PubMed Health⌕ Search

Biomedical subjects

C Robertson

Publications and source records attributed to C Robertson.

At least 19 recordsLinked to original sources
PubMed1992

Rapid ultrastructural changes in the dense tubular system following platelet activation.

The dense tubular system (DTS) functions to regulate platelet activation by sequestering or releasing calcium, similar to the sarcotubules of skeletal muscle. In resting platelets, the DTS exists as thin elongated membranes. Within 10 seconds of the addition of thrombin, platelets show a major ultrastructural change in their DTS: from the thin elongated form to a rounded vesicular form. These morphologic changes were demonstrated with two different stains and two different fixation methods. Platelets exposed to the calcium ionophore A23187 showed the same ultrastructural changes in the DTS. In contrast, the DTS remains in a thin elongated form when platelets are stimulated by the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and oleoylacetylglycerol (OAG). These morphologic changes may be related to the discharge of calcium from the DTS because this is stimulated by thrombin and A23187, but not by PMA. Preincubation of the platelets with the intracellular calcium chelator 5,5'-dimethyl-bis-(0-aminophenoxy)-ethane-N,N,N',N tetra acetic acid (BAPTA) largely prevented both the thrombin-induced rise in intracellular calcium and the changes in DTS morphology, suggesting that the changes in DTS morphology are secondary to the increase in cytosolic calcium. The results provide a morphologic correlate to existing biochemical evidence showing that the DTS is involved early during paltelet activation.

Blood Platelets↗
PubMed1992

A prospective assessment of quality of life after endoscopic intubation and laser therapy for malignant dysphagia.

BACKGROUND: This study evaluated the effect of endoscopic treatment for malignant dysphagia on quality of life (QL) as part of a prospective comparison of Nd:YAG laser therapy and intubation. METHODS: Two QL instruments were used: the Quality of Life Index (QLI) and a Linear Analogue Self-Assessment (LASA). Only 23 of 43 patients receiving laser therapy and 15 of 30 having endoscopic intubation agreed to partake in QL assessment; serial measurements until death were obtained in 13 and 9 patients, respectively. RESULTS: Dysphagia grade (DG) as measured on a 5-point scale, correlated significantly with LASA (n = 92; r = -0.51; P less than 0.0001) and QLI (n = 92; r = -0.43; P less than 0.0001) scores. In addition, there was a strong correlation between LASA and QLI scores (r = 0.678; P less than 0.0001). All patients followed up serially until death derived significant palliation of their dysphagia with laser treatment and intubation. Such therapy resulted in a significant initial improvement in QL, with the mean best LASA and QLI scores after treatment being higher than the corresponding mean pretreatment scores (P less than 0.004). However, this improvement proved transient; QL worsened significantly as a patient's general condition deteriorated during the final stages of the illness. The mean last post-treatment LASA and QLI scores in both groups (recorded within 5 weeks of death) were less than the corresponding mean pretreatment scores (P less than 0.004). CONCLUSIONS: Endoscopic palliation of malignant dysphagia results in a significant initial improvement in QL. Subsequently, QL worsens appreciably as a patient's general condition deteriorates during the terminal phase of disease.

Aged↗
PubMed1992

Sharing of antigenic epitopes between synaptophysin and granulophysin.

The immunological crossreactivity between the two granule-specific membrane glycoproteins, synaptophysin and granulophysin, was studied using a series of site-specific monoclonal and polyclonal antibodies. The epitope relatedness of six monoclonal antibodies against granulophysin was examined by competitive ELISA. The antibodies are shown to recognize distinct, but overlapping epitopes within a compact region that is constructed by the three-dimensional configuration of the molecule. All these antibody clones also recognize rat neuronal synaptophysin. Two monoclonal antibodies against synaptophysin, of which one is the well-characterized SY38 antibody, directed against the carboxy terminal of the molecule, are also shown to react with granulophysin. Characterized polyclonal antibodies against different peptide antigens of synaptophysin failed to recognize granulophysin. Synaptophysin and granulophysin are distinctly recognized in brain cell (white matter) and the pituitary both qualitatively and quantitatively. Based on these and other observations, it is suggested that the repeat motif in the cytoplasmic tail of synaptophysin represents an immunodominant construct that is the target for the observed crossreactive antibodies and that a similar tertiary construct has been preserved in granulophysin and in other transmembrane proteins.

Animals↗
PubMed1992

Dietary nonprotein calories and cerebral infarction size in rats.

BACKGROUND AND PURPOSE: Conventional diets may cause hyperglycemia in patients with neurological injuries. The purpose of this study was to examine the effect on the severity of cerebral infarction of replacing carbohydrates as the primary dietary source of nonprotein calories. METHODS: Sixty-nine Long-Evans rats were either fasted for 24 hours, fed isocaloric amounts of a control diet containing 51.5% of the calories as carbohydrates, or fed one of five experimental diets before middle cerebral artery occlusion for 45 minutes. In the experimental diets, 60% of the carbohydrate calories were replaced with one or more of the following substrates: 1,3-butanediol, triacetin, tributyrin, and long- and medium-chain triglycerides. RESULTS: The plasma glucose concentration in the fasted animals was 6.4 +/- 1.1 mumol/ml. In the animals receiving the control diet, which contained the greatest number of carbohydrate calories, plasma glucose was 9.1 +/- 1.4 mumol/ml. The 1,3-butanediol diet resulted in an intermediate plasma glucose concentration averaging 7.8 +/- 1.3 mumol/ml. Plasma beta-hydroxybutyrate levels were elevated in the fasted group and with the 1,3-butanediol diet. Plasma acetate levels were increased with the diets supplemented with triacetin. The smallest infarct volume (53 +/- 43 mm3) was found in the fasted group and the largest (162 +/- 56 mm3) in the control diet group. Infarct volumes that were significantly smaller were found with the 1,3-butanediol diet (98 +/- 41 mm3) and with the triacetin/tributyrin diet (105 +/- 53 mm3). The volume of the infarct was directly related to the plasma glucose concentration before ischemia (n = 69, r = 0.47, p less than 0.01), but not to plasma lactate, ketone body, or acetate levels. CONCLUSIONS: It may be possible to develop a diet for patients with neurological injuries using noncarbohydrate calorie sources, such as 1,3-butanediol, triacetin, or tributyrin, that would supply systemic caloric and protein requirements without the adverse effect of conventional diets.

Animals↗
PubMed1992

The ergonomic analysis of a trauma resuscitation room.

Ergonomics is the practical and scientific study of people in relation to their working environment. We describe its application to the operation of a trauma resuscitation room. We used specifically designed computer software. This methodology enables a unique and objective assessment of the design and operation of a clinical system. It may be particularly applicable to other hospital areas where the efficient interaction of staff, patients and equipment is crucial to the optimal clinical outcome.

Equipment and Supplies, Hospital↗
PubMed1992

The fecal osmotic gap: technical aspects regarding its calculation.

The fecal osmotic gap is considered to be useful in the investigation of chronic diarrhea. However, two important questions regarding the calculation of the osmotic gap remain unanswered: the effect of the method of measuring osmolality and the most appropriate means for its calculation. In 41 patients with varying causes of diarrhea, stool osmolalities and electrolyte concentrations were measured. Measurement of stool osmolality by a dew point technique underestimated results by a variable factor, which makes it an inappropriate method. Fecal osmolality measured by freezing point depression gave reliable results and so was considered to be preferable. The osmotic gap was calculated by two methods: subtraction of the calculated osmolality from (1) stool osmolality and (2) plasma osmolality. The former approach was found to be inappropriate on the basis of large variations in results when consecutive stool samples were analyzed, a poor correlation with the severity of osmotic diarrhea, poor resolution between results from patients with secretory diarrhea and those with osmotic diarrhea, and practical difficulties in ensuring adequate collection of stool samples.

Chronic Disease↗
PubMed1991

The effects of lipid lowering on diabetic retinopathy.

The effect of lipid lowering on hard exudates was determined in six consecutive patients with insulin-dependent diabetes mellitus. Diet and hypolipidemic drug therapy including the use of pravastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A reductase, were used to treat patients for one year. The total cholesterol concentration decreased from a mean baseline value of 231 mg/dl to a treatment mean value of 165 mg/dl. The mean low-density lipoprotein cholesterol concentration decreased from 157 mg/dl to 93 mg/dl. Masked grading of fundus photographs indicated an improvement in hard exudates in all six patients and a decrease in microaneurysms in four patients. Visual acuity improved in one patient and did not change (one line or less change) in five patients. No remarkable side effects resulting from treatment were observed. Our pilot study suggests that aggressive therapy of diabetic patients with hyperlipidemia may have a beneficial effect on background retinopathy.

Adult↗
PubMed1991

Synthesis of intracellular histamine in platelets is associated with activation of protein kinase C, but not with mobilization of Ca2+.

In previous reports, we have provided evidence indicating that newly formed histamine is an intracellular messenger in human platelets. The involvement of protein kinase C (PKC) and intracellular calcium (Ca2+i) in the synthesis of histamine was investigated. Human platelets were stimulated by phorbol 12-myristate 13-acetate (PMA), collagen and the Ca2+ ionophore A23187, with or without the PKC inhibitor staurosporine. Aggregation, histamine synthesis and phosphorylation of pleckstrin (47 kDa; P47) and myosin light chain (20 kDa; P20) proteins were monitored. Staurosporine inhibited PMA- and collagen-induced aggregation, histamine synthesis and phosphorylation of 47 kDa and 20 kDa proteins in a dose-dependent manner. For PMA, median inhibitory concentrations (IC50 values) for staurosporine inhibition of aggregation, histamine synthesis and phosphorylation were similar, suggesting that histamine synthesis induced by this agonist may be a consequence of PKC activation. Conversely, collagen-stimulated histamine synthesis was inhibited by staurosporine at concentrations significantly higher than those required to inhibit aggregation (P less than 0.005) or pleckstrin phosphorylation (P less than 0.01), indicating the possible involvement of non-PKC mechanism(s) in the synthesis of histamine induced by this agonist. A23187 failed to induce the synthesis of intracellular histamine in platelets, whereas staurosporine blocked A23187-induced aggregation and phosphorylation of the 20 kDa protein at significantly higher concentrations than those needed to inhibit PKC. When platelets were stimulated with a combination of A23187 and PMA, the increase in platelet histamine was less than that with PMA alone. The results provide evidence that the synthesis of intracellular histamine in platelets occurs as a consequence of PKC activation and may be down-regulated under conditions where there is a substantial rise in [Ca2+]i.

Adenosine Diphosphate↗
PubMed1991

Identification of a platelet dense granule membrane protein that is deficient in a patient with the Hermansky-Pudlak syndrome.

Monoclonal antibodies were raised after injecting mice with isolated human dense granules. Several of these monoclonals were found to recognize a 40-Kd dense granule membrane protein. Western blot and immunofluorescent analysis confirmed the dense-granule specificity. After thrombin activation, the protein was found in patches on the external platelet membrane. By Western blot and slot blot analysis, the protein was found to be markedly deficient in a patient with the Hermansky-Pudlak syndrome. Studies of neutrophils and endothelial cells show the presence of immunologically related granule-membrane protein(s). Western blots using four anti-synaptophysin antibodies and three antibodies to the platelet 40-Kd protein suggest that the protein may share some homology with, but is not identical to, the synaptosomal membrane protein synaptophysin.

Albinism, Oculocutaneous↗