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Biomedical subjects

M Small

Publications and source records attributed to M Small.

At least 163 records · Page 9Linked to original sources
PubMed1982

Factor IX thrombogenicity: in vivo effects on coagulation activation and a case report of disseminated intravascular coagulation.

An episode of defibrination with bleeding following high dose Edinburgh Factor IX (D.E.F.IX) replacement in a patient with haemophilia B undergoing knee joint replacement is reported. We have also monitored plasma fibrinopeptide A levels in patients with haemophilia B following ten standard doses of D.E.F.IX (15-20 u/kg) and have been unable to document any change. Activation of the coagulation system, as previously noted, appears to be related to the use of Factor IX concentrates in high doses.

Adult↗
PubMed1982

DDAVP stimulates prostacyclin production.

Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.

Animals↗
PubMed1982

Tumor enhancing T lymphocytes in mice: further studies on characteristics and mechanism of activity.

In order to test the possibility that tumor-enhancing T lymphocytes can suppress other lymphoid cells, such as those with anti-tumor activity, their effect was tested in an allogeneic response of cell-mediated lysis. Normal thymocytes and spleen cells from mice with advanced tumors, two populations which enhance the growth of solid tumors, both suppressed the generation of CML. Since these results suggest that the mechanism of enhancement by T cells may resemble suppression in other immune responses, we looked for Fc receptors on the sensitized cells involved in tumor enhancement. Cells expressing Fc receptors appeared to be necessary for enhancement of tumor growth to occur.

Animals↗
PubMed1982

Effects of the non-selective beta-adrenoceptor blocking agent, carteolol, on platelet function, blood coagulation and viscosity.

We have studied the effect of a new beta-adrenergic blocker, carteolol, on platelet function, blood coagulation and viscosity in 10 healthy male volunteers. Following carteolol (5 mg orally) we were able to demonstrate significant inhibition of platelet aggregation to ADP (p less than 0.05) and adrenaline (p less than 0.01) after 5 hours, but not at 2 or 24 hours. This maximum inhibition of platelet aggregation corresponded to peak plasma concentrations of carteolol measured. The platelet release reaction, as measured by plasma levels of the platelet specific protein beta-thromboglobulin (BTG) was unaltered and there was no significant effect on a panel of coagulation tests or on blood viscosity.

Adenosine Diphosphate↗
PubMed1982

Danazol and oral anticoagulants.

A case report of overt bleeding in a young woman on warfarin given the anabolic steroid danazol for menorrhagia is reported. This interaction appears to be poorly recognised and we suggest that when commencing such a treatment the dose of anticoagulant should initially be halved and thereafter tailored to the thrombotest.

Administration, Oral↗
PubMed1980

Cricopharyngeal myotomy in motor neurone disease.

Twenty-five patients with dysphagia caused by neurological disorders, mainly motor heurone disease, underwent cricopharyngeal myotomy. Nineteen patients showed slight to dramatic improvement of swallowing for variable periods of time. There were five postoperative deaths. The results indicate that this simple procedure is of benefit to a substantial proportion of patients with neurological causes of dysphagia.

Adult↗
PubMed1979

Purification of the messenger ribonucleic acid for the lipoprotein of the Escherichia coli outer membrane.

The mRNA for the lipoprotein of the Escherichia coli outer membrane has been purified to 85% homogeneity. The purification procedure involved phenol extraction, NaCl extraction, gel filtration on Sephadex G-100 and Sephadex G-200, and reversed-phase column chromatography on RPC-5. The purity of the final product was estimated to be 85% by analysis of the ribonuclease T1 fingerprint of the mRNA. The purified mRNA was able to direct the synthesis of cross-reactive material with antilipoprotein serum in both the E. coli and the wheat germ cell-free protein-synthesizing systems. The size of the mRNA was determined to be 8.2 S from its mobility in polyacrylamide--agrose gels. During the purification, two other RNA species, similar in size to the lipoprotein mRNA, were also isolated. Their sizes were determined to be 8.7 and 9.1 S. They both were inactive in an E. coli cell-free protein-synthesizing system.

Cell Membrane↗
PubMed1979

Release of immature cells from the thymus during solid tumor growth: identification by assay of TdT activity.

In vivo anti-tumor activity of spleen cells from C3H/eb mice bearing a syngeneic fibrosarcoma was shown previously to decline to an undetectable level and be replaced by tumor-enhancing activity as tumor growth proceeds. In the light of our findings that thymocytes in the early stages of thymic processing can bring about tumor enhancement, we postulated that premature release of thymocytes and their accumulation in the spleen might account for the loss of the anti-tumor response. In the present experiments an injection of thymocytes did in fact cancel the anti-tumor response of reactive splenocytes from tumor-bearing mice. In order to determine whether premature thymocyte release occurs naturally in the tumor-bearing animals, we assayed activity of the enzyme TdT (as a marker for thymus cells) in the spleens of these mice during progressive tumor growth. Cells with TdT activity were clearly evident in the spleens of the tumor-bearing animals, were derived from the thymus, and accumulated in parallel to the loss of anti-tumour reactivity.

Animals↗
PubMed1978

The cervical somatosensory evoked potential (SEP) in the diagnosis of multiple sclerosis.

Abnormalities of the potential evoked by stimulation of the median nerve and recorded over the cervical spine were found in 59% of patients with multiple sclerosis (MS) this proportion increasing to 69% of those in the definite diagnosis category and to 100% in the severely disabled. Abnormalities were often found in the absence of relevant clinical signs and the method appears to be capable of revealing clinically silent plaques. In patients with a single episode of neurological disease, including retrobulbar neuritis, and at least compatible with the onset of MS, the proportion of abnormalities did not rise above 18%. Only prolonged follow-up will permit assessment of the value of this and other evoked potential techniques in the detection of the early case of the disease.

Adolescent↗
PubMed1978

Opposing reactivities of subpopulations of T lymphocytes toward syngeneic tumor cells: separation of early thymocytes.

The present communication is a continuation of earlier studies which indicated that interaction between syngeneic tumors and those lymphocytes in the early stages of thymic processing can result in enhanced tumor growth in vivo. The thymocytes involved in this tumor enhancement were found previously in the rapidly dividing subpopulation of subcapsular cortical thymocytes, both in the untreated thymus and in the thymus undergoing repopulation after cortisone depletion. In the present experiments we have isolated this small subpopulation of early thymocytes. After cortisone injection such cells could be separated from the medullary cortisone-resistant thymocytes since the latter cells exhibit a high level of surface H-2 antigens and were thus lysed preferentially by anti-H-2 serum and complement. The repopulating subcapsular early thymocytes, which were resistant to this treatment, were incapable of responding to PHA while their basal proliferation rate was undiminished, and the majority of the cells were found to be dividing. When such low H-2 early thymocytes were injected together with three different tumors into syngeneic mice their tumor-enhancing activity was evident. It is clear that such early thymocytes are not devoid of biologic reactivity and their release from the thymus could have decisive results.

Animals↗
PubMed1977

Pattern reversal evoked visual potential in the diagnosis of multiple sclerosis.

The pattern reversal evoked visual potential (VEP) was recorded in 37 normal subjects and in 186 patients in whom a diagnosis of multiple sclerosis (MS) was established or suspected. Taking the upper limit of normal as the mean +2.5 SD (111 ms), prolonged latency was found in 75% of definite cases of MS, 58% of probable cases, and 38% of possible cases. A smaller number of patients without prolonged latency had abnormal asymmetry of latency or low amplitude potentials. In patients with a single acute episode of neurological disease resembling MS the incidence of abnormal VEP was very low. In patients examined within three months of an episode of retrobulbar neuritis (RBN), latency was prolonged in 81% of affected eyes, a similar proportion being found in patients with a more remote history of RBN. The importance of establishing the normal for every laboratory engaged on this investigation is emphasised. Prolonged latency of the VEP is common in established MS but has not yet been shown to be a sensitive diagnostic test of the early case.

Adolescent↗
PubMed1977

Characteristics of the immature cells involved in T cell-mediated enhancement of syngeneic tumor growth.

Enhancement of tumor growth was observed when non-sensitized thymocytes were injected together with tumor cells into syngeneic mice, although this tumor enhancement was less pronounced than that caused by tumor-sensitized T lymphocytes. The cells within the thymus which are responsible for this tumor enhancement were found to be rapidly dividing and to be absent from the thymus a day after cortisone administration. At a longer time interval the cortison-depleted thymus was repopulated by dividing cells which exhibited tumor-enhancing reactivity. The characteristics of these cells suggest that they are in the early stages of thymic processing. The enhancing thymocytes were sensitive to treatment with the thymic humoral factor which functions in T cell maturation, and their enhancing activity was cancelled by such treatment. These results are compatible with our hypothesis that exposure of immature T cells to a tumor stimulus may lead to tumor enhancement whereas interaction between mature T lymphocytes and tumor cells may be required for tumor inhibition.

Animals↗
PubMed1976

Kinetics of the response of spleen cells from tumor-bearing animals in an in vivo tumor neutralization assay.

The behavior of spleen cells from tumor-bearing mice, vis-à-vis isologous tumor cells, was investigated by means of an in vivo adoptive neutralization test. C3H/eB mice were challenged with tumor cells from a chemically induced fibrosarcoma. Spleens from these animals were removed at weekly intervals following tumor inoculation, mixed with tumor cells, and tested for their influence on tumor growth in syngeneic recipient mice. Two phases in the reactivity of spleen cells from tumor-bearing mice were clearly distinguishable. In a first stage of tumor growth, these mice yielded specific tumor-inhibitory cells conferring protection. Subsequently, the protective activity declined leading to a second phase characterized by tumor enhancement. Both protective and enhancing activities were shown to be mainly dependent on the presence of T cells.

Animals↗
PubMed1976

Separation of populations of sensitized lymphoid cells into fractions inhibiting and fractions enhancing syngeneic tumor growth in vivo.

Separation of subpopulations of lymphoid cells sensitized against a syngeneic tumor was attempted by means of velocity sedimentation and the fractions were injected together with tumor cells into syngeneic hosts. Spleen cells from tumor-bearing mice or spleen cells sensitized on tumor cell monolayers could be fractionated into a subpopulation capable of inhibiting growth of the same tumor and a separable fraction which enhanced tumor growth. Activity of the tumor-inhibiting lymphocytes was not apparent in the presence of the tumor-enhancing cells. The former activity was associated with small lymphocytes and the latter with injection of larger cells. Preliminary experiments investigated the developmental relation between the cells responsible for these opposing activities.

Animals↗