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J Lawry

Publications and source records attributed to J Lawry.

47 records · Page 3Linked to original sources
PubMed1989

DN 9693: a phosphodiesterase inhibitor with a platelet membrane effect.

We have examined the in vitro effects of DN 9693 (piperidinylimidazo-quinazolinone) on various aspects of platelet reactivity. Our results are consistent with its known function as a phosphodiesterase inhibitor in that it increased platelet cyclic AMP, particularly in conjunction with an adenylate cyclase stimulator, and exerted a profound inhibitory effect on platelet aggregation responses to a variety of agonists. DN 9693 also inhibited ristocetin-induced platelet agglutination (RIPA). We therefore examined its effect on ristocetin co-factor assays and on the binding of a monoclonal antibody (McAb) to platelet membrane glycoprotein Ib (GPIb). The drug inhibited the binding of the monoclonal antibody in a dose-dependent manner. This suggests an effect of the drug on the platelet surface membrane with reduced expression of GPIb. Our results indicate that in addition to its anticipated inhibitory effect on platelet aggregation, DN 9693 may also inhibit platelet adhesion.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Silver-binding nucleolar organizer regions (AgNORs) in benign and malignant breast lesions: correlations with ploidy and growth phase by DNA flow cytometry.

Silver-binding nucleolar organizer regions (AgNORs) have been counted in sections of routinely processed paraffin-embedded tissue blocks and have been shown to assist in the distinction between benign and malignant lesions. We have examined 214 benign and malignant breast lesions by this method. The AgNOR counts were fibroadenomas 1.87 +/- 0.20 (mean +/- SD; n = 39), papillomas 1.92 +/- 0.21 (n = 28), sclerosing adenosis 1.96 +/- 0.24 (n = 23), epitheliosis 2.21 +/- 0.30 (n = 38), lobular carcinoma in situ 2.67 +/- 0.54 (n = 9), intraduct carcinoma 3.75 +/- 1.33 (n = 37), and invasive carcinoma 4.22 +/- 1.18 (n = 40). However, the counts in 25-30 per cent of epitheliosis lesions and intraduct carcinomas overlapped in the region of 2-3 AgNOR dots per nuclear profile. The AgNOR counts in carcinomas were also compared with ploidy and growth phase fractions (S + G2 + M%) by flow cytometry. Thirty-three of the 46 cancers with counts over 3 AgNOR dots per nuclear profile contained aneuploid cells (greater than 10 per cent of the total), whereas 8 of the 12 with counts below 3 comprised diploid cells only (P less than 0.05). Similar trends were noted with regard to growth phase fractions which were 19.15 per cent +/- 12.31 and 13.98 per cent +/- 5.55, respectively, for the two groups (P greater than 0.10). We conclude that this method alone does not offer a reliable histological discriminant for malignancy in the breast. However, AgNOR counting may provide information on breast cancer prognosis supplementary to that obtained from DNA flow cytometric analyses.

Breast Diseases↗
PubMed1989

Estimation of DNA content in uveal melanomas by flow cytometry.

Flow cytometry was used to evaluate ploidy and tumour cycle kinetics in fresh tissue samples obtained from 19 uveal melanomas. The results were compared with other parameters including, histological cell type, tumour size and anatomical location. Three tumours (15.8%) were aneuploid (two mixed cell, one epithelioid cell). Cell turnover was estimated in the 16 diploid tumours by summating the total percentage of cells in S and G2/M phases. We found the mean percentage of cells in G2/M/S to be 5.96% (range 2.2-9.8%). Spindle cell neoplasms appeared to have lower cell turnover rates (4.5 +/- 1.2%) than epithelioid cell turnover (8.4 +/- 1.2%). There was no correlation between cell turnover and either tumour size or anatomical location.

Aged↗
PubMed1989

Flow cytometric analysis of the megakaryocyte DNA distribution in whole and partially purified human and rabbit bone marrow.

Megakaryocytes are polyploid cells that constitute less than 0.1% of the nucleated cells in the bone marrow of most mammals including man. The DNA content of megakaryocytes has previously been measured by microdensitometry. Flow cytometry has also been used in the analysis of bone marrow megakaryocytes, but the general prerequisite for prior enrichment has made this technology less attractive. We describe here a modification to the mode of analysis of megakaryocyte DNA content that can be applied to whole, partially purified and elutriated human and rabbit bone marrow. The electronic masking of low-ploidy cells makes it possible to visualize the DNA content of minority, high-ploidy populations of megakaryocytes within a few minutes. In addition, this rapid technique can be combined with monoclonal antibody analysis of bone marrow cells to aid megakaryocyte identification.

Animals↗
PubMed1989

The prediction of recurrence in meningiomas. A flow cytometric study of paraffin-embedded archival material.

Despite the complete macroscopic excision of meningiomas, there is a significant rate of recurrence approaching 20% at 20 years. The prediction of recurrence by clinical and histopathological means is inadequate. Flow cytometric analysis of deoxyribonucleic acid (DNA) in meningiomas has shown a correlation between a high proliferative index based on tumor cell-cycle stage (%S + %G2/M) and clinically aggressive behavior. Accordingly, the DNA analysis of meningioma tissue may be of value in predicting recurrence of these tumors. To test this hypothesis, the DNA of paraffin-embedded archival tissue from known recurrent meningiomas was compared with an age- and sex-matched nonrecurrent group. Both groups had comparable follow-up periods. Forty patients with total macroscopic removal at the time of surgery were analyzed. The paraffin blocks of these tumors were retrieved and reclassified histologically according to the World Health Organization system. Sections were then taken for flow cytometric study. The DNA analysis showed that the proliferative index of the recurrent group was significantly higher than that of the nonrecurrent group (p less than 0.002), although the histological subtyping of the two groups was similar. These results support the suggestion that flow cytometry may be of value in the prediction of recurrence of histologically benign, macroscopically removed meningiomas.

Flow Cytometry↗
PubMed1988

Megakaryocyte and vascular changes in rabbits on a short-term high cholesterol diet.

The effect of a short-term high cholesterol diet on thrombopoiesis and vascular ultrastructure was evaluated in rabbits. Six pairs of male litter-mate rabbits were randomized pairwise to feeding with either 2 g of cholesterol daily in addition to their normal diet or normal diet alone for 7 days. A significant 12-fold increase in median serum cholesterol (P less than 0.035) and an insignificant decrease in platelet count (P = 0.07) were found in the animals fed a high cholesterol diet. In these animals the total and cytoplasmic megakaryocyte size measured as planimetric areas in bone marrow sections were significantly decreased (P less than 0.035). No statistically significant difference in the megakaryocyte DNA content measured by flow cytometry in marrow suspensions enriched for megakaryocytes by density gradient centrifugation and centrifugal elutriation was observed between the cholesterol-fed animals and controls. Light microscopic, transmission and scanning electron microscopic examination of the aorta in both groups of animals showed a morphologically intact endothelium without any adhesion of blood-borne cells to the luminal surface. Transmission electron microscopic studies showed that cells with ultrastructural features resembling smooth muscle cells were present in the intima of the aortas of the animals on the high cholesterol diet, but not in control animals. A decrease in the size of bone marrow megakaryocytes and the occurrence of intimal smooth muscle cells are found in rabbits fed a high cholesterol diet for 7 days. These cellular events may be important features in early atherogenesis.

Animals↗
PubMed1988

Calcium/calmodulin regulation of the proliferation of human epidermal keratinocytes, dermal fibroblasts and mouse B16 melanoma cells in culture.

We have investigated the relationship between extracellular calcium, intracellular calmodulin and proliferation in normal keratinocytes. Keratinocyte proliferation and its sensitivity to calmodulin antagonists was compared with that of normal human dermal fibroblasts and neoplastic mouse B16 melanoma cells. Keratinocytes were similar to fibroblasts in showing reduced proliferation in low (0.15 mM) calcium medium and unlike B16 cells which continued to proliferate until calcium was reduced to submicromolar levels. Intracellular calmodulin was significantly higher in rapidly dividing keratinocytes in normal (1.15 mM) calcium medium than in slower dividing cells in low (0.15 mM) calcium. Fibroblasts and B16 cells maintained similar calmodulin levels in both low and normal calcium media. Calmodulin antagonists inhibited proliferation of all three cell types equally. Thus, keratinocyte calmodulin seems related to the proliferative state of the cell (unlike fibroblast calmodulin) and calmodulin antagonists may be of use in controlling the hyperproliferation of the psoriatic epidermis.

Animals↗
PubMed1988

The effect of fish oil on atherogenesis and thrombopoiesis in rabbits on high cholesterol diet.

The effect of fish oil supplementation on atherogenesis and thrombopoiesis was investigated in rabbits fed a high cholesterol diet for 7 weeks. There was no statistically significant difference between the area of lipid accumulation in the aorta of the animals fed fish oil and the control animals. There was no statistically significant difference in platelet count, mean platelet volume, megakarycoyte DNA content or serum cholesterol between the two groups. Serum triglyceride was significantly higher in the fish oil group than in the controls (p less than 0.035). Fish oil supplementation does not change atherogenesis or thrombopoiesis in the cholesterol fed rabbit.

Animals↗
PubMed1987

DNA in meningioma tissues and explant cell cultures. A flow cytometric study with clinicopathological correlates.

Flow cytometry was performed on stored frozen tissues and explant cell cultures from 39 meningiomas using ethidium bromide and mithramycin in a selective staining technique for deoxyribonucleic acid (DNA). The ploidy index and percentage of cells in the G0/G1, S, and G2/M phases were calculated for each specimen. The results were compared with the age and sex of the patients; the site, the histological subtype, and mitotic rate of the neoplasms; and the estrogen- and progesterone-receptor levels assayed in cytosol-enriched supernatants from cryostat-cut sections. Sixteen neoplasms (41%) were aneuploid. These included two recurrent neoplasms, seven of the eight neoplasms from patients with multiple meningiomas, and three clinically aggressive neoplasms (one hemangiopericytic and two anaplastic meningiomas). Significant correlations were found between values for the ploidy index (r = 0.75, p less than 0.01), the percentage of S-phase cells (r = 0.82, p less than 0.01), and the percentage of G2/M-phase cells (r = 0.69, p less than 0.05) in vivo and in vitro. The results support the suggestion that flow cytometry for DNA in meningiomas may be of value in predicting the behavior of these neoplasms, and indicate that under controlled conditions explant cell cultures may provide a useful model for the proliferative characteristics of meningiomas in vivo.

Brain↗
PubMed1984

Phenotype of cytotoxic effector cells infiltrating a transplanted, chemically induced rat sarcoma.

Previous work from this laboratory indicated that methylcholanthrene-induced sarcomas in the rat are infiltrated by cells with the cytotoxic properties of natural killer (NK) cells. Using a combination of velocity sedimentation and analysis and separation in the fluorescence-activated cell sorter, it has been possible to isolate and characterize these putative NK cells. The present results confirm that cytotoxicity is restricted to NK-sensitive targets (syngeneic, allogeneic and xenogeneic) and no evidence was found for cytotoxic T lymphocytes (CTL). In addition, effector cells have the morphology of large granular lymphocytes, and the pattern of expression of five monoclonal antibody-defined surface markers is identical with that of normal splenic NK cells.

Animals↗