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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 541 records · Page 30Linked to original sources
PubMed1991

Effect of glyceryl trinitrate and ice on dilation of hand veins.

Application of glyceryl trinitrate to a finger produced significant dilation of superficial hand veins. Gently rubbing ice over these veins for one minute slightly reduced this dilation, whereas rubbing ice over veins without glyceryl trinitrate caused significant venoconstriction. These results indicate that application of glyceryl trinitrate followed by local cooling may provide a simple and painless means of assisting venepuncture.

Female↗
PubMed1991

Platelet activation and alpha granule secretion in type IIB von Willebrand's disease.

Type IIB von Willebrand disease is characterized by enhanced ristocetin-induced platelet aggregation, spontaneous platelet aggregation, thrombocytopenia and the absence of the largest plasma von Willebrand factor (vWf) multimers. The absence of the largest plasma vWf multimers is related to their enhanced binding to platelets. The abnormal affinity of the IIB von Willebrand factor to platelets results in thrombocytopenia, but the mechanism is not known. We have studied the platelets from three patients with type IIB von Willebrand disease and have found evidence of platelet activation and alpha granule secretion as defined by increased amounts of von Willebrand factor, fibrinogen and the alpha granule protein PADGEM/GMP-140 on the surface of these platelets. The degree of thrombocytopenia appears to be directly related to the number of platelets with fibrinogen bound to the surface. PADGEM/GMP-140, an alpha granule membrane protein, fuses with the platelet plasma membrane after activation and is a site on platelets which binds to neutrophils or monocytes. This alpha granule protein may play an additional role in platelet clearance and thrombocytopenia in type IIB von Willebrand disease. This may, in part, explain the absence of thromboembolic phenomena despite the presence of activated platelets in patients with type IIB von Willebrand disease.

Blood Platelets↗
PubMed1991

Improved in-vitro quality of platelet concentrates stored in a dextrose-free synthetic medium.

The licensed balanced salt solution Plasma-Lyte, buffered with a clinical solution of sodium bicarbonate, was evaluated as a suspending fluid for platelet concentrates. Platelets suspended in this medium showed better pH maintenance over 5 days of storage compared to platelets stored in plasma (7.0 vs 6.45, P < 0.001). This was reflected in improvements in in-vitro indicators of platelet viability-hypotonic shock response (79 vs 48%, P < 0.05), aggregation to paired agonists (86 vs 62%, P < 0.05); and platelet size distribution (104 vs 119%, P < 0.001). Dissolved bicarbonate measurement showed less depletion of bicarbonate in the synthetic medium compared to plasma, which suggests a lower rate of lactate formation. A synthetic medium containing dextrose showed inferior platelet storage characteristics when compared to the plasma-lyte/bicarbonate medium in a paired study (Day 5, pH 6.53 vs 6.9, P < 0.05). The results suggest that utilization of substrates other than dextrose allows platelets to metabolize without the accumulation of lactate that leads to pH drops during storage in plasma, and continue to support the feasibility of storing platelets in a non-plasma environment.

Bicarbonates↗
PubMed1991

C-fos Induction in the Spinal Cord after Peripheral Nerve Lesion.

Immunocytochemical localization of a product of the proto-oncogene c-fos, Fos protein, was used to map the activity of a subset of rat spinal neurons at 3 days, 3 weeks and 3 months following section of the sciatic nerve. In a well-established experimental paradigm, the gene was induced by activation of primary afferent fibres with brief noxious sensory stimulation under anaesthetic. Central sciatic projections were demonstrated with isolectin B4 counterstain and GAP-43 immunocytochemistry. In Rexed's lamina II of the spinal cord, in which there is somatotopic organization of afferent terminals, Fos-positive neurons were largely restricted to the projection area of intact peripheral nerves. Three days after a sciatic nerve lesion, the number of Fos-positive neurons in a cord region innervated by the saphenous nerve was similar to control levels, but was markedly increased by 3 weeks, remaining elevated at 3 months. Three weeks after sciatic nerve section the lectin stain in the area of sciatic representation had almost completely disappeared, and conversely GAP-43 staining had greatly intensified. There was no evidence of invasion by Fos-immunoreactive cells of the area of sciatic representation. After 3 months both the size and the intensity of the lectin gap, and of the corresponding area of increased GAP-43 immunoreactivity, appeared reduced. Thus a peripheral nerve lesion was followed by a delayed increase in excitability of the spinal cord as assessed by c-fos expression, so that greater numbers of second-order neurons were activated by sensory stimulation of an adjacent intact nerve. These changes may be related to the sensory abnormalities which follow nerve damage.

Journal Article↗
PubMed1991

Hb Port Huron [alpha 56 (E5)Lys----ARG]: a new alpha chain variant.

We have determined the structural abnormality of a putative Hb E detected in an African-American family with no apparent Asian ancestry. The tryptic peptide map performed by high performance liquid chromatography showed that the electrophoretic variant was indeed Hb E [beta 26 (B8)Glu----Lys]. In addition, the tryptic map showed an abnormal peptide adjacent to the alpha T-6 peptide. The amino acid analysis and confirmatory restriction analysis of the DNA showed that a second mutation was also present, characterized by a substitution of arginine for lysine at residue 56 of the alpha chain. The variant is clinically silent and has been named Hb Port Huron for the city in Michigan where the family resides.

Base Sequence↗
PubMed1991

The measurement of complement fixation by autoantibodies directed against thyroid membrane antigens.

This paper describes the use of sensitized sheep red blood cells for the detection and titration of complement fixation by autoantibodies directed against human thyroid membranes in the serum of patients with autoimmune thyroid disease. Patients with elevated circulating levels of TPO antibodies and diagnosed as having autoimmune hypothyroidism (including Hashimoto's disease) or autoimmune hyperthyroidism (Graves' disease) were studied. Complement fixation titres were highest in those patients with autoimmune hypothyroidism compared with the autoimmune hyperthyroid group. Serum samples obtained from a group of patients with thyroid neoplasia and from normal healthy volunteers were negative in this test. The TPO antibody activity when "corrected" for its CF potency suggests that the autoantibodies found in autoimmune hypothyroidism are potentially more destructive than those found in the non-destructive autoimmune thyroid diseases.

Analysis of Variance↗
PubMed1991

Elisa for the measurement of complement C3 activation by autoantibodies directed against thyroid membrane antigens.

This paper describes the use of an ELISA technique to assess the involvement of the complement system in the pathogenesis of autoimmune thyroid disease (AITD). Microtitre plates coated with thyroid membrane antigen were exposed to serum samples obtained from AITD patients, all of whom showed elevated levels of circulating anti-thyroid autoantibodies, and dilute guinea pig serum, as a source of complement, was then added to the microtitre wells. The degree of activation of the classical complement pathway was assessed by measuring the bound complement component C3 using a peroxidase conjugated anti-guinea pig C3 antiserum. C3 fixation and activation was greater in the presence of serum from patients with Hashimoto's disease when compared with that seen in patients with autoimmune hyperthyroidism (Graves' disease). Serum samples obtained from normal healthy volunteers and from patients with thyroid neoplasia were negative in this assay. The method allows the calculation of a putative "biologically active autoantibody" level and analysis of these data confirm our earlier observation that the species of autoantibody found in autoimmune hypothyroidism are potentially more destructive than those found in other forms of AITD.

Animals↗
PubMed1991

Endogenous platelet fibrinogen surface expression on activated platelets.

Intracellular platelet fibrinogen surface expression was studied in arabinogalactan-purified, resting, and thrombin-stimulated platelets. Platelet fibrinogen is derived from endocytosis of plasma fibrinogen by megakaryocytes. Like a variety of other adhesive proteins, it is stored in the platelet alpha-granule. Platelet fibrinogen surface expression was studied by using the antigen-binding fragments of a murine monoclonal antibody to platelet fibrinogen, F26, and an immunopurified polyclonal antifibrinogen antibody. Studies correlating platelet fibrinogen surface expression with the presence of the glycoprotein IIb-IIIa (GPIIb-IIIa) complex showed that in the presence of ethylene glycol tetraacetic acid (EGTA) at 37 degrees C, neither the GPIIb-IIIa complex nor platelet fibrinogen was expressed on the surface of thrombin-activated platelets. Similar experiments performed in the presence of EGTA and calcium showed proportional expression of the GPIIb-IIIa complex and platelet fibrinogen. The addition of Arg-Gly-Asp-Ser-containing peptides, the pentadecapeptide of the fibrinogen gamma-chain carboxy terminus, or the monoclonal antibody 10E5, when directed against the GPIIb-IIIa complex before thrombin activation, inhibited 65% to 94% of the platelet fibrinogen expression, as determined with the polyclonal and monoclonal antigen-binding fragments. When these same inhibitory agents were added immediately after or 5 minutes after thrombin, the amount of inhibition decreased significantly. Similar studies with a washed platelet system revealed that when the inhibitors of platelet fibrinogen expression were added before thrombin stimulation, the degree of inhibition observed was only 24% to 38%. This suggests that the major portion of platelet fibrinogen expression involves the release of platelet fibrinogen and its subsequent binding to GPIIb-IIIa. This binding may occur within the open canalicular system or on the platelet surface; in either case, wherever the site of released platelet fibrinogen binding occurs, it can be markedly inhibited by the RGD-containing peptides and the gamma-chain fibrinogen peptides. Approximately 10% to 30% of platelet fibrinogen may be expressed prebound to a platelet receptor, or else it is released and binds to a platelet receptor other than the GPIIb-IIIa complex.

Amino Acid Sequence↗
PubMed1990

Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor.

Ten peptides, derived from human alpha 2-macroglobulin (alpha 2M) receptor by chemical or proteolytic digestion, were sequenced. Comparative analysis revealed that all of the resulting sequences were present within the cDNA-deduced structure of low density lipoprotein receptor-related protein (LRP) (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H., and Stanley, K. K. (1988) EMBO J. 7, 4119-4127). The findings provide evidence that the alpha 2M receptor and LRP are the same molecule. Further evidence comes from immunoprecipitation experiments using a monoclonal antibody specific for the alpha 2M receptor that show this molecule, like LRP, to contain two polypeptides of approximately 420 and 85 kDa that are noncovalently associated. An additional component of this receptor system is a 39-kDa polypeptide that co-purifies with the alpha 2M receptor during affinity chromatography. Solid phase binding studies reveal that the 39-kDa polypeptide binds with high affinity (Kd = 18 nM) to the 420-kDa component of the alpha 2M receptor. The apparent identity of LRP and the alpha 2M receptor suggests that this molecule is a multifunctional receptor with the capacity to bind diverse biological ligands and highlights a possible relationship between two previously unrelated biological processes, lipid metabolism and proteinase regulation.

Amino Acid Sequence↗
PubMed1990

Evaluation of immunohistochemical staining of breast tissue by an oestrogen-regulated protein, 24K according to epidemiological and radiological breast cancer risk criteria.

The staining characteristics of monoclonal antibodies (MAb) are often determined on small numbers of biopsies. The true staining profile can only properly be determined when large numbers of biopsies are stained. We have examined the staining profile of 24K MAb on 146 benign breast biopsies. The staining characteristics were then grouped according to whether the patients were at high or low risk of breast cancer by current epidemiological or radiological risk criteria. This was done to detect whether 24K MAb could be used as a marker of cancer risk. Only Wolfe coded risk criteria showed staining differences between the two risk categories. Cytoplasmic staining was more common in the low risk Wolfe coded groups (P = 0.03, Fisher's exact test). We recommend that further studies be undertaken to evaluate the role of 24K MAb as a marker of cancer risk.

Adolescent↗