Patients were randomly assigned to receive either placebo or 10, 25 or 50 mg of encainide 3 times daily (tid) for 2 weeks. Of the 125 patients who entered the study, 122 were available for efficacy analysis. Efficacy was determined using 24-hour Holter monitoring on days 1, 7 and 14. There was no difference in frequency of VPCs or of ventricular tachycardia events in the placebo and 10-mg-tid encainide arms. At doses of 25 and 50 mg of tid, encainide was effective in suppressing VPCs and in reducing the number of episodes of ventricular tachycardia. A positive dose-response relation was identified. The onset of effect of encainide was apparent at 3 hours and lasted for 24 hours with tid dosing. No difference in on-therapy conditions were found among the 4 study arms. No patients were discontinued from the study because of electrocardiographic changes. There was no statistically significant change in vital signs or physical examination data. In 1 patient an elevated serum glucose level developed. No symptomatic proarrhythmic events occurred and none required discontinuation of study medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Clostridial peritonitis associated with a mast cell tumor in a dog.

Recurrent peritonitis caused by Clostridium limosum was associated with a mast cell tumor of a cranial mesenteric lymph node in a dog. The diagnosis of mast cell tumor was obscured because of the peritonitis and the appearance and location of the mass, which resembled an abscess. Since clostridial infections frequently are associated with neoplasia in man, veterinarians should be aware of the possibility of a similar relationship in animals.

Animals↗
PubMed1986

The use of hydroxocobalamin in the Schilling test.

Hydroxocobalamin and cyanocobalamin have been compared as the 'flushing dose' in the Schilling test. In healthy, haematologically normal subjects excretion of the test dose was greater following a hydroxocobalamin flushing dose than following a cyanocobalamin flushing dose, and to a lesser extent this was also true in patients requiring investigation. There were occasional discrepant results, but in general it appears that, although reference values differ, hydroxocobalamin is a suitable replacement for cyanocobalamin in the Schilling test.

Adult↗