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Biomedical subjects

R C Jensen

Publications and source records attributed to R C Jensen.

17 recordsLinked to original sources

The Drosophila U1 and U6 gene proximal sequence elements act as important determinants of the RNA polymerase specificity of small nuclear RNA gene promoters in vitro and in vivo.

Transcription of genes coding for metazoan spliceosomal snRNAs by RNA polymerase II (U1, U2, U4, U5) or RNA polymerase III (U6) is dependent upon a unique, positionally conserved regulatory element referred to as the proximal sequence element (PSE). Previous studies in the organism Drosophila melanogaster indicated that as few as three nucleotide differences in the sequences of the U1 and U6 PSEs can play a decisive role in recruiting the different RNA polymerases to transcribe the U1 and U6 snRNA genes in vitro. Those studies utilized constructs that contained only the minimal promoter elements of the U1 and U6 genes in an artificial context. To overcome the limitations of those earlier studies, we have now performed experiments that demonstrate that the Drosophila U1 and U6 PSEs have functionally distinct properties even in the environment of the natural U1 and U6 gene 5'-flanking DNAs. Moreover, assays in cells and in transgenic flies indicate that expression of genes from promoters that contain the "incorrect" PSE is suppressed in vivo. The Drosophila U6 PSE is incapable of recruiting RNA polymerase II to initiate transcription from the U1 promoter region, and the U1 PSE is unable to recruit RNA polymerase III to transcribe the U6 gene.

Animals↗

Quantitative analysis of rat inner ear blood flow using the iodo[(14)C]antipyrine technique.

A number of different qualitative and quantitative techniques have been used to measure inner ear blood flow and all have required that the animal be anesthetized. It is well known that anesthesia can cause a variety of circulatory as well as other systemic changes. In this study, we have employed a technique commonly used for quantifying brain blood flow, the iodo[(14)C]antipyrine technique ([(14)C]IAP). Unlike other techniques, [(14)C]IAP can be used in unanesthetized animals under conditions that are nearly normal, it is non-invasive, it can be used reliably in regions of low local blood flow, and data can be acquired from both the periphery and central nervous system. Results show that blood flow to the lateral wall of the basal turn of the cochlea (387 +/- 19 microl/g/min) is significantly higher (P<0.001) than that of the utricular macula (189 +/- 23 microl/g/min), horizontal (186 +/- 22 microl/g/min), superior (185 +/- 22 microl/g/min), or posterior canal crista (185 +/- 25 microl/g/min). Surprisingly, blood flow to all of the vestibular end-organs is remarkably similar. The use of this technique should allow pharmacological experimentation on inner ear blood flow without the unknown complications of anesthesia or invasive procedures.

Animals↗

Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1.

The human antibody immunoglobulin G1 (IgG1) b12 neutralizes a broad range of human immunodeficiency virus-type 1 (HIV-1) isolates in vitro and is able to protect against viral challenge in animal models. Neutralization of free virus, which is an antiviral activity of antibody that generally does not require the antibody Fc fragment, likely plays an important role in the protection observed. The role of Fc-mediated effector functions, which may reduce infection by inducing phagocytosis and lysis of virions and infected cells, however, is less clear. To investigate this role, we constructed a panel of IgG1 b12 mutants with point mutations in the second domain of the antibody heavy chain constant region (CH2). These mutations, as expected, did not affect gp120 binding or HIV-1 neutralization. IgG1 b12 mediated strong antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of HIV-1-infected cells, but these activities were reduced or abrogated for the antibody mutants. Two mutants were of particular interest. K322A showed a twofold reduction in FcgammaR binding affinity and ADCC, while C1q binding and CDC were abolished. A double mutant (L234A, L235A) did not bind either FcgammaR or C1q, and both ADCC and CDC functions were abolished. In this study, we confirmed that K322 forms part of the C1q binding site in human IgG1 and plays an important role in the molecular interactions leading to complement activation. Less expectedly, we demonstrate that the lower hinge region in human IgG1 has a strong modulating effect on C1q binding and CDC. The b12 mutants K322A and L234A, L235A are useful tools for dissecting the in vivo roles of ADCC and CDC in the anti-HIV-1 activity of neutralizing antibodies.

Antibody-Dependent Cell Cytotoxicity↗

The proximal sequence element (PSE) plays a major role in establishing the RNA polymerase specificity of Drosophila U-snRNA genes.

Most small nuclear RNA (snRNA) genes are transcribed by RNA polymerase II, but some (e.g., U6) are transcribed by RNA polymerase III. In vertebrates a TATA box at a fixed distance downstream of the proximal sequence element (PSE) acts as a dominant determinant for recruiting RNA polymerase III to U6 gene promoters. In contrast, vertebrate snRNA genes that contain a PSE but lack a TATA box are transcribed by RNA polymerase II. In plants, transcription of both classes of snRNA genes requires a TATA box in addition to an upstream sequence element (USE), and polymerase specificity is determined by the spacing between these two core promoter elements. In these examples, the PSE (or USE) is interchangeable between the two classes of snRNA genes. Here we report the surprising finding that the Drosophila U1 and U6 PSEs cannot functionally substitute for each other; rather, determination of RNA polymerase specificity is an intrinsic property of the PSE sequence itself. The alteration of two or three base pairs near the 3'-end of the U1 and U6 PSEs was sufficient to switch the RNA polymerase specificity of Drosophila snRNA promoters in vitro. These findings reveal a novel mechanism for achieving RNA polymerase specificity at insect snRNA promoters.

Animals↗

Role of TATA box sequence and orientation in determining RNA polymerase II/III transcription specificity.

Work from a number of laboratories has indicated that the TATA box sequence can act as a basal promoter element not only for RNA polymerase II (RNAP II) transcription, but also for transcription by RNA polymerase III (RNAP III). We previously reported that, in the absence of other cis-acting elements, the canonical TATA sequence TATAAAAA specifically supported transcription by RNAP II in an unfractionated Drosophila nuclear extract, whereas the sequence TTTTTATA (the same sequence in reverse orientation) directed RNAP III transcription. We have now examined a variety of other TATA box sequences with regard to RNA polymerase selectivity and their ability to support RNAP III transcription. The results have allowed us to rank these TATA box sequences with respect to their relative strengths as RNAP III promoter elements in unfractionated Drosophila extracts. Further, the data indicate that T residues at positions 2 and 4 of the TATA box appear to be important determinants of RNAP III selectivity in this system, whereas A residues at these positions favor RNAP II transcription. Finally, the data suggest that transcription factors TFIID and TFIIIB, although both capable of binding a variety of TATA elements, have distinct sequence preferences for recognizing the TATA box and possibly the surrounding DNA.

Adenosine↗

Low back injuries among home health aides compared with hospital nursing aides.

Data were collected from all incident reports of low back injury during 1984-1986 among nursing aides at one hospital and home health aides at two agencies in the Baltimore-Washington area. Respective rates of injury were 5.9/100 FTE's and 15.4/100 FTE's (p < 0.001). A majority of injuries occurred during patient-related, planned activities and without the use of lifting equipment. Forty percent of the events occurred at the bedside. Eighty-eight percent of home health aides were working alone compared with 39 percent of NAs. Ergonomic interventions may be an effective strategy to reduce injuries, since 50 percent of the events involved lifting and pushing/pulling activities.

Accidents, Occupational↗

Agricultural machine-related deaths.

Analysis of 1980-1985 death certificate data for the United States indicated that an average of 369 occupational deaths per year involved agricultural machinery as the external cause of death. Out of all agricultural machine-related deaths, tractors accounted for 69 percent. Over half of these tractor-related deaths were rollovers. There is a need for public health programs to affect greater use of rollover protective structures (ROPS) on farm tractors.

Accident Prevention↗

Static pre-load effect on knee extensor isokinetic concentric and eccentric performance.

The effect of two static pre-load levels on isokinetic concentric (CON) and eccentric (ECC) performance of the knee extensors at 90 degrees.s-1 was evaluated in 35 healthy subjects. The low pre-load level was 50 N, and the high level was 75% of a maximal voluntary isometric contraction, performed at the start angles of 100 degrees (CON) and 30 degrees (ECC) of knee flexion. A two-way ANOVA with two repeated measures (load and angle) and a Newman-Keuls post hoc analysis were performed to compare the interaction of pre-load and angle at every 5 degrees in the ROM. The differences in average torque, peak torque, and peak torque angle between the pre-load levels were also analyzed with repeated-measures t-tests. The high pre-load condition had a significant increase in torque at 99, 95, 90, and 85 degrees concentrically and 31, 35, 40, 45, and 50 degrees eccentrically. In comparing the two pre-load conditions over the whole torque curve, there was a significant difference in average torque values of both CON and ECC, no significant difference in peak torque in either contraction, and a significant shift in peak torque angle with CON contractions only.

Adult↗

Effect of age and training status on pharmacokinetics of flunixin meglumine in thoroughbreds.

The effect of age and training status on the pharmacokinetics of flunixin meglumine was evaluated in 16 Thoroughbreds. Horses were assigned to 1 of 3 groups on the basis of age and training status: group A (n = 6), horses in active training and less than or equal to 5 years old; group B (n = 5), horses out of training for a minimum of 6 weeks and less than or equal to 5 years old; and group C (n = 5), horses out of training for at least 2 years and greater than or equal to 9 years old. After administration of 500 mg of flunixin meglumine IV, multiple serum and urine samples were obtained over 24 hours and assayed for flunixin by high-performance liquid chromatography. Although the mean distribution rate constant and volume of distribution were similar for the 3 groups, mean total body clearance and elimination rate constant were significantly (P less than 0.05) greater and half-life significantly (P less than 0.01) less in groups A and B, compared with group C. Differences in pharmacokinetic values were not observed between the horses in group A and B. In addition, the changes in clearance, elimination rate constant, and half-life of flunixin were found to significantly (P less than 0.05) correlate with age. The results of this investigation indicated that age, but not training status, influences disposition of flunixin meglumine in Thoroughbreds.

Age Factors↗

Disabling back injuries among nursing personnel: research needs and justification.

The need for more research on the problem of work-related back injuries among nursing personnel is documented by two comparisons based on the ratio of back injury workers' compensation claims to eligible employees. The first analysis of occupations across industries indicated that nursing aides, licensed practical nurses, and registered nurses all had high back injury ratios compared to other occupations. The second analysis of occupations within four parts of the health care industry indicated that aides in nursing and personal care facilities had the greatest problem with disabling back disorders. The article concludes with a list of research needs and suggested research methodologies.

Back Injuries↗

Sudden death in training and racing Thoroughbred horses.

We reviewed case records, necropsy reports, and histologic sections from 25 Thoroughbred racehorses that died suddenly at 3 Chicago racetracks. These were young horses ranging in age from 2 to 5 years. There were more females (n = 16) than males (n = 9), and the incidence of death increased slightly in the spring and summer. Twenty-one of the 25 horses died while racing or training. Only 8 of the 25 horses (32%) had lesions sufficient to account for the death. In 6 of those 8 cases, death was caused by massive thoracic or abdominal hemorrhage. The site or nature of the vascular defect in these cases could not be determined. One horse died of severe preexisting pulmonary disease, and one died of encephalitis and cardiac papillary muscle fibrosis. The cause of death was undetermined in 17 horses (68%). Nearly all horses had pulmonary edema, congestion, and/or hemorrhage. We postulate that these unexplained deaths were a result of exercise-induced acute cardiovascular failure.

Animals↗

Assessment of workers' compensation claims for back strains/sprains.

Workers' compensation claim data for 1979 obtained from the Bureau of Labor Statistics' Supplementary Data System (SDS) were utilized to examine the demographic and occupational incidence of back strains/sprains among U.S. industrial employees covered by state compensation systems. These data were combined with estimated employment figures to provide incidence ratios, which allowed better approximations of industry- and occupation-specific risk. Industries found to have the largest incidence ratios were construction (1.6 claims/100 workers) and mining (1.5 claims/100 workers). Occupations with the largest ratios were miscellaneous laborers (12.3 claims/100 workers) and garbage collectors (11.1 claims/100 workers). The 285,468 compensation claims due to back strains/sprains filed in the 26 SDS states in 1979 suggest that back injuries continue to be a large and costly problem for U.S. workers and their employers.

Adolescent↗

Investigation of the after-reach hazard in two-hand controlled power press operations.

One hazard inherent to hand-feeding operations at a power press occurs when a worker reaches into the point of operation after initiating the downward stroke of the press ram. One approach for controlling this hazard is to locate a two-hand actuator at a distance sufficiently far from the point of operation to prevent the operator from getting his hand into the die area before the ram completes its descent. In a study of this problem, the activities of a power press were simulated in the laboratory with the use of a model power press and two locations for the actuator controls, an upper and a lower location. The subjects performed simulated work cycles using the laboratory power press. Randomly an after-reach condition was created in which the subjects were to each into the press die area to reposition a dislodged work blank. The after-reach time, ie, the time needed to reach from the actuator controls to the press die area, was measured. The results of this study indicated that there is a difference in hand-reach speed depending upon the location of the actuator controls. It was concluded that, to define hand-reach speed adequately, more research is needed to characterize the effect of other variables.

Accidents, Occupational↗

The determination of effective injury controls for metal-cutting lathe operators.

Operators of metal-working lathes are one of the largest manufacturing machine worker populations in the United States. Machines (other than vehicular) account for over 10% of occupational injuries each year. An estimated 3,400 operators of metal-working lathes suffer lost-time injuries annually in the United States. Some of these are fatal. Therefore an investigation was undertaken to determine methods for reducing injuries to lathe operators. Three methods were used: (i) review of injury reports, (ii) human factors analysis, and (iii) fault-tree procedures. The investigation followed the man-machine systems approach of looking for injury-producing dysfunctions between the lathe and the lathe operator. The major sources of injury were found to be chips and workholding devices. Secondary tasks were found to be more hazardous than is generally recognized. The use of three methods for approaching the problem was found to be useful in that injury controls were identified which are likely to be adopted because of their potential for improving safety without adversely affecting productivity.

Accidents, Occupational↗