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Biomedical subjects

H Falk

Publications and source records attributed to H Falk.

At least 109 records · Page 6Linked to original sources

Differential inhibition of DNA polymerase and RNase H activities of the reverse transcriptase by phosphonoformate.

Three potential inhibitors of reverse transcriptase activities, phosphonoformate (PF), phosphonoacetate (PAA), and ethyl-diethyl phosphonoformate (Et-PF), were compared in this study. Only PF was found to inhibit the DNA polymerase activity of the purified reverse transcriptase of Moloney murine leukemia virus (M-MuLV) and avian myeloblastosis virus (AMV). The degree of DNA polymerase inhibition was linear with PF concentration; 50% inhibition was achieved at 10 muM. Whereas PF inhibited both the RNA and DNA dependent DNA polymerase activities, the RNase H activity of the reverse transcriptase was unaffected. Both the endogenous DNA polymerase activity in detergent disrupted virus and the activity of the purified enzyme with the isolated virus genome 70S RNA were inhibited by PF. However, higher concentrations of PF were needed to inhibit the endogenous reaction. The inhibition by PF appeared to be reversible and noncompetitive with respect to the substrate deoxythymidine triphosphate (dTTP). Addition of PF after the initiation of DNA synthesis immediately arrested the reaction.

Animals↗

Inhibition of cell-free protein synthesis by low-molecular-weight RNAs from free cytoplasmic ribonucleoprotein particles.

Free cytoplasmic messenger ribonucleoprotein (mRNP) particles from rat liver were treated with EDTA and separated into two populations of RNP particles with sedimentation maxima of 20 S and 35 S respectively. The 20-S and 35-S RNP particles, treated with 0.5 M KCl, have protein-to-RNA ratios of 0.31:1 and 5.7:1 respectively. Whereas 20-S and 35-S RNP particles exhibit a similar protein complement of seven major polypeptides, the low-molecular-weight RNA components of the two particle populations are different. A characteristic set of distinct low-molecular-weight RNAs is found for 20-S and 35-S RNP particles. When the individual low-molecular-weight RNAs of 20-S and 35-S RNP particles isolated from preparative polyacrylamide gels were assayed for their capability to inhibit protein synthesis in vitro, several potent translational inhibitory RNAs were detected. In particular, the low-molecular-weight RNAs of 147, 203 and 263 nucleotides in length associated with the 35-S RNP particles turned out to be strong inhibitors of protein synthesis.

Animals↗

Mount St Helens eruptions, May 18 to June 12, 1980. An overview of the acute health impact.

Thirty-five known deaths were caused by the landslide and lateral blast of the May 18 eruption of Mount St Helens and at least 23 persons are missing. In 18 of 23 cases that reached autopsy, asphyxiation from ash inhalation was the cause of death. A rapidly established hospital surveillance system detected increases in the number of emergency room (ER) visits and admissions for asthma and bronchitis in communities with the heaviest ashfall after the May 18 eruption and the eruptions on May 25 and June 12. There were also increases in the number of ER visits for ash-related eye complaints in some areas. laboratory studies indicated that the May 18 ash was not acutely toxic, but the respirable portion contained 3% to 7% of crystalline free silica, a potential pneumoconiosis hazard to certain heavily exposed occupational groups. Continuing volcanic activity of Mount St Helens and future eruption of other volcanoes in the Cascade Range may pose a variety of health hazards, including blast, ashfalls, flooding, damage to public utilities, and possible psychosocial effects.

Asphyxia↗

Review of four cases of childhood hepatic angiosarcoma--elevated environmental arsenic exposure in one case.

Four cases of childhood hepatic angiosarcoma (HAS), representing the malignant form of infantile hemangioendothelioma, are described. The morphologic appearance of childhood HAS differs from the adult form in the following features: the associated presence of benign infantile hemangioendothelioma; the presence of dysontogenetic features; and an altered appearance of the angiosarcoma itself. It is postulated for these cases that the benign infantile hemangioendothelioma progressed to the malignant angiosarcoma. One of the four cases had exposure to elevated levels of arsenic in the environment that may have contributed to this progression. This latter case adds to published reports associating arsenic exposure with increased risk for hepatic angiosarcoma.

Arsenic↗

Arsenic-related hepatic angiosarcoma.

Data from several small autopsy series in German vintners in the 1940s and 1950s and a number of case reports have previously suggested that arsenic is a cause of hepatic angiosarcoma (HAS). In a nationwide review of deaths from HAS in the United States, we identified seven cases with a history of prolonged use of Fowler's solution (inorganic potassium arsenite), which provide further support for the association of arsenic exposure and HAS. An epidemiologic study of a cohort of individuals treated long-term with Fowler's solution might confirm this association.

Adult↗

Epidemiology of hepatic angiosarcoma in the United States: 1964-1974.

A nationwide survey of hepatic angiosarcoma (HAS) in the United States during the years 1964 through 1974 identified 168 cases. Of these, 42 cases (25%) were associated with known etiologic factors, such as vinyl chloride monomer exposure during preparation of poly(vinyl chloride), use of Thorotrast in angiography, exposure to inorganic arsenic, and treatment with androgenic-anabolic steroids; 126 cases (75%) are of uncertain etiology. HAS most often affects males (ratio of approximately 3:1), peaks in the sixth and seventh decades of life (somewhat earlier than other sarcomas of the liver) and appears to occur more often in the industrialized Northeast and Midwest (although reporting artifact may be a factor). There is an extraordinary relative risk for poly(vinyl chloride) polymerization workers; there may also be other chemical-industrial associations that require further investigation. Prospective epidemiologic studies of HAS should be considered as a means of identifying other causative factors (e.g., chemicals or drugs) related to HAS.

Adolescent↗

Excess lung cancer risk in a synthetic chemicals plant.

A standardized mortality ratio of 1.49 for respiratory system cancer (42 observed deaths versus 28.2 expected, p less than 0.01) was observed among a cohort of 4806 males employed at a synthetic chemicals plant since its startup in 1942. Upon review of pathologic material, the excess was found to be limited to adenocarcinoma and large cell undifferentiated lung cancer. Many of the workers had been exposed to vinyl chloride, as well as to chlorinated solvents, poly(vinyl chloride) (PVC) dust, acrylates and acrylonitrile. To evaluate the association between lung cancer and occupational chemical exposures, detailed work histories for each cohort member were combined with exposure ratings for each of 19 chemicals for each job for each calendar year since 1942. A serially additive expected dose model was then constructed which compared the doses of the chemicals observed for the lung cancer cases to the doses expected based on subcohorts without lung cancer individually matched to the cases. PVC dust appeared to be the most likely etiologic agent (p = 0.037). Time trends of PVC dust exposure indicated a potential latent period of 5-16 years before death.

Adenocarcinoma↗

[The recovery room - function and organization (author's transl)].

Postanaesthetic observation and control of the patient, independently of surgery, is an integral part of the anaesthetic course. The anaesthetic procedure is terminated in the recovery room only, where all negative effects of anaesthesia and surgery or their sequels can be properly assessed and eliminated. After restoration of vital functions and protective reflexes only the patient may be transferred to normal wards or intensive care units for further control of his postoperative condition. Following long-term surgery, and in any high-risk case in general, postoperative mechanical ventilation or application of continuous positive airway pressure (CPAP) can reduce the incidence of respiratory complications. The additional and extensive therapeutic and diagnostic tasks to be covered in the recovery room call for special consideratons in equipping and staffing. Adequately trained nurses in sufficient number, respiratory devices covering any mode of ventilation and an emergency laboratory are indispensable prerequisites for proper function. Only then the anaesthesiologist will be able to satisfactorily perform his comprehensive task of providing stable vital functions, preoperatively in establishing the state of operability, intraoperatively by corrective therapy and postoperatively until anaesthetic effects and surgical trauma have subsided.

Humans↗

The protochlorophyllide holochrome of barley (Hordeum vulgare L.). Isolation and characterization of the NADPH:protochlorophyllide oxidoreductase.

The NADPH:protochlorophyllide oxidoreductase of barley has been solubilized from etioplast membranes and purified to apparent homogeneity. The highest specific activity measured for the purified enzyme was 1.6 nmol chlorophyllide formed (mg protein-1) per flash. Electrophoretic analysis of the purified enzyme on sodium dodecylsulfate/polyacrylamide gels revealed only one polypeptide of Mr 36000. Durig glycerol gradient centrifugation the enzyme migrates as a low-molecular-weight component. It is proposed that each enzyme molecule contains only one polypeptide chain. Assuming a molecular weight of 36000 for the enzyme, it was calculated that two or three protochlorophyllide molecules are bound to each enzyme molecule.

Chlorophyll↗

Envelope polypeptides of Friend leukemia virus: purification and structural analysis.

Roughly 10% of surface glycoproteins in the envelope of mature Friend murine leukemia virus are coupled to membrane polypeptides by disulfide bridges. The remaining 90% of these glycoproteins are associated noncovalently. However, they could also be linked to membrane polypeptides by the treatment of purified Friend murine leukemia virus with 2,2'dithiobis(m-nitropyridine). These amphiphilic heterodimer polypeptides, gp84/86, were recovered almost quantitatively in the form of aggregates, termed rosettes, when prepared by solubilization of the viral membrane with Triton X-100 and subsequent velocity sedimentation. gp69/71 and p12(E)/15(E) were purified from these protein micelles after reduction of the disulfide bonds by gel chromatography. Electron micrographs of rosettes, as well as of purified p12(E)/15(E), showed structures different from native viral knobs. Isolated gp84/86 could be reassociated and then displayed more similarity to these viral surface projections. As shown by peptide mapping, the primary structures of the glycoproteins gp69/71 are highly related as are those of the membrane polypeptides p12(E) and p15(E). Furthermore, it was shown by two-dimensional polyacrylamide gel electrophoresis and re-electrophoresis of purified gp84/86 that the larger component, gp86, was composed of gp71 associated with p15(E) and p12(E), whereas the smaller component, gp84, was formed by gp69 bound only to p12(E).

Animals↗

Hepatic angiosarcoma associated with androgenic-anabolic steroids.

A retrospective epidemiological study of deaths from hepatic angiosarcoma (HAS) in the U.S. showed that during 1964--74 there were 168 such cases, of which 37 (22%) were associated with previously known causes (vinyl chloride, 'Thorotrast', and inorganic arsenic) and 4 (3.1%) of the remaining 131 cases with the use of androgenic-anabolic steroids. It is suggested that the long-term use of androgenic-anabolic steroids is the fourth cause of HAS, the majority of cases still being of unknown aetiology. Moreover, the presented cases serve as a link in a spectrum of hepatic disorders recently recognised to be caused by environmental agents such as vinyl chloride, arsenic, and thorotrast, and by contraceptive and anabolic steroids. Similar precursor stages, usually not recognised by clinical laboratory tests and consisting of areas of hyperplasia of hepatocytes and sinusoidal cells and sinusoidal dilatation, lead potentially to hepatic adenoma, carcinoma, peliosis, and angiosarcoma.

Androstanes↗

Influence of a between-run component of variation, choice of control limits, and shape of error distribution on the performance characteristics of rules for internal quality control.

A computer-stimulation study has been performed to determine how the performance characteristics of quality-control rules are affected by the presence of a between-run component of variation, the choice of control limits (calculated from within-run vs. total standard deviations), and the shape of the error distribution. When a between-run standard deviation (Sb) exists and control limits are calculated from the total standard deviation (St, which includes Sb as well as the within-run standard deviation, Sw), there is generally a loss in ability to detect analytical disturbances or errors. With control limits calculated from Sw, there is generally an increase in the level of false rejections. The presence of non-gaussian error distribution appears to have considerably less effect. It can be recommended that random error be controlled by use of a chi-square or range-control rule, with control limits calculated from Sw. Optimal control of systematic errors is difficult when Sb exists. An effort should be made to reduce Sb, and this will lead to increased ability to detect analytical errors. When Sb is tolerated or accepted as part of the baseline state of operation for the analytical method, then further increases in the number of control observations will be necessary to achieve a given probability for error detection.

Chemistry, Clinical↗