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Biomedical subjects

R Falk

Publications and source records attributed to R Falk.

At least 73 records · Page 4Linked to original sources

The characterization and partial purification of hepatocyte proliferation factor.

This report presents further evidence that the liver is the source of the factor responsible for the initiation and/or stimulation of hepatic regeneration. Initial experiments for the isolation and characterization of the active factor are presented. The factor was isolated from the cytosol of regenerating livers (RLC). After an in vivo exposure to RLC, hepatocytes were pulsed in vitro with 3H-thymidine to measure DNA synthesis. Rat and porcine RLC stimulated DNA synthesis in hepatocytes isolated from growing (nonhepatectomized) livers of weanling rats, or from regenerating livers of adult rats. The ability of porcine RLC to stimulate hepatocyte DNA synthesis demonstrated that the factor responsible was not species-specific. In contrast, normal non-regenerating liver cytosol did not stimulate hepatocyte DNA synthesis. Further experiments also revealed that the factor is heat stable. The activity responsible for the increased DNA synthesis was called hepatocyte proliferation factor (HPF). The assay for detecting HPF activity in the nonhepatectomized recipient will facilitate further characterization and purification of HPF.

Animals↗

Long-term lung clearance in humans studied with Teflon particles labeled with chromium-51.

Six healthy nonsmoking males inhaled 4-micron diameter Teflon particles labeled with chromium-51. Lung retention was measured for approximately 300 days. Three subjects inhaled "high-leaching" particles and three "low-leaching" particles. The high-leaching leaching particles leached 0.26%/day in water at 37 degrees C for the first 100 days and the low-leaching particles 0.065%/day. On an average, urine sampled for 24 h contained 0.13% of the lung burden for the high-leaching particles and 0.02% for the low-leaching particles. Thirty percent of the long-term clearance occurred with a fast phase, with half-times ranging from 4.5-45 days, and 70% with a slow phase, with half-times ranging from 200-2500 days. The fast phase was similar for the high-leaching and low-leaching groups. The slow phase varied widely among the subjects. There was no clear-cut relationship between half-time and type of particle. However, it seems probable that the slow phase was dependent on the degree of leaching, i.e., the half-times for elimination of intact particles from the lung are even slower. The large differences in long-term clearance among subjects indicate that long-term exposure to highly insoluble particles will result in large differences in lung burden. Subjects with a low capacity to eliminate alveolarly deposited particles are thus expected to be more susceptible to diseases in the alveolar part of the lung, i.e., diseases caused by certain insoluble particles.

Adult↗

The gene in search of an identity.

The concept of the difference between the potential for a trait and the trait proper, i.e., between the genotype and the phenotype, became clear only during the first decade of the century, mainly through the work of Johannsen. Although Johannsen insisted on that the terms he coined were only helpful devices to organize data about heredity, it is obvious that they were bound from the beginning to the hypothesis that there was "something" in the gametes that could be rendered to analysis as discrete units. These units were the genes. This reductionist yet materially non-committed attitude has been developed into what I called instrumental-reductionism: the genes were hypothetical constructs that were accepted "as if" they were real entities. The research program developed on such a concept was very successful, not least because this instrumental approach allowed maximum flexibility in the attachment of meaning of the genes. While most geneticists accepted one or another position of this flexible concept, others took more extreme positions. At the one extreme end of the conceptual continuum was the realist approach that argued that genes were discrete, measurable, material particles, and on the other end, the claim that the attempts to identify discrete units only led to hyperatomism of a holistic view appropriate to heredity. The acceptance of the gene as a material and discrete unit, in the beginning of 1950s, opened the way to a deeper level of conceptualizing both its structure ("cistron-recon-muton") and function ("one gene--one enzyme"). The discovery of the structure of DNA finally offered a chemical-physical explanation to the geneticist's requirements of a material gene. Thus, within less than 20 years the gene has been established as a "sharply limited segment of the linear structure" that is involved in the structure of a product or its regulation. However, with turning of much of the attention to the eucaryotic DNA, it was necessary to accommodate the gene to an increasing flood of findings that did not tally with its concept as a discrete material unit. Without much heart-seeking among geneticists, the gene regained its role as an instrumental unit, or even as just an intervening variable, "a quantity obtained by specified manipulation of the values of empirical variables".(ABSTRACT TRUNCATED AT 400 WORDS)

DNA↗

Saturation of the internal sodium site of the sodium pump can distort estimates of potassium affinity.

The Na+/K+ exchange pump in cardiac Purkinje strands has been well studied with the voltage clamp and Na+-selective microelectrodes. Models describing the observed results suggest that the pump rate can be considered proportional to [Na+]i over the range examined and depends on external [K+] in accordance with Michaelis-Menten kinetics. Estimates of the external [K+] that achieves a half-maximal pump rate (Km) range from 0.9 to 6.3 mM depending on the preparation and method of estimation. Here we show that much of the variability in the estimates of the Km can be eliminated when saturation of the internal Na+ pump site is taken into account. If the half-activation concentration for saturation of this Na+ site is sufficiently high (greater than 20 mM), removal of intracellular Na+ in response to a Na+ load will approximate first-order kinetics. Under these conditions however, Na+ saturation will nevertheless cause large systematic errors in estimates of the K+ dependence of pump activity.

Animals↗

Mechanism of enhanced humoral response in rodents by a synthetic polymer.

We previously reported that administration of a low molecular weight (MW=800) synthetic polymer, NED 137, significantly increases humoral and cellular immune responses in the rat. The effect of NED 137 on the murine humoral response to T-dependent (TD) and T-independent (TI) antigens was studied in C57 BL/6, CBA/J and Balb/c mice. The TD antigens (SRBC, DNP-DA with adjuvant) or TI antigen (DNP-Ficoll) were administered simultaneously with NED 137. The polymer significantly increased the direct PFC response to all antigens tested in normal mice. However, it could not restore the PFC response to SRBC in athymic (nu/nu) mice. The effect of NED 137 on accessory cells was studied by the assessment of the in vitro response to SRBC in normal and macrophage-depleted rat spleen cultures. The polymer stimulated both, the primary and secondary IgM response and its immunopotentiating activity was the greatest in macrophage-depleted spleen cell preparations. The lack of effect of NED 137 in systems devoid of functional T cells, dependency on and specificity for a sensitizing antigen and its ability to stimulate a secondary response suggest that this polymer does not act as a "conventional" B-cell polyclonal activator.

Adjuvants, Immunologic↗

Nerve allograft response: a quantitative immunological study.

The nerve allograft response between closely and distantly related inbred strains of rats was investigated. Lewis rats (RTl1) and Fischer rats (RTl1) have only minor histocompatibility differences, whereas Buffalo rats (RTlb) and ACI rats (RTla) differ from Lewis rats at the major histocompatibility locus. Lewis rats served as the recipient animals; the other three strains of rats provided donor nerves. The 51 Cr release cytotoxicity assay was used to asses antigen recognition. The results showed sensitization with ACI and Buffalo nerves as early as Day 8. When the donor and recipient were matched (Lewis/Fischer), sensitization occurred very late (Day 80). By contrast, with skin allografts, sensitization occurred early with all strains (Day 10), even when the animals differed only at the minor histocompatibility loci. Histological changes were similar in all three donor strains (Fischer, Buffalo, ACI). The strain of origin of the nerve could not be deduced by an unbiased examiner.

Animals↗

Membrane currents following activity in canine cardiac Purkinje fibers.

Recent experiments in canine Pukinje fibers (Gadsby and Cranefield, 1979) have shown that following a period of sodium loading in K+-free solution a slowly decaying outward current is observed. This current has been attributed to the activity of the electrogenic Na+-K+ exchange pump. In the present paper we show that similar slowly decaying outward currents are observed following prolonged periods of overdrive with action potentials or with brief depolarizing voltage clamp pulses. The dependent of the prolonged outward current on the duration and frequency of the preceding period of overdrive and on the potential following overdrive is reported. We also present results which indicate that a large portion of this current can be induced by phasic Na+ loading through the fast-inward channel.

Animals↗

Personality factors related to black teenage pregnancy and abortion.

48 pregnant adolescents who applied for therapeutic abortions (TAs) were compared with 55 adolescents who planned to have their babies (Terms) and 67 adolescents who were not pregnant (Controls) on the California Psychological Inventory (CPI). All the subjects were single, black, and ages 15-16. CPI results point to psychological differences with the Controls being most socialized, followed by the TAs, and then the Terms. Term girls seem to be experiencing a void and appear to be trying to fill it by assuming an adult role and having a baby; the TAs do not seem to have these same needs. In addition, those girls who became pregnant and described the relationship with the putative father as casual, appear on the CPI to have more daily problems, lack socialization, be less clear thinking, and have poor self-control. Pregnant girls who have good communication with their mothers showed no differences on the CPI from girls with poor communication with their mothers.

Abortion, Induced↗

Activity-dependent extracellular K+ fluctuations in canine Purkinje fibres.

Cardiac Purkinje fibres are important in cardiac electrophysiology and pathology due to their specialized role in the ventricular conducting system, and their properties as a second cardiac pacemaker. Changes in extracellular K+ activity (Ko) affect the conduction velocity and the natural automatic rate of the Purkinje fibre. Both anatomical and electrophysiological studies of the Purkinje fibres have demonstrated the possibility of Ko fluctuations in the narrow intercellular clefts. We investigated using K+ selective electrodes, the effect of the Ko fluctuations observed during activity in canine Purkinje fibres. Summation of Ko fluctuations during single action potentials leads to elevation of baseline Ko during rapid trains. However, unlike in ventricular muscle where depolarization is seen, membrane potential is non-automatic Purkinje fibres hyperpolarizes in response to rapid beating. Prolonged depletions of extracellular K+ following long periods of overdrive are associated with slowly changing membrane currents, which markedly influence automaticity, action potential duration, and membrane potential.

Action Potentials↗

Oral administration of BCG as an adjuvant to surgical treatment of carcinoma of the bronchus.

A controlled clinical trial of the value of bacille Calmette--Guérin (BCG) vaccine given orally to patients with resectable carcinoma of the lung was conducted in 18 centres across Canada. A total of 308 patients were included in the analysis, 155 in the BCG group and 153 in the control group. The two groups were similar at the time of admission to the trial. BCG (120 mg) was given orally at weekly intervals for 1 month, every 2 weeks up to 3 months and then every 3 months until the total duration of therapy was 18 months. Over a 3- to 5-year follow-up period after the operation there was no difference in survival between the two groups, the proportion alive at 2 years being 61% in the BCG group and 58% in the control group. There was also no evidence of differences in the time to the detection of recurrent or metastatic disease or in the distribution of such disease. An analysis of prognostic factors confirmed the poor survival associated with histologically confirmed lymph node involvement. It may be concluded that no favourable effect from the oral administration of BCG was demonstrated.

Adjuvants, Immunologic↗

Adolescent sexual activity: contraception and abortion.

One hundred twenty-five pregnant adolescents 16 years of age or younger and their parents were studied prior to abortion and were compared with 72 nulligravid control subjects. The control group reported less incidence of sexual intercourse and more causal heterosexual relationships of shorter durations. A significantly larger percentage of the abortion group approved of premarital sexual intercourse "when the couple is going steady." Sixty-eight per cent of the adolescents who were seeking abortions had never used a contraceptive. Abortion "on demand" was favored by the majority of the abortion group, whereas the control group favored "abortion under special circumstances." Neither were the pregnant teenagers' parents aware of nor had they discussed their daughter's sexual activities, much less contraception. Prevention of unwanted pregnancies in early adolescence should encompass an educational effort on the part of the health professions, involving both the adolescents and their parents.

Abortion, Induced↗

Sexual experimentation and pregnancy in young black adolescents.

Young black adolescents (13 to 16 years of age) and their parents were interviewed and psychological tests were administered. They were divided into three groups; (1) abortion group, (2) pregnancy to term group, and (3) a control group of never-pregnant adolescents matched by age and socioeconomic status. We focus the present report on their performance in school and educational goals, sexual experimentation to intercourse, their use of contraceptives, theirs and their parents' attitudes toward abortion, their reaction to their pregnancy in the two pregnant groups, and their attitudes in choosing for or against abortion.

Abortion, Legal↗