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Biomedical subjects

D Pollock

Publications and source records attributed to D Pollock.

At least 37 records · Page 2Linked to original sources
PubMed1995

The microcirculatory effects of peripheral sympathectomy.

Microvascular physiology following peripheral artery sympathectomy was evaluated in seven hands with refractory pain (n = 7) and ulceration (n = 7) by serial isolated cold stress testing, which measures digital temperature and cutaneous perfusion (laser Doppler fluxmetry). All patients (n = 6) had vasospasm (secondary Raynaud's phenomenon) and arteriographically proven digital and palmar occlusive disease. Microcirculatory flow responses were correlated with symptoms and signs (including ulcer healing) before and after (2-8 weeks, 12-15 weeks, and 24 weeks) peripheral sympathectomy. Baseline data were compared with those of controls (n = 7 extremities). Following surgery, all seven hands had diminished pain; six had ulcer healing and one had ulcer reduction. Isolated cold stress testing demonstrated abnormalities in temperature and laser Doppler fluxmetry response between patients and controls. Although total flow (reflected by temperature) was not significantly increased after surgery, peripheral sympathectomy increased nutritional flow in these patients with combined vasospastic vessels and occlusive injury. The clinical changes observed following peripheral sympathectomy appear to be related to postsurgical correction of abnormal arteriovenous shunting and to improved nutritional blood flow to ischemic areas. This accounts for the resultant diminution of pain and healing of ulcers observed in these patients after surgery.

Adult↗
PubMed1995

Prevention by blockade of angiotensin subtype1-receptors of the development of genetic hypertension but not its heritability.

1. We determined whether early inhibition of angiotensin II subtype1 (AT1) receptors by the newly synthesized nonpeptidic antagonist, A-81988, can attenuate the development of hypertension in spontaneously hypertensive rats (SHR) and if the altered blood pressure phenotype can be passed on to the subsequent generation, not exposed to the antagonist. 2. Pairs of SHR were mated while drinking tap water or A-81988 in tap water, and the progeny was maintained on the parental regimen until 14 weeks of age. At this stage, A-81988-treated rats showed lower systolic blood pressure and body weight values (136 +/- 5 versus 185 +/- 4 mmHg and 247 +/- 4 versus 283 +/- 4 g in controls, P < 0.01); while heart rate was similar. In addition, mean blood pressure was reduced (101 +/- 7 versus 170 +/- 7 mmHg in controls, P < 0.01), and the pressor responses to intravenous or intracerebroventricular angiotensin II were inhibited by 27 and 59%, respectively. Heart/body weight ratio was smaller in A-81988-treated rats (3.2 +/- 0.1 versus 3.8 +/- 0.1 in controls, P < 0.01). 3. The antihypertensive and antihypertrophic effect of A-81988 persisted in rats removed from therapy for 7 weeks (systolic blood pressure: 173 +/- 4 versus 220 +/- 4 mmHg, heart/body weight ratio: 3.4 +/- 0.1 versus 4.1 +/- 0.1 in controls at 21 weeks of age, P < 0.01 for both comparisons), whereas the cardiovascular hypertensive phenotype was fully expressed in the subsequent generation that was maintained without treatment. 4. These results indicate that chronic blockade of angiotensin AT1-receptors attenuates the development of hypertension in SHR but it does not prevent the transmission of hypertension to the following generation. Thus, heritability of the SHR's hypertensive trait is not affected by pharmacological manipulation of the cardiovascular phenotype.

Administration, Oral↗
PubMed1993

Tobacco.

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Adolescent↗
PubMed1992

Structured ambiguity and the definition of psychiatric illness: adjustment disorder among medical inpatients.

Adjustment disorder is one of the most common psychiatric diagnoses given to patients hospitalized for medical and surgical problems. This article argues that the diagnosis, in this context, often serves strategic, non-clinical ends for consultation-liaison psychiatrists, who must negotiate their interstitial position through an essentially ambiguous diagnosis. In these cases, 'adjustment disorder' emerges from and reproduces tensions between such cultural dichotomies as mind/body and social/individual that marginalize psychiatry in medical settings.

Adjustment Disorders↗
PubMed1991

Construction, expression and characterization of humanized antibodies directed against the human alpha/beta T cell receptor.

Completely humanized antibodies with specificity for the human alpha/beta TCR have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 CD regions and human EU framework regions were synthesized and replaced into previously isolated genomic fragments. These fragments were inserted into mammalian expression vectors containing the human kappa and gamma 1 C region exons. Two variants were constructed each containing selected BMA 031 amino acids within the human frameworks. The humanized genes were transfected into Sp2/0 hybridoma cells by electroporation and transfectomas secreting humanized antibody were isolated. Levels of antibody expression up to 7 pg/cell/24 h were obtained. The humanized antibody, BMA 031-EUCIV2, competed poorly with murine BMA 031 for binding to T cells. BMA 031-EUCIV3, however, bound specifically to T cells and competed effectively with both the murine BMA 031 antibody and a previously constructed chimeric BMA 031 antibody for binding to these cells. The relative affinity of BMA 031-EUCIV3 was about 2.5 times lower than BMA 031. The ability to promote antibody dependent cell-mediated cytolysis was significantly enhanced with the engineered antibodies as compared to murine BMA 031. Humanized BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft vs host disease, and autoimmunity.

Amino Acid Sequence↗
PubMed1991

Application of a monoclonal antibody-based enzyme-linked immunosorbent assay for detection of an inflammatory response antigen in subclinical mastitic milk samples.

A monoclonal antibody to a 23.5-kDa bovine inflammatory antigen present in high levels in mastitic milk has been used in an antigen-capture enzyme-linked immunosorbent assay (ELISA) to screen milk samples from herds of cattle for subclinical mastitis. The results from 20 herds with a total of 2,612 quarter samples are presented. Good correlation was observed between the ELISA level and the milk cell count (MCC). The results demonstrated an average of 5% false negatives (1.8% associated with isolates of Staphylococcus aureus and/or Streptococcus spp.) and 7.7% false positives for each herd in relation to mastitic (greater than 400,000 cells per ml) or nonmastitic (less than 400,000 cells per ml) MCCs.

Acetylglucosaminidase↗
PubMed1990

Cardiovascular effect and stimulus-dependent inhibition of superoxide generation from human neutrophils by tibenelast, 5,6-diethoxybenzo(b)thiophene-2-carboxylic acid, sodium salt (LY186655).

Tibenelast (LY186655), 5,6,-diethoxybenzo(b)thiophene-2-carboxylic acid, sodium salt, is an orally active anti-anaphylactic compound in guinea pigs, and has been shown to prevent bronchospasm in moderately severe asthmatic patients. Pharmacological studies with tibenelast demonstrated that it is a selective phosphodiesterase (PDE) inhibitor in that it is moderately active against the lung and stomach enzyme while being a very weak inhibitor of the heart enzyme. The compound was without cardiovascular effects at anti-anaphylactic doses. In contrast to theophylline, tibenelast did not have a direct inotropic effect in the cat papillary muscle system. The concentration that inhibited 50% of the enzymatic activity (IC50) for tibenelast was 20- to 30-fold lower for neutrophil PDE than for PDE of other tissues. It was 100 times more potent than aminophylline in inhibiting superoxide generation from platelet-activating factor (PAF)-primed polymorphonuclear leukocytes (PMNL) challenged with chemotactic factor, N-formyl-methionyl-leucyl-phenylalanine. However, tibenelast was less effective in the tumor necrosis factor-primed system, and did not inhibit superoxide generation during phagocytosis or when other soluble stimuli, such as phorbo-12-myristate-13-acetate or the calcium ionophore A23187, were used. Furthermore, tibenelast did not inhibit enzymes involved in arachidonic acid metabolism. These results suggest that tibenelast probably inhibits superoxide release from PMNL via a selective inhibition on PDE.

Animals↗
PubMed1990

Impairment of relaxations to acetylcholine and nitric oxide by a phorbol ester in rat isolated aorta.

1. This study compared the abilities of acetylcholine (ACh) (endothelium-dependent) and nitric oxide (NO) (endothelium-independent and which may be the active component of the endothelium-derived relaxing factor) to relax rat isolated aortic rings contracted with equi-effective concentrations of noradrenaline (NA) or phorbol 12-myristate 13-acetate (PMA). 2. ACh and NO induced concentration-dependent relaxations of aortic rings contracted with NA (EC70 value: 0.2 microM). However, relaxations to both ACh and NO were markedly reduced in rings contracted with PMA (EC80 value: 0.5 microM). NO-induced relaxations of tissues were not affected by removal of the endothelium, but ACh-induced relaxations were confirmed to be endothelium-dependent. 3. ACh (10 microM) induced a 10 fold increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels above control values in aortic rings contracted with NA (0.2 microM), but did not affect cyclic GMP levels in rings contracted with PMA (0.5 microM). 4. NO (3 microM) induced a 100 fold increase in cyclic GMP levels above control values in aortic rings contracted with NA (0.2 microM), but only an 11 fold increase in tissues contracted with PMA (0.5 microM). 5. It is concluded that the action (s) of EDRF (NO) are impaired in the presence of PMA by a mechanism that may involve the stimulation of protein kinase C in vascular smooth muscle cells.

Acetylcholine↗
PubMed1989

Tissue-type plasminogen activator variants with domain duplications and rearrangements.

The interactions between tPA domains that are important for catalysis are poorly understood. We have probed the function of interdomain interactions by generating tPA variants in which domains are duplicated or rearranged. The proteins were expressed in a transient mammalian expression system and tested in vitro for their ability to activate plasminogen, induce fibrinolysis and bind to a forming fibrin clot. Duplication of the heavy chain domains of tPA produced enzymatically active tPA variants, many of which demonstrated similar in vitro amidolytic and fibrinolytic activity and similar fibrin affinity to the parent molecule. Zymographic analysis of the domain duplication tPA variants showed one major active species for each variant. Selection of the residues duplicated and the interdomain spacing were found to be critical considerations in the design of tPA variants with duplicated domains. We also rearranged the domains of tPA such that kringle 1 replaced the second kringle domain and vice versa. An analysis of these variants indicates that the first kringle domain can confer fibrin affinity to a tPA variant and function in place of kringle 2. Therefore, in wild-type tPA, the functions of kringle 1 and kringle 2 must be dependent partially on their orientation within the heavy chain of the protein. The functional autonomy of the heavy and light chains of tPA is demonstrated by the activity of a tPA variant in which the order of the heavy and light chains was reversed.

Base Sequence↗
PubMed1989

Structure-function analysis of tissue-type plasminogen activator by linker-insertion, point and deletion mutagenesis.

We undertook a structure--function analysis of human tissue plasminogen activator (tPA) using linker-scanning and deletion mutagenesis. Synthetic oligonucleotide linkers were introduced into the tPA cDNA at pre-existing restriction enzyme sites. This generated a series of tPA variants which contained small primary sequence alterations consisting of point mutations, deletions or insertions. The majority of the linker-insertion variants demonstrate a significant reduction in amidolytic and fibrinolytic activity in comparison to wild-type tPA. The exceptions are the variants with linker-inserts placed at the BglII(115) and StyI(277) sites of the tPA cDNA (4SLEG5 and 57LEA58 respectively), which encode insertions at the boundaries of the finger domain. The variants with linker-inserts in the light chain (protease domain) of tPA are the lowest in enzymatic activity. Particularly sensitive to mutation are highly conserved amino acids. Heavy chain deletion variants were constructed from point mutants at the domain boundaries of tPA. Deletion of the kringle domains lowers the fibrinolytic activity to a greater extent than deletion of the finger or growth factor domains. We conclude that alterations in any domain of the tPA molecule, and particularly in the highly conserved residues within these domains, can affect fibrinolytic activity.

Amino Acid Sequence↗
PubMed1989

Excitatory effect of morphine and opioid peptides in the rat isolated colon.

Morphine and the opioid peptides cause isolated segments of rat colon to contract and relax rhythmically. This study re-examines two hypotheses to explain this phenomenon: Release of 5-hydroxytryptamine (5-HT)/acetylcholine by morphine or inhibition of a tonically active non-adrenergic, non-cholinergic (NANC) inhibitory mechanism. Rhythmic contractions induced by morphine (5 x 10(-6) M) were naloxone sensitive (10(-6) M) but unaffected by methysergide (10(-6) M), atropine (10(-6) M) or pretreatment of rats with p-chlorophenylalanine (200 mg kg-1 i.p. for four days) which lowered the 5-HT level in the colon from 3.73 +/- 0.83 mg g-1 in controls to 0.41 +/- 0.06 mg g-1 (P less than 0.001). The pattern of rhythmic contractions produced by morphine was unlike those produced by 5-HT (5 x 10(-6) M), acetylcholine (5 x 10(-6) M) or potassium chloride (30 mM). Tetrodotoxin (10(-6) M), apamin (10(-8) M), clonidine (2 x 10(-8) M), phentolamine (10(-5) M) or oxprenolol (10(-5) M) caused rhythmic contractions which were unaffected by naloxone. Clonidine contractions were inhibited by yohimbine (10(-7) M) but not by prazosin (10(-6) M). Electrical field stimulation at the peak of a contraction induced by morphine, apamin or clonidine, produced an inhibitory response which was unaffected by atropine, phentolamine, propranolol and guanethidine (all 10(-5) M). It persisted in colon segments from the rats with reserpine or 6-hydroxydopamine. These results suggest that neither the 5-HT/acetylcholine hypothesis nor inhibition of the NANC mechanism adequately explains the excitatory effect of morphine in the rat colon.

Acetylcholine↗
PubMed1988

Transcription of the Rhodobacter capsulatus nifHDK operon is modulated by the nitrogen source. Construction of plasmid expression vectors based on the nifHDK promoter.

We characterized the Rhodobacter capsulatus nifHDK promoter by nucleotide sequencing and nuclease S1 analysis of mRNA-protected DNA probes. Comparison of this promoter to nifP and ntrP promoters from other species reveals extensive homology to the canonical nifP consensus sequence. Using lac fusions we have demonstrated that transcription of the nifHDK operon is totally repressed when the growth medium is supplemented with ammonia, becomes fully derepressed in ammonia-free medium, and proceeds at intermediate levels when other nitrogen sources are used. Based on this information, we constructed plasmid expression vectors in which the rates of transcription from cloned DNA fragments are determined by the nitrogen source used in the growth medium.

Base Sequence↗
PubMed1988

Clonidine and morphine increase [3H]-noradrenaline overflow in mouse vas deferens.

1. Field stimulation of mouse isolated vas deferens produced a biphasic contraction that consisted of an initial brief non-adrenergic, non-cholinergic (NANC) twitch, followed by a more prolonged noradrenergic component. 2. Field stimulation of vasa, previously loaded with [3H]-noradrenaline ([3H]-NA), increased the amount of radioactivity in the Krebs bathing solution; 77% of this radioactivity was derived from [3H]-NA. 3. Tetrodotoxin (3 x 10(-6) M) abolished the biphasic motor response to field stimulation and the accompanying increased overflow of [3H]-NA. 4. Morphine (10(-7)-10(-5) M) inhibited the initial NANC component but potentiated the secondary noradrenergic component of the motor response to field stimulation. Morphine also increased the field stimulation-induced overflow of radioactivity. Naloxone (10(-6) M) antagonized the effects of morphine on the motor response and also on the overflow of radioactivity. 5. Clonidine (10(-9)-10(-7) M) inhibited the initial NANC component but potentiated the secondary noradrenergic component of the motor response to field stimulation. Clonidine also increased the field stimulation-induced overflow of radioactivity. 6. The ability of morphine (10(-7) M) and of clonidine (10(-9) M) to potentiate the field stimulation-induced overflow of radioactivity persisted in the presence of a combination of tranylcypromine (10(-5) M), desmethylimipramine (10(-5) M) and 17-beta-oestradiol (10(-5) M). 7. The inhibition of the initial NANC component of the motor response to field stimulation produced by morphine and clonidine may be related to the ability of these drugs to potentiate both the secondary noradrenergic component and the overflow of radioactivity, if the NANC transmitter is involved in regulating NA release.

Animals↗
PubMed1987

Depression in patients referred for psychiatric consultation. A need for a new diagnosis.

The authors analyzed 329 referrals for psychiatric consultation from medical and surgical wards. They found depression to be the most prevalent diagnosis (34%), with Major Depression being the most common DSM-III subtype (49%). Depression was predominant in the elderly (p less than 0.05), in women (p less than 0.05), and in patients with a high degree of psychosocial stressors (p less than 0.01). There were significant differences among the DSM-III subtypes of depression in some of these correlates. The authors emphasize the importance of DSM-III in differentiating among the subtypes of depression in referred patients but they suggest the need for a new diagnosis for depression in the physically ill.

Adjustment Disorders↗