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Biomedical subjects

J Rosenblatt

Publications and source records attributed to J Rosenblatt.

At least 73 records · Page 4Linked to original sources
PubMed1990

Early events in hepatitis C virus infection of chimpanzees.

The cytoplasmic antigen and ultrastructural changes we described previously for chimpanzees (Pan troglodytes) infected with hepatitis C virus (HCV) or with hepatitis D virus have recently been shown to be indirect measures of viral replication and appear to represent a host response to the expression or action of interferon. The time of appearance of these changes in hepatocytes during HCV infection, when compared with similar changes in hepatitis D virus infection, suggests a very early replicative phase for HCV. To investigate the early events in HCV infection, we infected two chimpanzees with HCV and obtained blood and liver biopsy samples from them daily during the first 10 days of infection. The early stage of infection with regard to HCV replication, antigen expression, and ultrastructural changes was similar in both chimpanzees. When tested by cDNA/polymerase chain reaction, HCV sequences became detectable in the serum as early as 3 days after inoculation and remained positive through the peak of aminotransferase elevations. In one chimpanzee the peak of virus production appeared to be 7 weeks after inoculation, which was coincident with rising enzyme values. The cytoplasmic antigen, detected by immunofluorescence, and ultrastructural changes, detected by electron microscopy, became positive in hepatocytes 3 and 6 days, respectively, after HCV sequences were first detected in serum. Circulating anti-HCV appeared 13 weeks and 32 weeks after inoculation, respectively, in the chimpanzees. These data indicate a very early replicative phase for HCV and a potentially long period of infectivity before the appearance of anti-HCV.

Animals↗
PubMed1990

Effect of exercise and recovery on muscle protein synthesis in human subjects.

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.

Adult↗
PubMed1988

Cubic splines.

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Regression Analysis↗
PubMed1988

Calculation of substrate flux using stable isotopes.

The use of stable isotope tracers to calculate substrate kinetics in humans is favored over the use of radioactive isotopes because of their greater safety and versatility. However, potential complications not met when dealing with radioactive tracers are caused by 1) the natural occurrence of the stable isotope used as a tracer and 2) the necessity to administer the tracer in an amount that cannot be treated as "massless." We therefore found it desirable to derive a theoretically valid equation for calculating the rate of appearance, Ra, of a substrate under steady-state conditions using a stable isotope tracer. This theoretically valid equation yields results that differ from those of the equations conventionally used to calculate (endogenous) Ra in steady state. Quantitative determination of the error in one of these equations revealed that for tracers commonly used in metabolic studies the error is negligible, whereas the error made in the other equation is likely to be quite high in commonly encountered situations. Finally, to allow for proper use of different definitions of isotopic enrichment that have arisen from practical considerations, we use the results derived above to determine valid equations for Ra appropriate to the two prevalent definitions.

Humans↗
PubMed1988

A more direct approach to compartmental modelling.

By first using some simple linear curve fitting method, (such as spline fitting), on data following a compartmental model, direct application of linear regression can then be made to the system of differential equations describing this data. This allows information about the parameters governing the system to be obtained from tracer and tracee measurements. It simplifies both the process of determining which parameters are estimable from various measurements, as well as the estimation process itself. Since it does not rely on knowledge of a simple closed form of the solution it has the potential to make full use of data measured over very long time periods under nonequilibrium conditions. Essentially it allows introduction of sequential estimation methods of statistics. These results can then be used to predict future substrate concentration from known substrate production, or determine substrate production from concentration measurements. A byproduct of these methods is the ability to estimate parameters in data assumed to be a finite linear combination of exponentials or sinusoids of unknown exponents or frequencies, without use of complicated nonlinear regression methods.

Animals↗
PubMed1987

Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects.

In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion (0.015 microgram X kg-1 X min-1) were determined. The rate of appearance (Ra) of free fatty acids (FFA) and glycerol were quantified by infusion of [1-13C]palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2(18)O dilution. In normal volunteers, the basal Ra FFA and Ra glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.

Adult↗
PubMed1986

Economic considerations for dispensing pharmacists: the impact of price-quality evaluations on brand categorization.

This paper examines consumer brand categorization in view of price-quality evaluations. In particular it examines the relationship of the Brisoux and Laroche (1980) brand categorization process and the Bliemel (1984) conceptualization of consumers' price-quality evaluations, in a pharmaceutical marketing context. The findings suggest that: the Brisoux-Laroche conceptualization is supported in a pharmaceutical/industrial marketing scenario; and, the pharmacists' categorization of brands (i.e., into the evoked, hold, foggy, and reject sets) can be partially explained as an outcome of a price-quality evaluation process.

Canada↗
PubMed1984

The comparative molecular biology of HTLV-I and HTLV-II.

The human T-cell leukemia viruses (HTLV) I and II, have been implicated in naturally occurring T-cell malignancies in man. We are engaged in ongoing comparative studies of HTLV-I and HTLV-II in our laboratory. We have isolated a replication-competent clone of HTLV-II, as well as several defective HTLV-II proviruses from the Mo-T hairy-cell leukemia line. HTLV-II is able to transform normal T-lymphocytes, and can replicate in both T- and B-cell lines. We have devised a convenient system allowing direct transfection of the HTLV-II genome into a B-cell line, followed by selection of HTLV-infected cells. Transfection studies with HTLV-II indicate that the virus can replicate in lymphoid cells, but not in fibroblasts. Transfection of recombinant constructs demonstrates that the viral long terminal repeat (LTR) can function as a promoter in lymphoid cells, but not in fibroblasts, suggesting a role for the viral LTR in conferring target cell specificity. Structural similarities between the HTLV-I and HTLV-II LTRs, including the presence of similar repeated base sequences in the U3 region, may account for this LTR specificity. The X region of HTLV-II has been sequenced and compared to that of HTLV-I. We have identified an mRNA species encoded by the major open reading frames in the X region of HTLV-I and HTLV-II and have located the splice acceptor site. Using antisera generated to short peptide sequences encoded by X, we have identified specific X-encoded viral proteins in HTLV infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗
PubMed1982

Estrogen receptor status as a prognostic indicator for stage I breast cancer patients.

The prognostic value of estrogen receptor determination was studied for 510 stage I (axillary node negative) breast cancer patients treated by mastectomy alone. Results at 60 months after mastectomy indicate that stage I patients whose tumors lack estrogen receptors fall into a significantly poorer prognostic group for both recurrence and survival than those whose tumors contain estrogen receptors. Within the postmenopausal group, estrogen receptor negative (ER -) patients are recurring more rapidly than estrogen receptor positive (ER +) patients. Within the premenopausal group, ER + patients have a recurrence rate identical to ER - patients, which is apparent only after prolonged follow-up. In contrast to postmenopausal ER + patients, premenopausal ER + patients appear to have no prognostic advantage over the ER - patients, and thus constitute a high risk group for which adjuvant endocrine therapy might prove beneficial.

Breast Neoplasms↗
PubMed1981

Adjuvant therapy of stage II breast cancer: 48-month follow-up of a prospective randomized clinical trial.

A prospective, randomized clinical trial of adjuvant treatment of 318 stage II breast cancer patients, using chemotherapy, the antiestrogen tamoxifen, and immunotherapy is reported at 48 months follow-up. Women whose primary tumors have no estrogen receptors fall into a significantly poorer prognostic group than those whose tumors contain estrogen receptors. None of the adjuvant regimens appeared to offer any clear-cut advantage for the estrogen receptor negative patients. Those women whose primary tumor contains estrogen receptors appear to be in a prognostically favorable group, when their treatment regimen included the antiestrogen, tamoxifen. The adjuvant use of BCG immunotherapy does not appear to offer additional benefit, but the follow-up period of these treated patients is too brief to be conclusive. A longer period of observation is needed to determine whether this systemic treatment in estrogen receptor positive patients is preventing recurrence or merely delaying it.

Antineoplastic Agents↗
PubMed1980

Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial.

The results of adjuvant chemotherapy (CMF), endocrine therapy (t), and immunotherapy (BCG) in 318 women who had undergone mastectomy for Stage II breast cancer are reported after 45 months of life table analysis. CMFT therapy was found to be more effective than CMF alone in increasing recurrence-free survival. This beneficial effect appears to be limited to patients with estrogen receptor-positive tumors (ER+). Patients with estrogen receptor-negative tumors (ER-) (< 3 fmol/mg) have increased recurrence rates and higher mortality.

Antineoplastic Agents↗