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Biomedical subjects

H Falk

Publications and source records attributed to H Falk.

At least 91 records · Page 5Linked to original sources

Toxicity of D-galactosamine for rat hepatocytes in monolayer culture.

Hepatocellular injury was induced by exposure of primary cultures of rat hepatocytes to 4 mM D-galactosamine. The cell damage was very similar to that seen in vivo and in the isolated perfused rat liver, both in biochemical and in structural terms. The severity of the lesions caused by D-galactosamine was dependent on the age of the culture being treated. Less severe damage was found with older cultures. Since the primary metabolic effects of D-galactosamine were age-independent, the reduction in cell damage seems to be due to progressive cell dedifferentiation. Dexamethasone (1 microM) suppressed the full development of the injury, while 1 microM triiodo-L-thyronine enhanced it. A protection of hepatocytes by alpha 2-macroglobulin against the effects of D-galactosamine could be observed neither in vivo nor in vitro. Direct cytotoxic effects of endotoxin from Salmonella minnesota R 595 could be demonstrated only on hepatocytes in the early phases of primary culture using rather high doses of the purified lipopolysaccharide. It is unlikely that they play a major role in the hepatocellular injury seen following endotoxinemia in vivo. Lowering of extracellular Ca2+ concentration and additions of calcium/calmodulin inhibitors did not prevent cell injury after treatment with D-galactosamine. The results suggest that cell death is not due to an increased influx of Ca2+ into the cells.

Albumins↗

The syndrome of unexplained generalized lymphadenopathy in young men in New York City. Is it related to the acquired immune deficiency syndrome?

To establish whether the syndrome of unexplained generalized lymphadenopathy in homosexual men was new and related epidemiologically to the acquired immune deficiency syndrome (AIDS), we reviewed 3,139 pathology reports of lymph node biopsies performed at seven hospitals in New York City during the years 1977 through 1981. Three hundred twenty-nine patients (10%) were categorized as having unexplained lymph node hyperplasia; a detailed medical record review of 30% of these patients revealed three, two, six, eight, and 16 cases of unexplained generalized lymphadenopathy in the five years studied, respectively. Of these 35 cases, 26 (74%) occurred in males aged 16 to 44. A record review of 68 additional male patients aged 16 to 44 years with unexplained lymph node hyperplasia in two of the hospitals showed a similar increase in cases of unexplained generalized lymphadenopathy during the five-year period. Twenty-one of 25 cases in males with known sexual orientation were homosexual or bisexual. The increase in the syndrome of unexplained generalized lymphadenopathy from 1978 to 1981 and the characteristics of the population affected are similar to those observed for AIDS.

Acquired Immunodeficiency Syndrome↗

Health implications of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) contamination of residential soil.

Extrapolations from animal toxicity experiments (including carcinogenicity and reproductive effects) to possible human heath effects can be used to estimate a reasonable level of risk for 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD). Extrapolations are derived from: (1) review of published studies, (2) a complex set of assumptions related to human exposure to contaminated soil, and (3) estimates of (a) a dose response curve, (b) appropriate margins of safety, and/or (c) applicable mechanisms of action. One ppb of 2,3,7,8-TCDD in soil is a reasonable level at which to begin consideration of action to limit human exposure for contaminated soil.

Animals↗

Inhalation exposure to formaldehyde: an overview of its toxicology, epidemiology, monitoring, and control.

Increasing production and use of formaldehyde in consumer products have resulted in widespread recognition of its acute irritant effects at exposure levels below the current occupational health standard [3 parts per million parts of air (ppm)]. Formaldehyde is an allergic (immunologically mediated) skin sensitizer which may also cause or exacerbate respiratory distress in individuals with preexisting or formaldehyde-induced bronchial hyperreactivity. Formaldehyde gas is a very reactive alkylating agent which is mutagenic in several in vitro test systems. At exposure levels less than one order of magnitude greater than those often found in human occupational and nonoccupational environments, it induces squamous cell carcinomas in the nasal cavity of rats. Recent reviews suggest that formaldehyde exposure should be treated as though it poses a carcinogenic risk to humans and should be reduced to the lowest feasible level. This report reviews information on the epidemiologic evaluation of health effects which may result from hazardous levels of exposure to formaldehyde. Methods for monitoring exposure are discussed in detail because of considerable diversity in the methods used by state health departments for recognition, evaluation and control of nonoccupational exposures. Current guidelines for the evaluation and control of exposures to formaldehyde gas are suggested.

Acute Disease↗

Evidence for the association of core histones with poly(U) to nucleosome-like complexes.

As was shown in a recent paper [Klump, H. & Hütig, H. (1980) Ber. Bunsenges. Phys. Chem. 84, 250-253] by one of the authors (H.K.), nucleosome-like histone complexes can be formed on ribopolynucleotides as well as on deoxyribopolynucleotides. The conditions used for complex formation have to be such that single strands and triple strands as secondary structures of the polynucleotides employed are excluded under all ionic-strength conditions. There is clear evidence however for ordered poly(U)/histone complexes. In this paper we further characterize these poly(U) complexes and present electron micrographs of both DNA histone complexes and poly(U) histone complexes to show their close resemblance.

Animals↗

Nonoccupational exposures to indoor air pollutants: a survey of state programs and practices.

A national survey of health department activities in 1982 revealed that 32 states (63 per cent) had a program or person(s) responsible for evaluating exposures to one or more nonoccupational indoor air pollutants (NIAPs). Only four states (8 per cent) had existing or proposed NIAP exposure standards. Twenty-nine (57 per cent) of the states had a program to evaluate nonoccupational exposures to formaldehyde, but these varied widely. There is a need for coordinated, consistent approaches to defining and controlling emerging environmental public health problems such as indoor air pollution.

Air Pollutants↗

A quality control simulator for design and evaluation of internal quality control procedures.

A computer simulation program has been developed to aid clinical chemists in the design and theoretical evaluation of statistical control procedures. This "QC simulator" permits the user to study the effects of different parameters characterizing the measurement procedure (method standard deviation, components of variation, rounding of results) and parameters of the control procedure (decision criteria, control limits, number of observations). The performance of control procedures is characterized by the probability for rejection, estimated at several different levels of random and systematic error. Predictive values for reject and accept signals are also calculated at different error incident rates, given a specified error model. The relative performance of different control procedures can be compared based on these performance characteristics. Another important application of the program is the design of control procedures to assure that a specified level of analytical quality is achieved in routine analyses. Various optimization criteria may be applied, e.g., in terms of test yield and cost.

Chemistry, Clinical↗

Clinical epidemiology of toxic-oil syndrome. Manifestations of a New Illness.

An epidemic of a new illness involving multiple organ systems began in Spain in May 1981, with 19,828 cases and 315 deaths reported by June 1, 1982. An epidemiologic investigation has linked the occurrence of illness with ingestion of an unlabeled, illegally marketed cooking oil. To elucidate the natural history of this illness, we reviewed the medical records of 121 patients in one severely affected town 100 km northwest of Madrid. The findings during the first week after onset were those of a febrile, pneumonia-like illness. Gastrointestinal findings and striking eosinophilia became prominent later in the first month. Although the disease followed a self-limited course in many patients, severe neuromuscular manifestations (myalgia severe enough to restrict movement, motor deficits, atrophy of major muscle groups, and contractures of the jaw and extremities) occurred late in the course of the illness (an average of 96 days after onset) in 23 per cent of the patients. The onset of disease early in the epidemic and particularly severe initial systemic findings were associated with progression to neuromuscular illness.

Adolescent↗

Mortality and cancer frequency among military nuclear test (Smoky) participants, 1957 through 1979.

Follow-up of health status has been completed through 1979 for 3,072 (95.5%) of 3,217 nuclear test participants on military maneuvers during the 1957 nuclear test "Smoky." In these participants, 112 cases of cancer were diagnosed, compared with 117.5 cases expected. During the same follow-up period (1957 through 1979), 64 persons died of cancer, compared with an expected 64.3. Statistically significantly increased frequency of occurrence and mortality was found only for leukemia. The amount of cumulative gamma radiation exposure for 1957 ranged from 0 to 10,397 mrem as measured by individual personnel film badges. Although uncertainty remains about the exact amount of radiation exposure, the lack of a significant increase after 22 years in either the incidence of or the mortality from any other cancer and the apparent lack of a dose effect by unit lead to the consideration that the leukemia findings may be attributable either to chance, to factors other than radiation, or to some combination of risk factors possibly including radiation.

Follow-Up Studies↗

Waterborne outbreak of Campylobacter enteritis.

A report is given on an outbreak of enteritis which occurred in July 1982 in a kibbutz near Jerusalem. About 150 of the 512 inhabitants were affected. Campylobacter jejuni was isolated from ten out of 42 stool samples examined toward the end of the outbreak. No other enteric pathogen was found. Strong circumstantial evidence indicated an association between the outbreak and the use of water from an unprotected reservoir, but no bacteriological confirmation was obtained.

Adolescent↗

Virosomes constructed from lipid and purified Friend leukaemia virus glycoprotein.

Liposomes were loaded by a dialysis technique with purified envelope glycopolypeptide, gp85, of the Friend murine leukaemia virus (F-MuLV). The gp85 liposomes prepared from cellular lipid had a buoyant density of 1.05 g/ml and an apparent diameter of 50 to 300 nm. The gp85 was not simply entrapped by liposomes nor adsorbed non-specifically to their outer surface. Experiments with radioactively labelled protein, electron microscopic examinations, protease treatment and concanavalin A binding showed that gp85 is anchored in the liposomal membrane and oriented asymmetrically as in the virus envelope. Moreover, gp85-covered liposomes displayed some functions of the intact F-MuLV envelope, such as absorption of antibodies to gp70 and haemagglutination after enzyme treatment. To some extent, these lipid vesicles appeared to be reconstituted F-MuLV envelopes and thus, by analogy to other systems, were named retrovirosomes.

Dialysis↗

Inhibition by interferon of herpes simplex virus thymidine kinase and DNA polymerase in infected and biochemically transformed cells.

The induction of thymidine kinase (TK) and DNA polymerase was inhibited by interferon (IFN) in mouse L-cells infected with herpes simplex virus type 1 (HSV-1). The inhibitory activity of IFN at this early stage of HSV-1 replication was followed by a reduced virus yield and was dependent on the multiplicity of infection. The expression of a cloned thymidine kinase (tk) gene of HSV-1, in biochemically transformed L-cells (LTK+), was not affected by IFN. These same LTK+ cells, however, developed an antiviral state since, upon HSV-1 infection, the induction of TK and DNA polymerase of the replicating virus was inhibited by IFN. Furthermore, IFN inhibited the transactivation of the HSV-1 tk gene in the biochemically transformed LTK+ cells, which followed infection by a virus mutant defective in the tk gene (HSV-1 TK-). This transactivation is dependent on expression of immediate-early HSV-1 alpha-genes. These results indicate that IFN inhibits HSV-1 replication at an early step prior to DNA synthesis. In addition, IFN displays a differential effect on the HSV-1 thymidine kinase gene, either when part of the replicating virus or when expressed as a cellular gene in biochemically transformed cells.

Animals↗

In vitro nuclear transport of ribosomal ribonucleoprotein: temperature affects quantity but not quality of exported particles.

The in vitro export of ribosomal ribonucleoprotein (rRNP) from Tetrahymena nuclei was investigated at the optimal growth temperature of 28 degrees C and at the nonlethal temperature of 8 degrees C. At both temperatures, nuclei exported ribosomal precursor particles that revealed the same physical qualities of size, appearance in negative-staining electron microscopy, sedimentation coefficient, buoyant density, and rRNA pattern. Surprisingly, fewer rRNP particles were exported at 8 than at 28 degrees C, as was revealed by a lower saturation plateau in the export kinetics from nuclei prelabeled with [3H]uridine. Upon a temperature increase from 8 to 28 degrees C, additional rRNP particles were exported. We conclude that nuclei export only a defined portion of rRNP particles at a given temperature, although enough potentially transportable rRNP particles are present in nuclei. Obviously, the reactivity of at least one of the reactants involved directly or indirectly in rRNP export changes with temperature.

Biological Transport↗

[Particles in infusion solutions].

The significance of infusion therapy has increased considerably in the last two decades because of a constant expansion of indications and therapeutic possibilities. Like all other types of therapy, the efficiency of infusion therapy depends on the care taken in determining the indication and in administration. It is therefore imperative that everybody directly involved in this type of therapy is informed of the problems connected with the use of infusion solutions and aware of the specific risks of the infusion techniques in use. One essential risk inherent in the use of infusion solutions is the hazard of particulate contamination. This paper describes the potential sources which can lead to an influx of particles into the organism. Furthermore it is demonstrated that nowadays the primary or intrinsic contamination rate of commercially available solutions during manufacture and storage--as a result of the stringent regulations of the GMP (good manufacturing practice) is far below the high standard of the Australian pharmacopoea. The in-use or extrinsic contamination of infusion solutions, however, must be taken seriously as shown by the sharp increase of particulate contamination during routine hospital work. Under this aspect contamination of the organism with particles particularly increases because of additional injections into the tubing of the infusion system. Besides reducing additional administration of drugs into the infusion bottle or the infusion line to an absolutely necessary minimum, 5-micron filters have been found to effect a more than 90% reduction of particle influx as well as being easy to handle during routine clinical work.

Drug Contamination↗