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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 865 records · Page 48Linked to original sources
PubMedDate not supplied

VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity.

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.

Animals↗
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Integrating residency training in geriatrics into existing outpatient curricula.

In recent years, the need for increasing the geriatrics component of residency training has been repeatedly addressed; however, there are still many programs that have been unable to meet this need. While alternative sites, such as geriatric evaluation units and nursing homes, may be the ideal sites to teach some aspects of geriatrics, this article argues that the ambulatory care program, required in all residency programs, is the appropriate setting for teaching many of the core skills needed to care for most older adults. Teaching geriatrics in the ambulatory setting, which eliminates the strategic and financial obstacles of developing non-hospital-based sites, can be accomplished with relatively modest additional resources. This article describes the methods used to integrate geriatrics into the ambulatory care component of one internal medicine residency program and the necessary faculty resources as well as the documentation, via chart audit, of the interns' compliance with recommended practice patterns in five categories. With the exception of vaccination status, interns documented 18% or less of possible pieces of information for their patients. While this assessment showed statistically significant improvement in interns' care of older patients after the program intervention, the overall level of performance was still low, underscoring the need for the integration of geriatrics principles in the ambulatory curriculum.

Ambulatory Care↗
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Comparison of the treadmill exercise score and single-photon emission computed tomographic thallium imaging in risk assessment.

BACKGROUND: This study compared the prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging with that of treadmill exercise score in medically treated patients with coronary artery disease (CAD). METHODS AND RESULTS: The treadmill exercise score was derived from exercise duration, degree of ST segment depression, and the treadmill anginal index. There were 121 patients with no CAD and 316 patients with angiographically defined CAD (> or = 50% diameter stenosis of one or more vessels). During a mean follow-up of 29 months, there were 35 cardiac deaths or nonfatal myocardial infarctions. Multivariate Cox survival analysis showed the extent of thallium imaging abnormality and CAD to be independent predictors of prognosis. On the other hand, the treadmill exercise score was not a significant predictor even on univariate analysis. The results of thallium uptake were the strongest independent predictors of prognosis and in addition provided incremental prognostic power to coronary angiography (chi 2 = 29 for SPECT, 27 for coronary angiography, and 37 for both). CONCLUSIONS: Thus exercise SPECT thallium imaging is significantly better than the treadmill exercise score in risk assessment. The size of the perfusion abnormality is an important predicator of prognosis.

Adult↗
PubMedDate not supplied

Ionic modulation of the effects of heparin and 6-aminohexanoic acid on plasminogen activation by streptokinase: the role of ionic strength, divalent cations and chloride.

Studies were conducted on the effect of heparin or 6-aminohexanoic acid (6-AH) on the activation of glutamic plasminogen (Glu-Plg) by streptokinase in the presence of different concentrations of buffer, NaCl and divalent cations. Heparin and 6-AH inhibited streptokinase-mediated activation of Glu-Plg using 10 mM Tris-HCl buffer pH 7.4. This inhibition was partially reversed by the addition of 0.2-1.0 mM of Mg ions. Increasing the ionic strength of Tris-HCl buffer from 10 to 50 mM or addition of 50-150 mM of NaCl to 50 mM Tris-HCl pH 7.4 inhibited the activation of Glu-Plg by streptokinase while decreasing the % inhibition by heparin over the control samples. Double reciprocal plot of the activation of Glu-Plg by streptokinase using 50 mM Tris-HCl pH 7.4 containing 100 mM NaCl showed that the addition of heparin lowered Vmax by 50% without affecting Km. To determine whether the inhibitory effect of heparin was specifically directed towards Glu-Plg or streptokinase, the ratios of the initial rate of plasmin generation in the presence of heparin over the controls were plotted against the inverse of the volume fraction of Glu-Plg or streptokinase after serial dilutions. The results indicated that the dilutions of streptokinase but not of Glu-Plg influenced the ratios, suggesting an interaction of heparin with streptokinase. Addition of 6-AH reversed the inhibitory effect of NaCl on the activation of Glu-Plg by streptokinase and the results of the near UV CD spectra of Glu-Plg showed that addition of 6-AH enhanced the spectra in this region with an increase in the ellipticity which was not affected by addition of NaCl.

Aminocaproic Acid↗
PubMedDate not supplied

Student satisfaction with classroom use of computer-assisted instruction.

In summary, the number of schools using CAI is increasing, and available CAI programs are multiplying rapidly. We believe that a critical factor in classroom use of CAI is the selection of appropriate topics for presentation by this method of media instruction. Faculty must know students' reactions and level of satisfaction with CAI to ensure that selection of this teaching methodology is made wisely, and that this methodology is an effective one for the student. Therefore students must be included in the process of evaluating media instruction.

Computer-Assisted Instruction↗
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Frontal cortex and basal ganglia metabolic rates assessed by positron emission tomography with [18F]2-deoxyglucose in affective illness.

Twenty affective disorder patients (16 bipolar and 4 unipolar) and 24 normal controls received scans with positron emission tomography (PET) using [18F]2-deoxyglucose (FDG) as a tracer. Subjects received a series of brief electrical stimuli to their right arms during FDG uptake. Patients with bipolar affective illness had significantly lower frontal to occipital glucose metabolic rate ratios (relative hypofrontality) and significantly lower metabolic rates in their basal ganglia in comparison to whole slice metabolism than normal controls. Patients with unipolar illness showed significantly higher frontal to occipital ratios, and also showed relatively decreased metabolism in the basal ganglia. All results in unipolar patients should be considered exploratory due to the small number of patients. Clinical depression ratings correlated negatively with whole slice metabolic rate.

Adult↗
PubMedDate not supplied

Dose effects of nicotine gum.

Nicotine gum has been shown to be effective in improving abstinence rates, and in reducing post-cessation withdrawal distress and weight gain. However, the dose effects of nicotine gum on these outcomes is not known. In the present study, we varied the amount of 2 mg nicotine gum prescribed to motivated quitters to explore the hypotheses (a) that motivated quitters would use more pieces of gum when coached and counseled to do so and (b) that there would be a dose-related effect of gum use on abstinence, withdrawal symptoms, and weight gain. One hundred seventy-seven volunteers were assigned to chew either 0, 7, 15, or 30, pieces per day of 2 mg nicotine gum. Biological verification of gum use and smoking abstinence were assessed in community volunteers who attended an intensive behavioral counseling program for smoking cessation while using nicotine gum for 3 months. In the survival analysis at 12 weeks, gum-group assignment was not related to successful abstinence. In the subset of 42 abstinent subjects, there was a strong positive relationship between pieces per day of nicotine gum used and saliva cotinine. However, there was substantial variability in groups of subjects reporting similar amounts of gum use. Withdrawal symptom reporting was not related to either gum use or cotinine levels. Weight gain was significantly related in a dose-dependent manner to salivary cotinine levels, but not to gum group assignment, with high and low cotinine subjects gaining on average, 4.0 and 6.6 pounds, respectively. Discussion of the use of high levels of nicotine gum is addressed. Consistent with earlier work, the study provided further support for the relationship between nicotine replacement level and post-cessation weight gain.

Dose-Response Relationship, Drug↗
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In vitro activity of ampicillin/sulbactam against enterococci determined by the time-kill method.

Time-kill studies demonstrated that at clinically achievable serum concentrations, ampicillin/sulbactam was equivalent in activity to ampicillin alone against non-beta-lactamase producing isolates of Enterococcus faecalis and Enterococcus faecium. Sulbactam possessed no antibacterial activity against these organisms. It is not yet known if the activity of ampicillin will be increased with the addition of sulbactam when tested against beta-lactamase-producing enterococci.

Ampicillin↗
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Group intervention with pre-recovery patients.

This article examines treatment outcomes of alcohol and drug abusing patients admitted to a university-based alcohol and drug outpatient clinic. Treatment effectiveness of two treatment models were evaluated. The psycho-educational approach utilized a teacher-student model with the goal of imparting information about drugs and consequences of use. The recovery-oriented approach utilized a patient-counselor collaborative model where patients were encouraged to be active in progressing through sequential stages of pre-recovery tasks. Patients in the psycho-education group stayed in treatment longer and were more likely to rate treatment as useful. Results showed minimal differences between the two groups in terms of Addiction Severity Index scores, Drug Attitude, and urine drug screen results.

Adult↗
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The effects of oral and intraperitoneal administration of ethanol on the activities of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rats.

The activities of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases decreased significantly only in male rats, when rats of both sexes were fed a 2% sucrose solution containing 25% ethanol for six weeks. Sucrose (2%) activation of these enzymes was significant only in female rats. The daily administration of ethanol (5 g/kg body wt.) by intraperitoneal injection for two weeks significantly decreased the activities of these enzymes and eliminated the sex differences in the response to ethanol ingestion.

Administration, Oral↗
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Neuropsychological deficits in probands from multiply-affected schizophrenic families.

This study was designed to determine if schizophrenics from families with more than one psychotic relative show more severe neuropsychological deficits than schizophrenics with only one psychotic relative, non-familial schizophrenics, and a group of matched normal controls. Eighty-one schizophrenic-spectrum patients were divided into three groups on the basis of the presence of psychotic disorder among first- and second-degree relatives. The three groups of schizophrenics and the normal controls were compared for differences on a brief neuropsychological testing battery. The four groups showed significant multivariate differences. Patients from multiply-affected families showed significantly greater neuropsychological dysfunction on measures of abstract concept formation, visuomotor-coordination, and attention than patients from families that had only one psychotic relative. Schizophrenics from low-density families showed more severe deficits in fine motor-control than non-familial schizophrenics. These data suggest that abnormalities in those frontal systems that are likely to mediate fine motor control and abstract concept formation may be related to the degree of familial loading for psychotic disorder.

Adolescent↗
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Comparison of left ventricular performance in healthy young women and men during exercise.

BACKGROUND: Previous studies show sex-related differences in left ventricular (LV) response to exercise. It is not clear, however, whether these differences are also seen in younger healthy subjects. METHODS AND RESULTS: This study examined the changes in LV performance during dynamic upright exercise in 11 healthy men and 19 healthy young women according to the Bruce protocol and an individualized ramp protocol. There were no significant differences between the two protocols for either men or women in heart rate, blood pressure, LV ejection fraction (EF) (measured by ambulatory nuclear detector), and measured oxygen consumption. The peak oxygen consumption was higher in men than in women (44 +/- 13 vs 36 +/- 9 ml/kg/min; p < 0.05), but the peak heart rate, systolic blood pressure, and EF were similar. The change in EF (from rest to exercise) was 19% +/- 8% in men and 19% +/- 11% in women with the Bruce protocol (difference not significant) and 26% +/- 9% in men and 19% +/- 6% in women with the ramp protocol (difference not significant). At peak exercise, both men and women showed an increase in end-diastolic volume (29% +/- 14% vs 23% +/- 11%; difference not significant) and a decrease in end-systolic volume (41% +/- 15% vs 43% +/- 21%) (difference not significant). The increase in cardiac output during exercise was due to an increase in heart rate and stroke volume in both men and women. At submaximal exercise, however, the decrease in end-systolic volume was less in women than in men (p < 0.05). CONCLUSIONS: There are no sex-related differences in compensatory mechanism during dynamic exercise in healthy subjects. The changes in contractility and LV volume are not affected by the exercise protocol.

Adult↗
PubMedDate not supplied

An evaluation of autopsy review as a technique for infection control: a procedure of questionable value.

Review of necropsy reports for evidence of undiagnosed antemortem infection is included by the Joint Commission on Accreditation of Hospitals as an element of an effective hospital infection control program. We reviewed records of 155 patients autopsied at St. Paul-Ramsey Medical Center between January 1, 1980 and March 31, 1981. In 13 patients (8%), there was a discrepancy between documentation of infection during the patient's hospitalization and at autopsy. However, in none of these cases was this information useful in our infection control program. We doubt the effectiveness of necropsy review as a tool for nosocomial infection control.

Aspergillosis↗
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Somatostatin inhibits calcium influx into rat rod bipolar cell axonal terminals.

In the retina, somatostatin (SST), an inhibitory peptide that influences neuronal activity, is predominantly expressed by sparsely occurring amacrine cells. The SST subtype 2A receptor is expressed by rod bipolar cells, including their axonal terminals. We used Ca2+-imaging techniques and the ratiometric Ca2+ indicator dye fura-2 AM to investigate Ca2+ dynamics in rod bipolar cell terminals. Depolarization of rod bipolar cells by the addition of high K+ (50 or 100 mM) elicited a sustained increase in [Ca2+]i in rod bipolar terminals that returned to basal levels following K+ removal. The Ca2+ response was dependent on extracellular Ca2+, and was inhibited by the Ca2+ channel blocker Cd2+ and by the selective L-type Ca2+ channel blocker, nimodipine, SST inhibited a K+ depolarization-induced [Ca2+]i response in rod bipolar terminals. This inhibition was observed with 1 nM SST and was maximal with 1 microM SST. These findings indicate that SST may regulate transmitter release from rod bipolar terminals by activating the SST subtype 2A receptor through modulation of intracellular Ca2+.

Animals↗
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DNA complexing with polyamidoamine dendrimers: implications for transfection.

DNA and polyamidamine (PAMAM) dendrimers form complexes on the basis of the electrostatic interactions between negatively charged phosphate groups of the nucleic acid and protonated (positively charged) amino groups of the polymers. Charge neutralization of both components and subsequent increases of the net positive charge of the complex result in changes in the physicochemistry and biological properties of the complexes. The formation of soluble, low-density and insoluble, high-density complexes was analyzed using UV light absorption and measurements of radioactive labeled DNA. Formation of high molecular weight and high-density complexes depended mainly on the DNA concentration and was enhanced by increasing the dendrimer-DNA charge ratio. Electrostatic charge related effects (attraction or repulsion of charged particles) appeared to be modulated by the generation of dendrimer (size of the polymer). With the progressive increases in the dendrimer-DNA charge ratio (above 20), an increase in the amount of low-density, soluble complexes was observed. Functional analysis revealed that the great majority (>90%) of transfection is carried by low-density, soluble, complexes which only represent approximately 10-20% of total complexed DNA. The ability of the dendrimer to complex and form aggregates with DNA is crucial for efficient transfection and the function of the complexed DNA.

Animals↗
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Identification of novel antitumor agents from mixture-based synthetic combinatorial libraries using cell-based assays.

A new strategy is presented here which integrates combinatorial library technology with the antitumor in vitro screening system at the National Cancer Institute in the search for novel antitumor agents. Mixture-based synthetic combinatorial libraries (SCLs) representing hundreds of thousands to millions of individual compounds were screened against the cell-based assay, which evaluates compounds for their ability to inhibit the growth of 60 different human tumor cell lines. Five different SCLs, composed of peptides, peptidomimetics, polyamines or small molecules were first tested against three cell lines to identify the most active SCLs. Two SCLs, namely the N-perbenzylated pentamine and the N-acylated permethylated triamine, were deconvoluted to yield individual compounds having significant activities against the 60 tumor cell lines. Active compounds were tested in mice to determine the maximum tolerated dose, followed by in vivo testing in a hollow fiber assay. Using this strategy, three different compounds identified directly from SCLs are currently being evaluated in human tumor xenografts. This study demonstrates for the first time the use of in vitro cell-based assays to identify antitumor lead compounds from mixture-based combinatorial libraries.

Animals↗