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Biomedical subjects

G J Johnson

Publications and source records attributed to G J Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1983

Hereditary diseases as causes of blindness in Newfoundland: preliminary report.

Hereditary disease appeared to account for more cases of registered blindness in Newfoundland and Labrador than indicated by the statistics of the Canadian National Institute for the Blind. The files of all 1013 people registered as of Dec. 31, 1981 were therefore reviewed, many persons were interviewed and examined, and pedigrees were researched. In 14.6% of cases either the diagnostic or the etiologic code had to be revised. The largest etiologic category was "genetic, established", which accounted for 24.0% of the cases registered. When cases of blindness presumed to be of genetic origin or due to polygenic inheritance were included it was estimated that 33% of all 1013 registered persons had a hereditary eye disease; this figure is higher than most of the previously published figures. Strategies for preventing blindness must be reconsidered, and genetic counselling and low-vision services must be made more widely available.

Blindness↗
PubMed1983

Spherophakia in a Newfoundland family: 8 years' experience.

In a family with eight siblings, five siblings have had spherophakia. One patient has died, but the other four have been followed up for 8 years. Two have undergone peripheral iridectomy because of steadily rising intraocular pressure. The operations were only partially successful in controlling the pressure. Whether associated with the Weill-Marchesani syndrome or not, spherophakia is difficult to manage. The lenticular myopia must be corrected (sometimes an additional reading correction is needed), and the intraocular pressure and visual field must be carefully monitored. The ability of the retinal circulation to withstand a high intraocular pressure for long periods may not be matched by a corresponding resilience of the drainage mechanism. Therefore, early peripheral iridectomy is probably advisable.

Adolescent↗
PubMed1982

Incomplete manifestations of myotonic dystrophy in a large kinship in Labrador.

In a large kinship affected by myotonic dystrophy (MyD), 133 subjects, including 21 spouses, were examined independently by a neurologist and an ophthalmologist to determine the earliest identifying evidence of the disease. Assessment included tonometry, slit-lamp examination, facial measurements, and electromyography (EMG). Thirty-two subjects, all of whom had EMG characteristics of myotonia, were definitely affected. Low intraocular tensions were a more consistent finding than lens opacities; endocrine abnormalities were absent. Twenty-seven subjects had one to five features but lacked clinical or electrographic evidence of myotonia; they were designated as having a "partial syndrome." Signs most commonly found included weakness of the upper face, brachial hyporeflexia, low intraocular tensions, and the presence of sparse colored specks at the posterior poles of the lenses. All but 2 subjects (siblings) with the partial syndrome had a parent with either MyD or the partial syndrome. Linkage studies indicated that 7 subjects should not be carrying the gene, while others could be regarded as having a minor expression of MyD. In most persons with the partial syndrome, we could not predict whether typical MyD would develop later. Transmission of the disease may depend upon more than a single autosomal dominant gene, and nongenetic influences may also be important.

Adult↗
PubMed1982

Erythrocyte membrane protein changes in glucose-6-phosphate dehydrogenase mutants with chronic hemolytic disease: an example of postsynthetic modification of membrane proteins.

1. G6PD mutants with CHD have decreased GSH, despite reticulocytosis, and increased membrane polypeptide aggregates. Aggregates increase logarithmically with decrease in RBC GSH. 2. These aggregates contain spectrin and can be depolymerized by disulfide reducing agents. Disulfide bonds between spectrin molecules and between the cytoskeleton and the cytoplasmic protein rigidify the red cell membrane and decrease RBC survival. 3. Direct oxidative damage of the RBC membrane, not Heinz body formation, explains the hemolytic anemia of G6PD mutants with CHD. This membrane damage may constitute a useful model system of oxidant-induced injury of other cells, and is an example of postsynthetic modification of membrane proteins by a nonmembrane gene.

Anemia, Hemolytic↗
PubMed1981

Peninsula pupil. Anomaly unique to Newfoundland and Labrador?

Forty cases of an unusual form of iris atrophy that results in a characteristically oval pupil have been seen in Newfoundland and Labrador. The anomaly is an atrophy of part of the sphincter pupillae, is confined to the iris, and is not associated with any systemic disorder. The great majority of those affected are male, and all have blue eyes. We suggest that it may be an inherited trait.

Aged↗
PubMed1981

Auer rod positive dysmyelopoietic syndrome.

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2-27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.

Aged↗
PubMed1981

Rapid return of cyclo-oxygenase active platelets in dogs after a single oral dose of aspirin.

A single dose of oral aspirin in human subjects inhibits the aggregation response of platelets to arachidonate and other agents for approximately one week after ingestion. In the present study we have evaluated the rate at which cyclo-oxygenase active platelets return to the circulation in humans and dogs and compared the response curves obtained to improvements in cyclo-oxygenase activity produced by the aspirin platelets. After a single dose of aspirin, dog platelet function was compromised for several days. Normal responses to arachidonate and other aggregating agents were restored six days after aspirin, and the pattern of recovery was the same for dogs and human subjects. However, cyclo-oxygenase active platelets returned to the circulation in dogs more rapidly than in humans and chemical competence was restored in both species well before correction of the defective response to aggregating agents. The delay of 1-3 days before return of significant numbers of cyclo-oxygenase active platelets most likely reflects acetylation of bone marrow megakaryocytes by the drug. More rapid return of chemically competent cells in dogs than humans probably relates to the more rapid turnover and shorter life span of canine platelets. The basis for the discrepancy in return of chemical integrity compared to functional activity after aspirin in vivo compared to simultaneous correction of chemistry and function when 10% normal platelets are added to aspirin platelets in vitro remains unresolved.

Administration, Oral↗
PubMed1981

Effect of Amrinone, a cardiotonic drug, on hemodynamics and platelet function.

In the present study we have investigated the effect of Amrinone on the hemodynamics, platelet counts, prostacyclin and thromboxane synthesis and platelet function. Results show that infusion of the drug increased the heart rate and lowered left atrial, aortic and pulmonary artery pressures within five minutes after a single bolus injection of 2 mg/kg IV dose. Platelet counts made from the blood obtained from anesthetized dogs after the drug infusion showed severe loss of platelets. However, infusion of a similar dose in awake dogs showed no such detrimental effect on platelets. Examination of formalin fixed blood for aggregates showed no more clumps in the treated samples than in the control. Platelets obtained from canine blood drawn at 30 minutes post infusion of the drug showed no aggregatory response to arachidonate. However, the response of these platelets to ADP was quite normal. Amrinone infusion had no inhibitory effect on the ability of vascular tissue to convert arachidonic acid to prostacyclin. Similarly, no inhibitory action could be observed on platelet cyclo-oxygenase activity at this concentration (2 mg/kg). In vitro studies on human platelets showed significant inhibition of cyclo-oxygenase at high concentrations (0.5 mg/ml). Therefore it is unlikely that the drug caused inhibition of the platelet response to arachidonate by the inhibition of prostaglandin synthesis during infusion, as the dose used was quite low (2 mg/kg) compared to what is required for the inhibition of cyclo-oxygenase.

Adenosine Diphosphate↗
PubMed1981

Aetiology of spheroidal degeneration of the cornea in Labrador.

To determine the aetiology of spheroidal degeneration of the cornea (Labrador keratopathy), total population surveys were conducted in 5 communities in coastal Labrador and northern Newfoundland. For 4 years records were also kept on all clinic patients aged 40 or more throughout the region. Both methods gave a peak prevalence at latitudes 55 degrees--56 degrees north. The greatest severity and earliest age of onset occurred around the same latitudes. Of the proposed environmental causative agents only ultraviolet radiation, reflected from ice and snow, explains the distribution of the disease. The high cumulative UV dosage is due to the unique geographical and climatic features of the region.

Adult↗
PubMed1981

Effect of inhibition of platelet function with carbenicillin or aspirin on experimental canine sudden death.

The role of blood platelets in the pathogenesis of experimental sudden death was evaluated in dogs. Coronary artery embolization resulted in acute myocardial ischemia that was followed by sudden death (death within 15 min of embolization) in 51% of anesthetized control animals. Pretreatment with carbenicillin, which markedly inhibited platelet aggregation or estradiol cypionate, which induced severe thrombocytopenia, significantly reduced the incidence of sudden death to 9% and zero, respectively. Pretreatment with aspirin, which uniformly inhibited platelet aggregation, was associated with a reduced incidence of sudden death (25%), but the difference between aspirin-treated and control animals lacked statistical significance. Drug treatment did not prevent myocardial infarction, and the sizes of myocardial infarcts observed in animals that survived 30 days were not different from those of control animals. Sudden death was preceded by a significantly greater fall in mean arterial pressure than that observed in survivors, but the frequency of ventricular ectopic beats did not differ in survivors and nonsurvivors. These studies suggest that (1) platelets play an important role in experimental sudden death which follows acute coronary embolization and (2) inhibition of platelet function protects against experimental sudden death by a mechanism that prevents severe hypotension but is not antiarrhythmic. Drug-induced platelet dysfunction and thrombocytopenia may protect against experimental sudden death by preventing intravascular platelet aggregation and embolization.

Animals↗
PubMed1981

Mechanisms of decreased erythrocyte deformability and survival in glucose 6-phosphate dehydrogenase mutants.

We have studied the nature of the oxidative lesion of the erythrocyte membrane in glucose-6-phosphate dehydrogenase (G6PD) mutants with chronic hemolysis, comparing these membranes with those from normal red cells (RBC) subjected to oxidative stress in vitro. Disulfide-linked polypeptide aggregates are found in membranes from fresh RBC of these G6PD mutants and from aerobically incubated normal erythrocytes. As further evidence of oxidative damage, increased disulfide bonds were found in the RBC membranes from both the mutants and incubated normal RBC. The intermolecular bonds which cross-link membrane polypeptides to form the observed aggregates, however, only accounted for a fraction of the membrane disulfide bonds present. Thus, most of the disulfide bonds in the G6PD mutants were intramolecular. These intramolecular disulfide bonds were widely distributed on the membrane polypeptides, but were found to be concentrated on cytoskeletal anchoring proteins, bands 2.1-2.3, using [14C] iodoacetamide labelling of the sulfhydryls involved in disulfide bonds. The intermolecular bonds, on the other hand, were concentrated in spectrin. When G6PD mutant membranes were examined on sucrose density gradients, a subpopulation of dense membranes was observed which resembled the membranes of oxidatively stressed normal RBC both in increased density and in increased binding of nonhemoglobin cytoplasmic protein. To study the relationship between sulfhydryl oxidation, membrane density and RBC viscosity the sulfhydryl oxidant diamide (diazine dicarboxylic acid bis-[dimethylamide]) was used. Diamide treated erythrocytes, like the G6PD mutants, had decreased GSH, increased polypeptide aggregates, increased viscosity, but no change in ATP. We conclude that in G6PD mutants with chronic hemolysis oxidative damage includes aggregate formation due to intermolecular disulfide bonds, and intramolecular disulfide bond formation associated with increased binding of non-hemoglobin cytoplasmic proteins to the membrane. The relative importance of intermolecular and intramolecular disulfide bond formation and the mechanism whereby these changes may produce decreased RBC deformability and survival remain to be determined.

Anemia, Hemolytic↗
PubMed1981

Sucrose density gradient analysis of erythrocyte membranes in hemolytic anemias.

To investigate the membrane abnormalities that may play a pathophysiologic role in several hemolytic anemias we determined the density distribution on sucrose density gradients of human red blood cell (RBC) membranes from patients with these disorders, from normal controls, and from incubated normal RBC. We analyzed the fractions for membrane-adsorbed hemoglobin (Hb), globin, and nonglobin cytoplasmic proteins. The relationship between the cytoplasmic proteins adsorbed on the membranes and the specific gravity (SG) of the membranes was linear. An increase in SG of the entire membrane population was seen in Hb C disease due to adsorbed Hb. Subpopulations of membranes with increased SG due to adsorption of nonglobin protein were evident in the membranes from two splenectomized patients with hemolytic glucose-6-phosphate dehydrogenase (G6PD) variants. Dense membrane subpopulations found in RBC membranes from three splenectomized patients with Hb Köln were associated with adsorbed globin, while similar subpopulations in RBC membranes from three splenectomized patients with hereditary spherocytosis demonstrated increased SG due to adsorbed Hb. Splenectomized normals had no such abnormality in membrane density. Sucrose density gradients demonstrate that membrane bound cytoplasmic protein is characteristic of the RBC membranes in several hemolytic disorders. Additionally, gradients are useful for the isolation and further analysis of those subpopulations of RBC membranes with abnormal SG and exaggerated membrane protein abnormalities.

Adsorption↗
PubMed1980

Nodular mixed lymphocytic-histiocytic lymphoma (NM): response and survival. Eastern Cooperative Oncology Group.

Eighty patients with nodular mixed lymphocytic-histiocytic lymphoma (NM) entered on four different Eastern Cooperative Oncology Group chemotherapy studies were analyzed for response and survival. They were compared with 249 patients with nodular lymphocytic poorly differentiated lymphoma (NLPD), who were treated similarly. The response rates in NM were: CR 45%, PR 30%, NC-PD 25%. In NLPD the quality of response had little effect on survival (CR 91%, PR 90%, NC-PD 76%), whereas in NM the two year survivorship of 85% for CR dropped drastically to 33% for the partial responders (P less than 0.01). Ninety percent of the previously untreated NLPD, but only 59% of the comparable group of NM, survived 2 years. In 23 patients with NM in which the pattern was reported as both nodular and diffuse (ND-M), the 2-year survival of 35% was markedly inferior to a 66% 2-year survivorship observed in 57 patients with the pure nodular pattern (P less than 0.05). It appears that NM is a less favorable lymphoma type than NLPD. In NM achievement of a CR affects survival favorably; consequently, the use of aggressive chemotherapy regimens in an attempt to achieve high rates of CR are recommended. In NLPD, on the other hand, since survival curves of partial and complete responders are almost identical, suboptimal treatments may be justified.

Antineoplastic Agents↗
PubMed1980

Influence of epinephrine on the aggregation response of aspirin-treated platelets.

We have evaluated the influence of epinephrine on the sensitivity of aspirin-treated platelets to aggregating agents. Concentrations of ADP, thrombin and arachidonate that caused reversible stimulation of aspirin platelets produced irreversible aggregation when the aspirin samples had been pretreated with epinephrine. The correction was not due to improvement in the ability of aspirin platelets to synthesize prostaglandins or secrete products of the release reaction. Epinephrine induced correction of refractory aspirin platelets may help to explain why aspirin is not a universally effective anti-thrombotic agent.

Adenosine Diphosphate↗