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Biomedical subjects

J F Martin

Publications and source records attributed to J F Martin.

At least 199 records · Page 11Linked to original sources
PubMed1989

Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis?

To investigate the present status of pulmonary embolism as a cause of death in a general hospital patient population, a 5-year retrospective study of all autopsy reports and associated hospital records was undertaken. Pulmonary embolism was thought to be the cause of death in 239 of 2388 autopsies performed (10%): 15% of these patients were aged less than 60 years and 68% did not have cancer. Of these patients, 83% had deep-vein thrombosis (DVT) in the legs at autopsy, of whom only 19% had symptoms of DVT before death. Only 3% of patients who had DVT at autopsy had undergone an investigation for such before death. Twenty-four per cent of patients who died from pulmonary embolism had undergone surgery a mean of 6.9 days before. Screening tests for DVT should be applied widely in the hospital population.

Adult↗
PubMed1989

Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes.

The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.

Adult↗
PubMed1988

Bleeding time and platelet volume in acute myocardial infarction--a 2 year follow-up study.

The bleeding time is shortened and the mean platelet volume is increased in the acute phase of myocardial infarction. In this follow-up study we repeated the measurement of the bleeding time, the platelet count and the platelet volume distribution in 18 patients who had suffered from a definite acute myocardial infarction two years before and in 16 control patients who had been admitted with chest pain but no definite myocardial infarction at that time. At the time of follow-up the bleeding time was significantly lengthened in the myocardial infarction group (median values = 169 s and 209 s respectively), whereas it had shortened in the control group (median values = 258 s and 228 s respectively). Comparison of the platelet volume distribution curves of the myocardial infarction patients at time of infarction and 2 years later revealed a significantly higher percentage of small platelets and significantly lower percentages of both medium-sized and large platelets at the time of infarction. These changes in the platelet volume distribution could indicate consumption of medium-sized and large platelets at the time of myocardial infarction. None of the measured variables predicted which of the patients with acute myocardial infarction would subsequently re-infarct or die. In the patients studied with definite ischaemic heart disease (n = 26) a significant negative correlation between bleeding time and mean platelet volume was found. The shortened bleeding time in myocardial infarction is related to the acute event itself or proceeds it, but is reversed two years later.

Bleeding Time↗
PubMed1988

The bleeding time is inversely related to megakaryocyte nuclear DNA content and size in man.

The relation between the bleeding time and the megakaryocyte nuclear DNA content and size was evaluated in eleven consecutive patients with normal steady state thrombopoiesis undergoing thoracotomy. A statistically significant inverse correlation was found between the bleeding time and both megakaryocyte DNA content (r = -0.71, p less than 0.05), megakaryocyte total size (r = -0.58, p less than 0.05), megakaryocyte cytoplasmic size (r = -0.64, p less than 0.05) and megakaryocyte nuclear size (r = -0.58, p less than 0.05). The megakaryocyte total size and the megakaryocyte cytoplasmic size were statistically significantly larger in men than women (p less than 0.02 and p less than 0.03 respectively). Changes in the megakaryocytes in the bone marrow are associated with changes in primary haemostasis in normal individuals.

Adult↗
PubMed1988

The effects of amrinone, cyclophosphamide and anti-platelet serum on platelet production in the Gunn rat.

The effect of amrinone on platelet production was differentiated from that of a known bone-marrow cytotoxic agent (cyclophosphamide) and anti-platelet serum (APS). The rate of platelet production has been observed over a 4-day period in the Gunn rat using [75Se]selenomethionine cohort labelling of platelets following administration of either amrinone, 160 mg kg-1 day-1, cyclophosphamide, 30 mg kg-1 day-1 or APS, 0.75 ml. Platelet numbers were reduced by amrinone, cyclophosphamide and APS. The rate of platelet production was increased following APS and suppressed by cyclophosphamide, but the rate of platelet production when expressed as the selenomethionine incorporation in counts per minute (cpm) per 10(8) platelets appeared to be increased in amrinone-treated animals. When these values are expressed as radioactivity per unit platelet volume the difference between the control and the amrinone-treated group was reduced but the difference between the control, APS- and cyclophosphamide-treated groups remained unchanged. It is concluded that in the Gunn rat amrinone affects platelet production by producing fewer, larger platelets.

Amrinone↗
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

Human megakaryocyte size varies with anatomical site.

Whole megakaryocyte, megakaryocyte cytoplasmic and nuclear size were evaluated in human bone marrow obtained from posterior iliac crest and rib of subjects undergoing thoracotomy for repair of hiatal hernia. In addition the nuclear DNA content (ploidy) of the cells from each site was measured. Significantly larger mean megakaryocyte (P less than 0.002), and megakaryocyte cytoplasmic volumes (P less than 0.002), and different volume distributions were observed in costal marrow compared to the iliac crest. No change in mean nuclear volume was found. This was paralleled by no significant difference in mean ploidy. This suggests that the variation in megakaryocyte size with anatomical site is determined by the concomitant volume of cell cytoplasm, but not the nuclear volume.

Adult↗
PubMed1988

Glucokinase-deficient mutant of Penicillium chrysogenum is derepressed in glucose catabolite regulation of both beta-galactosidase and penicillin biosynthesis.

One glucokinase-deficient mutant (glk1) of Penicillium chrysogenum AS-P-78 was isolated after germ tube-emitting spores were mutated with nitrosoguanidine and selected for growth on lactose-containing medium in the presence of inhibitory concentrations of D-2-deoxyglucose (3 mM). Penicillin biosynthesis was greatly reduced (55%) in D-glucose-grown cultures of the parental strain, but this sugar had no repressive effect on the rate of penicillin biosynthesis in the mutant glk1. This mutant was deficient in ATP-dependent glucokinase and showed a greatly reduced uptake of D-glucose. The parental strain P. chrysogenum AS-P-78 showed in vitro ATP-dependent phosphorylating activities of D-glucose, D-2-deoxyglucose, and D-galactose. The glk1 mutant was deficient in the in vitro phosphorylation of D-glucose and D-2-deoxyglucose but retained a normal D-galactose-phosphorylating activity. D-Glucose repressed both beta-galactosidase and isopenicillin-N-synthase but not acyl coenzyme A:6-aminopenicillanic acid acyltransferase in the parental strain. The glucokinase-deficient mutant was simultaneously derepressed in carbon catabolite regulation of beta-galactosidase and isopenicillin-N-synthase, suggesting that a common regulatory mechanism is involved in carbon catabolite regulation of both sugar utilization and penicillin biosynthesis.

Carbon↗
PubMed1988

Inflatable surface coil for MR imaging of the prostate.

An inflatable surface coil for transrectal magnetic resonance imaging of the prostate was designed. The coil was tested during imaging of an insulated saline phantom and of the prostates of four patients. Phantom images were comparable to those obtained with commercial coils of similar size. High spatial resolution and excellent contrast were noted in coronal images of the prostates. Use of this coil could substantially improve studies of the prostate and cervix.

Humans↗
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↗
PubMed1988

Ultrastructural demonstration of tubular inclusions coinciding with von Willebrand factor in pig megakaryocytes.

The appearance of von Willebrand factor (vWF) in bone marrow megakaryocytes was studied by standard electron microscopy (EM) and immuno-EM using an original purification technique. Eighty percent pure megakaryocytes were isolated from porcine rib bone marrow using Percoll gradients followed by counterflow centrifugation. Activation was prevented by prostacyclin and prefixation with low concentrations of glutaraldehyde. In early megakaryoblasts, standard EM revealed the presence of tubular structures in the small vesicles located in the Golgi area, in the small immature alpha-granules and in the rare mature alpha-granules. Immunolabeling for vWF was simultaneously observed in small vesicles and small alpha-granules, mainly in the Golgi zone. In mature megakaryocytes, standard EM showed that tubular structures were numerous, regularly spaced, and aligned in parallel. Immunolabeling for vWF was intense, restricted to the alpha-granules, and distributed in a similar manner to porcine platelets. Gold particles were located eccentrically at one pole of the alpha-granule, labeling only its periphery or outlining one side of an elongated granule. Tubule profiles could be seen underlying the immunolabeling and were usually located at one side of the granule. In conclusion, this study demonstrates the presence of tubular structures in megakaryocyte alpha-granules, their association with vWF, and the appearance of both in the Golgi-associated vesicles.

Animals↗
PubMed1987

Megakaryocytes and platelet clumps as the cause of finger clubbing.

There is now strong evidence that megakaryocytes continually emerge from the bone marrow but are trapped by the pulmonary capillary bed and fragment there into platelets. It is suggested that in disorders in which megakaryocytes or megakaryocyte fragments bypass the lung capillary network (eg, right-to-left intracardiac shunts, carcinoma of the bronchus), or in which large platelet clumps form on the left side of the heart or in large arteries (eg, subacute bacterial endocarditis, subclavian aneurysm), or in which there tends to be a chronic platelet excess (eg, chronic inflammatory bowel disease), these large particles may reach the fingertips in axial vascular streams and impact there, releasing platelet-derived growth factor. This material is known to cause increased capillary permeability and connective tissue hypertrophy. It is suggested that this mechanism is the cause of clubbing of the fingers.

Cell Aggregation↗
PubMed1987

The platelet volume distribution: a signature of the prethrombotic state in coronary heart disease?

A coronary care unit population of 175 consecutive patients was studied. A clinical diagnosis of acute myocardial infarction was made in 103 cases (MI group) while 72 had chest pain, ECG indications of myocardial ischaemia, but no other clinical signs of acute myocardial infarction (control group). Based on bivariate Gaussian statistics the MI group could be divided in two groups, with respect to the platelet parameters of count and volume. The majority (65%) had large mean platelet volume and low count, while the remainder were indistinguishable from the control group. Patients with a large mean platelet volume also had significantly different volume distributions when assessed for volume dispersion, asymmetry and convexity. It is argued that this platelet volume distribution provides a signature for the prethrombotic state in ischaemic heart disease. Identification of such a platelet signature in a patient with coronary artery disease may allow appropriate prophylactic action to be taken and reduce the risk of subsequent acute myocardial infarction.

Blood Platelets↗
PubMed1987

Acute and chronic changes in platelet volume and count after cardiopulmonary bypass induced thrombocytopenia in man.

Patients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 +/- 0.11 X 10(11)/1 (n = 26) fell significantly to 1.35 +/- 0.09 X 10(11)/1 immediately post-operatively (p less than 0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 +/- 0.66 X 10(11)/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 +/- 0.14 and 7.20 +/- 0.14 fl respectively to a minimum of 6.16 +/- 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 +/- 0.33 X 10(11)/1, significantly higher than the pre-operative value (p less than 0.05), while their average mean platelet volume was 6.63 +/- 0.21 fl, significantly lower than before surgery (p less than 0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.

Adult↗