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Biomedical subjects

J Weissman

Publications and source records attributed to J Weissman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Lack of effect of cyclophosphamide on the immunogenicity of a melanoma antigen vaccine.

Melanoma antigen vaccines are a conceptually attractive approach to prevent or delay disease recurrence in patients with surgically resected malignant melanoma. However, the immunogenicity of current vaccines is relatively low. Cyclophosphamide, when given in low doses prior to antigen exposure, is an immunomodulator which has been shown to enhance both humoral and cellular antitumor responses in animals and humans. We conducted a prospective, randomized, clinical trial to study whether pretreatment with cyclophosphamide augments the immunogenicity of a polyvalent, allogeneic, melanoma antigen vaccine in patients with melanoma and low tumor burden. Forty-five patients with resected stage II melanoma (regional metastases) were randomly allocated to treatment with melanoma vaccine or melanoma vaccine plus cyclophosphamide. All patients received the same dose and schedule of vaccine immunizations; those randomized to cyclophosphamide received 300 mg/m2 i.v. 3 days prior to each vaccine immunization. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) skin reactivity to a test dose of vaccine at baseline (prior to treatment) and following the fourth immunization. Humoral immune responses were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiographic analysis of indirect immunoprecipitates of patients' sera at the same time points. Twenty-four patients were randomized to cyclophosphamide pretreatment and 21 to vaccine alone; 22 and 18 patients were evaluable in each group, respectively. Differences were statistically nonsignificant with respect to either cellular (DTH) or humoral (antibody) responses between the two groups. DTH responses were induced in 16 of 22 (73%) and 15 of 18 (83%) patients treated with cyclophosphamide plus vaccine and vaccine alone, respectively. The mean posttreatment augmentation in DTH response in the cyclophosphamide group was 9.5 mm, compared with 9.9 mm in the vaccine-only group. Eight of 12 (66%) cyclophosphamide-pretreated patients and 9 of 12 (75%) vaccine-only patients produced increased titers of antimelanoma antibodies following treatment. No differences were observed between the groups in disease-free or overall survival. In summary, low-dose cyclophosphamide pretreatment failed to augment the immunogenicity of a polyvalent, allogeneic, melanoma vaccine in patients with completely resected early-stage melanoma.

Adult↗
PubMed1991

Iodoacetate-induced contracture in rat skeletal muscle: possible role of ADP.

The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic contraction of IAA-treated muscles produced contracture. The onset of contracture was not associated with a change in sarcolemmal electrical properties or reduction in intracellular [ATP]; however, [creatine phosphate] was reduced by 75% and free [ADP] was increased by 665%. Continued stimulation of IAA-treated fibers resulted in depolarization, loss of membrane excitability, further depletion of creatine phosphate, and reduction in [ATP]. The effects seen in IAA-treated muscle did not appear to result from a direct action of IAA on the surface membrane, contractile proteins, or excitation-contraction coupling. The contractures in IAA-treated muscle may have resulted from increased Ca sensitivity of the contractile proteins, increased myoplasmic [Ca], or both. Both effects may have resulted from increased [ADP]. In addition, the reduced acidification during ischemic contraction of IAA-treated fibers compared with control fibers may have further increased the Ca sensitivity of IAA-treated fibers compared with controls.

Adenosine Diphosphate↗
PubMed1987

Risk factors of drug impairment in random samples of physicians and medical students.

The prevalence of hypothesized risk factors of drug impairment is estimated and correlated with drug use in random samples of physicians and medical students. Substantial percentages of both physicians and medical students reported access to drugs, family histories of substance abuse, stress at work and home, emotional problems, and sensation seeking. Each of these factors correlated with drug use in physicians or medical students, and analysis suggested that in most cases the hypothesized risk factors were more likely to be causes rather than consequences of drug use.

Adult↗
PubMed1986

Psychoactive drug use among practicing physicians and medical students.

We surveyed random samples of 500 practicing physicians and 504 medical students in a New England state during 1984-1985; 70 percent of the physicians and 79 percent of the students responded. Fifty-nine percent of the physicians and 78 percent of the students reported that they had used psychoactive drugs at some time in their lives. In both groups, recreational use most often involved marijuana and cocaine, and self-treatment most often involved tranquilizers and opiates. In the previous year, 25 percent of the physicians had treated themselves with a psychoactive drug, and 10 percent had used one recreationally. Although most of the use was experimental or infrequent, 10 percent of the physicians reported current regular drug use (once a month or more often) and 3 percent had histories of drug dependence. More physicians and medical students had used psychoactive drugs at some time than had comparable samples of pharmacists and pharmacy students. The results suggest a need for renewed professional education about the risks of drug misuse.

Cannabis↗
PubMed1985

Focal fatty liver lesions in alcoholic liver disease: a broadened spectrum of CT appearances.

The CT examinations of 26 consecutive alcoholic patients with focal fatty infiltration of the liver were analyzed. Five different patterns of focal fatty infiltration were noted. In most alcoholic patients these appearances present no diagnostic problem and further confirmation can be obtained by repeating the CT scan within 1-2 weeks to see if interval resolution occurs following enforced abstinence. In select instances, more invasive and definitive procedures such as superselective angiography or liver biopsy may be necessary to differentiate these findings from other more serious diseases they may closely resemble, such as primary or secondary liver neoplasms.

Adult↗
PubMed1985

Metabolism of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by liver homogenate fractions.

The metabolic fate of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been examined in rat and rabbit liver mitochondrial and rabbit liver microsomal preparations. The mitochondrial preparations rapidly oxidized MPTP, in a pargyline-sensitive reaction, to a polar material that was shown to contain the 1-methyl-4-phenylpyridinium species as the principal product. NADPH-supplemented microsomal preparations converted MPTP to two principal products: 4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide. Carbon monoxide and SKF 525A selectively inhibited the oxidation of MPTP to the nor compound, indicating that this N-demethylation reaction is cytochrome P-450 catalyzed. Attempts to trap possible unstable iminium metabolites of MPTP in microsomal incubation mixtures with sodium cyanide led to the isolation of a monocyano adduct that proved to be the N-cyanomethyl derivative. Thus, hepatic mitochondrial and microsomal enzyme systems catalyze the oxidation of MPTP by different pathways, the former leading to the generation of species that may possess neurotoxic properties.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Hepatocellular carcinoma. Diagnostic and prognostic features in North American patients.

Diagnostic and prognostic characteristics of 121 North American patients with hepatocellular carcinoma seen in one metropolitan area over a 6-year period were assessed using multivariate analysis. Presenting symptoms commonly included abdominal pain (53%) or mass (34%), anorexia (31%), and ascites (20%); however, the ability to make an early diagnosis was complicated by a variety of unusual symptoms accounting for 25% of presentations. While cirrhosis (63%) and hepatitis B surface antigen (HBsAg) positivity (52%) were common associated findings, the majority of patients (67%) had no prior diagnosis of liver disease. Despite the vascular nature of these malignancies, percutaneous biopsy procedures performed in 66 patients provided diagnostic material in over 85% of cases with little morbidity. Histologic diagnosis was made by blind percutaneous biopsy (41 done, 83% positive), peritoneoscopy with directed percutaneous biopsy (25 done, 88% positive), laparotomy (42 done, 98% positive), or autopsy (19). Percutaneous hepatic biopsy procedures were associated with no mortality and rare bleeding (three cases). Overall median survival was only 18 weeks; multivariate analysis indicated increased bilirubin or presence of pulmonary metastases adversely influenced outcome. Unexpectedly, patients younger than 45 years of age had a significantly (P less than 0.01) greater survival (median, 40 versus 9 weeks) than did older patients with this disease. We conclude: (1) hepatocellular carcinoma can be rapidly and safely diagnosed using percutaneous biopsy procedures; (2) North American patients with hepatocellular carcinoma younger than 45 years of age have a more favorable prognosis.

Actuarial Analysis↗
PubMed1981

Acute interstitial nephritis due to amoxicillin therapy.

Acute interstitial nephritis (AIN) has been reported in association with therapy with a number of drugs. We report a patient who developed drug-related AIN while receiving intravenous amoxicillin therapy. The patient developed rash, secondary temperature elevation, and eosinophilia in association with nonoliguric renal failure. Renal biopsy showed evidence for AIN and the renal failure was responsive to corticosteroid therapy. AIN may occur in patients receiving any drug of the penicillin class. This reversible form of acute renal failure must not be overlooked in patients with other forms of renal disease.

Acute Disease↗
PubMed1977

Renal calcium binding protein in the diabetic and vitamin D-depleted rat.

A calcium binding protein has been purified 220 fold from rat kidney. The molecular weight of this protein (26 000-28 000) is more than double that of the duodenal calcium binding protein of the rat. In response to the stimuli of both streptozotocin diabetes and depletion and repletion with vitamin D, changes in the renal protein are minimal. This contrasts markedly with responses of the duodenal protein to the same stimuli: (a) there was marked depression of duodenal calcium binding protein by vitamin D depletion and diabetes; (b) duodenal calcium binding protein was restored by vitamin D treatment of depleted rats. The renal protein appears to be identical with a previously described 28 000 molecular weight protein from the kidney purified by a different technique (Hermsdorf, C.L. and Bronner, F. (1975) Biochim. Biophys. Acta 379, 553-561). In contrast to findings of the current study, previous investigators were unable to isolate the protein from vitamin D-deficient rats and postulated vitamin D dependence. The protein activator of cyclic AMP phosphodiesterase is a calcium binding protein found in many tissues including kidney. Based on lack of response to stimuli we used and similarity in method of isolation and properties, our renal calcium binding protein may be this protein activator.

Animals↗