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Biomedical subjects

F Hofmann

Publications and source records attributed to F Hofmann.

At least 217 records · Page 12Linked to original sources
PubMed1995

[Epidemiology of spinal diseases in nurses].

Epidemiology of spinal pathology among nurses. A cross-sectional study of 3300 German nurses was carried out in the course of an investigation of the prevention of occupation--related back problems. A much higher incidence of lumbar-spinal problems was observed than in a control group of office staff, not required to lift or carry. Evidence of much greater risk, especially of severe sciatic symptoms, was supported by a case-controlled study of patients with the diagnosis of disc-prolapse or disc-protrusion, carried out in two neuroradiology units. Nurses were significantly over represented. A lack of preventive measures for carrying and lifting patients was clearly demonstrated (availability and use of mechanical aids). To what extent the perception of spinal problems is influenced by psychological factors and not only by physical factors will be demonstrated by the recording of stress factors.

Humans↗
PubMed1994

Phosphorylation of the calmodulin binding domain of the plasma membrane Ca2+ pump by protein kinase C reduces its interaction with calmodulin and with its pump receptor site.

Two versions of the calmodulin binding domain of the plasma membrane Ca2+ ATPase, a 24-amino acid peptide, C24W (Q-I-L-W-F-R-G-L-N-R-I-Q-T-Q-I-R-V-V-N-A-F-R-S-S-NH2), and the corresponding phosphothreonine containing peptide, C24W-P (Q-I-L-W-F-R-G-L-N-R-I-Q-T(phospho)-Q-I-R-V-V-N-A-F-R-S-S-NH2), were synthesized. They were used to investigate the effect of threonine phosphorylation by protein kinase C on the binding of calmodulin by the calmodulin binding domain and on the inhibitory role of the domain on the activity of the Ca2+ pump. The phosphopeptide C24W-P was obtained after global phosphorylation of the free Thr side chain on the protected resin bound peptide. The phosphorylated calmodulin binding domain failed to bind calmodulin; this was shown by gel shift experiments, by fluorescence energy transfer studies and by competition experiments against calmodulin stimulation of the pump. The inhibition of the Ca2+ pump activity by the calmodulin binding domain in the absence of calmodulin was also affected by the phosphorylation of the threonine; the inhibition of the fully active calpain-truncated pump by the phosphothreonine containing peptide was lower than that by the unphosphorylated synthetic domain.

Adenosine Triphosphatases↗
PubMed1994

Double-pulse facilitation of smooth muscle alpha 1-subunit Ca2+ channels expressed in CHO cells.

Frequent strong depolarizations facilitate Ca2+ channels in various cell types by shifting their gating behavior towards mode 2, which is characterized by long openings and high probability of being open. In cardiac cells, the same type of gating behavior is potentiated by beta-adrenoceptors presumably acting via phosphorylation of a protein identical to or associated with the channel. Voltage-dependent phosphorylation has also been reported to underlie Ca2+ channel facilitation in chromaffin adrenal medulla and in skeletal muscle cells. We studied a possible voltage-dependent facilitation of the principal channel forming alpha 1-subunit of the dihydropyridine-sensitive smooth muscle Ca2+ channel. Single channel and whole-cell Ca2+ currents were recorded in Chinese hamster ovary cells stably expressing the class Cb Ca2+ channel alpha 1-subunit. Strong depolarizing voltage-clamp steps preceding the test pulse resulted in a 2- to 3-fold increase of the single Ca2+ channel activity and induction of mode 2-like gating behavior. Accordingly we observed a significant potentiation of the whole-cell current by approximately 50%. In contrast to the previous suggestions we found no experimental evidence for involvement of channel phosphorylation by protein kinases (cAMP-dependent protein kinase, protein kinase C and other protein kinases utilizing ATP gamma S) in the control and facilitated current. The data demonstrate that the L-type Ca2+ channel alpha 1-subunit solely expressed in Chinese hamster ovary cells is subject to a voltage-dependent facilitation but not to phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Another member of the cyclic nucleotide-gated channel family, expressed in testis, kidney, and heart.

Cyclic nucleotide-gated cation channels are essential in visual and olfactory signal transduction. An additional member of the cGMP-gated channel family, termed CNG-3, has been cloned from bovine kidney. Its deduced amino acid sequence is 60% and 62% identical with the CNG-channel proteins from bovine rod outer segment and bovine olfactory epithelium, respectively. Northern analysis and sequences amplified by the PCR showed that the CNG-3 mRNA is present in testis, kidney, and heart. Calcium permeated the expressed channel in the presence of extracellular Mg2+ and Na+ at membrane potentials from -100 to +45 mV. It is likely that CNG-3 protein is responsible for cGMP-induced Ca2+ entry in cells other than sensory cells.

Animals↗
PubMed1994

Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit.

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis possess immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti-voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore-forming alpha 1 subunit of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel alpha 1 subunit-directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel-binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both alpha 1 and beta subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells.

Using a combination of PCR based cloning and Northern blot analysis we have investigated the tissue expression of cyclic nucleotide-gated (CNG) cation channels in a variety of non-excitable tissues and cells. Partial sequences of all three known CNG channels and of an auxiliary subunit of the rod photoreceptor channel were determined. The expression of CNG channel genes is both tissue and species specific. Southern blot analysis with human genomic DNA revealed specific patterns of hybridization with probes derived from the different CNG channel types indicating that they are encoded by distinct genes. Analysis of human genomic sequences showed that all three genes are derived from a common ancestral gene and might have a similar gene structure. We were not able to identify additional genes encoding CNG channels. The CNG3 channel, which was originally cloned from bovine kidney may be expressed also in bovine cone photoreceptor cells. These data suggest that some of the effects of cGMP in peripheral tissues and cells might involve the activation of CNG channels.

Animals↗
PubMed1994

[The epidemiologic significance of varicella].

A total of 552 persons working in the university hospital of Freiburg, Germany (nurses, pediatric nurses, administration--and technical personnel) was screened for antibodies to varicella zoster virus. Prevalence of antibodies to VZV among men was higher than among women. While the degree of immunity of nurses and administration/technical personnel was comparable, pediatric nurses had a significantly higher seroprevalence (< 20 years 89.3%, -30 years 95.7%, > 30 years 98.6%). Therefore, pediatric nurses should be screened and susceptible persons should be vaccinated.

Adult↗
PubMed1994

Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP-dependent phosphorylation.

Enhancement of cardiac L-type Ca2+ channel activity by norepinephrine via phosphorylation by protein kinase A (PKA) underlines the positive inotropic effect of this transmitter and is a classical example of an ion channel modulation. However, it is not clear whether the channel protein itself (and which subunit) is a substrate for PKA. We have expressed various combinations of the cardiac Ca2+ channel subunits in Xenopus oocytes by injecting subunit mR-NAs. Expression of beta or alpha 2/delta + beta subunits potentiated the native (endogenous) Ca2+ channel currents in the oocyte (similar to T or N but not L-type). This potentiated endogenous current was enhanced by intracellular injection of cAMP or of the catalytic subunit of PKA, and this effect was reversed by the injection of a PKA inhibitor suggesting the presence of basal phosphatase activity. When a cardiac channel of alpha 1 + beta, alpha 1 + alpha 2/delta or alpha 1 + alpha 2/delta + beta composition was expressed at levels high enough that the contribution of the endogenous current became negligible, cAMP and PKA failed to increase the Ca2+ channel current, whereas PKA inhibitors and the catalytic subunit of protein phosphatase 1 reduced the amplitude of the current. Reduction of the current by PKA inhibitors was observed regardless of the presence of the beta subunit, suggesting a major role for the alpha 1 subunit in this process. These results suggest that, like in the heart, when expressed in Xenopus oocytes, the cardiac L-type Ca2+ channels are phosphorylated in basal state and dephosphorylation reduces their activity. However, unlike the situation in the heart, the activity of the channel cannot be enhanced by PKA-catalyzed phosphorylation, suggesting that the channel is already fully phosphorylated in its basal state.

Animals↗
PubMed1994

[Acceptance of preventive vaccinations by physicians and the general population].

The acceptance of vaccinations depends on the quality of information on effects and side effects. This publication deals with the results of three questionnaire studies: Questionnaire 1 was directed to the general population and contained questions on vaccination history and acceptance of vaccinations, questionnaire two and three were addressed to practitioners (general medicine/paediatrics/internal medicine) with additional questions on the number of vaccinations performed per year. An average of 50% of the persons taking part in the questionnaire study had been vaccinated within the last 10 years against diphtheria, tetanus, polio and/or influenza. The acceptance of these vaccinations was quite satisfactory whereas opinions on mumps and measles vaccinations were quite negative. In the course of the questionnaire study with practitioners it could be demonstrated that vaccinations against diphtheria, tetanus, polio and influenza were regarded as useful while immunisation against mumps, measles, tuberculosis, pertussis and chicken-pox were not regarded as useful. Information programes on vaccinations and the need for further investigations are discussed as well as the problem of mandatory vaccinations.

Adolescent↗
PubMed1994

[Vaccination in adults].

While immunization programs for children are well accepted in Switzerland, vaccinations of adults are still a problem. This paper deals with indications for vaccinations in adults. While the whole adults population should be immunized (boostered) against diphtheria, poliomyelitis and tetanus, other vaccinations (CEE, hepatitis A, hepatitis B, influenza, measles, mumps, rubella, rabies, varicella) should be administered according to risks at the workplace. Guidelines for vaccination programs in occupational medicine are presented and discussed.

Adult↗
PubMed1994

The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels.

The effects of Ro 40-5967, a nondihydropyridine Ca++ channel blocker, on low-voltage activated (T-type) and high-voltage activated (L-type) Ca++ channels were compared. L-type barium currents were measured in Chinese hamster ovary cells stably transfected with the alpha 1 subunit of the class Cb Ca++ channel. T-type barium currents were investigated in human medullary thyroid carcinoma cells. The Ba++ currents of human medullary thyroid carcinoma cells were transient, activated at a threshold potential of -50 mV with the maximum at -14 +/- 3.2 mV and blocked by micromolar Ni++. The T- and L-type current inactivated with time constants of 33.4 +/- 4.1 and 416 +/- 26 msec at maximum barium currents, respectively. Ro 40-5967 inhibited reversibly the T- and L-type currents with IC50 values of 2.7 and 18.6 microM, respectively. The inhibition of the L-type current was voltage-dependent, whereas that of the T-type current was not. Ro 40-5967 blocked T-type current already at a holding potential of -100 mV. The different types of block, i.e., voltage-dependent vs. tonic block, may contribute to the pharmacological profile of Ro 40-5967 in intact animals.

Animals↗
PubMed1994

Detection of skeletal muscle calcium channel subunits in cultured neonatal rat cardiac myocytes.

A monoclonal antibody (mAb) 8B7, that recognizes specifically the alpha 1-subunit of dihydropyridine-sensitive calcium channels in skeletal muscle, exerted a dose-dependent positive chronotropic effect on cultured spontaneously beating neonatal rat cardiac myocytes. The antibody-induced increase in beating frequency was similar to that elicited by 1 microM of (-)-isoprenaline. The mAb 8B7 recognized a polypeptide that is analogous to the 170-kDa calcium channel alpha 1-subunit of rabbit skeletal muscle in wheat germ lectin purified proteins solubilized from cultured rat heart myocytes by Western blot analysis. Furthermore, the mAb 7C3, previously shown to recognize specifically the skeletal muscle calcium channel beta-subunit, reacted with a 55-kDa polypeptide in these cultured myocytes. No immunoreactivity, however, was obtained when proteins solubilized from both neonatal or adult rat heart tissue were employed in Western blotting or immunoprecipitation experiments. RNA-hybridization analysis revealed that primary cultures derived from neonatal rat hearts expressed two types of mRNA encoding the skeletal muscle as well as the cardiac calcium channel alpha 1-subunit, while neonatal rat heart tissue expressed only the message for cardiac calcium channel. These results provide evidence for a functional expression of skeletal muscle-type calcium channel subunits during the cultivation of neonatal rat heart cells.

Animals↗
PubMed1993

High-level expression of functional cGMP-dependent protein kinase using the baculovirus system.

The understanding of the structure and function of cGMP-dependent protein kinase (cGMP kinase) has been hindered by the difficulty to obtain large quantities of functional enzyme. A recombinant baculovirus encoding bovine cGMP kinase I alpha was constructed and purified. Infected insect cells synthesized large amounts of soluble and biologically active cGMP kinase I alpha representing up to 10% of the total cell extract protein. The recombinant enzyme had an identical apparent molecular mass, cGMP affinity and kinase activity as the native bovine lung enzyme. The high-level expression of functional cGMP kinase I alpha should provide an excellent tool to study further the structure and function of cGMP kinase.

Animals↗