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Biomedical subjects

T J Hall

Publications and source records attributed to T J Hall.

At least 109 records · Page 6Linked to original sources

Decreased natural killer cell activity in atopic eczema.

We have studied NK cell activity in atopic and non-atopic subjects using a standard 51Cr-release assay and K562 target cells. In atopics (AT) with allergic rhinitis and/or asthma, NK cell activity was similar to that in non-atopic (N) subjects, whilst patients with severe atopic eczema (AE) had depressed NK cell activity compared to AT or N subjects. In addition, circulating T-cell numbers and Con A responsiveness was decreased in AE, although neither parameter was correlated with decreased NK cell activity. However, decreased NK cell activity in atopic eczema was positively correlated with decreased numbers of Fc gamma + lymphocytes (P = 0.01) and decreased effector: target cell binding (P = 0.05), and negatively correlated with increased monocytes in AE (P = 0.09). AE NK cell activity was equally or more sensitive to the inhibitory effects of drugs such as dibutyryl cyclic AMP, prostaglandins (PG) D2,E2 and histamine. The relative percentage increase in NK cell activity by the interferon inducer poly I:C was similar in AE patients and controls. The results suggest that reduced numbers of circulating NK cells and pre-NK cells account for the depressed level of NK cell activity in subjects with severe atopic eczema.

Adult↗

Does oxpentifylline ('Trental') have a place in the treatment of intermittent claudication?

In a randomized double-blind study, the clinical and haemorrheological responses of 40 patients receiving oxpentifylline (200 mg 3-times daily) were compared with those of 40 patients receiving placebo. The treatment period in both groups was 2 months. The parameters measured before and after treatment were: subjective response; claudication and maximum walking distances; ankle systolic indices; maximum blood flow in the lower limb by gravimetric plethysmography; plasma fibrinogen; erythrocyte deformability and whole blood viscosity. There was a significant increase (p less than 0.05) in mean erythrocyte deformability in the oxpentifylline group but not in the placebo group; this apparent difference between the groups, however, was not significant. The placebo group showed a significant improvement (p less than 0.05) in claudication distance and mean plasma fibrinogen concentration, but no such improvements were observed in the oxpentifylline group. There were no significant differences in either of the two groups with regard to the subjective response, ankle systolic indices, maximum limb blood flow or whole blood viscosity. It is concluded that oxpentifylline , when taken in oral form at the dose used in this study, increased erythrocyte deformability without conferring any clinical or haemorrheological benefit to patients with intermittent claudication.

Adult↗

Isolation of repetitive DNA sequences from human chromosome 21.

We have developed a method for the isolation of phage from the human genomic library that carry repetitive DNA sequences highly represented on specific human chromosomes. We have used this technique to select recombinants carrying inserts concentrated on chromosome 21. Five clones, representing two families of sequences, have been characterized. Members of each family show cross-homology, but the two families show no homology with each other. In all but one case, the clones do not contain members of the human Alu repeat family. Single chromosome-concentrated repetitive sequences should prove to be useful in studies of the origin, evolution, and function of repetitive DNA and in regional chromosome mapping.

Animals↗

Inhibition of human natural killer cell activity by prostaglandin D2.

We have studied the effect of prostaglandin (PG) D2 on human natural killer (NK) cell activity using 51Cr-labelled K562 target cells. PGD2 caused a dose dependant inhibition of NK cell activity, producing maximal, non-toxic inhibition at a concentration of 1 X 10(-6) M. This inhibition was not due to interference with effector:target cell binding (E:TCB) and was seen using Percoll-enriched NK cells. A time dependent inhibition of NK cell activity was seen when dibutyryl cyclic AMP (DiBcAMP) and PGD2 were added in parallel to the NK cell assay suggesting that PGD2 directly inhibits NK cell activity via the adenylate cyclase system which modulates the killing process.

Adult↗

The role of prostaglandins in the modulation of histamine suppression of mitogen responses in atopic and normal subjects.

We have shown that lymphocytes from atopics are more sensitive to histamine-induced suppression of mitogen transformation than are cells from normal subjects. Recent reports have suggested that histamine suppression may act via prostaglandin synthesis. We have investigated this and found that indomethacin partially reversed the histamine suppression seen in atopics, but not that in normals. This effect was seen even when the direct enhancing effect of indomethacin was taken into account. The direct effect of indomethacin on mitogen-induced transformation was similar in both normal and atopic cultures, which suggests that these results are not due to the presence of PG producing cells in atopic cultures, but rather that histamine modulates the function of these cells. It was found that a specific H2 agonist, but not an H1 agonist could partially mimic the effect of histamine this system.

Adolescent↗

The lack of effect of histamine--protein conjugates on human lymphocyte responses to concanavalin A and histamine.

We have studied the effect of depleting human peripheral blood lymphocytes (PBL) on plates coated with histamine-rabbit serum albumin (H-RSA) or control (E-RSA) conjugates, on the concanavalin A (Con A) response and the histamine suppression of Con A responses. Low H10-RSA-substituted conjugate depletion had little effect on [3H]-thymidine incorporation of Con A-stimulated cells compared to control (E10-RSA) conjugates and unseparated cells, but significantly increased unstimulated cell counts, therefore reducing stimulation index (SI). Highly histamine-substituted (H30-RSA) and control (E30-RSA) conjugates decreased SI in a similar way, but also decreased the [3H]-thymidine incorporation of Con A-stimulated cells. Histamine suppression of Con A responses was reduced by both E10- and H10-RSA-coated plates at suboptimal but not optimal mitogen concentrations. The induction of Con A-induced suppressor cells was unaffected by prior depletion of cells on H10- or E10-RSA conjugate-coated plates. Addition of H10- and E10-RSA to Con A cultures had a slight enhancing effect on transformation, but no effect on histamine suppression of the Con A response. Thus, whilst it is clear from other studies in vitro that functional histamine receptors are present on suppressor T cells, the results presented here show that histamine-protein conjugates do not specifically bind to histamine receptor-bearing human peripheral blood suppressor T lymphocytes.

Concanavalin A↗

Modulation of human natural killer cell activity by pharmacological mediators.

We have studied the effects of various pharmacological mediators on human NK cell activity. Prostaglandin E2 (PGE2) inhibits NK cell activity in a dose-dependent fashion, whereas PGF2 alpha has no significant effect over the same concentration range. Histamine at high doses (10(-4) M) induced a small but significant inhibition of NK cell activity which was mimicked by both H1 and H2 specific histamine receptor agonists. Inhibition of endogenous prostaglandin production by indomethacin did not alter NK cell activity. Inhibition of NK activity by cAMP but not cGMP analogues, together with other data presented suggests that the mechanism of PGE2-induced inhibition of NK cell activity is not due to impairment of effector cell movement or effector: target cell interaction, but through the adenylate cyclase system which modulates the killing process.

Bucladesine↗

Does the type of suture material contribute to the strength of the lateral paramedian incision?

A prospective randomized trial was carried out on 231 consecutive laparotomies in which the lateral paramedian incision was used in all cases. Closure of the wound was identical except for the anterior rectus sheath where closure was randomized to (a) chromic catgut, (b) polyglycolic acid or (c) polypropylene. Follow-up for 1 year has revealed no wound dehiscences and only one incisional hernia (in the catgut group). We conclude that the lateral paramedian incision is inherently strong, and that this strength is due to splintage of the wound by the rectus abdominis muscle itself and is unrelated to the type of suture material used.

Abdomen↗

The lateral paramedian incision--experience with 850 cases.

We present our experience in 850 consecutive patients who had a laparotomy through a lateral paramedian incision during the period 1977-1981. These patients underwent both elective and emergency procedures covering a wide range of intra-abdominal conditions, and had a high incidence of factors known to predispose to wound dehiscence and incisional hernia formation. Follow-up in each case for at least 1 year revealed no wound dehiscences and 3 incisional hernias (0.37 per cent). We conclude that the lateral paramedian incision is inherently strong and that this strength is due to the splintage of the wound by the rectus abdominis muscle and the wide shutter mechanism that this provides.

Adolescent↗

Radionuclide and contrast venography following caval interruption by the Mobin-Uddin umbrella filter.

Either radionuclide or contrast venography, or both, were performed in nine patients 2 months to 4 years after insertion of Mobin-Uddin caval umbrella filter for prevention of recurrent pulmonary embolism. In six patients the cava was occluded, and three major groups of collaterals were observed (central, intermediate and superficial). Large gonadal veins, which may predispose to recurrent embolism, were seen in two cases. Radionuclide venography gave a clear indication of caval patency or occlusion, and distinguished central from superficial collaterals. Identification of specific gonadal veins required contrast femoral or iliac venography.

Collateral Circulation↗

Effect of histamine, H1 and H2 agonists on E-rosette formation in normal and atopic subjects.

The effect of histamine on the capacity of human peripheral blood lymphocytes to form E rosettes was studied in normal and atopic subjects. Histamine had little effect on E-rosette formation (E-RF) in atopic subjects, but significantly inhibited E-RF in normal subjects in a dose-dependent fashion. To investigate this phenomenon further, specific histamine type 1 and 2 receptor agonists were used in the rosette assay. The H1 receptor agonist caused significant inhibition of E-RF in both normal subjects and atopics, whereas the H2 agonist produced significant inhibition of E-RF in normal but not atopic subjects. The results indicate a histamine type 2 receptor dysfunction in a subpopulation of atopic peripheral blood T lymphocytes.

Animals↗

Kinetic and equilibrium metal-ion-binding behaviour reflected in a metal-ion-dependent antigenic determinant in bovine prothrombin. Comparison with bovine prothrombin fragment 1.

Rabbit anti-(bovine prothrombin fragment 1) antibodies were fractionated by using fragment-1 affinity chromatography in the absence of metal ions, and showed an absolute requirement for the presence of metal ions in their interactions with bovine fragment 1 or prothrombin. These antibodies were employed to evaluate both the rate constants for a protein conformation change and the equilibrium metal-ion binding to isolated bovine fragment 1 and intact prothrombin. The close similarity of the rates obtained for the conformation change in fragment 1 and those observed in prothrombin indicated that the same process is involved in both proteins and that the non-fragment-1 region of the prothrombin has essentially no effect on this process in the fragment-1 region. Equilibrium metal-ion-binding studies indicate that the details of the metal-ion-binding process in fragment 1 and prothrombin are essentially the same. We conclude that the metal-ion-binding behaviour of the fragment-1 domain of intact prothrombin is identical with that of isolated fragment 1.

Animals↗

Evolutionary distances in Hawaiian Drosophila measured by DNA reassociation.

Comparisons of the sequence divergence of three species of Hawaiian Drosophila have been made by hybridization of single-copy tracer DNA of each of the species with driver DNA from each species, and measurement of the average melting temperature (Tma) in a chaotropic solvent (2.4 M tetraethylammonium chloride) which minimizes differences due to base composition. Correction was made for the length of hybrid duplex regions to obtain the reduction in thermal stability due to divergence. An accuracy of +/- 0.2 degrees C was achieved and the mean reduction in Tm for hybridization between D. heteroneura and D. silvestris (found only on the island of Hawaii) was 0.55 degrees C and between D. picticornis, found only on the island of Kauai, and the other two species was 2.13 degrees C. The rate of DNA change is estimated to be between 0.2 and 0.4%/My by assuming that the D. heteroneura-D. silvestris divergence occurred 0.8 My ago and the divergence between these species and D. picticornis between 4 and 6 My ago. The general single copy DNA sequence divergence appears to be very much greater than the minimal coding region sequence divergence previously estimated from allozyme studies.

Animals↗

Vertical abdominal incisions--a choice?

A prospective randomized trial was carried out on 207 patients undergoing laparotomy using three different vertical abdominal incisions--midline, 'medial' paramedian incision and 'lateral' paramedian incision. The lateral paramedian incision is slightly more time-consuming to perform than the other two incisions but there is a statistically greater incidence of incisional hernia in midline and medial paramedian wounds than with the lateral paramedian incision. It is suggested that when a vertical abdominal incision is being considered the lateral paramedian should be the incision of choice.

Adolescent↗

The value of laparoscopy under local anaesthesia in 250 medical and surgical patients.

This study reports our experience of laparoscopy under local anaesthesia in 250 patients; the procedure was safe, quick and easy to perform with minimal inconvenience to the patient. We advocate the early use of laparoscopy in patients with ascites and when there is difficulty in the diagnosis of patients with jaundice and hepatomegaly, an accurate histological diagnosis being obtained in the majority. In patients with intra-abdominal malignancy, in whom surgery is planned, laparoscopy can detect disseminated disease and so avoid an unnecessary laparotomy. Laparoscopy may also provide a diagnosis in patients presenting with a variety of vague symptoms such as abdominal pain, weight loss, lethargy etc. We have found laparoscopy an excellent investigation if positive but, as if only allows the surface inspection of viscera, when negative, we recommend caution in its interpretation.

Abdominal Neoplasms↗

Evolution of sea urchin non-repetitive DNA.

New methods have been applied to the determination of single copy DNA sequence differences between the sea urchin species Strongylocentrotus purpuratus, S. franciscanus, S. drobachiensis, and Lytechinus pictus. The thermal stability of interspecies DNA duplexes was measured in a solvent (2.4 M tetraethylammonium chloride) that suppresses the effect of base composition on melting temperature. The lengths of duplexes were measured after digestion with S1 nuclease and correction made for the effect of length on thermal stability. The degree of base substitution that has occurred in the single copy DNA during sea urchin evolution is significantly larger than indicated by earlier measurements. We estimate that 19% of the nucleotides of the single copy DNA are different in the genomes of the two sea urchin congeners, S. purpuratus, and S. franciscanus, which apparently diverged only 15 to 20 million years ago.

Animals↗