Search PubMed⌕ Search

Biomedical subjects

J Hoffman

Publications and source records attributed to J Hoffman.

At least 199 records · Page 11Linked to original sources
PubMed1982

Pharmacokinetics of cisplatin regional hepatic infusions.

Cisplatin (DDP), a potent antineoplastic agent, is usually administered via a peripheral vein. Recently, there has been considerable interest in intraarterial regional infusions of DDP. The pharmacokinetics of DDP when administered by this technique have not been explored in detail. We studied DDP pharmacokinetics in dogs given DDP by infusion and bolus injection in the hepatic artery (H.A.), portal vein (portal V), and peripheral vein (P.V.). Blood and biliary platinum concentrations ([Pt]) were assayed by flameless atomic absorption spectrophotometry. During an infusion into the H.S., peak [Pt] in the vessel were markedly higher (mean value 19 micrograms/ml) than those found, simultaneously, in the portal V or superior vena cava. Following a bolus injection of DDP into the H.A., higher H.A. [Pt] were also seen, but [Pt] rapidly (within 5-10 minutes) equilibrated in all sites sampled. During the H.A. infusion, most [Pt] was in its free (active) form. Bile and hepatic tissue were also sampled. Hepatic artery infusions of DDP give high drug concentrations in the perfusing blood, while systemic [Pt] are much lower. During the infusion, the majority of DDP is in its active (unbound) state.

Animals↗
PubMed1982

An evaluation of the initial treatment of acute asthma.

Two treatment regimens for the initial treatment of acute asthma in 50 patients between the ages of 12 and 20 years seen in the emergency room were evaluated. The treatments were randomized such that 26 patients received 2.5 mg of the beta 2-agonist fenoterol by nebulizer and 24 patients received 0.3 mg of epinephrine followed by 0.75 mg of Sus-Phrine. Clinical assessment and spirometry were performed over a two-hour period. Both groups responded within ten minutes and peak improvement was reached within one hour. Peak expiratory flow and clinical score were better following fenoterol treatment in the first hour (P less than .05). The one-second forced expiratory volume and the forced expiratory flow in the middle half of the vital capacity were greater at 20 minutes with fenoterol (P less than .05). Those with more severe obstruction (forced expiratory volume less than 30%) receiving aerosol therapy also had significantly greater improvement in the first 20 minutes compared with those who received injections. Four patients failed to respond to epinephrine whereas all patients showed improvement with fenoterol (P less than .05). These results demonstrated that an inhaled beta 2-agonist is effective in the initial treatment of acute asthma in children, regardless of severity, and avoids the need for injections.

Acute Disease↗
PubMed1982

Lymphocyte enzymes in the detection of Niemann-Pick Carriers.

An improved method for the detection of Niemann-Pick disease type A and B carriers is described. Niemann-Pick disease is a genetic disorder characterized by the accumulation of sphingomyelin in several organs, among them spleen, liver and brain. A deficiency in sphingomyelinase activity is the characteristic defect in this lipid storage disorder, and the decreased enzyme activity in these types can be demonstrated in various cells and tissues. Low activity levels of enzymes were found in leukocyte fractions of peripheral blood from patients screened for Niemann-Pick disease. In heterozygote patients levels were within the lower range of control values. We therefore determined sphingomyelinase activity in discrete cell types isolated by two different methods from the total leukocyte fraction. In normal subjects sphingomyelinase activity is five to ten-fold higher in lymphocytes than in granulocytes. Monocytes have an intermediate level. pH profile and stability to heat inactivation were tested in separated lymphocytes and granulocytes and were found to be insignificantly different. Detection of carriers for Niemann-Pick type A and B by using separated lymphocyte as enzyme source, overcomes the difficulty of overlapping values with normal controls and serves as an excellent tool to detect heterozygotes.

Genetic Carrier Screening↗
PubMed1981

Intramolecular integration within Moloney murine leukemia virus DNA.

By screening a library of unintegrated, circular Moloney murine leukemia virus (M-MuLV) DNA cloned in lambda phage, we found that approximately 20% of the M-MuLV DNA inserts contained internal sequence deletions or inversions. Restriction enzyme mapping demonstrated tht the deleted segments frequently abutted a long terminal repeat (LTR) sequence, whereas the inverted segments were usually flanked by LTR sequences, suggesting that many of the variants arose as a consequence of M-MuLV DNA molecules integrating within their own DNA. Nucleotide sequencing also suggested that most of the variant inserts were generated by autointegration. One of the recombinant M-MuLV DNA inserts contained a large inverted repeat of a unique M-MuLV sequence abutting an LTR. This molecule was shown by nucleotide sequencing to have arisen by an M-MuLV DNA Molecule integrating within a second M-MuLV DNA molecule before cloning. The autointegrated M-MuLV DNA had generally lost two base pairs from the LTR sequence at each junction with target site DNA, whereas a four-base-pair direct repeat of target site DNA flanked the integrated viral DNA. Nucleotide sequencing of preintegration target site DNA showed that this four-base-pair direct repeat was present only once before integration and was thus reiterated by the integration event. The results obtained from the autointegrated clones were supported by nucleotide sequencing of the host-virus junction of two cloned M-MuLV integrated proviruses obtained from infected rat cells. Detailed analysis of the different unique target site sequences revealed no obvious common features.

Bacteriophage lambda↗
PubMed1980

Structural studies of the lipopolysaccharide from Salmonella typhimurium 902 (ColIb drd2).

Salmonella typhimurium infected with the plasmid ColIb drd2 gave rise to changes in the composition of the bacterial lipopolysaccharide. Bacteria carrying the wild-type ColIb, the revertant of drd2 to the wild type, or the noncolicinogenic strain resulting from the elimination of ColIb drd2, showed no changes in the sugar composition of the lipopolysaccharide. The structure of the O-specific side chains of the lipopolysaccharide produced by S. typhimurium 902, infected with derepressed ColIb mutants has been investigated. As a result of these studies, it is proposed that the O-specific side chains are composed of chemical repeating units with the following structure: (formula: see text).

Carbohydrate Sequence↗
PubMed1980

[Cyclic 3',5'-adenosine monophosphate in macrophages, intestinal mucosa, and blood plasma of germ-free and ordinary animals].

The level of cAMP in macrophages, intestinal mucosa and blood plasma as well as its formation in intestinal mucosa of germfree animals under the effect of lipopolysaccharide E. coli 055 (LPS) were studied in experiments on germfree and ordinary mice and guinea-pigs. The concentration of cAMP in intestinal mucosa of ordinary guinea-pigs was 5-fold higher than in germfree animals. LPS induced an increase in cAMP level in intestinal mucosa, but this level did not reach that in ordinary animals. The levels of cAMP in blood plasma of germfree guinea-pigs in macrophages of germfree mice increased 2-fold and 4-fold, respectively, 30 minutes following the treatment with LPS. The increased level of cAMP was accompanied by its intensive secretion into the exocellular medium. Macrophages of ordinary animals had a moderate output of cAMP. A conclusion is made about the relationship between cAMP formation and microbial contamination of the microorganism as well as about an important role of the cyclic nucleotide in the mechanism of nonspecific resistance and homeostatic reactions of the body to microbial exposure.

Animals↗
PubMed1978

Mutation affecting thermostability of sigma subunit of Escherichia coli RNA polymerase lies near the dnaG locus at about 66 min on the E. coli genetic map.

The Escherichia coli strain, ts-rnp5, originally described in 1975 by G. D. Burdick and H. Berger, is shown to possess an RNA polymerase (RNA nucleotidyltransferase) sigma subunit with an activity 4--6 times less thermostable at 45 degrees than sigma from wild-type strains. This defect remains associated with the sigma polypeptide through a variety of purification stages, including renaturation of sigma after its elution from sodium dodecyl sulfate/polyacrylamide gels. The mutation responsible for decreased thermostability of sigma, called rpoD1, cotransduces with dnaG and therefore is located at about 66 min of the E. coli genetic map.

Chromosome Mapping↗
PubMed1978

Effects of attributions for success and failure on the performance of retarded adults.

Seventy-two TMR adults were given success and failure experiences at a coding task, as well as one of three causal attributions (ability, effort, or task difficulty [ease]). The data revealed that causal ascriptions interacted with outcome in influencing speed of performance and that success enhanced performance only when coupled with an ability ascription. The data suggested that some of the contradictions in the success-failure literature may be due to differential causal attributions elicited across the various investigations. The implications of these data for training programs also were discussed.

Achievement↗
PubMed1977

The proliferative patterns of human breast cancer cells in vivo.

The cell proliferation pattern in human breast cancer has been studied in eight patients in vivo using intravenously administered 3HTdR as a pulse and as a continous label. Two to 4% of the tumor cells were engaged in DNA synthesis in six patients, and 7% and 11%, respectively, in two others. From the composite percent labeled mitosis curve the estimated time for G1 + (M/2) was about 4 hours and for DNA synthesis about 24 hours. Many cells which entered the cycle spent longer intervals in DNA synthesis and in the post-DNA synthetic phase before entering mitosis. There was a wide range of intermitotic times among the tumor cells. These findings are of significance in the planning of drug therapy.

Adult↗
PubMed1977

A rapid in vitro method for measuring cell proliferation in human breast cancer.

A method has been developed for studying in vitro the cell proliferation kinetics of human breast cancer, Surgical specimens from primary tumors were studied in 56 patients. Viable cell suspensions for assay were obtained by the dissociation of tumor tissue with collagenase. Mean Labeling indices of 2.43 +/- S.D 2.05 and 4.48 +/- S.D. 3.73, respectiviely, were found after incubation with 3HTdR for 2 hours and 24 hours. Mean S-times of 21.9 +/- S.D. 4.3 hours were estimated by 3H and 14C-TdR double-labeling. The kinetic data have been validated by parallel labeling studies in vivo and in vitro in four patients. The processing of autoradiographs using gold latensification provided slides for kinetic analysis within 3 days. The assay offers a method that is useful in the planning and monitoring of drug therapy.

Autoradiography↗
PubMed1976

Structural studies of the polysaccharide antigen of Eubacterium saburreum, strain 49.

The polysaccharide antigen produced by Eubacterium saburreum, strain L 49, is composed of D-glycero-D-galacto-heptose and a new sugar, tentatively identified as 6-deoxy-D-altro-heptose. It contains chains of alternating (1 leads to 3)- and (1 leads to 6)- linked beta-D-glycero-D-galacto-heptopyranosyl residues, the latter being substituted with 6-deoxy-alpha-heptofuranosyl groups at O-3. The polysaccharide further contains 0-acetyl groups, linked to O-7 of part of the heptosyl residues and to O-2 of part of the 6-deoxyheptosyl groups.

Chromatography, Gas↗