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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
PubMed1987

Deposition of large particles in human lung.

Twenty-four nonsmoking males, all without history of pulmonary disease, were randomly divided into four groups of six subjects each. The subjects in each group inhaled monodisperse Teflon particles labelled with 111In (half-life 2.83 days); 8.2, 11.5, 13.7 and 16.4 micron aerodynamic diameter, respectively. Radioactivity in head and throat, lung and stomach was determined after 0, 3 and 24 hrs using a profile scanner. For some subjects radioactivity was also determined using a whole-body scanner at 3.5 and 24 hrs. After the 24-hr determination the subjects inhaled labelled Teflon particles again, this time with a filter in front of the mouth. Average values for total deposition in the body, obtained using a profile scanner, whole-body scanner and filter measurements, agreed fairly well. Lung retention values obtained by whole-body and profile scanning also agreed well. The average deposition in the lung, expressed as a percentage of total deposition, was 49, 31, 21 and 13% for the four particle sizes (8.2-16.4 micron). Alveolar deposition, determined as retention at 24 hrs and expressed in percent of total deposition, was 15, 4, 4 and 1%. For the smallest particle sizes the deposition values agreed with earlier investigations. However, for the larger particles the two deposition values were higher than expected when compared to earlier studies.

Administration, Inhalation↗
PubMed1986

Childhood familial pheochromocytoma. Conflicting results of localization techniques.

Childhood familial pheochromocytoma was investigated in four patients by abdominal computed tomographic scan, [131I]metaiodobenzylguanidine scan, and vena caval catecholamine sampling. Results conflicted with surgical findings. Computed tomographic scan identified all four adrenal tumors but missed two midline tumors in one patient. [131I]metaiodobenzylguanidine scan identified two of three adrenal tumors but also suggested extra-adrenal tumors not confirmed at operation in two of three patients. Vena caval sampling for catecholamines confirmed all adrenal tumors but suggested additional tumors not verified at operation in two of three patients. All patients are asymptomatic and have normal urinary catecholamines 15 to 51 months after operation. Because of the frequency of multiple tumors in familial pheochromocytoma, different diagnostic techniques were employed. False-positive results were more frequent with [131I]metaiodobenzylguanidine and vena caval sampling. Reinterpretation of the [131I]metaiodobenzylguanidine scans at a later date led to less false-positive interpretation, although the false-negative rate remained unchanged. More pediatric experience with [131I]metaiodobenzylguanidine scans and vena caval sampling in familial pheochromocytoma is needed. Confirmation of tumor and its localization rest with meticulous surgical exploration.

3-Iodobenzylguanidine↗
PubMed1986

Role of amniocentesis in ultrasound-detected fetal malformations.

Sixty-three patients with antenatally diagnosed fetal malformations over the period of 14 months were prospectively offered genetic amniocentesis, irrespective of gestational age. An additional 15 patients were excluded from the study because of a known lethal malformation (13 anencephaly, two amniotic bands). Twenty patients accepted amniocentesis, and seven chromosomal disorders were found. Obstetric management was altered in some of these patients as a result of the anomalies.

Adult↗
PubMed1986

Prevention of cyclosporine (CyA) nephrotoxicity by synthetic prostaglandins.

Acute and chronic nephrotoxicity directly attributable to cyclosporine (CyA) administration remains an obstacle to its successful use. The studies presented in this report characterize the cytoprotective properties of 16,16-dimethyl prostaglandin E2 in a lethal CyA-induced nephrotoxic rodent model. Wistar-Furth rats (200-250 g) receiving CyA alone (100 mg/kg/day) showed marked deterioration in renal function with severe histologic renal lesions and death of the majority of animals by day 7. The prostaglandin treated group (10/micrograms/kg/day) administered concomitantly with CyA demonstrated near normal renal function and histology by the eighth day after CyA discontinuation, and in a significant improvement in animal survival of 85% (p less than 0.001, n = at least 20 rats/group). These studies demonstrate a novel approach to a major problem with cyclosporine and should have exciting clinical potential.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1981

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↗