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Biomedical subjects

G J Johnson

Publications and source records attributed to G J Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1986

Disparate effects of the calcium-channel blockers, nifedipine and verapamil, on alpha 2-adrenergic receptors and thromboxane A2-induced aggregation of human platelets.

Calcium-channel blockers inhibit human platelet aggregation in vitro and ex vivo. To further evaluate the mechanism(s) responsible for the inhibition induced by this structurally heterogeneous group of compounds, we studied the effect of nifedipine and verapamil on human platelet aggregation in vitro. Neither 10 microM nifedipine nor 10 microM verapamil consistently inhibited the aggregation response of platelet-rich plasma to threshold concentrations of ADP, sodium arachidonate, epinephrine, or collagen. However, both 10 microM nifedipine and 10 microM verapamil epinephrine-potentiated, thromboxane A2 (TXA2)-induced aggregation of aspirin-incubated, gel-filtered platelets. Aggregation of similarly prepared platelets induced by TXA2 alone was abolished by 10 microM nifedipine but not by 10 microM verapamil. Even 100 microM verapamil gave only partial and inconsistent inhibition of aggregation. Both drugs had essentially the same effects on platelet aggregation induced by the stable endoperoxide and TXA2 mimic, U46619, with or without epinephrine. Neither 10 microM nifedipine nor 10 microM verapamil elevated platelet cyclic AMP. Verapamil (10 microM) inhibited binding of [3H]-yohimbine (an alpha 2-adrenergic receptor antagonist) to intact human platelets (KD 10.5 nM vs 2.4 nM for control platelets) without altering the number of binding sites. In contrast, 10 microM nifedipine had no effect on KD or number of binding sites. These results indicate that nifedipine and verapamil inhibit epinephrine-potentiated, TXA2-induced human platelet aggregation by different mechanisms. Verapamil inhibits the epinephrine contribution to the aggregation response by blocking alpha 2-adrenergic receptor binding. Nifedipine blocks the platelet response to TXA2 without affecting alpha-adrenergic receptor binding. These observations have potential clinical implications with regard to the mechanisms by which calcium-channel blockers inhibit vascular spasm and myocardial ischemia.

Adenosine Diphosphate↗
PubMed1986

The significance of bone marrow involvement in non-Hodgkin's lymphoma: the Eastern Cooperative Oncology Group experience.

Data from four clinical trials conducted by the Eastern Cooperative Oncology Group (ECOG) were used to investigate the importance of bone marrow involvement as a prognostic factor in patients with non-Hodgkin's lymphoma (NHL). A total of 502 patients, 275 with nodular, poorly differentiated lymphocytic lymphoma (NLPD) and 227 with diffuse histiocytic lymphoma (DHL) or diffuse mixed-cell lymphoma (DML), were included in this analysis. Patients were separated into four categories: stage III, stage IV with bone marrow involvement (stage IV-M), stage IV without marrow involvement (stage IV-O), and stage IV with bone marrow and other organ involvement (stage IV-OM). Among the DHL and DML patients, the incidence of marrow involvement was 23%. However, stage IV-M patients had a prognosis that is similar to stage IV-O and stage IV-OM and worse than stage III patients. In contrast, the incidence of involvement with NLPD was 59% and patients with stage IV-M had a survival not different than stage III and not worse than stage IV-O and stage IV-OM. The results suggest that the current emphasis on bone marrow biopsy(s) as a routine diagnostic staging procedure for patients with NHL should be reevaluated. The necessity for this procedure in stage III patients with NLPD is not apparent from our data. One can still justify a bone marrow biopsy in stage I and II patients and can confirm the complete clinical response when all nodes have regressed in more advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Congenital cataract with microcornea and Peters' anomaly as expressions of one autosomal dominant gene.

Hereditary congenital cataract is a well recognized but heterogeneous group of disorders; the cataracts may occur alone, or with other ocular or systemic abnormalities, and with all three common modes of inheritance. Peters' anomaly has usually been regarded as a sporadic condition with an insignificant risk of recurrence. A family is described in which congenital cataracts with microcornea, and Peters' anomaly, appear to be variable expressions of a generalized anterior segment disorder inherited as an autosomal dominant condition.

Cataract↗
PubMed1985

Human platelets exert cytotoxic effects on tumor cells.

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.

Blood Platelets↗
PubMed1984

Central nervous system relapse in unfavourable-histology non-Hodgkin's lymphoma: is prophylaxis indicated?

In 2 randomised, prospective Eastern Co-operative Oncology Group trials, the frequency of central nervous system (CNS) involvement after chemotherapy in 347 adults with stage III and IV unfavourable-histology, non-Hodgkin's lymphoma was 8.4%. The frequency varied from 0% in diffuse mixed lymphoma to greater than 30% in lymphoblastic and diffuse-undifferentiated lymphoma. Of the 42% of patients who achieved complete remission after chemotherapy, CNS involvement developed in 5.4% during relapse, but in only 2.7% was the CNS the sole site of relapse. CNS lymphoma arose in 6.6% of 197 patients with diffuse histiocytic lymphoma, but in only 1 subject (1%) was the CNS the sole site of relapse. Therefore, CNS prophylaxis is not indicated for the common diffuse-histology subtypes of adult non-Hodgkin's lymphoma including diffuse-histiocytic, diffuse-mixed and diffuse poorly differentiated lymphocytic lymphoma. The relatively high frequency of CNS lymphoma in lymphoblastic and diffuse undifferentiated lymphoma justify further studies of CNS prophylaxis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Inhibition of platelet aggregation by monoclonal antibody reactive with beta 2-microglobulin chain of HLA complex.

A mouse monoclonal antibody that reacts with beta 2-microglobulin, the light chain of class I major histocompatibility antigens, inhibited the second wave of human platelet aggregation induced by adenosine diphosphate and epinephrine and blocked aggregation and platelet protein phosphorylation induced by sodium arachidonate. Thrombin-induced platelet aggregation was inhibited at threshold concentrations but not at higher concentrations. The antibody also inhibited aggregation and secretion in response to thromboxane A2 or the stable endoperoxide analog, U46619. These results suggest that beta 2-microglobulin in the histocompatibility complex is intimately associated with transmission of the endoperoxide-thromboxane signal at the platelet membrane.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1984

Enteric-coated aspirin, platelet cyclooxygenase activity and function.

Recent studies evaluating the effect of slow releasing enteric-coated aspirin formulations have reported contradictory findings regarding the bioavailability of the active molecule in the circulating blood and the length of duration of the inhibitory effect on platelet function. In the present study, we have evaluated the effect of a single dose of two commercially available enteric-coated aspirins on platelet arachidonic acid metabolism and function. A single dose of slow releasing aspirin was as effective as fast acting regular aspirin in its effect on cyclooxygenase activity and platelet function in both human and canine platelets. However, in view of its slow releasing property, the onset of inhibition was considerably delayed compared to the action of fast acting aspirin in those subjects who ingested enteric-coated aspirins.

Animals↗
PubMed1984

Survey of ophthalmic conditions in a Labrador community: II. Ocular disease.

An ophthalmic examination of 87% of the resident population of Nain, Labrador (latitude 56 degrees 33'N) was carried out, and the findings in 330 Inuit, 236 persons of mixed racial ancestry (Inuit-Caucasian) and 80 Caucasians were analysed. Legal blindness was present in 1.2% of the survey population, compared with 1.6% of the study population of the Arctic Ophthalmological Survey of 1970-71. Of the age group 52 to 85 years, 10.8% were legally blind, compared with 0.6% of the same age group surveyed in the Framingham (Massachusetts) Eye Study. The leading causes of unilateral or bilateral blindness in Nain were trauma, especially in the Inuit, and spheroidal degeneration (Labrador keratopathy); neither senile macular degeneration nor diabetic retinopathy had caused legal blindness. External diseases, particularly spheroidal degeneration (which affected 19% of the population), phlyctenular keratoconjunctivitis and epiblepharon, were the commonest diagnoses in Nain. No diabetic retinopathy was detected, but evidence of toxoplasmosis was encountered. Compared with the study population of the Arctic Ophthalmological Survey, the Nain population had a higher prevalence of spheroidal degeneration and other corneal diseases.

Adolescent↗
PubMed1983

Sequential cyclophosphamide-prednisone and vincristine-bleomycin (CPOB). An effective, schedule-dependent treatment for advanced diffuse histiocytic lymphoma.

In an Eastern Cooperative Oncology Group non-Hodgkin's lymphoma clinical trial, 90 patients with Stage III or IV diffuse histiocytic lymphoma (DHL) were treated with one of four chemotherapy regimens. All patients were previously untreated with chemotherapy, and careful restaging was required to document responses. Each treatment included cyclophosphamide, vincristine and prednisone (COP) plus Adriamycin (COPA), BCNU (BCVP) or bleomycin (COPB and CPOB). The two bleomycin-containing regimens differed only in the schedule of drug administration. CPOB-treated patients received cyclophosphamide on day 1, prednisone on days 1 to 5 and vincristine and bleomycin on day 15 of each 21-day cycle. COPB-treated patients received the same four drugs in the same dosage; however, the schedule was changed so that vincristine and bleomycin were given on day 1. Treatment of responders was continued for 8 cycles. Those with a complete response (CR) were randomized to maintenance therapy with BCVP or no treatment. Treatment with CPOB yielded a CR rate of 55% compared to 25% for COPB (P = 0.07). In contrast to COPB, treatment with CPOB was associated with a significantly longer median duration of CR (26.5 versus 5.7 months; P less than 0.05) and median survival (27.7 versus 11.2 months; P less than 0.02). The CR rate was 31% for BCVP and 45% for COPA, and the median survivals were 10.7 months and 14.4 months, respectively. One half of the CPOB-treated patients who achieved CR remained alive in continuous CR after 30 to 72 months. No advantage for maintenance therapy was observed. Myelotoxicity was greater with CPOB than COPB, but comparable to COPA. This trial demonstrated that the results of treatment of DHL with COP plus bleomycin were strikingly dependent upon the schedule of administration of bleomycin and vincristine. Bleomycin effectively combined with COP, as in CPOB, yielded results comparable to those obtained when Adriamycin was added to COP. CPOB appears to be an effective treatment for DHL that should be considered as an alternative to other regimens, particularly for patients who cannot receive Adriamycin.

Antineoplastic Agents↗
PubMed1983

Changes in vitamin E concentrations in human plasma and platelets with age.

It has been postulated that vitamin E compounds (tocopherols) can retard the aging process. Therefore, changes in concentrations of tocopherols in human plasma and platelets with aging were studied. Fasting blood samples were obtained from 48 healthy male volunteers aged 24-91 years. Concentrations of the tocopherols in plasma and platelets were determined by a liquid chromatographic method. Alpha and gamma tocopherols were the major forms of vitamin E found in both plasma and platelets. The concentrations of alpha and total tocopherols in plasma did not change significantly with age. However, the plasma gamma tocopherol and the platelet alpha, gamma, and total tocopherol concentrations decreased significantly with age. The platelet to plasma ratios of tocopherol concentrations also decreased with age.

Adult↗
PubMed1983

Chronic myelodysplastic syndrome: short survival with or without evolution to acute leukaemia.

The myelodysplastic syndromes represent a prognostically diverse group of disorders. Their study has recently been facilitated by the classification proposed by the French-American-British (FAB) Cooperative Group. Using this scheme it is now possible to define more precisely their natural history and clinical relationship to acute leukaemia. Using the longitudinal case control technique, we reviewed the clinical data and morphology of 69 patients (all elderly males) with chronic irreversible haematological cytopenia and dysplasia. Applying FAB criteria we found: refractory anaemia (RA) in 43%; sideroblastic anaemia (RA-S) in 33%; refractory anaemia with excess blasts (RAEB) in 13%; RAEB in transformation (RAEB-T) in 9% and chronic myelomonocytic leukaemia (CMML) in 1%. The median survival for the entire group was 27 months (RA, 52; RA-S, 29; RAEB, 12; RAEB-T 11; and CMML, 2 months). Short survival was predicted by transfusion requirement and other manifestations of severe cytopenia, as well as by myeloid immaturity. The presence or absence of sideroblastosis did not correlate with survival. Acute leukaemia developed in only eight patients (12%), six of whom initially had RA. Leukaemic transformation was not predicted by progressive cytological immaturity. This study demonstrates that even in the absence of leukaemic transformation, chronic myelodysplasia is a lethal haematological disorder.

Adult↗
PubMed1983

Oxidant damage of the lipids and proteins of the erythrocyte membranes in unstable hemoglobin disease. Evidence for the role of lipid peroxidation.

Since unstable hemoglobins have been considered a source of reactive oxygen radicals, and oxidative membrane damage a prehemolytic event, we examined the erythrocyte membranes of six patients (three splenectomized) with hemoglobin Köln disease. In the hydrogen peroxide stress test, the patients' erythrocytes generated more than twice the malonyldialdehyde (a lipid peroxidative product) than control erythrocytes. Fluorescence spectra of lipid extracts of the patients' erythrocytes showed an excitation maximum at 400 nm and an emission maximum of 460 nm, characteristic of malonyldialdehyde lipid adducts. Two types of membrane polypeptide aggregates were found in the erythrocytes of the splenectomized patients. The first, which were dissociable by treatment with mercaptoethanol, contained disulfide-linked spectrin, band 3 and globin. The second, not dissociable by mercaptoethanol, had an amino acid composition similar to that of erythrocyte membranes and spectrin (unlike globin) and like that of aggregates produced by the action of malonyldialdehyde on normal erythrocyte membranes. Atomic absorption spectroscopy of hemoglobin Köln erythrocytes showed no increase in calcium content implying that these cross-links were not due to calcium-stimulated transglutaminase. Using a micropipette technique, we demonstrated that erythrocytes containing membrane aggregates from splenectomized patients were less deformable while aggregate-free erythrocytes from non-splenectomized patients had normal deformability. We conclude that the erythrocyte membranes in hemoglobin Köln disease show evidence of lipid peroxidation with production of malonyldialdehyde, and that the nondissociable membrane aggregates formed in this disease are likely cross-linked by malonyldialdehyde. Because the erythrocytes containing membrane aggregates from splenectomized patients with unstable hemoglobin disease show decreased membrane deformability, we hypothesize that this abnormality results in premature erythrocyte destruction in vivo.

Blood Proteins↗