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Biomedical subjects

K Reynolds

Publications and source records attributed to K Reynolds.

At least 55 records · Page 3Linked to original sources

Resource utilization among neonatologists in a university children's hospital.

OBJECTIVE: We studied factors affecting length of hospital stay and resulting hospital charges among patients managed by two separate groups of neonatologists in the same academic health science center. DESIGN: Retrospective analysis of clinical and financial data base information. METHODS: Neonatal intensive care was provided in the same acute care nursery in a large university children's hospital by: (1) neonatologists in a full-time academic division (group A) and (2) a group associated with a private managed care organization (group B). Clinical and financial parameters of all neonates admitted in fiscal year 1994 were compared for the two provider groups. Stepwise regression analysis was used to evaluate factors influencing hospital charges and length of hospital stay (LOS) and to adjust for differences in clinical variables between the two groups. RESULTS: Group A physicians provided care for 340 infants, while 137 were treated by those of group B. Group A included older patients, more outborns, more level III patients, more sepsis, more intermittent positive pressure ventilation, and more patent ductus arteriosus. The incidence of transient tachypnea of the newborn was higher among group B patients. Hospital charges were primarily determined by LOS, which was similar for the two groups. When the data were corrected for differences in risk and patient acuity, however, a significant relationship between physician group and LOS was demonstrated, with LOS being an average of 7.8 days shorter for group A. A net reduction of $3 114 969 in hospital charges might have been realized had group A physicians provided care for all study patients. CONCLUSIONS: Hospital charges were determined by LOS. In this setting, academic neonatologists produced shorter LOS and comparable clinical outcomes, despite caring for a population at greater risk. The reduction in LOS could have resulted in more than $3.1 million in annualized savings had the academic group provided care for all of the study patients.

Analysis of Variance↗

Load carriage using packs: a review of physiological, biomechanical and medical aspects.

This paper reviews the biomedical aspects of transporting loads in packs and offers suggestions for improving load-carriage capability. Locating the load mass as close as possible to the body center of gravity appears to result in the lowest energy cost when carrying a pack. Thus, the double pack (half the load on the front of the body and half the load on the back) has a lower energy cost than the backpack. However, backpacks provide greater versatility in most situations. The energy cost of walking with backpack loads increases progressively with increases in load mass, body mass, walking speed or grade; type of terrain also influences energy cost. Predictive equations have been developed for estimating the energy cost of carrying loads during locomotion but these may not be accurate for prolonged (>2 h) or downhill carriage. Training with loads can result in greater energy efficiency since walking with backpack loads over several weeks decreases energy cost. Load-carriage speed can be increased with physical training that involves regular running and resistance training. Erector spinae electrical activity (EMG) is lower during load carriage than in unloaded walking until loads exceed 30-40 kg, at which point erector spinae EMG activity is higher than during unloaded walking. EMGs of the quadriceps and gastrocnemius, but not the tibialis anterior or hamstrings, increase with load. Framed packs with hip belts reduce the electrical activity of the trapezius muscles, presumably by shifting forces from the shoulders to the hips. Increases in the backpack load mass result in increases in forces exerted on the grounds, amount of knee flexion and the forward inclination of the trunk. Compared to backpacks, double packs produce fewer deviations from normal walking. Common injuries associated with prolonged load carriage include foot blisters, stress fractures, back strains, metatarsalgia (foot pain), rucksack palsy (shoulder traction injury) and knee pain. Closed-cell neoprene insoles and use of an acrylic or nylon sock, combined with a wool sock, reduce blister incidence. A framed pack with a hip belt reduces the incidence of rucksack palsy. Backpack load carriage can be facilitated by lightening loads, optimizing equipment, improving load distribution and by preventive action aimed at reducing the incidence of injury.

Journal Article↗

Regulation of RAR beta 2 mRNA expression: evidence for an inhibitory peptide encoded in the 5'-untranslated region.

Regulation of mRNA translation and stability plays an important role in the control of gene expression during embryonic development. We have recently shown that the tissue-specific expression of the RAR beta 2 gene in mouse embryos is regulated at the translational level by short upstream open reading frames (uORFs) In the 5'-untranslated region (Zimmer, A., A.M. Zimmer, and K. Reynolds. 1994. J. Cell Biol. 127:1111-1119). To gain insight into the molecular mechanism, we have performed a systematic mutational analysis of the uORFs. Two series of constructs were tested: in one series, each uORF was individually inactivated by introducing a point mutation in its start codon; in the second series, all but one ORF were inactivated. Our results indicate that individual uORFs may have different functions. uORF4 seems to inhibit translation of the major ORF in heart and brain, while uORFs 2 and 5 appear to be important for efficient translation in all tissues. To determine whether the polypeptide encoded by uORF4 or the act of translating it, is the significant event, we introduced point mutations to create silent mutations or amino acid substitutions in uORF4. Our results indicate that the uORF4 amino acid coding sequence is important for the inhibitory effect on translation of the downstream major ORF.

Amino Acid Sequence↗

Effects of an antiperspirant with emollients on foot-sweat accumulation and blister formation while walking in the heat.

BACKGROUND: Friction blisters are a common injury in sports activities and military operations. Blisters can compromise performance, so it is important to devise preventive strategies to reduce these injuries. OBJECTIVE: This study investigated the influence of an antiperspirant with emollient additives on frequency and severity of friction blisters, hot spots, and irritant dermatitis. METHODS: Twenty-three healthy men walked on a treadmill (1.39 m/sec, 1% grade) in a warm environment (28 degrees C, 25% relative humidity) carrying a total mass of 21 +/- 1 kg. For 4 consecutive days before the walk, the subjects' feet were treated with either (1) an antiperspirant (20% aluminum zirconium tetrachlorohydrex glycine concentration plus water) with emollient additives, (2) emollient additives alone (placebo control), or (3) nothing (nontreated). In two separate trials (1 month apart) each participant received the antiperspirant treatment and both control treatments (emollient [placebo] and no treatment). RESULTS: No differences were seen among treatment conditions for sweat accumulation (p = 0.86), blister incidence (p = 0.36), hot spot incidence (p = 0.83), or blister severity (p = 0.31). Irritant dermatitis was not reported in any of the treatment conditions. CONCLUSION: The use of an antiperspirant with emollients reduces irritant dermatitis but does not reduce total foot-sweat accumulation, blister or hot spot incidence, or blister severity.

Adult↗

Maintenance requirements for dietary protein in 11- and 18-month-old male rats.

Body weight, lean body mass (total weight less body fat), carcass protein, and serum protein were examined as potential parameters by which to assess the effect of age on protein requirements for maintenance in male rats, aged 11 months and 18 months, fed diets containing 1.53, 3.41, 4.98, 6.52, or 8.05% dietary protein, casein plus methionine, for a 5-week period. Body weight change was maintained in older animals at 6.52% dietary protein and in younger animals at 4.98% dietary protein. Older animals consuming the two diets highest in protein had a greater percent body fat and less percent body protein than younger animals. Significant effects of diet and the interaction of diet and age on serum protein were also observed. As dietary protein level increased, serum protein increased gradually in younger rats, but only between 3.41 and 4.98% dietary protein in older rats. Lean body mass and total carcass protein increased as dietary protein level increased, but there were no significant differences due to age or the interaction of diet and age. Changes in body weight indicate a greater protein requirement for 18-month-old rats compared with 11-month-old rats, although complicated by greater food intake and fat deposits in older animals. Measures of body protein indicate that age has some influence on protein needs for maintenance purposes.

Aging↗

Compatibility of high-intensity strength and endurance training on hormonal and skeletal muscle adaptations.

Thirty-five healthy men were matched and randomly assigned to one of four training groups that performed high-intensity strength and endurance training (C; n = 9), upper body only high-intensity strength and endurance training (UC; n = 9), high-intensity endurance training (E; n = 8), or high-intensity strength training (ST; n = 9). The C and ST groups significantly increased one-repetition maximum strength for all exercises (P < 0.05). Only the C, UC, and E groups demonstrated significant increases in treadmill maximal oxygen consumption. The ST group showed significant increases in power output. Hormonal responses to treadmill exercise demonstrated a differential response to the different training programs, indicating that the underlying physiological milieu differed with the training program. Significant changes in muscle fiber areas were as follows: types I, IIa, and IIc increased in the ST group; types I and IIc decreased in the E group; type IIa increased in the C group; and there were no changes in the UC group. Significant shifts in percentage from type IIb to type IIa were observed in all training groups, with the greatest shift in the groups in which resistance trained the thigh musculature. This investigation indicates that the combination of strength and endurance training results in an attenuation of the performance improvements and physiological adaptations typical of single-mode training.

Adaptation, Physiological↗

Generation and characterization of monoclonal antibodies to human type-5 tartrate-resistant acid phosphatase: development of a specific immunoassay of the isoenzyme in serum.

We have characterized four monoclonal antibodies (mAbs) to the purple ("tartrate-resistant," band 5) acid phosphatase of the human osteoclast (TRAP) and used these to develop a specific serum immunoassay. All four mAbs are of high affinity (Ka = 1-5 x 10(8) L/mol) with a very fast Kassoc (0.2-2.0 x 10(5) L mol-1 s-1) and a moderate Kdissoc (1-3 x 10(-3) s). Two of the mAbs were selected to develop a time-resolved fluorescence immunoassay to measure serum concentrations of TRAP. The mean serum immunoreactive TRAP in a group of healthy premenopausal women and men was 3.7 +/- 1.8 micrograms/L (mean +/- SD) and 3.5 +/- 1.6 micrograms/L, respectively. Significantly higher concentrations of TRAP were found in postmenopausal women (6.3 +/- 2.3 micrograms/L) and in eight patients with Gaucher disease (19.3 +/- 4.7 micrograms/L). Further studies are required to investigate the value of serum TRAP as a marker of bone resorption.

Acid Phosphatase↗

Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor.

BACKGROUND: At the present time, the pathogenesis of ovarian cancer remains poorly understood, with invasive diagnosis and ineffective treatment for women with the disease. Despite scientific and medical advances in oncology, the overall 5-year survival rate of 30% for ovarian cancer patients has not changed in 20 years. An understanding of the angiogenic process as it occurs in ovarian cancer would not only increase our knowledge of the pathogenesis of this cancer but also might offer novel opportunities for therapeutic intervention. PURPOSE: Our aim was to study the expression of messenger RNA (mRNA) coding for four putative angiogenic factors in normal ovaries and benign and malignant ovarian tumors: platelet-derived endothelial cell growth factor (thymidine phosphorylase), vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor-beta 1. METHODS: Four normal ovaries and 25 tumors (seven benign, one of borderline malignancy, and 17 malignant) were collected from 29 patients during elective oophorectomy. The site of sampling (areas of high-velocity blood flow) was directed by transvaginal color Doppler imaging performed within 24 hours of the surgery. Increased blood flow within the tissues was demonstrated by the presence of color (i.e., the velocity was > 7 cm/s) and, together with a pulsatile index of less than 1.0, constituted a positive scanning result. In scan-positive tissues, the area of maximum blood flow was chosen. In scan-negative tissues, a solid area was chosen in complex lesions, or the cyst wall was chosen in simple lesions. Ovarian RNA was subsequently extracted from areas of high-velocity flow (i.e., tissues with a positive scanning result) or from solid areas or septa in tissues with a negative scanning result. A ribonuclease protection assay was used to assess the expression of mRNA coding for the four angiogenic factors. RESULTS: Two normal ovaries (containing a corpus luteum) and one benign and 17 malignant tumors (plus the borderline) gave a positive scanning result. There was a significant difference between the expression of mRNA for platelet-derived endothelial cell growth factor between scan-positive and scan-negative tissues (P < .001) and between benign and malignant tumors (P < .001). CONCLUSIONS: Areas of high blood velocity in ovarian tumors are associated with increased expression of platelet-derived endothelial cell growth factor. IMPLICATIONS: Drugs that affect the angiogenic activity of platelet-derived endothelial cell growth factor offer a potential route for therapeutic intervention.

Autoradiography↗

Host fidelity is an effective premating barrier between sympatric races of the apple maggot fly.

Models of sympatric speciation for phytophagous insects posit a central role for host plant-associated mating as a premating isolating mechanism in lieu of geographic barriers to gene flow. Here, by means of three mark-and-recapture studies, we confirm that host fidelity (i.e., the tendency of an insect to reproduce on the same host species that it used in earlier life-history stages) restricts gene flow between sympatric apple- and hawthorn-infesting races of Rhagoletis pomonella (Diptera: Tephritidae) to approximately 6% per generation. Genetically based differences in host preference, adult eclosion under the "correct" host species, and allochronic isolation contribute to host fidelity in various degrees in the races. The results verify that host-associated adaptation can produce reproductive isolation as a correlated character (a key premise of sympatric speciation). The study also represents one of the few or perhaps only example in animals where the intra-specific isolating effects of specific phenotypes have been quantified in nature.

Journal Article↗

Gene targeting constructs: effects of vector topology on co-expression efficiency of positive and negative selectable marker genes.

Targeting of DNA into specific chromosomal loci often involves the use of a negative selectable marker gene to enrich for cell clones that have undergone homologous recombination. In this study we asked if the arrangement of the positive and negative markers in 'knockout' constructs can influence the expression of a lacZ gene that was used as a negative marker. We show that constructs which differ only in their topology have vastly different co-expression efficiencies. The site of DNA linearization was critical. While linearizing at the 5'-end of the lacZ gene was compatible with efficient lacZ expression, linearizing at the 3'-end was always detrimental. We also demonstrate that the topology of the template was more important than the promoter used to drive lacZ expression.

Animals↗

The potential role of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer.

We have assessed the potential role of a test based upon the measurement of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer. A sample of peripheral blood was taken from 1502 self-referred, asymptomatic women whose pedigree showed that at least one close relative had developed the disease. All women in the study underwent one screening by transvaginal ultrasonography (consisting of one or more scans) to detect any persistent lesion and a change in ovarian volume. Women with a positive result were referred for surgery. The concentration of serum CA 125 was measured in all samples at the end of the study. Seven ovarian cancers (4 invasive and 3 of borderline malignancy; 5 FIGO stage Ia, 1 stage IIa, 1 stage III) and 55 benign lesions were detected. We calculated the effect that a prescreening test (based on different threshold values for serum CA 125) would have had on the number of women entering the ultrasound-based screening program, and on the detection rate and false-positive rate of the overall procedure. There was a direct relationship between the number of women referred for ultrasound screening and the detection rate. The use of a threshold value for serum CA 125 > or = 20 U/ml would have meant that 380 women (25.3%) were referred for ultrasonography and 5 out of 7 cancers (71%) would have been detected with a false-positive rate of 1.1%. The odds of a woman with a positive screening result having cancer at surgery would have been about 1:3 (which would improve to about 1:1 if observational indices of color Doppler imaging and a morphological score had been used throughout). We concluded that a prescreening immunochemical test based on the measurement of serum CA 125 (with a threshold value of > or = 20 U/ml) would increase the prior odds for familial ovarian cancer by 2.8, but would lower the overall detection rate by 29% at the prevalence screening.

Adolescent↗

Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5'-noncoding region.

The 40-S subunit of eukaryotic ribosomes binds to the capped 5'-end of mRNA and scans for the first AUG in a favorable sequence context to initiate translation. Most eukaryotic mRNAs therefore have a short 5'-untranslated region (5'-UTR) and no AUGs upstream of the translational start site; features that seem to assure efficient translation. However, approximately 5-10% of all eukaryotic mRNAs, particularly those encoding for regulatory proteins, have complex leader sequences that seem to compromise translational initiation. The retinoic-acid-receptor-beta 2 (RAR beta 2) mRNA is such a transcript with a long (461 nucleotides) 5'-UTR that contains five, partially overlapping, upstream open reading frames (uORFs) that precede the major ORF. We have begun to investigate the function of this complex 5'-UTR in transgenic mice, by introducing mutations in the start/stop codons of the uORFs in RAR beta 2-lacZ reporter constructs. When we compared the expression patterns of mutant and wild-type constructs we found that these mutations affected expression of the downstream RAR beta 2-ORF, resulting in an altered regulation of RAR beta 2-lacZ expression in heart and brain. Other tissues were unaffected. RNA analysis of adult tissues demonstrated that the uORFs act at the level of translation; adult brains and hearts of transgenic mice carrying a construct with either the wild-type or a mutant UTR, had the same levels of mRNA, but only the mutant produced protein. Our study outlines an unexpected role for uORFs: control of tissue-specific and developmentally regulated gene expression.

Amino Acid Sequence↗

The epidemiology of Lyme disease in Delaware 1989-1992.

OBJECTIVES: The study was conducted to describe the temporal, geographic, demographic and treatment characteristics of Lyme disease in Delaware and to assist health planners in developing and implementing control strategies. METHODS: All physician-submitted Centers for Disease Control and Prevention (CDC) follow-up Lyme disease report forms from 1989 through 1992 were reviewed for completeness. Data were gathered from completed forms only. All cases were classified according to the 1990 CDC surveillance case definition. Cases were further subdivided into two groups. Antibiotic usage patterns were then identified for each group. Data on the percentage of infected ticks by county were obtained from a 1988 study conducted by the University of Delaware; Delaware Health and Social Services, Division of Public Health; and the Department of Natural Resources and Environmental Control. RESULTS: Reported cases of Lyme disease increased 246 percent between 1989 and 1992. The 1992 statewide incidence rate was 12.6 cases per 100,000 population. Whites were four times more likely to contract Lyme disease than were blacks. The majority of cases were reported between June and October. The number of patients being treated with oral antibiotics for localized disease for three weeks or longer increased from 52 percent in 1991 to 94 percent in 1992. Ixodid ticks infected with Borrelia burgdorferi were found in all three counties. CONCLUSION: The Delaware State Board of Health made Lyme disease reportable in September 1989. This requirement increased the quality of Lyme disease surveillance; however, the disease is probably under-reported since Delaware does not actively solicit Lyme disease reports. Delaware's case data reflect national data which indicate an increase in reported cases. A trend toward longer duration of treatment for localized Lyme disease is evident.

Adolescent↗

Whole chromosome 17 loss in ovarian cancer.

Chromosomal deletions, associated with the loss of normal function of tumour suppressor genes, have been identified in a variety of both familial and sporadic human cancers. Although the molecular pathology of ovarian cancer is not understood, several studies have reported deletions in chromosome 17 in ovarian tumours. We have used 13 restriction site polymorphic, microsatellite, and variable number tandem repeat markers to make a detailed analysis of chromosome 17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11 malignant tumours were informative for at least one marker on each arm of the chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all informative markers) in 5 malignant tumours from four women (three with the disease at FIGO stage Ia). In a further bilateral ovarian tumour a partial LOH affecting 17q22-q25 was present in one ovary only. By contrast to a number of previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2 (17q12-22) amplification. The data presented show that the loss of a whole copy of chromosome 17 is a frequent and relatively early event in the development of some ovarian cancers. This suggests the possible involvement of multiple chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is that the loss of a whole chromosome copy could be the product of chromosomal instabilities induced by loss of the normal allele of tumour suppressors, such as TP53, located on this chromosome.

Adenofibroma↗

Tetanus toxin light chain expression in Sertoli cells of transgenic mice causes alterations of the actin cytoskeleton and disrupts spermatogenesis.

Tetanus toxin is a powerful neurotoxin known to inhibit neurotransmitter release. The tetanus toxin light chain is a metalloprotease that cleaves some members of the synaptobrevin gene family with high specificity. Here, we report the expression of a synthetic gene encoding the tetanus toxin light chain in the seminiferous epithelium of transgenic mice. Spermatogenesis was severely impaired and mature spermatozoa were completely absent. Late spermatids exhibited pleomorphic shapes and acrosomal distortions. The number of Leydig cells was greatly increased. In situ hybridization analysis revealed that the toxin acts on Sertoli cells. Affected cells exhibited an aberrant distribution of actin filaments and many cells contained large vacuoles. Our results demonstrate that tetanus toxin is active in non-neuronal cells and suggest an important function for members of the synaptobrevin gene family during the late stages of spermatogenesis.

Actins↗

Physical fitness, age, and injury incidence in infantry soldiers.

Injuries are a common occurrence in young, active civilian and military populations. This study examined injury incidence and the association of musculoskeletal injuries with age and physical fitness in soldiers. Subjects were a cohort of 298 male soldiers assigned to an infantry battalion in Alaska. The soldiers' ages were obtained from the battalion records and their physical fitness was assessed from 2-mile run times, sit-ups, and push-ups. Injuries were documented from a retrospective review of the soldiers' medical records for a 6-month period (October to March) before the fitness testing. Fifty-one percent of the soldiers suffered one or more injuries. The most common injury diagnosis was musculoskeletal pain, followed by strains, sprains, and cold-related injuries. Soldiers experienced a total of 212 separate injuries, which resulted in 1764 days of limited duty. The crude annualized injury rate was 142 injuries per 100 soldiers (one soldier could experience more than one type of injury). The proportion of soldiers injured decreased as age increased. Slower 2-mile run times and fewer sit-ups were associated with a higher incidence of musculoskeletal injuries. This study documents the injury incidence in infantry soldiers and identifies younger age and low physical fitness as potential risk factors for these injuries.

Accidents, Occupational↗