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Biomedical subjects

R Falk

Publications and source records attributed to R Falk.

At least 37 records · Page 2Linked to original sources

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

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

Interpretive accuracy of abbreviated MMPIs.

The interpretive accuracy of the standard MMPI and three abbreviated forms was assessed and compared with a sample of psychiatric inpatients. Psychiatric teams evaluated the accuracy of the interpretation of one abbreviated form and the standard form for their patients. Only the MMPI-168 obtained comparable ratings to the standard form.

Adolescent

Partial losses of sex chromosomes induced by X-rays in spermatozoa of Drosophila melanogaster.

The frequency of induced partial and complete losses of sex chromosomes from spermatozoa of Drosophila melanogaster was determined by mating irradiated males to females heterozygous for an attached-X Y chromosome and for a bb-deficient chromosome. The relative involvement of the X- and Y-chromosomes in partial losses was determined by (a) irradiating males with an X-chromosome centromere marked by a y+ translocated to the short right arm, and a Y-chromosome marked by w+, and (b) comparing the frequencies of fragments recovered from irradiated males with a normal, marked Y-chromosome and from irradiated males and a deleted bb Y-chromsome. 50-80% of the induced losses of sex-chromosomes in rod-X/Y males were partial losses, whereas only 25% of those induced in ring-X/Y males were partial losses. More than 70% of the recovered fragments were of Y-chromosome origin. Fragments recovered from attached-X-Y sons of irradiated males wer checked for the presence of the most proximal euchromatic X-chromosome genes. Most fragments of the rod-X were broken more proximally than bb. In the ring-X there was an excess of fragments broken in the proximal euchromatin. It was concluded that many fragments of the Y-chromosome was due to breaks induced by one-hit events, in both arms of the chromosome that were folded upon themselves. A similar mechanism had been postulated earlier for fragments of the ring-X chromosome.

Animals