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Biomedical subjects

J Starck

Publications and source records attributed to J Starck.

At least 19 recordsLinked to original sources

Developmental regulation of human gamma- and beta-globin genes in the absence of the locus control region.

Two lines of transgenic mice carrying a normal 40-kb Kpn I beta-globin cluster transgene lacking the locus control region (LCR) were analyzed for the expression of human gamma- and beta-globin genes during mouse development. After RNase protection assays, the ratios of human G gamma-, A gamma-, or beta-mRNAs relative to endogenous mouse zeta + alpha mRNAs were obtained for each stage of development. The two gamma transgenes were expressed in day-11.5 blood (embryonic stage) and day-13.5 blood (early fetal stage), but their expression was markedly decreased by day 16.5 of fetal life. Expression of the beta transgene was essentially absent at day 13.5, appeared at a low level by day 16.5, and was maximal by day 18.5, reaching a level similar to that observed in adult mice. Therefore, developmentally regulated expression of the human gamma- and beta-globin transgenes was obtained in the absence of the LCR. The relative expression of human gamma- and beta-globin genes was also examined in mice carrying 40-kb Kpn I beta-cluster transgenes with two different base substitutions associated with nondeletion forms of hereditary persistence of fetal hemoglobin (HPFH), -202 C-->G G gamma HPFH and -117 G-->A A gamma HPFH. The ratio of G gamma- to beta-globin transcripts was markedly increased in red blood cells of adult mice from three different lines carrying the transgene with the -202 G gamma HPFH mutation. This result confirms our previous preliminary results (Tanaka et al: Ann NY Acad Sci, 612:167, 1990) indicating that the -202 G gamma HPFH phenotype was reproduced in transgenic mice. The relatively low levels of G gamma-mRNA expression in adult mice carrying the non-HPFH transgene excludes a major influence of the 3' beta-globin enhancer, present upstream of the G gamma gene because of the tandem repeat insertion, as a factor in the persistent G gamma gene expression observed in blood of adult mice carrying the -202 G gamma HPFH transgene. This conclusion is also supported by the fact that, in mice carrying the -117 A gamma HPFH transgene, G gamma-globin mRNA was detected in blood of adult animals only at low levels similar to that observed in the non-HPFH lines. However, the A gamma-HPFH phenotype was not reproduced in the transgenic lines carrying the -117A gamma HPFH mice.

Animals

Effect of hand-arm vibration on inner ear and cardiac functions in man.

To evaluate distant effects of hand-arm vibration we studied Finnish forestry workers using chain saw during the years 1972 through 1990. The hearing was tested annually and individual regression curves for sensorineural hearing loss (SHL) were calculated. Robinson's model was used in prediction of SHL. The heart rate variation (HRV) indexes at rest and during deep breathing test were analyzed to measure autonomic nervous function. In Robinson's model the measured SHL (17.8 dB) respected the predicted SHL (17.2 dB). The subjects with VWF had on average, 10 dB greater hearing loss than those who did not have VWF. The regression model based increase of hearing loss during follow up correlated with ageing, not to VWF. The intercept differed significantly in those with VWF from those without VWF. We found a significant difference between HRV indexes during deep breathing test in those with the shortest and those with the longest vibration exposure. The HRV decreased with age, but multiple regression analysis showed that the total exposure time to vibration had an independent negative association with HRV indexes. Our results suggest that prolonged exposure to vibration caused by chain saw has negative effects an autonomic functions. The aggravated hearing loss in subjects with VWF may be due to vibration induced changes in the autonomic nervous system or internal factors of the blood vessels.

Arm

Vibration exposure and prevention in Finland.

The number of annually compensated occupational diseases due to exposure to hand-arm vibration (HAV) has decreased during the last 15 years. The number of exposed workers has been declining in Finland, especially in forestry work, as harvesters have increasingly replaced manual chain saw operations. During the entire 1970s, forest work caused more cases of vibration-induced occupational diseases than all industrial branches together. The decrease is mainly due to the technical development of chain saws, but also to the effective health care services in Finland. Other factors such as warm transport, warm rest cabins in which to take pauses at work, warm meals, adequate protective clothing, and vocationally adjusted early medical rehabilitation have helped to cut down health hazards, especially in forest work. The number of new cases has been decreasing in Finland not only in forestry but also in other industries. In Finland a considerable amount of research has been conducted to hand-arm vibration, resulting in the increased awareness of the health risks related to certain occupations. This has helped to carry out the Primary Health Care Act (1972) followed by the Occupational Health Care Act (1979) which obligates employers to arrange occupational health care for their employees. We believe that the research activity has contributed significantly to achieving the present health in Finnish work places. The purpose of the present paper is to describe the cases of occupational exposure to HAV, and the effectiveness of different preventive measures in Finland.

Finland

Vibration syndrome among Finnish forest workers between 1972 and 1990.

A longitudinal study on vibration syndrome among professional forest workers was carried out in Finland from 1972 to 1990. In the course of the follow-up the weighted vibration acceleration of chain saws decreased from about 14 to 2 m/s2. The prevalence of vibration-induced white finger (VWF) decreased gradually from 40% to 5%. Numbness occurred mainly at night, and its prevalence decreased from 78% to 28%. During part of the follow-up period (1975-1990) the complaints of hand muscle weakness decreased from 19% to 9%. Disorders of the musculoskeletal system were considered to cause more disability than VWF. The decreased vibration acceleration and the lighter weight of chain saws were considered the main reasons for the decrease in the prevalence of vibration-induced symptoms.

Adult

In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure.

Measurements of bone lead concentrations in the tibia, wrist, sternum, and calcaneus were performed in vivo by x ray fluorescence on active and retired lead workers from two acid battery factories, office personnel in the two factories under study, and control subjects. Altogether 171 persons were included. Lead concentrations in the tibia and ulna (representative of cortical bone) appeared to behave similarly with respect to time but the ulnar measurement was much less precise. In an analogous fashion, lead in the calcaneus and sternum (representative of trabecular bone) behaved in the same way, but sternal measurement was less precise. Groups occupationally exposed to lead were well separated from the office workers and the controls on the basis of calculated skeletal lead burdens, whereas the differences in blood lead concentrations were not as great, suggesting that the use of concentrations of lead in blood might seriously underestimate lead body burden. The exposures encountered in the study were modest, however. The mean blood lead value among active lead workers was 1.45 mumol l-1 and the mean tibial lead concentration 21.1 micrograms (g bone mineral)-1. The kinetics of lead in the tibia appeared to be noticeably different from that in the calcaneus. Tibial lead concentration increased consistently both as a function of intensity of exposure and of duration of exposure. Calcaneal lead concentration, by contrast, was strongly dependent on the intensity rather than duration of exposure. This indicated that the biological half life of lead in calcaneus was less than the seven to eight year periods into which the duration of exposure was split. Findings for retired workers clearly showed that endogenous exposure to lead arising from skeletal burdens accumulated over a working lifetime can easily produce the dominant contribution to systemic lead concentrations once occupational exposure has ceased.

Adult

Relevance of the Tullio phenomenon in assessing perilymphatic leak in vertiginous patients.

The Tullio phenomenon was studied in 57 control subjects, in 7 patients with confirmed PLF and in 149 patients with different types of inner ear pathology. The subjects were exposed to low-frequency sound (LFS) with sound pressure levels ranging from 130 to 132 dB and at frequencies of 25, 50, and 63 Hz. The duration of each stimulation was 30 seconds. The postural responses were measured using a force platform and analyzed with a computer. In control subjects the LFS stimulation somewhat improved the postural stability. All patients with PLF showed significantly altered postural stability during LFS exposure. Also about 20 percent of patients with labyrinthine vertigo, patients with Menièré's disease, patients with chronic middle ear disease (with vertigo) had pathologic response to LFS. None of the patients with pure sensorineural hearing loss without vertigo responded to LFS. Post-urography with LFS loading is a new, promising tool in detection of PLF, but the specificity of the test is still unsatisfactory.

Adolescent

Tullio phenomenon and postural stability: experimental study in normal subjects and patients with vertigo.

The effect of low-frequency sound (LFS) on postural stability was studied in 55 healthy volunteers and in 152 patients with vertigo due to different types of inner ear disease. The sound pressure levels ranged from 130 to 132 dB and were given at frequencies of 25, 50, and 63 Hz. The duration of each stimulation lasted 30 seconds. The postural responses were measured with a force platform. The LFS stimulation improved the postural stability of the healthy subjects through the alerting response. We did not observe any difference in the body sway according to whether the LFS was delivered with monaural or binaural stimulation. Twenty-six percent of the patients with Meniere's disease, 40% with chronic otitis media with vertigo, and 26% with vertigo of peripheral origin experienced significant postural instability at least at two of the three test frequencies during stimulation with LFS. The results demonstrate that in subjects with different types of inner ear disease the vestibular system starts to respond to LFS. The activation of vestibulospinal responses by LFS seems to be an expression of the Tullio phenomenon.

Acoustic Stimulation

Postural stability on moving platform oscillating at high frequencies. Effect of vestibular lesion.

The effect of linear perturbation at a frequency range of 8 to 24 Hz on postural stability was studied in 7 patients with unilateral vestibular function loss. Force platform technique was used with automatic analysis resulting in the sway velocity of the center point of force. In all patients the support surface movement produced increased sway velocity which was significantly greater than in the controls. Tests at lower frequencies (8 and 10 Hz) produced higher sway velocities than tests at higher frequencies (12, 14, 16 and 24 Hz). The results indicate that the vestibular system controls postural reflexes at a substantially higher frequency range than hitherto suggested.

Adult

Repeatability and effect of instruction of body sway.

The effect of instruction and repeatability of posturography measurement was studied in 24 healthy volunteers. In an instruction, "stable" (inverted pendular model) and "relaxed" (segmental oscillating model) positions were studied. In addition, the effect of habituation adaptation, and day-to-day variation were investigated. Sway velocity and average and maximum displacement during vibration perturbated stance were analysed. In individual responses, no statistically significant day-to-day variation could be observed and the individual variation was small. In the "relaxed" condition, the instability was greater when maximum displacement was analysed. No significant changes in sway velocity and average displacement were observed. The results demonstrated remarkable stability of normal postural control mechanism.

Adult

The Tullio phenomenon in patients with Menière's disease as revealed with posturography.

The effect of low frequency sound (LFS) on postural stability was studied in 55 healthy volunteers and in 50 patients with Menière's disease. The sound levels ranged from 130 to 132 dB and were given at frequencies of 25, 50 and 63 Hz. The patients with Menière's disease displayed increased body sway during stimulation. In the individual response, 26% of the patients with Menière's disease experienced significant body sway. The results demonstrate that subjects with Menière's disease are sensitive to low frequency sound. The activation of vestibulo-spinal responses by low frequency sound seems to be a result of the Tullio phenomenon, in which sound energy activates the vestibular end-organ.

Acoustic Stimulation

Extent and high frequency of a short conversion between the human A gamma and G gamma fetal globin genes.

Southern blotting and DNA sequencing after polymerase chain reaction (PCR) amplification provide evidence for the frequent occurrence (in 7 out of 24 chromosomes) of a short conversion G gamma----A gamma in the 3' end of the human fetal A gamma globin gene. This short conversion is characterized by the presence, 3 nucleotides downstream from the termination codon of the A gamma gene, of the TCAC sequence that is normally present at the equivalent position at the 3' end of the G gamma gene; it is therefore identical to a conversion already described. Interestingly, we have found that this conversion is associated with the presence of the HindIII polymorphic restriction site in the A gamma IVS2, occupying an equivalent position in both the G gamma and A gamma genes. Our observations strengthen the hypothesis that the presence of the HindIII polymorphic restriction site in A gamma IVS2 and the presence of the sequence TCAC at the 3' end of the A gamma gene might be the result of a single conversion event.

Base Sequence

Vibration perception threshold of forest worker's finger during temporary obstructed blood circulation.

Vibration detection threshold (VPT) of 149 professional forest workers was measured during a compulsory annual health examination. The authors' earlier developed measuring method for VPT of finger was modified. The blood circulation of the hand was obstructed for 6 min and VPT was measured 4 min after releasing the obstruction. VPTs of all forest workers increased during obstruction. In forest workers suffering from decreased hand grip force (decreased HGF) the increase of VPT differed significantly from forest workers without symptoms, and VPT in the former group still increased after releasing the obstruction. VPT remained also at the raised level after releasing the obstruction with forest workers suffering from vibration-induced white finger (VWF). Nevertheless, on an individual basis even the modified measuring method failed to discriminate subjects without symptoms from those with symptoms of hand-arm vibration syndrome. The raised VPT and sensitivity for obstruction of blood circulation suggest that the reason for decreased HGF in forest workers may be a consequence of an injury in the peripheral nerves.

Adult

Measuring method for vibration perception threshold of fingers and its application to vibration exposed workers.

A measuring method for the vibration perception threshold (VPT) of fingers has been developed. The VPTs of 118 and 149 professional forest workers were measured during a compulsory annual health examination in 1979 and 1983, respectively. Also the VPTs of eight pedestal grinders, who were suffering vibration-induced white finger (VWF), were measured in 1979 and 1983. The control group consisted of 20 research workers who had no vibration exposure in the past and no symptoms in their hands. The measuring system for VPT gave repeatable results. The frequency of the most sensitive VPT of vibration exposed workers alternated between 63 and 125 Hz instead of 125 Hz of subjects without vibration exposure. The VPT of the pedestal grinders and forest workers with decreased hand grip force and with vibration-induced white finger were significantly higher than those of the controls. The VPTs of the forest workers decreased slightly and that of the grinders increased from 1979 to 1983. In spite of long vibration exposure in the past and continuing lower level vibration exposure, the increased VPT of forest workers does not seem to be permanent.

Adult

Physical characteristics of vibration in relation to vibration-induced white finger.

Predicted and observed prevalences and latency periods of vibration-induced white finger (VWF) were examined among workers exposed to hand-arm vibration. The different physical characteristics of vibration--spectra and impulsiveness--were measured. The following groups of workers were included in the study: forest workers (n = 199), pedestal grinders (n = 12), stone workers (n = 16), shipyard workers (n = 171), and platers (n = 5). The exposure to vibration was measured according to the ISO 5349 method. The impulsiveness of vibration was defined as the difference between peak levels and RMS levels. A good agreement was observed between the predicted and observed data for prevalence and latency of VWF in the forest workers. For the tools with high impulsiveness used in grinding, stone works, and shipyard assembly hall, the results were nonconfirmative; and there was a poor correlation between vibration and VWF. The ISO 5349 standard does not consider the high peak values of the vibration signal which may comprise high-frequency components and cause short transients in the underlying tissue of the worker's hand. These characteristics in vibration may be hazardous in the genesis of VWF and cannot be predicted when measuring vibration by the present standard method.

Cross-Sectional Studies

Carpal tunnel syndrome in vibration disease.

The presence of carpal tunnel syndrome (CTS) in 125 forestry workers with exposure to vibration was examined clinically by electromyography and by determining vibration detection thresholds. Numbness of the hands was present in 43%, history of diminished hand muscle force in 15%, and Raynaud's phenomenon in 27%. The muscle weakness correlated significantly with motor nerve conduction velocity in the median nerve in both hands. In 25 forestry workers CTS was diagnosed. The condition was bilateral in 48%; otherwise it was more common on the right side. Fifteen patients were referred for surgery but because of spontaneous recovery or refusal by the patients only five underwent surgery; of these four improved. The motor conduction velocity of the ulnar nerve was decreased among patients with CTS supporting the idea that entrapment neuropathies in the hands may be due to tissue swelling caused by vibration at work. Total exposure time to vibration correlated with the decrease in motor conduction velocity in the ulnar nerve.

Adult

Postural stability in shooters.

Ten competition shooters were tested during simulated race using the force platform technique to investigate the effect of training on postural stability. The shooters were tested at 30-min intervals during a race simulating actual race conditions. Sway velocity was calculated during 27-second periods. The postural stability was evaluated with and without competition clothing. The shooters had significantly better stability than untrained control subjects, when tested without supportive clothing. The competition clothing reduced the sway velocity further both in visual and nonvisual conditions. The Romberg quotient was higher in shooters than in normal controls, indicating that the shooters used to an increased amount proprioceptive and vestibular cues to stabilize their posture. The good postural stability of the shooters apparently results from assiduous training aimed to improve postural stability.

Adolescent

Two elliptocytogenic alpha I/74 variants of the spectrin alpha I domain. Spectrin Culoz (GGT----GTT; alpha I 40 Gly----Val) and spectrin Lyon (CTT----TTT; alpha I 43 Leu---Phe).

Spectrin alpha I/74 elliptocytosis results from abnormalities involving the "head" region of spectrin dimer. Increased susceptibility to trypsin enhances cleavage of the alpha spectrin chain, yielding an increased amount of the alpha I 74-kD fragment at the expense of the alpha I 80-kD parent fragment. Recently we showed that the mutations causing the Sp alpha I/74 abnormality may lie in the alpha- or the beta-chain, and that spectrin Culoz and spectrin Lyon were two (alpha I/74) alpha-variants, respectively. We now show that the spectrin Culoz alpha I domain undergoes prominent tryptic cleavage after Lys 42, whereas cleavage prevails after Arg 39 in spectrin Lyon. Applying the polymerase chain reaction (PCR) technique to exon 2 of the spectrin alpha I domain, we have established that the mutation responsible for spectrin Culoz is alpha I 40 Gly----Val; GGT----GTT. Applying the PCR technique to the cDNA derived from reticulocyte mRNA, we have shown that the mutation responsible for spectrin Lyon is alpha I 43 Leu----Phe; CTT----TTT. Studies of normal controls and of family members using dot blot hybridization with allele-specific oligonucleotide probes confirmed these results. Variants such as spectrin Culoz and spectrin Lyon should provide insight into a region that participates in spectrin dimer self-association and whose susceptibility to proteolysis must reflect subtle conformational changes.

Amino Acid Sequence