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Biomedical subjects

M A Rogers

Publications and source records attributed to M A Rogers.

At least 19 recordsLinked to original sources
PubMed1996

The region coding for the helix termination motif and the adjacent intron 6 of the human type I hair keratin gene hHa2 contains three natural, closely spaced polymorphic sites.

Mutations in distinct sites of epidermal keratins, in particular in the helix initiation and termination regions, cause human genodermatoses due to faulty intermediate filament formation. Extension of this observation to human hereditary hair and nail diseases includes population analyses of human hair keratin genes for natural sequence variations in the corresponding sites. Here we report on a large-scale genotyping of the short helix termination region (HTR) of the human type I cortical hair keratins hHa1, a3-I, and a3-II, and the cuticular hair keratin hHa2. We describe two polymorphic loci, P1 and P2, exclusively in the cuticular hHa2 gene, both creating dimorphic protein variants. P1 is due to a C to T mutation in a CpG element leading to a threonine to methionine substitution; P2 concerns a serine codon AGT that also occurs as an asparagine coding variant AAC. A third polymorphism, P3, is linked with a C to T point mutation located at the very beginning of intron 6. The three polymorphic sites are clustered in a 39-nucleotide sequence of the hHa2 gene. Both allelic frequency calculations in individuals of different races and pedigree studies indicate that the two-allelic hHa2 variants resulting from P1 and P2 occur ubiquitously in a ratio of about 1:1 (P1) and 2:1 (P2) respectively in our survey, and are clearly inherited as Mendelian traits. A genotype carrying both mutations simultaneously on one allele could not be detected in our sampling, and there was no association of a distinct allelic hHa2 variant with the known ethnic form variations of hairs. Sequence comparisons of the HTR of hHa2 with those of other type I hair keratins including the hHa2-ortholog from chimpanzee provide evidence that the P1- and P2-linked mutations must have occurred very early in human evolution and that the two P2-associated codon variants may be the result of two independent point mutations in an ancestral AGC serine codon. These data describe natural polymorphisms in the HTR of a member of the keratin multigene family.

Alleles↗
PubMed1996

The fibrinolytic system is not impaired in older men with hypertension.

The fibrinolytic system is thought to be impaired in older hypertensive adults, thus contributing to the elevated risk of atherothrombosis, stroke, and acute myocardial infarction in this population. However, studies that have examined the fibrinolytic system in hypertensive individuals have failed to control for the confounding effects of other metabolic risk factors, making it difficult for one to determine the independent effect of hypertension on the fibrinolytic system. The purpose of the present study was to test the hypothesis that the fibrinolytic system is not impaired in older sedentary hypertensive men when the confounding effects of cardiovascular disease, diabetes, and dyslipidemia are controlled. Plasma concentrations of tissue-type plasminogen activator antigen and activity as well as plasminogen activator inhibitor-1 antigen and activity were measured under resting conditions in 12 hypertensive (69.4 +/- 1.4 years) and 11 normotensive 65.2 +/- 1.3 years) older men. The hypertensive and normotensive subjects had similar anthropometric and metabolic characteristics. There were no significant differences between the hypertensive and normotensive men in tissue-type plasminogen antigen (7.3 +/- 0.5 versus 6.1 +/- 0.6 ng/mL) and activity (1.8 +/- 0.3 versus 1.7 +/- 0.2 IU/mL) or plasminogen activator inhibitor-1 antigen (14.1 +/- 2.3 versus 10.8 +/- 2.2 ng/mL) and activity (17.4 +/- 1.2 versus 17.5 +/- 1.8 arbitrary units [AU]/mL) levels. In addition, the molar concentration ratio of active tissue type plasminogen activator to active plasminogen activator inhibitor-1 did not differ between the hypertensive (1:9.7 +/- 2.3) mmol/L) and normotensive (1:10.5 +/- 2.2 mmol/L) subjects, indicative of no impairment in fibrinolytic potential in either group. These results support the hypothesis that hypertension does not directly result in impaired fibrinolytic function in older adults. Furthermore, our findings suggest that abnormalities in fibrinolytic function in older hypertensive men are likely due to the primary effects of other metabolic disorders that usually accompany hypertension, such as hyperinsulinemia and dyslipidemia.

Aged↗
PubMed1995

ET-18-OCH3 inhibits nuclear factor-kappa B activation by 12-O-tetradecanoylphorbol-13-acetate but not by tumor necrosis factor-alpha or interleukin 1 alpha.

1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is a synthetic diether phospholipid that is competitive with phosphatidylserine binding to the regulatory domain of protein kinase C (PKC). Our previous studies indicate that the selective inhibition of tumor cell growth by ET-18-OCH3 may be due to altered signal transduction mechanisms, including the inhibition of PKC. To further define the mechanism of action of ET-18-OCH3, we have used it to study the role of PKC in regulation of the transcription factor NF-kappa B, which is activated by diverse stimuli. In the 293.27.2 human kidney cell line, as in hematopoietic cells of all lineages, NF-kappa B is stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha). The response to either TNF-alpha or IL-1 alpha is synergistically enhanced by TPA. However, the regulatory mechanisms and signal transduction systems responsible for NF-kappa B activation in response to these different stimuli have not been determined in detail. We have used ET-18-OCH3 and auranofin, which inhibit PKC by different mechanisms, to assess the role of PKC in NF-kappa B activation. ET-18-OCH3 markedly inhibits TPA-induced NF-kappa B activation, as measured by HIV long terminal repeat-directed expression of beta-galactosidase. The IC50 for inhibition by ET-18-OCH3 is approximately 2 microM, a noncytotoxic concentration. Inhibition of TPA-induced NF-kappa B activation was dependent upon preincubation with ET-18-OCH3, and the drug was active at approximately 2 mol% of total cellular phospholipid. ET-18-OCH3 did not inhibit NF-kappa B activation by either TNF-alpha or IL-1 alpha, indicating that there are multiple distinct signal transduction pathways leading to activation of NF-kappa B. We have confirmed these results using auranofin, an antirheumatic drug that is a specific PKC inhibitor interacting with the catalytic domain. Like ET-18-OCH3, auranofin blocked NF-kappa B activation by TPA but not by TNF-alpha or IL-1 alpha. Also like the ether lipid, auranofin only partially blocked the synergy exhibited by TPA and TNF-alpha. To confirm the role of NF-kappa B in this response, we measured NF-kappa B by electrophoretic mobility shift assay. Both ET-18-OCH3 and auranofin inhibited cellular induction of the active NF-kappa B complex in response to TPA but not in response to TNF-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1995

A cDNA encoding the human type I hair keratin hHal.

A full-length cDNA of a human type I hair keratin was isolated that encodes a protein of 416 amino acids. Northern blot analysis shows that the mRNA is present in human scalp but not in hairless skin. Based on sequence homology comparisons with the four known mouse type I hair keratins mHal-4 the keratin could be identified as the human hair keratin hHal.

Amino Acid Sequence↗
PubMed1995

Sequence data and chromosomal localization of human type I and type II hair keratin genes.

A cDNA library constructed with poly(A)+ RNA from human scalp was screened with selected fragments of both murine type I and type II hair keratin cDNAs. Two keratin clones, one type I, phKI-2, and one type II, phKII-1, were isolated and sequenced. In Northern blots, cDNA probes containing the 3'-noncoding sequences of the clones specifically hybridized to scalp mRNA species. Based on sequence homology comparisons with the four known murine type I hair keratins mHa1-4, the phKI-2 encoded keratin could be identified as human hair keratin hHa2. Similarly, sequence comparison with the four type II sheep wool keratins K2.9-12 revealed an orthologous relationship between the largest member of the type II wool keratin subfamily, K2.9 (i.e., sHb1) and the phKII-1 encoded human hair keratin (hHb1). The specific 3'-noncoding sequences of hHa2 and hHb1 were also used to isolate genomic fragments for both keratins from human genomic libraries which were than used for fluorescence in situ hybridization to human metaphase chromosomes. The hHa2 gene could be mapped to the long arm of chromosome 17, whereas the hHb1 gene was found on the long arm of chromosome 12. DAPI banding of the chromosomes allowed sublocalization of the hHa2 gene to 17q12-q21 and the hHb1 gene to 12q13, i.e., gene loci that have also been previously determined for human type I and type II epithelial keratins.

Amino Acid Sequence↗
PubMed1995

Effects of strength training on muscle hypertrophy and muscle cell disruption in older men.

To determine whether a total body, heavy resistance, strength training (ST) program can significantly increase muscle strength and hypertrophy without muscle cell disruption and soreness in older men, 35 sedentary male subjects between the ages of 50 and 69 years of age (60 +/- 5, mean +/- SD) were studied. Twelve served as inactive controls. Muscular strength, cross-sectional muscle area, serum creatine kinase (CK) activity and perceived soreness were assessed before and after a 16 wk heavy resistance ST program. The ST program resulted in a 43% increase in muscular strength (p < 0.001), and a 7.2% increase in midthigh muscle area (153 +/- 24 vs 164 +/- 23 cm2, p < 0.001). There were no significant changes in strength or muscle area in the inactive control group. Peak serum CK levels were approximately twofold above baseline (278 +/- 175 vs 133 +/- 88 U/l, p < 0.01) 8 h after the first regular training session. At the end of training, the peak rise in CK levels was also reached 8 h after exercise, but was reduced substantially at the same absolute (p < 0.01) and relative resistance loads (p < 0.01) compared to the first training session. Muscle soreness after exercise was only occasionally reported at the beginning of training and was almost nonexistent after training. These results indicate that middle-aged and older men can safely participate in a total body strength training program, intense enough to produce substantial increases in muscle strength and hypertrophy, without promoting muscle soreness or significant muscle cell disruption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Testosterone, growth hormone and IGF-I responses to acute and chronic resistive exercise in men aged 55-70 years.

We investigated the responses of serum testosterone (T) and human growth hormone (hGH) concentrations to a bout of heavy resistive exercise and the responses of T, hGH, and insulin-like growth factor I (IGF-I) to a 16 wk progressive resistive training program in 13 men (60 +/- 4 yrs). Body composition via hydrostatic weighing and muscle strength using a 3 repetition maximum (3RM) test on 6 variable resistance exercise machines were assessed before and after the training program. Fasting blood samples were drawn on 2 consecutive days prior to training and again on 2 consecutive days after the last day of exercise. Blood was also drawn immediately before and approximately 10 min after a single exercise session during the first wk of training, and after an exercise session of the same relative resistance during the last wk of training. The training program resulted in a 37% increase in upper body strength and a 39% increase in lower body strength (both p < 0.01). Lean body mass increased significantly (61.8 +/- 2.1 vs 63.7 +/- 7.8 kg; p < 0.001) while % fat decreased (26.5 +/- 1.5 vs 24.9 +/- 6.0%; p < 0.01) as a result of training. Serum T concentration was unchanged, but GH increased approximately 18-fold in response to a single bout of resistive exercise before (0.24 +/- 0.08 vs 4.60 +/- 1.35 mg/l) and after (0.26 +/- 0.06 vs 4.66 +/- 1.46 mg/l; p < 0.01) training. Baseline serum concentrations of T, hGH, and IGF-I were unaffected by the training program. We conclude that an acute bout of resistive exercise causes a substantial hGH response in older men, but 16 wks of progressive resistive training does not affect baseline concentrations of the anabolic hormones.

Aged↗
PubMed1995

Indicators of poor dietary habits in a high risk population.

OBJECTIVE: This study was conducted to determine whether individuals attending an urban outpatient clinic met the National Health Promotion and Disease Prevention nutritional objectives and to assess factors associated with poor dietary habits. METHODS: Individuals who attended the general medicine outpatient clinic at the State University of New York Health Science Center in Syracuse were interviewed using an expanded version of the Health Habits and History Questionnaire. Usual dietary intake, medical history, occupation, stress, physical activity, tobacco use and other life-style factors were recorded. Of particular interest were the percentage of calories from fat in the diet and whether individuals consumed the daily requirements of the base-foods in the USDA Pyramid (grains, vegetables and fruits). Unconditional logistic regression was used to determine odds ratios (OR) and 95% confidence intervals for variables associated with high fat consumption and low consumption of vegetables, fruit and high-fiber grains. RESULTS: None of the patients met the minimal recommended daily servings for the three base-food categories combined (grains, vegetables and fruits) and 84% of subjects had fat intakes which constituted over 30% of daily energy intake. Individuals with less education, who were disabled or unemployed, and who participated in little physical activity were twice as likely to have poor dietary habits (i.e. low consumption of vegetables, fruit, and/or high-fiber grains) as other subjects (p < 0.05). Younger patients (20-49 years of age), especially those who were nonsmokers and who reported little physical activity were more likely to consume fat and less likely to consume fruit than older patients (> or = 50 years of age). Nonwhite subjects were less likely to consume high-fiber grains and whole-wheat breads than white patients (p = 0.04). CONCLUSIONS: Nutritional screening should be considered for all patients attending similar inner-city general medicine clinics, regardless of the primary diagnosis in order to provide early dietary intervention. In particular, young adults, the unemployed, and the disabled should not be overlooked.

Adult↗
PubMed1994

Estrogen receptor expression of benign breast epithelium and its association with breast cancer.

We conducted a case-control study of estrogen receptor (ER) and progesterone receptor (PgR) expression in benign breast epithelium from 120 women (51 breast cancer cases and 69 benign disease controls) who underwent breast operations at University Hospital, Syracuse, New York. Benign samples were obtained and processed immunohistochemically for ER and PgR (Abbott, Chicago, IL). Receptor positivity was defined as any nuclear immunostaining. Proportionately more cases than controls were ER positive (84% versus 57%); PgR positivity was similar in cases and controls (86%). Logistic regression yielded an adjusted odds ratio of 6.5 for breast cancer among ER-positive women (95% confidence interval of 1.5 and 27.4); odds ratio of PgR positivity was 0.3 (95% confidence interval of 0.1 and 1.9). Adjustment for known risk factors for breast cancer did not change the odds ratio. ER-positive breast epithelium needs evaluation as a possible risk marker for breast cancer.

Adult↗
PubMed1994

Nystagmus and joint position sensation: their importance in posterior occipitocervical fusion in rheumatoid arthritis.

It is widely believed that brain stem dysfunction and cranial nerve palsies in patients with rheumatoid arthritis (RA) are common and related to the vertical translocation of the odontoid process. In our database of 235 patients with seropositive RA and craniocervical junction involvement, we have found a very low incidence of such problems. Long tract signs were common, but loss of proprioception (joint position sensation) as the sole neurologic deficit was rare. Nystagmus was found to be associated with the tonsillar herniation of a Chiari 1 malformation and loss of joint position sensation with severe compression of the posterior aspect of the spinal cord at the craniocervical junction. The implications for posterior occipitocervical fusion, particularly by sublaminar wiring, are discussed.

Adolescent↗
PubMed1994

Enhanced left ventricular performance in endurance trained older men.

BACKGROUND: The age-associated decline in aerobic exercise capacity is partially reversible by endurance exercise training. Moderate-intensity endurance exercise training increases aerobic exercise capacity mediated, in part, by improvement of stroke volume and left ventricular performance in older men. The present study was designed to characterize the nature of cardiovascular adaptations to strenuous endurance exercise of long duration and to delineate the mechanisms underlying increased stroke volume and cardiac output in highly trained older endurance athletes. METHODS AND RESULTS: Nine male master athletes (MA: 64 +/- 2 years old, mean +/- SEM) and 9 older sedentary healthy men (controls: 63 +/- 1 year) were studied. Left ventricular systolic function was evaluated with the use of cardiac blood pool imaging and echocardiography. Maximal O2 uptake (VO2max) was 50.4 +/- 1.7 mL.kg-1 x min-1 in the MA and 29.6 +/- 1.4 mL.kg-1 x min-1 (P = .0001) in controls. Systolic and mean blood pressures at rest and during exercise were not different in the two groups. Left ventricular systolic function at peak exercise was higher in the MA than in sedentary controls as evidenced by (1) a higher left ventricular functional reserve (delta EF: 12.4 +/- 2 versus 5.6 +/- 2.5, P = .05), (2) a large decrease in end-systolic volume during exercise (MA: 56 +/- 4 mL at rest and 42 +/- 5 mL at peak exercise, P = .007; controls: 43 +/- 2 mL at rest and 42 +/- 6 mL at peak exercise, P = .35) with no differences in systolic blood pressure, (3) a higher left ventricular fractional shortening at peak exercise (MA: 52 +/- 2.6%; controls: 45 +/- 1%, P = .046) at comparable values for end-systolic wall stress (MA: 56 +/- 12 g/cm2; controls: 53 +/- 7 g/cm2, P = .50), and (4) a greater decrease in end-systolic diameter at peak exercise in the MA than in controls (MA: -1.2 +/- 0.16 cm versus -0.57 +/- 0.13 cm, P = .014) despite no significant differences between the changes in end-systolic wall stress during exercise (MA: -15.5 +/- 7.5 g/cm2, controls: -11.0 +/- 9.0 g/cm2, P = .6). MA had a larger end-diastolic volume at rest (153 +/- 6 versus 132 +/- 4 mL, P = .009) with a normal wall thickness-to-radius ratio (0.34 +/- 0.02). Peak exercise stroke volume was higher (P = .023) in the MA (132 +/- 6 mL/min) than in the sedentary controls (111 +/- 6 mL/min). Changes in stroke volume correlated strongly with changes in ejection fraction in the MA (r = .80, P = .010) but not in sedentary controls (r = .59, P = .097). Further, changes in stroke volume from rest to exercise correlated strongly with changes in end-diastolic volume in both MA (r = .78, P = .013) and sedentary controls (r = .73, P = .026), suggestive of reliance of stroke volume on end-diastolic volume and preload. However, for a given increase in end-diastolic volume, the rise in stroke volume during exercise was significantly larger in the MA than in controls, which, in the absence of differences in mean blood pressures, indicates that enhanced left ventricular systolic function independent of preload plays an additional role in maintaining a higher stroke volume at peak exercise in the highly trained older men. CONCLUSIONS: Cardiac adaptations in older endurance trained men are characterized by volume-overload left ventricular hypertrophy and enhancement of left ventricular systolic performance at peak exercise. These adaptive responses contribute to enhanced stroke volume at peak exercise in older endurance trained men.

Aging↗
PubMed1994

Adherence to exercise programmes. Recommendations.

Despite the widespread dissemination of information concerning the negative health consequences associated with sedentary living, adult physical activity in many industrialised nations remains well below recommended levels. Approximately 50% of individuals who start an aerobic exercise programme will stop within the first 6 months, even though it is well known that to obtain the health benefits associated with physical activity, participation must be maintained. Programmes involving the use of behaviour management techniques appear to increase short term adherence to exercise. Recently, an adherence rate of greater than 95% over 6 months was achieved in a large group of university employees who participated in aerobic training using a 'behavioural treatment packages' approach. Unfortunately, inconsistencies in the literature on definitions and measurement of adherence make valid comparisons among studies difficult. Also, long term follow-up of behavioural intervention methods and their effect on exercise adherence is generally lacking. It is likely that strategies to increase physical activity participation in the general population will demand multiple levels of intervention (personal, organisational, environmental and societal) if they are to succeed in the long term.

Attitude to Health↗
PubMed1994

Surgical treatment of the symptomatic herniated thoracic disk.

Symptomatic herniated thoracic disks are rare, for their incidence is calculated at about one in 1,000,000 persons per year. Although these are usually associated with degenerative disease, there are a number of other conditions in which thoracic disk herniation is now recognized as being an uncommon but important feature. Increased use of noninvasive scanning techniques, together with greater clinical awareness, is likely to disclose more cases of herniated disks. Surgical treatment of these herniated disks has undergone extensive modification during the past 50 years. Microsurgical approaches applied to the spine are major contributors to reduced neurologic morbidity. The authors prefer to use the transthoracic approach for surgery. High, low, and far lateral approaches are also discussed, however, as are other surgical approaches used in the mid to low region. Treatment of this difficult diagnostic and management problem is ideally managed by a team of medical professionals which includes highly specialized surgeons.

Humans↗
PubMed1993

Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise.

Plasma free fatty acid (FFA) levels tend to be lower and the plasma lipolytic hormone response to prolonged exercise of the same intensity is blunted after endurance exercise training. To determine whether training elicits a corresponding decrease in plasma FFA turnover and metabolism during prolonged exercise, we measured plasma [1-13C]palmitate kinetics and oxidation and respiratory gas exchange in 13 subjects during the latter portion of a 90- to 120-min bout of cycle ergometer work performed before and after 12 wk of alternate-day cycling and running. Training increased total fat oxidation during prolonged exercise by 41% (P < 0.005). However, for the final 30-60 min of the cycle ergometer protocol, the rate of 13CO2 production from [1-13C]palmitate oxidation was 27% lower (P < 0.05), the rate of palmitate turnover was 33% less (P < 0.05), and plasma FFA and glycerol concentrations were 32 and 20% lower (P < 0.05), respectively, than in the untrained state. Thus endurance exercise training results in decreased plasma FFA turnover and oxidation during a 90- to 120-min bout of submaximal exercise because of a slower rate of FFA release from adipose tissue.

Adult↗
PubMed1993

Changes in skeletal muscle with aging: effects of exercise training.

There is an approximate 30% decline in muscle strength and a 40% reduction in muscle area between the second and seventh decades of life. Thus, the loss of muscle mass with aging appears to be the major factor in the age-related loss of muscle strength. The loss of muscle mass is partially due to a significant decline in the numbers of both Type I and Type II muscle fibers plus a decrease in the size of the muscle cells, with the Type II fibers showing a preferential atrophy. There appears to be no loss of glycolytic capacity in senescent skeletal muscle whereas muscle oxidative enzyme activity and muscle capillarization decrease by about 25%. Vigorous endurance exercise training in older people, where the stimulus is progressively increased, elicits a proliferation of muscle capillaries, an increase in oxidative enzyme activity, and a significant improvement in VO2max. Likewise, progressive resistive training in older individuals results in muscle hypertrophy and increased strength, if the training stimulus is of a sufficient intensity and duration. Since older individuals adapt to resistive and endurance exercise training in a similar fashion to young people, the decline in the muscle's metabolic and force-producing capacity can no longer be considered as an inevitable consequence of the aging process. Rather, the adaptations in aging skeletal muscle to exercise training may prevent sarcopenia, enhance the ease of carrying out the activities of daily living, and exert a beneficial effect on such age-associated diseases as Type II diabetes, coronary artery disease, hypertension, osteoporosis, and obesity.

Adult↗
PubMed1992

Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women.

To examine the effects of aging on human skeletal muscle, 10 men and 10 women, 64 +/- 1 yr old (Mean +/- SE), and 10 men and 10 women, 24 +/- 1 yr old, were studied. All subjects were sedentary nonsmokers who were carefully screened for latent cardiovascular, metabolic, or musculoskeletal disease. Needle biopsy samples were obtained from the lateral gastrocnemius muscle and examined using histochemical and biochemical techniques. The percentage of Type I, Type IIa, and Type IIb fibers did not differ with age. However, Type I fibers occupied a larger percent of total muscle area in the older men and women (60.6 +/- 2.6 vs 53.6 +/- 2.0%; p less than .05), because Type IIa and Type IIb fibers were 13-31% smaller (p less than .001) in these subjects. Muscle capillarization and mitochondrial enzyme (i.e., succinate dehydrogenase, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase) activities were also approximately 25% lower (p less than .001-.05) in the old subjects. Although it is difficult to determine whether these differences are due to aging itself or are simply due to inactivity, these structural and biochemical changes probably contribute to the decreases in muscle mass, strength, and endurance often observed in healthy but sedentary older men and women.

Adult↗