Search PubMed⌕ Search

Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 451 records · Page 25Linked to original sources
PubMed1995

Interferon-alpha and survival in renal cell cancer.

OBJECTIVE: To establish whether the use of interferon-alpha might result in improved survival, using two large series of patients with advanced renal cell cancer treated during studies of chemotherapy and biological therapy, respectively. PATIENTS AND METHODS: Patients treated either in the Eastern Cooperative Oncology Group (ECOG) chemotherapy protocols (327 patients) or in protocols employing interferon as part of a European randomized study or phase II studies at the Norwegian Radium Hospital (231 patients) were retrospectively analysed. Groups for comparison were matched by exclusion of those with an ECOG performance status > 2, no prior nephrectomy, brain metastases or prior chemotherapy. Univariate analysis of prognostic factors for survival was performed by the log rank method and multivariate analysis by Cox regression. RESULTS: Univariate analysis of the whole population showed that performance status, time from diagnosis to treatment, sites of metastases and the use of interferon carried the greatest prognostic significance. In multivariate analysis, the use of interferon remained a significant predictor of survival (P < 0.001). Subgroup analysis suggested that the impact of interferon treatment was greatest in those patients with two of the following characteristics: good performance status, an interval of > 2 years from diagnosis to treatment and no more than one site of metastasis. CONCLUSION: Although a prospective randomized trial is needed to establish definite benefit from the use of interferon in advanced renal cell cancer, this analysis supports the rationale for performing such a trial, particularly in patients with relatively good prognostic features. Patients should be entered into the Medical Research Council study comparing interferon with medroxyprogesterone acetate.

Adult↗
PubMed1995

Heat shock protein studies in type 1 and type 2 diabetes and human islet cell culture.

Heat shock proteins (HSP) play an important role in auto-immunity and infection. Glutamic acid decarboxylase (GAD) the prime antigen in Type 1 diabetes has similar amino acid sequences to HSP65. An ELISA was developed using a plant-derived HSP65 antibody. HSP65 antibody was present in the serum of all normal subjects (median 1.64 AU, IQ range 1.49-1.74). Lower levels were found in established Type 1 diabetes (1.41 AU, 1.32-1.61, p < 0.001) and Type 2 diabetes (1.45 AU, 1.35-1.59, p < 0.006). In Type 1 HSP antibody levels fell with age (p = 0.007) and with duration (p = 0.008) and women with Type 1 had lower levels than men (p = 0.009). Human islet cell culture subjected to heat shock revealed an approximate four fold increase in heat shock protein antigen in the surrounding medium. The release of HSP antigen from stressed islet cells together with the finding of HSP antibody in the serum of all subjects suggest that HSP65 should not be completely discarded as having a possible role in the development of Type 1 diabetes. Low levels of HSP antibody in patients with established diabetes is probably a manifestation of impaired immunity induced by the diabetic state.

Adolescent↗
PubMed1995

Oncogene proteins and proliferation antigens in thymomas: increased expression of epidermal growth factor receptor and Ki67 antigen.

AIMS: To examine thymomas for proteins encoded by oncogenes and to determine whether their presence correlates with tumour growth and associated myasthenia gravis. METHODS: Sections of 24 thymomas were incubated with anti-EGF receptor (EGF-R), anti-Ki67 antigen, anti-p53, and anti-bcl-2 antibodies, and then stained using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Cell suspensions and epithelial cell cultures from some of the tumours were also studied. RESULTS: Whereas EGF-R expression was not detected in any of the controls (but only in a 20 week old fetus), it was detected in neoplastic epithelial cells of all thymomas, and was most strongly expressed in metastases and in samples from donors with severe myasthenia gravis. Ki67 labelling was also increased, especially in the larger thymomas. Epithelial expression of both of these markers was confirmed in fresh cell suspensions and monolayer cultures from the five available cases. In contrast, p53 and bcl-2 were not detected in the neoplastic cells, but bcl-2 was present in the intermingling thymocytes. CONCLUSIONS: Neoplastic thymoma cells express EGF-R and Ki67, but there is no concomitant increase in the expression of p53 and bcl-2 proteins. Increased EGF-R expression may result in increased proliferation of neoplastic cells and also in myasthenia gravis. Measurement of EGF-R concentrations may be of prognostic value. The bcl-2 staining pattern in T lymphocytes illustrates the broad spectrum of maturational stages in thymoma lymphocytes.

Adolescent↗
PubMed1995

HIV seroprevalence and risk behaviors among lesbians and bisexual women in San Francisco and Berkeley, California.

Few data are available on human immunodeficiency virus (HIV) infection and risk behaviors among lesbians and bisexual women. A total of 498 lesbians and bisexual women was sampled from public venues in San Francisco and Berkeley, Calif, during 1993. The overall HIV seroprevalence was 1.2%. Ten percent of participants reported injecting drugs since 1978. Forty percent of the participants reported unprotected vaginal or anal sex with men during the past 3 years, including unprotected sex with gay and bisexual men and male injection drug users. The high rates of injection drug use and unsafe sexual behaviors suggest that lesbians and bisexual women frequenting public venues in San Francisco and Berkeley are at risk for HIV infection.

Adolescent↗
PubMed1995

Measuring technetium-99m-MAG3 clearance with an improved camera-based method.

UNLABELLED: Because commercially available camera-based methods are not optimized, they fail to account for dose infiltration, table attenuation and correspondence between time of injection and starting the camera. We have developed a more optimized technique to calculate camera-based clearances and applied this technique in the design of a camera-based clearance method for 99mTc-MAG3. METHODS: Technetium-99m-MAG3 scintigraphy was performed in 20 patients who had varying degrees of renal function. Data were acquired posteriorly in supine patients at 2 sec/frame for 24 frames, 15 sec/frame for 16 frames and 30 sec/frame for 40 frames. Background correction was performed using an automated elliptical region of interest. Renal depth was estimated using improved regression equations and an empirically determined attenuation coefficient derived from phantom studies. Corrections were made for table attenuation and time discrepancies between dose injection and starting the camera. The percent injected dose in the kidney at 1-2, 1-2.5 and 2-3 min postinjection and the percent injected dose at those time periods corrected for body surface area were correlated with MAG3 clearance based on a single injection, two-compartment model. RESULTS: There was high correlation between the percent injected dose in the kidney at all three time periods and the multisample clearance. Correcting for body surface areas significantly improved the correlation coefficients. Consequently, regression equations were developed to predict multisample clearance based on percent dose and body surface area. CONCLUSION: The optimization features described in this method should improve precision when sequential studies are conducted in the same patient.

Adult↗
PubMed1995

Clinical evaluation of an optimized 1.1% amino-acid solution for peritoneal dialysis.

A significant percentage of dialysed patients have inadequate protein intake. One strategy for treating the protein malnutrition in peritoneal dialysis patients is to replace glucose in the dialysis solution by amino acids. A new peritoneal dialysis solution containing 1.1% amino acids in a formulation optimized for renal patients and with a lactate concentration of 40 mmol/l has been evaluated. Fifteen CAPD patients completed a non-randomized prospective 3-month study. Each patient received 2 litres of the optimised 1.1% amino acid solution for the second exchange of the day with a dwell time of 5-6 h. Indicators of efficacy were serum albumin and transferrin. After 3 months of intraperitoneal amino acids, serum albumin levels significantly increased from 32.7 +/- 2.3 to 35.1 +/- 2.2 g/l (mean +/- SD; P < 0.01). This occurred in parallel with a significant increase in transferrin levels from 2.21 +/- 0.26 to 2.39 +/- 0.27 g/l (P < 0.05). As expected, urea rose from 23.7 +/- 6.8 to 29.9 +/- 9.4 mmol/l. Interestingly bicarbonate did not change (25.5 +/- 4.2 versus 25.2 +/- 3.3 mmol/l). These results suggest that the optimized formulation is effective in improving nutritional parameters in CAPD patients while avoiding unwanted side-effects such as acidosis.

Adult↗
PubMed1995

Accelerated healing of cardiovascular textiles promoted by an RGD peptide.

Polytetrafluoroethylene (PTFE) and polyethylene terephthalate (Dacron polyester) fabrics are used extensively in cardiovascular devices, e.g. heart valve sewing cuffs and vascular prostheses. While devices containing these fabrics are generally successful, it is recognized that fabrics cause complications prior to tissue ingrowth due to their thrombogenic nature. A surface active synthetic peptide, called PepTite Coating (PepTite), which was modeled after the cell attachment domain of human fibronectin has been marketed as a biocompatible coating. This peptide stimulates cell attachment through the arginine-glycine-aspartic acid (RGD) sequence. Modification of medical implants with PepTite has been shown to promote ingrowth of surrounding cells into the material leading to better tissue integration, reduced inflammation and reduced fibrotic encapsulation. In this study, polyester and PTFE textiles were modified with PepTite. The effectiveness of this coating in enhancing wound healing was investigated in a simple vascular and cardiac valve model. Our results indicate that the RGD-containing peptide, PepTite, promoted the formation of an endothelial-like cell layer on both polyester and PTFE vascular patches in the dog model. PepTite was also found to promote the formation of a significantly thinner neointima (pannus) on polyester as compared to that on its uncoated control. These results were corroborated in the cardiac valve model in which a greater amount of thin pannus and less thrombus were seen on coated polyester sewing cuffs than on control uncoated cuffs. This research shows the promising tissue response to RGD coated textiles and the potential role of this peptide in material passivation via accelerated healing.

Amino Acid Sequence↗
PubMed1995

[Possibility for clinical use of mitral valve allograft: an experimental histopathological study in consideration with aortic valve allograft].

Morphologic studies were made on antibiotic preserved mitral valve allograft implanted in 8 sheep for 12 to 24 weeks. All allograft showed severe deterioration of connective tissue due to autolysis and immunological/inflammatory reactions. Compared with aortic valve allograft, mitral valve allograft failed more quickly and more severely, presumably because of differences in structure (presence of chordae tendineae and increased surface area of leaflets) and in closing pressure. The durability of cardiac valve allograft is influenced by the degree of preservation of collagen and elastic fibers in the graft. attenuation of immunologic reactions and control of fibrous sheathing.

Animals↗
PubMed1994

A novel trans-platinum coordination complex possessing in vitro and in vivo antitumor activity.

As part of a drug discovery program to discover more effective platinum-based anticancer drugs, a series of platinum complexes of trans coordination geometry centered on trans-ammine(cyclohexylaminedichlorodihydroxo)platinum(IV) (JM335) has been evaluated in vitro against a panel of cisplatin-sensitive and cisplatin-resistant human tumor cell lines (predominantly ovarian). In vitro, against 5 human ovarian carcinoma cell lines, JM335 was comparably cytotoxic to cisplatin itself and over 50-fold more potent than transplatin (mean 50% inhibitory concentrations: JM335, 3.1 microM; cisplatin, 4.1 microM; transplatin, 162 microM). With the use of seven pairs of human tumor cell lines (parent and subline with acquired resistance to cisplatin and encompassing all of the known major mechanisms of resistance to cisplatin) JM335 exhibited a different cross-resistance pattern to that of its cis isomer (JM149). JM335 showed non-cross-resistance in six of the seven resistant lines, cross-resistance in the A2780cisR line possibly being associated with high levels of glutathione. Preliminary intracellular DNA binding studies showed that in contrast to transplatin, JM335 was efficient at forming DNA-DNA interstrand cross-links. In vivo, JM335 produced growth delays in excess of 15 days against 4 of 6 human ovarian carcinoma xenografts and was unique among the complexes studied in retaining some efficacy against a cisplatin-resistant subline of the murine ADJ/PC6 plasmacytoma. JM335 is the first trans-platinum complex to demonstrate marked antitumor efficacy against both murine and human s.c. tumor models and represents a significant structural lead to complexes capable of circumventing cross-resistance to cisplatin.

Animals↗
PubMed1994

Male circumcision.

Explore the source record for details and available documents.

Circumcision, Male↗
PubMed1994

The anemia of primary autonomic failure and its reversal with recombinant erythropoietin.

OBJECTIVE: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. DESIGN: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. SETTING: A referral service for autonomic failure in a tertiary teaching hospital. PATIENTS: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. INTERVENTION: Open-label trial with human recombinant erythropoietin. RESULTS: Anemia was present in 32 of 84 patients (38%; 95% Cl, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns 3); serum iron, 16.5 mumol/L (92 micrograms/dL); total iron binding capacity, 43.3 mumol/L (242 micrograms/dL); ferritin, 184 micrograms/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). CONCLUSIONS: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Aged↗
PubMed1994

Schedule dependency of orally administered bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) in vivo.

JM216 is a novel antitumor platinum(IV) complex displaying oral activity, dose-limiting myelosuppression, and a lack of nephro- and neurotoxicity in rodents. It has been selected for clinical evaluation. The schedule dependency of its antitumor action against a murine (ADJ/PC6 plasmacytoma) and a human tumor model (PXN109T/C ovarian carcinoma xenograft) was studied in vivo. Single dose (q21d), once a day dosing for 5 consecutive days (q21d or q28d), and once a day dosing indefinitely (chronic daily dosing) administration schedules were compared. Against the murine ADJ/PC6 plasmacytoma, daily x5 administration improved the tolerance, antitumor potency, and therapeutic index of oral JM216, compared to single dose administration, whereas no advantage was found for fractionating cisplatin dosages. Against the PXN109T/C human ovarian carcinoma xenograft, oral JM216, given at dose levels delivering a equivalent total dose on single dose (200 mg/kg q21d), daily x5 (40 mg/kg/day q21d) and chronic daily dosing (9.5 mg/kg/d) schedules, showed superior tumor growth delays (55 +/- 15 days; P < 0.05) and maximal tumor regression (10 +/- 11% of initial tumor volume; P < 0.001) with the daily x5 schedule. Gastrointestinal toxicity (P < 0.05) and mild nephrotoxicity (P < 0.01) complicated the chronic daily dosing schedule, while leukopenia (P < 0.02) and thrombocytopenia (P < 0.01) were dose-limiting for the single dose and daily x5 administration, respectively. Peak plasma ultrafiltrate (PUF) platinum levels were below cytotoxic levels (PUF Cmax, 0.11 +/- 0.066 mg/l) at the maximally tolerable dose for the chronic dosing schedule (9.5 mg/kg). Peak PUF platinum levels did not increase significantly with a 5-fold increase in dosage from 40 mg/kg (PUF Cmax 1.5 +/- 0.11 mg/l) to 200 mg/kg (PUF Cmax, 2.4 +/- 0.44 mg/l; P > 0.05). In conclusion, these data demonstrate antitumor schedule dependency for oral JM216 in vivo, independently in two tumor model systems, and with nonlinear pharmacokinetics after its oral administration to mice. Optimal antitumor activity, tolerance, and pharmacokinetics occurred with daily x5 dosing, and this has prompted the clinical evaluation of this administration schedule.

Adenocarcinoma, Papillary↗
PubMed1994

Risk factors for repeatedly reactive HIV-1 EIA and indeterminate western blots. A population-based case-control study.

OBJECTIVE: Causes of indeterminate results of Western blot testing (IWB) for human immunodeficiency virus (HIV) type 1 include seroconversion, HIV-2 cross-reactivity, and autoimmune disease, but most IWB results remain unexplained. This case-control study assessed risk factors for IWB results, including early HIV infection, other retroviral infection, autoantibodies, and other medical conditions. DESIGN: Prospective study to determine HIV seroconversion rate, with a case-control design to assess other risk factors for IWB. Cases (persons with one or more repeatedly reactive HIV-1 enzyme immunoassay with IWB), their current sexual partners, and controls (persons with negative enzyme immunoassay and Western blot results) were recruited from blood banks, health department and prenatal clinics, and private providers in Washington and Oregon. RESULTS: Of 244 cases enrolled, 206 were followed up for 6 months or longer, and six (3.0%; 95% confidence interval [CI], 0.7% to 5.3%) with recent HIV risk behaviors seroconverted. The Western blot banding patterns differed among groups; cases usually had p17 or p24 bands, while controls and cases' sexual partners usually had polymerase bands. Conditional logistic regression indicated that independent risk factors for IWB among male cases and controls were a tetanus booster in the past 2 years (odds ratio, 3.2; 95% CI, 1.2 to 8.6) and sexual contact with a prostitute (odds ratio, 3.0; 95% CI, 1.0 to 9.5). Independent risk factors for women were parity (odds ratio, 1.2; 95% CI, 1.02 to 1.4) and autoantibodies, either rheumatoid factor or antinuclear antibodies (odds ratio, 2.3; 95% CI, 1.03 to 5.6). No cross-reactivity was detected with HIV-2, human T-lymphotrophic virus type 1, feline immunodeficiency or feline leukemia, or bovine immunodeficiency viruses. CONCLUSIONS: Evaluation of persons with reactive HIV-1 enzyme immunoassays and IWB should include an assessment of HIV risk and other possible risk factors, such as alloimmunization (ie, parity or recent immunization) or autoantibodies (ie, antinuclear antibodies and rheumatoid factor). The relationship of IWB among men who reported sex with prostitutes is intriguing and warrants further study.

Adolescent↗
PubMed1994

Enhancement in amount of P1 (hsp60) in mutants of Chinese hamster ovary (CHO-K1) cells exhibiting increases in the A system of amino acid transport.

Mutants of CHO-K1 cells with varied levels of A system activity, probably the result of increases in absolute amount of the A system transporter, have corresponding increases in levels of peptides banding at 62-66 and 29 kDa. Mutant alar4-H3.9, showing the highest increase of A system activity and of 62- to 66- and 29-kDa peptides, was selected for this study. The N terminus 16-amino acid sequence of the 62- to 66-kDa peptide(s) of this mutant showed between 80% and 100% identity with the mammalian mitochondrial 60-kDa heat shock protein P1 (hsp60). Two-dimensional gel electrophoresis of the 62- to 66-kDa band showed two major, a minor, and several smaller spots (of same mass but different pI values) for both wild type (WT) and mutant, with the two major spots being of greater density in the mutant. Immunoblots with antibody to P1 identified the two major and minor peptides as P1 related. Two-dimensional gels of whole cell extracts of the WT and alar4-H3.9 confirmed these findings and indicated that the two major bands of the mutant were 2.4 times as abundant as that found for the WT. A plasma membrane fraction of the mutant, exhibiting 4.8 times more A system activity than the WT, contained 3.6 times as much P1 as the WT. Immunoblots with antibodies to P1, mitochondrial malate dehydrogenase, and to the mitochondrial F1/F0-ATPase demonstrated that the increased amount of P1 observed in the mutant was not the result of increases in amount of mitochondrial protein. Northern blot analysis demonstrated that the mutant had 2.5 times as much mRNA for P1 as the WT. The close analogy with the relationship between A system and Na+,K(+)-ATPase suggests that there is a coordinate regulation of the A system of amino acid transport, Na+,K(+)-ATPase, and P1 protein, probably as a result of mutation in a shared regulatory element. The possible role of P1 in A system function is discussed.

Amino Acids↗
PubMed1994

Lack of neurotoxicity of oral bisacetatoamminedichlorocyclohexylamine-platinum(IV) in comparison to cisplatin and tetraplatin in the rat.

This study compared the effect on sensory nerve conduction velocity in the hind limb of chronically treated age-matched rats of a novel lipophilic p.o. platinum complex [bisacetatoamminedichlorocyclohexylamine-platinum(IV)], with that of neurotoxic platinum complexes cisplatin and tetraplatin. Tetraplatin (i.p.) first caused slowing of sensory nerve conduction (-14.4% of controls; P < 0.05) at a dose (1 mg/kg) that was free of constitutional toxicity. Cisplatin (i.p.) first caused slowing of sensory nerve conduction (-17.5% of control; P < 0.05) at a dose (2 mg/kg) approximating the maximal tolerated dose. Bisacetatoamminedichlorocyclohexylamineplatinum(IV) (p.o.) showed no slowing of sensory nerve conduction either after 20.5 weeks of treatment at a dose (25 mg/kg) approximating the maximal tolerated dose or after 6 weeks of treatment at a dose (50 mg/kg) which eventually proved intolerable. In conclusion, p.o. bisacetatoamminedichlorocyclohexylamineplatinum(IV) shows a lack of neurotoxicity compared to parenterally administered cisplatin and tetraplatin at the maximal tolerated dose in rats.

Administration, Oral↗