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G J Miller

Publications and source records attributed to G J Miller.

At least 145 records · Page 8Linked to original sources
PubMed1995

Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines.

Although prostatic cancer is often viewed as an androgen-dependent malignancy, a number of other hormones including 1alpha, 25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] are now recognized to modulate its growth and differentiated phenotype. Seven different continuous human prostatic carcinoma cell lines were examined for the presence of biologically active receptors for 1alpha,25(OH)2D3. All seven lines were found to contain mRNA for the vitamin D receptor using an RNase protection assay. Six of the seven cell lines were found to have high-affinity saturable binding sites for 1alpha,25(OH)2D3. The seventh line was found to contain vitamin D receptors by sucrose gradient analysis. All seven lines were found to express 24-hydroxylase activity by a HPLC assay that measures the conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3. 24-Hydroxylase activity was up-regulated in all seven cell lines by preincubation with 1alpha,25(OH)2D3. In the presence of fetal bovine serum, the growth of four of the seven cell lines was inhibited. In the majority of cell lines growth inhibition was related not only to the number of receptors per cell, but also in inverse proportion to the 24-hydroxylase activity of each cell line. The ubiquitous presence of vitamin D receptor and 24-hydroxylase activity in human prostatic carcinoma cells suggests new alternatives for the pharmacological treatment of advanced prostatic cancer and implies that chemoprevention strategies could also make use of this endocrine axis.

24,25-Dihydroxyvitamin D 3↗
PubMed1994

Prostate specific antigen density in patients with histologically proven prostate carcinoma.

BACKGROUND: Prostate specific antigen (PSA) does not appear to have the specificity to distinguish between benign prostate hyperplasia and cancer when the PSA is low. PSA density is thought by many to improve the specificity for cancer; however, this theory remains controversial. METHODS: The authors retrospectively reviewed 220 carcinomas in radical prostatectomy specimens and examined the relationship of PSA and PSA density to prostate volume, Gleason sum, and pathologic stage. RESULTS: Prostate specific antigen and PSA density parallel each other and do not appear to correlate statistically with displaced volume of the prostate, Gleason sum, or pathologic stage. However, PSA density in the PSA 4.1-10 ng/ml group may have conferred unique information secondary to increased variation in prostate volume. Furthermore, PSA density was associated more than PSA with carcinoma in the PSA < or = 4.0 ng/ml group. A PSA density cutoff of greater than 0.05 ng/ml/ml was accurate in the diagnosis of 94.9% of the patients with cancer. Finally, carcinomas with a Gleason sum of greater than 6 in patients with a PSA density of greater than 0.3 ng/ml/ml had a high probability of being extra-capsular at the time of surgery. CONCLUSIONS: Although PSA and PSA density appear to mirror each other in many ways, PSA density confers unique information and may be used as an adjunct to PSA and digital rectal examination in the detection and staging of prostate cancer. If prostate needle biopsy is performed, PSA density and Gleason sum may help identify patients who are at high risk for surgical failure.

Biopsy↗
PubMed1994

Functional assessment for prediction of lifting capacity.

OBJECTIVE: This study investigated the ability to predict maximal functional lifting capacity from peak isometric lumbar extension torque and submaximal lifting mechanics. METHODS: Peak isometric lumbar extension torques were measured on 26 healthy men and women, ages 18 to 39 years. In addition, their lifting mechanics were evaluated while they lifted a submaximal load. Each subject's maximal lifting capacity (kg) then was predicted from the peak torque and submaximal kinetic analysis using a linear regression model. RESULTS: Mean values for the predicted and actual maximum weight the subjects lifted were not significantly different (50.3 +/- 15.6 kg and 48.5 +/- 17.0 kg, respectively, P > or = 0.05). The correlation between predicted and criterion values was high (r = 0.96), and the total error of the prediction was 5.1 kg, which represented 10.5% of the actual maximum value. CONCLUSIONS: This multi-faceted functional assessment model involving biomechanical analysis of a submaximal lift and maximal isometric lumbar extension strength accurately predicted a subject's maximum functional lifting capacity.

Adult↗
PubMed1994

A serum-free defined medium capable of supporting growth of four established human prostatic carcinoma cell lines.

This paper describes a serum-free defined medium (Gc) that was initially designed to support growth of the human prostatic carcinoma cell line LNCaP. Our studies indicate that this medium formulation is capable of supporting short-term, long-term, and clonal growth of the LNCaP cell line. Component deletion experiments have shown that the three most critical components for LNCaP short-term growth are insulin, triiodothyronine (T3), and fetuin. Additionally, this medium was found to support short-term and clonal growth of three other human prostatic carcinoma cell lines, DU 145, PC-3, and ALVA-31. The availability of such a medium should aid in the distinction of the regulatory factors involved in growth and differentiation of malignant prostatic epithelium.

Adenocarcinoma↗
PubMed1994

Morphology of prostate cancer: the effects of multifocality on histological grade, tumor volume and capsule penetration.

A series of 151 radical prostatectomy specimens were subjected to whole-mount analysis. Features examined included histological grade, tumor volume, pathological stage and multifocality. Only 43.7% of the prostates contained a single carcinoma, 31.1% had 2 separate foci and the remaining 25.2% contained 3 to 6 tumors. Multifocality was greatest among tumors with the lowest mean volumes. Tumors with volumes of less than 3 cc were found in all grades (Gleason sums of 2 through 10). The highest volume tumors were those of intermediate grade (Gleason sums 4 through 8). Among tumors with volumes of less than 1 cc 70% that were confined within the prostatic capsule had Gleason sums of 4 or less. However, tumors with volumes of less than 3 cc that had invaded through the prostatic capsule were nearly equally divided between Gleason sums of 2, 3 or 4 and those of 5, 6 or 7. While studies examining the largest tumor per prostate have suggested that histological grade and volume are closely related, our results indicate that this is not necessarily the case. Furthermore, it is clear that tumors need not acquire either large volume or high grade before they can become locally invasive. It is likely, therefore, that the prediction of prognosis for patients with prostatic cancer is greatly influenced by tumor multifocality.

Carcinoma↗
PubMed1994

Lipoproteins and the haemostatic system in atherothrombotic disorders.

The early belief that the haemostatic system has no active role in the formation of the atheromatous plaque is no longer tenable. Rather, the association between hypercholesterolaemia and atherosclerosis appears to arise in part because of various effects of high concentrations of LDL and VLDL particles on the cellular and humoral components of the system, thereby promoting plaque growth and thrombosis. These may be summarized as follows: 1. High concentrations of native LDL have been reported to promote the adhesion of monocytes to the endothelial cell, suggesting that the latter undergoes a form of activation upon such exposure. Oxidized LDL is more potent in this respect, and persistent exposure of endothelium to such particles can eventually lead to cell injury. 2. Activated endothelial cells acquire characteristics on their luminal surface conducive to thrombin generation and fibrin production. Thrombin has several actions on the endothelial cell, monocyte, smooth muscle cell and platelet which in the presence of hypercholesterolaemia will promote the formation of atheroma. 3. Oxidatively modified LDL can activate circulating monocytes, when they also acquire procoagulant properties which favour thrombin production. 4. Platelets show an increased tendency to aggregate when exposed to hypercholesterolaemic plasma. This effect may arise in part because the platelet of the hypercholesterolaemic patient expresses an increased number of fibrinogen binding sites on its surface following activation by agonists such as ADP. These hyperaggregable platelets adhere to activated endothelial cells which express von Willebrand factor on their surface, and to subendothelial proteins exposed in the gaps that open between injured endothelial cells. Platelets exposed to raised LDL levels also show a reduced sensitivity to prostacyclin, an antiaggregatory agent. Oxidatively modified LDL has been reported to stimulate aggregation of platelets in the absence of other agonists such as ADP or thrombin (spontaneous aggregation). 5. Platelet aggregation and fibrin deposition at sites of endothelial injury will create microthrombi which become incorporated into the lesion by organization, thereby increasing the fibrous and cellular content of the atheromatous plaque. 6. Lipolysis of triglyceride-rich lipoproteins at the endothelial cell surface leads to transient activation of the coagulation mechanism with activation of factor VII. Activated factor VII is a potent procoagulant when it forms a complex with tissue factor in the atheromatous lesion. Persistent hypertriglyceridaemia is accompanied by raised concentrations of factor X, factor IX, factor VII and prothrombin. 7. Hypertriglyceridaemia is associated with an increased plasma concentration of PAI-1 and a reduction in plasma fibrinolytic activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Arteriosclerosis↗
PubMed1994

Clustering of human T lymphotropic virus type I seropositive in Montserrat, West Indies: evidence for an environmental factor in transmission of the virus.

A community survey of human T cell lymphotropic virus type I (HTLV-I) in Montserrat, West Indies, identified 22 instances in which 2 HTLV-I-seropositive adults lived within 60 m of each other (close pairs), compared with 7.8 expected (P < .001). Five of these close pairs were mother-offspring or husband-wife. The remaining 17 pairs were of unrelated members in separate households. The percentages of male-female (41%), female-female (41%), and male-male (18%) types in these 17 pairs were very similar to those among the 1377 similarly defined pairs in which neither or only 1 member was seropositive, affording no support for extramarital heterosexual activity as an explanation for the clustering observed. Thus, the demography of HTLV-I was not accounted for completely by sexual and mother-to-offspring transmission. The predominance of clustering of unrelated HTLV-I-seropositive individuals in locations with high mosquito infestation raised the possibility of sporadic transmission of HTLV-I by hematophagous insects.

Adolescent↗
PubMed1994

Factor VIII, ABO blood group and the incidence of ischaemic heart disease.

Relations of factor VIII activity, FVIIIC, and von Willebrand factor antigen (vWFAg), with ischaemic heart disease (IHD) were examined in 1393 men aged between 40 and 64 years at entry to the Northwick Park Heart Study (NPHS) who experienced 178 first major episodes of IHD during an average follow-up period of 16.1 years. After allowing for the large factor VIII differences between the main ABO blood groups, FVIIIC was probably associated with IHD incidence, possibly more strongly with fatal than non-fatal episodes. Thus, an increase of 1 standard deviation in FVIIIC raised the risk of fatal IHD by about 28%. vWFAg was also significantly associated with fatal events. The observed relation of FVIIIC with IHD incidence probably underestimates the true strength of the association because of the considerable within-person and laboratory variability in factor VIII measurements. FVIIIC and vWFAg were strongly correlated (r = 0.57) and in statistical terms there may be little to choose between them in long-term studies of IHD. Taking account of evidence that haemophiliacs seem to experience less IHD than expected, high factor VIII levels may contribute to the incidence of IHD by increasing thrombogenic potential. The incidence of IHD was significantly higher in those of blood group AB than in those of groups O, A or B, particularly for fatal events. There was no evidence that the FVIIIC and vWFAg associations with IHD are determined by ABO group. The factor VIII and ABO blood group effects therefore appeared to be independent. Group AB may be a genetic marker of characteristics influencing other indices of IHD risk such as short stature, NPHS men (though not women) of group AB being about 2 cm shorter than those of other groups.

ABO Blood-Group System↗
PubMed1994

Factor VII coagulant activity and antigen levels in healthy men are determined by interaction between factor VII genotype and plasma triglyceride concentration.

Ischemic heart disease is caused by a combination of and interaction between a number of genetic and environmental factors. In a study of a group of healthy men from the United Kingdom, such an interaction was identified between the levels of plasma triglycerides and genetic variation determining plasma levels of factor VII, a clotting factor that is associated with risk of ischemic heart disease. We previously reported a common genetic polymorphism of the factor VII gene that changes arginine at residue 353 to a glutamine (Arg353-->Gln) and showed that healthy men who carry the allele for Gln353 had lower plasma levels of factor VII coagulant activity. This association is strongly confirmed in a new sample. Compared with 301 men with the allele for Arg353, 63 men with one or two alleles for Gln353 had levels of factor VII coagulant activity that were 20% lower (97.8% [95% confidence interval (CI), 95.2% to 100.4%] and 78.2% [CI, 73.8% to 82.9%], respectively; P < .0001), with similar genotype-associated differences observed for levels of factor VII antigen. The 6 men who were homozygous for the Gln353 allele had mean levels of factor VII coagulant activity and antigen that were lower by 40% and 50%, respectively. In an assay using bovine thromboplastin, which is specific for the cleaved (activated) form of factor VII, they had levels lower by 60%, suggesting that the major effect of the Gln353 substitution is to reduce the proportion of the circulating zymogen that is activated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1994

Dietary fat induces changes in factor VII coagulant activity through effects on plasma free stearic acid concentration.

Previous studies have demonstrated activation of the contact system of coagulation and an increase in factor VII coagulant activity (VIIc) when citrated plasma is incubated in the presence of micellar stearate. The products of contact activation, factors XIIa and IXa, were responsible in this system for the activation of factor VII, thereby increasing factor VIIc. To obtain evidence that these in vitro interactions also operate in vivo, factor VIIc was examined in relation to plasma free fatty acid concentrations in five healthy individuals during the consumption of isocaloric high-saturated fat, high-unsaturated fat, and low-fat diets, each taken for 4 weeks in random order and separated by intervals of 12 weeks. For all but the final 3 days of each phase, subjects selected appropriate foods from prepared lists to meet the dietary requirements. Experimental diets of predetermined fat content and composition were fed on days 26 through 28 in each phase. Fat supplied on average 62% of energy in two of the experimental diets and less than 20% of energy in the third. On the final day of each dietary phase, the concentrations of the various free fatty acids and factor VIIc were measured before breakfast and at three 150-minute intervals thereafter. Plasma factor VIIc was, respectively, 6.5% and 13.1% of standard higher on the unsaturated and saturated fat diets than on the low-fat diet. Furthermore, the plasma concentration of stearic acid was strongly associated with factor VIIc (r = .58; P < .0001), and this relation remained significant (P = .003) after allowance for the plasma concentrations of palmitic, oleic, and linoleic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Factor VII coagulant activity and cholesterol changes in premenopausal women consuming a long-term cholesterol-lowering diet.

We periodically obtained blood samples from mildly hypercholesterolemic, but otherwise healthy, premenopausal women who were recruited to participate in a study of a long-term, cholesterol-lowering diet. All meals were prepared and most meals were consumed in the study center dining facility. Tests performed on blood samples included fibrinogen, cholesterol, factor VII coagulant activity (VIIc), and other measures of factor VII. We found that when women switched from a typical American diet (37% fat, polyunsaturated fatty acid to saturated fatty acid [P/S] ratio 0.5, 300 mg cholesterol/d) to a diet lower in fat and cholesterol (American Heart Association phase 2 diet: 30% fat, P/S ratio of 1, 150 to 200 mg cholesterol/d) and maintained that diet for 20 weeks, their plasma cholesterol levels decreased by approximately 6% after 4 weeks and remained at that level until study termination. Likewise, VIIc decreased by approximately 11% while factor VII antigen, total factor VII activity, and fibrinogen concentration did not change appreciably from baseline values. Our results show that premenopausal women benefit from a diet lower in total and saturated fat by a reduction in blood cholesterol and VIIc. Extrapolation from data on men in the Northwick Park Heart Study indicates that the 11% decrease in VIIc activity would correspond to an approximately 30% decrease in risk of mortality from coronary heart disease.

Adult↗
PubMed1994

A biomechanical comparison of four fixation methods of first metatarsophalangeal joint arthrodesis.

A simulated metatarsophalangeal joint arthrodesis was performed on 18 pairs of cadaveric great toes. One toe of each pair was fixed with a 4.0-mm oblique AO cancellous screw. The contralateral toe was fixed with one of three techniques: (1) a miniplate placed dorsally; (2) a 4.5-mm Herbert cannulated screw placed from the metatarsal neck into the medullary canal of the proximal phalanx; or (3) a 3/32-inch Steinmann pin placed longitudinally. An oblique 0.045 Kirschner wire was added with each method. The specimens were tested to failure in dorsiflexion. The miniplate was significantly stronger than the AO screw in force to failure and initial stiffness. The Herbert cannulated screw was also significantly stronger in force to failure than the AO screw. There was no significant strength difference between the Steinmann pin and the AO screw.

Arthrodesis↗
PubMed1994

The mechanical properties of equine third metacarpals as affected by age.

Twenty-five pairs of equine third metacarpals (McIII) were collected from horses of varying breeds and ranging in age from 1 d to 27 yr. Standard three-point bending tests were performed on the McIII to obtain comparative data on breaking load (BL), breaking strength (BS), and elasticity (E). Broken bones were reassembled and 2-cm sections cut from the bone 1 cm below the nutrient foramen and at the site of the break. Bone mineral content (BMC) and geometrical properties of these sections were determined. Maximum BMC (17.3 g/2 cm) was reached at 6.0 +/- 1.8 yr of age. Horses in this study achieved 76% of maximum BMC by 1 yr of age. Maximum BL (1,888 kg) was reached at 4.6 +/- 1.8 yr of age. The coefficient of determination (r2) between BMC and BL was .92 (P < .001). Breaking strength peaked at 2,272 kg/cm2 at 6.3 +/- 1.2 yr of age. The correlation between BS and BMC was .84 (P < .0001). At 1 yr of age BS was 1,919 kg/cm2, or 85% of maximum BS. Elasticity increased linearly with log 10 age (r2 = .91). The r2 of BMC and E was .79 (P < .001). Area moment of inertia (I) of the cortex of the bone was best approximated by the area of an ellipse (r2 = .91; P < .01). Results suggest that bone strength in horses peaks after most race horses have completed their careers.

Aging↗
PubMed1994

Histopathology of localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

Future handling of patients with localized prostate cancer will undoubtedly depend upon a more sophisticated prognostication than that available today. The basis will continue to be the histopathological evaluation of tumor size, grade, localization and distribution within the gland. The aim of this section is to summarize current concepts of the morphological characteristics of localized prostate cancer and their prognostic implications as well as to give guidelines for standardization of the methods involved in morphological evaluation. First, baseline recommendations for the tissue processing procedures are given: Needle core biopsies, taken in a systematic way, potentially contain the information necessary for estimation of grade, size, distribution and extension to seminal vesicles, and could yield material for DNA-measurements, cytogenetic and genetic information. For TUR specimens it is suggested that at least 10 grams should be embedded or 8 to 10 cassettes employed minimally. The prostatectomy specimens should be carefully examined. Material should be frozen both from tumor tissue and from other areas eg by taking 'mapping' biopsies in a standardized way. After fixation (in 10% buffered formalin for at least 24 hours) and appropriate inking of surgical margins, whole mount sections at 2.5-5 mm intervals should be cut. The extension of the tumor should be outlined and at least the two largest tumors should be graded. Capsule penetration and extension to surgical margins and seminal vesicles should be indicated. Grading of malignancy should always include the Gleason grade and where possible Gleason score (ie the sum of the dominant and the secondary grade or pattern). The WHO and the Boecking systems combine a grading of glandular architecture with a grading of the nuclear atypia. It is stressed that in core biopsies the amount of cancer is sometimes scanty, which limits the possibility to find dominant and secondary patterns. In such cases, a grading of glandular differentiation and of nuclear grade seems rational. Also, for comparison with cytological grading, the WHO system is suitable, since in both cases both tissue differentiation and nuclear atypia are judged. The future need for objective techniques is recognized. Prostatectomy pathology includes important features with high correlation to postoperative prognosis: eg capsular penetration. The extent of capsular penetration and the extent of involvement of the surgical margins is of importance. Only focal penetration or focal involvement of the margin carry a relatively low risk of of progression.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗
PubMed1994

The effects of intravenous Triton WR-1339 on factor VII coagulant activity and plasma lipoproteins in normocholesterolaemic and hypercholesterolaemic rabbits.

The hypothesis that lipolysis of large lipoproteins by lipoprotein lipase (LPL) has an important influence on the activation of the contact system of coagulation and subsequently on factor VII activation was tested in rabbits rendered hyperlipidaemic by dietary means and/or by injection of Triton WR-1339. The dietary treatment involved a control diet and two isocaloric diets containing either a 0.5% cholesterol or 0.5% cholesterol and 7.5% safflower oil supplement. Other groups of rabbits were given either a standard diet or the standard diet supplemented with 1% cholesterol. All supplemented diets increased many-fold the concentrations of cholesterol associated with the chylomicron, very low-(VLDL), intermediate-(IDL) and low-density (LDL) lipoprotein fractions. Factor VII coagulant activity (FVIIc) increased significantly in all groups of rabbits fed the cholesterol supplement. The intravenous injection of Triton WR-1339 into rabbits fed either the standard or 1% cholesterol-supplemented diet resulted in increases of plasma cholesterol and triglyceride concentrations up to 36-48 h thereafter, followed by decreases up to completion of the experiment at 72 h. Most of these increases in plasma lipids were associated with the chylomicron and VLDL fractions. Following injection of Triton into rabbits fed either the standard or cholesterol-supplemented diet, changes in FVIIc were biphasic with a decrease in activity in the early intervals when rates of accumulation of plasma lipid were constant, and a progressive increase in activity at later intervals when rates of lipid accumulation declined and then reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Factor VII-deficient substrate plasmas depleted of protein C raise the sensitivity of the factor VII bio-assay to activated factor VII: an international study.

Plasma from healthy individuals, pregnant women and patients on warfarin were distributed to 3 laboratories supporting major cardiovascular surveys (Northwick Park, Muenster and Houston) for assay of factor VII coagulant activity (VIIc) with their own bio-assays. The mean VIIc in 147 samples agreed to within 1% of standard in Northwick Park and Houston, but was 14% of standard lower in Muenster owing to its more potent standard. In samples with an increased VIIc the Northwick Park assay gave a higher result than the other assays owing to its increased responsiveness to activated factor VII (VIIa). Thus when VIIa concentrations were determined directly with a clotting assay which utilises a soluble recombinant tissue factor, the increase in VIIc with increase in VIIa was considerably greater with the Northwick Park assay than the Muenster assay. This feature of the Northwick Park assay was traced to the virtual absence of protein C in its substrate plasma. Factor Va appears rate-limiting for the coagulant expression of VIIa in test plasma. If the thrombotic response to release of tissue factor is determined by the circulating concentration of VIIa, then the Northwick Park factor VII bio-assay may be preferable to other bio-assays currently employed to estimate risk of acute coronary events.

Adult↗
PubMed1994

Gunshot wounds: 10-year experience of a rural, referral trauma center.

The 10-year experience of a Level II trauma center with 122 gunshot wounds referred from a large rural area was analyzed to illustrate differences from the experience of urban centers. Most frequent causes of injury were attempted suicide in 38 (31%) patients, hunting mishaps in 32 (26%), unintentional accidents in 29 (24%), and intentional assault in 18 (15%). Of weapons specified, rifles were documented in 48 (39%) instances, shotguns in 25 (21%), and handguns in 24 (20%). Body regions injured were the trunk in 47 (39%) patients, head in 35 (29%), lower extremity in 31 (25%), and upper extremity in 29 (24%). Twenty-five patients (20%) died as a result of their injuries. The cause of death was brain injury in 18 (72%), exsanguination from truncal wounds in 5 (20%), myocardial infarction in 1 (4%), and multiple organ failure in 1 (4%). We conclude that the distributions of cause and type of gunshot wounds are unique in a rural setting. These differences have profound consequences in designing effective prevention programs for our area and support the design of more efficient trauma systems for rural North America.

Accidents↗