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Biomedical subjects

D E Anderson

Publications and source records attributed to D E Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22.

Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma.

Adolescent↗
PubMed1992

Familial versus sporadic breast cancer.

BACKGROUND: Studies comparing patients with familial and sporadic breast cancer have indicated that a family history of the disease can increase a woman's risk for having the disease twofold to threefold and that patients with familial breast cancer have a younger age at diagnosis and have a higher frequency of bilateral disease than those with sporadic breast cancer. Also, at least four types of breast cancers have been shown to be inherited. These findings led to the hypothesis that familial and sporadic breast cancer are the consequence of two biologically distinct mechanisms. METHODS: A two-step mutation model proposed by Knudson in 1971 provides a link between the molecular mechanisms underlying familial and sporadic breast cancer. According to this model, both cancers involve the same genomic change in homologous chromosomes. The only difference is that the first mutation is inherited and the second is somatic in familial cancer, whereas in sporadic cancer both mutations are somatic. Mutation is used in a broad sense and refers to either a point mutation at a specific locus or the loss of a locus by deletion or nondysfunction. RESULTS: This model has been shown to apply to several childhood and adult cancers, including breast cancer. Based on this model, patients with familial breast cancer will have their disease earlier in life and will have more bilateral cancer than patients with sporadic breast cancer. Moreover, the two types of patients should show no differences in clinicopathologic characteristics because both types involve the same genomic change and the pathogenesis of both types should be the same, thus arguing against the early hypothesis that patients with familial and sporadic breast cancer are the consequence of biologically distinct mechanisms. CONCLUSIONS: Breast cancer appears to involve the cumulative effect of several genetic lesions involving the activation of oncogenes and the inactivation of tumor-suppressor genes. Which genes are involved specifically as causative factors of breast cancer (the inherited gene or genes) and which are important somatically in its continued development and progression (oncogenes and tumor-suppressor genes) requires additional study.

Adult↗
PubMed1992

Breast cancer risks in relatives of male breast cancer patients.

BACKGROUND: Previous studies have provided conflicting results concerning the familial effect of male breast cancer on breast cancer risks in female relatives. PURPOSE: We studied breast cancer risks in first-degree relatives of male patients and compared them with relatives of female patients. METHODS: Our study included 88 consecutively ascertained male patients and 320 of their first-degree relatives as well as 186 consecutively ascertained female patients and 633 of their first-degree relatives. Observed numbers of breast cancers in relatives were compared with the expected number derived from the Connecticut Tumor Registry. Multiple logistic regression analysis was also performed. RESULTS: Relatives of male patients exhibited a significant twofold increased risk when compared with expected rates and no difference in risk when compared with that of relatives of female patients. Prostate cancer in the family of a male patient resulted in a significant fourfold increased breast cancer risk compared with a risk of 1.4 in families with no history of prostate cancer. A family history of lung cancer, colon cancer, or melanoma had no effect on increasing risks of breast cancer. CONCLUSION: The familial effect of male breast cancer is the same as that of female breast cancer. IMPLICATIONS: Any estimates of breast cancer risk provided to individuals should also consider the occurrence of prostate cancer in the family, since prostate cancer appears capable of at least doubling the underlying twofold risk.

Age Factors↗
PubMed1992

Social and behavioral factors associated with episodes of inhibitory breathing.

Previous research has shown that episodes of inhibitory breathing, characterized by low-frequency breathing, occur both in laboratory animals during intervals preceding avoidance tasks and in humans in the natural environment. The present study investigated social and behavioral factors accompanying episodes of inhibitory breathing that occur in the natural environment. Breathing frequency and tidal volume of ambulatory subjects were monitored via inductive plethysmography. Information concerning location, social environment, behavior, and mood was self-recorded in a computerized diary. The percentage of episodes of inhibitory breathing was found to be significantly greater in social situations than when subjects were alone. Additional analyses eliminated talking as an explanation for these effects. Inhibitory breathing was more frequent when subjects were sedentary rather than active, and inhibitory breathing was not associated with changes in mood or appraisal. Additional research is needed to determine the nature of the social interactions that elicit inhibitory breathing, its physiological concomitants, and its long-term health implications.

Adult↗
PubMed1992

Reliability of the serial sampling technique for determination of gastric emptying.

The purpose of this study was to determine if gastric emptying data obtained in one trial (using the intubation and aspiration method) is representative of that obtained in subsequent trials or on repeated days. Nine healthy adults consumed a volume of water (5.5 ml/kg body weight) which contained a nonabsorbable marker. Following a fifteen-minute rest period, the stomach contents were aspirated using a 50 ml syringe. This procedure was repeated three additional times on the same day with a fifteen minute interval separating each trial. On two other days the identical procedures were performed. A significant daily variation was found for residue volume, gastric secretion, and percent of original drink emptied. However, no significant difference between trials within a day was found for the residue volume, gastric secretion, and percent of original drink emptied. Generalizability coefficients, which are "reliability-like" coefficients, were also calculated. These coefficients indicate that a combination of at least 2 days with at least 2 trials/day should be used in order to obtain reliable gastric emptying data.

Adult↗
PubMed1992

Ambulatory monitoring of respiration: inhibitory breathing in the natural environment.

Because previous work found that sustained inhibitory breathing (i.e., low frequency breathing without increased tidal volume) can occur in laboratory animals under conditions of behavioral stress, this study sought to determine whether a comparable respiratory pattern could be observed in ambulatory human subjects in their natural environments. Tidal volume, breathing frequency, and minute ventilation were monitored continuously during 24-hour sessions via inductive plethysmography and a portable microprocessor. Mean tidal volume and minute ventilation were significantly higher during the daytime than at night for all subjects. However, mean breathing frequency was not consistently higher during the daytime, because episodes of low frequency breathing offset episodes of high breathing frequency. Tidal volume during low frequency breathing was comparable to that observed during medium or high frequency breathing. Thus, low frequency breathing was indicative of low minute ventilation. The eliciting stimuli, physiological concomitants, and relevance to health of this energetically inefficient breathing pattern remain to be determined.

Adult↗
PubMed1992

The effects of a carbonated carbohydrate drink on gastric emptying, gastrointestinal distress, and exercise performance.

To determine the effect of a carbonated carbohydrate (CHO) drink on gastric function and exercise performance, eight male cyclists completed four 120-min bouts of cycling. Each bout consisted of a 105-min ride at 70% VO2max followed by a 15-min self-paced performance ride. During each trial, one of four test solutions was ingested: carbonated CHO (C-10%), noncarbonated CHO (NC-10%), carbonated non-CHO (C), and noncarbonated non-CHO (NC). Following the performance ride, the subjects had their stomach contents removed by aspiration. There were no significant differences in gastric emptying (GE) except for Trial C-10%, which averaged 13.3% less than NC. However, there was no difference in the perception of gastrointestinal comfort between this trial and any other. Average power output during the performance ride was not significantly different between carbonated and noncarbonated trials, or between CHO-fed and no-CHO trials; however, the subjects worked at a greater intensity when fed CHO. Finally, acid base status did not change when a carbonated drink was ingested. This indicates that adding carbonation to a sport drink does not significantly alter gastric function, the perception of GI comfort, or exercise performance.

Adult↗
PubMed1992

Time course of glycogen accumulation after eccentric exercise.

This study examined the time course of glycogen accumulation in skeletal muscle depleted by concentric work and subsequently subjected to eccentric exercise. Eight men exercised to exhaustion on a cycle ergometer [70% of maximal O2 consumption (VO2max)] and were placed on a carbohydrate-restricted diet. Approximately 12 h later they exercised one leg to subjective failure by repeated eccentric action of the knee extensors against a resistance equal to 120% of their one-repetition maximum concentric knee extension force (ECC leg). The contralateral leg was not exercised and served as a control (CON leg). During the 72-h recovery period, subjects consumed 7 g carbohydrate.kg body wt-1.day-1. Moderate soreness was experienced in the ECC leg 24-72 h after eccentric exercise. Muscle biopsies from the vastus lateralis of the ECC and CON legs revealed similar glycogen levels immediately after eccentric exercise (40.2 +/- 5.2 and 47.6 +/- 6.4 mmol/kg wet wt, respectively; P greater than 0.05). There was no difference in the glycogen content of ECC and CON legs after 6 h of recovery (77.7 +/- 7.9 and 85.1 +/- 4.9 mmol/kg wet wt, respectively; P greater than 0.05), but 18 h later, the ECC leg contained 15% less glycogen than the CON leg (90.2 +/- 8.2 vs. 105.8 +/- 8.9 mmol/kg wet wt; P less than 0.05). After 72 h of recovery, this difference had increased to 24% (115.8 +/- 8.0 vs. 153.0 +/- 12.2 mmol/kg wet wt; P less than 0.05). These data confirm that glycogen accumulation is impaired in eccentrically exercised muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Improved cerebral blood flow and CO2 reactivity after microvascular anastomosis in patients at high risk for recurrent stroke.

The medical community has not yet identified cerebrovascular pathophysiological factors that distinguish patients at high risk for stroke or aid in selecting patients for microvascular cerebral bypass. In this study, we describe the courses of 13 patients, all of whom suffered recurrent episodes of transient cerebral ischemia after previous cerebral infarction. These patients underwent regional cerebral blood flow studies using xenon inhalation with a CO2 challenge before and at various times after extracerebral-to-intracerebral microvascular anastomosis. Collateral circulation was assessed in all patients before surgery using four-vessel cerebral angiography. Patients were followed for a mean of 30 months (range, 1-7 yr) after the anastomosis. Measurements of mean cortical cerebral blood flow, as measured using the initial Slope Index, and CO2 cerebrovascular reactivity of these 13 patients were compared with those in a group of 20 patients designed as controls. Hemispheric cortical blood flow was significantly depressed in these patients before surgery compared with those in the control group (P less than 0.05). After the bypass, the mean resting Initial Slope Index in these patients increased 14% (P = 0.0005). Cerebral blood flow both before and after CO2 inhalation improved significantly in these patients after surgery (P = 0.001). Detectors bordering computed tomographic or magnetic resonance image documented infarctions, identified as peri-infarct regions, and demonstrated significant mean increases in both cerebral blood flow (38.8-43.2 ml/min/100 g, P = 0.05) and CO2 cerebrovascular reactivity in these patients after bypass (1.71 + 1.91% to 4.00 + 2.38% change Initial Slope Index/mm Hg CO2, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Structural and thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme.

To determine the energetic and structural consequences of placing a charged group within the core of a protein, two "buried charge" mutants, Met 102----Lys (M102K) and Leu 133----Asp (L133D) were constructed in phage T4 lysozyme. Both proteins fold at neutral pH, although they are substantially less stable than wild type. The activity of M102K is about 35% that of wild type, while that of L133D is about 4%. M102K could be crystallized, and its structure was determined at high resolution. The crystal structure (at pH 6.8) of the mutant is very similar to that of wild type except for the alpha-helix that includes residues 108-113. In wild-type lysozyme, one side of this helix is exposed to solvent and the other contacts Met 102. In the M102K structure this alpha-helix becomes much more mobile, possibly allowing partial access of Lys 102 to solvent. The stability of M102K, determined by monitoring the unfolding of the protein with CD, is pH-dependent, consistent with the charged form of the substituted amino acid being more destabilizing than the uncharged form. The pKa of Lys 102 was estimated to be 6.5 both by differential titration and also by NMR analysis of isotopically labeled protein with 13C incorporated at the C epsilon position of all lysines. As the pH is lowered below pH 6.5, the overall three-dimensional structure of M102K at room temperature appears to be maintained to pH 3 or so, although there is evidence for some structural adjustment possibly allowing solvent accessibility to the protonated form of Lys 102.

Amino Acid Sequence↗
PubMed1991

Analysis of the interaction between charged side chains and the alpha-helix dipole using designed thermostable mutants of phage T4 lysozyme.

It was shown previously that the introduction of a negatively charged amino acid at the N-terminus of an alpha-helix could increase the thermostability of phage T4 lysozyme via an electrostatic interaction with the "helix dipole" [Nicholson, H., Becktel, W. J., & Matthews, B. W. (1988) Nature 336, 651-656]. The prior report focused on the two stabilizing substitutions Ser 38----Asp (S38D) and Asn 144----Asp (N144D). Two additional examples of stabilizing mutants, T109D and N116D, are presented here. Both show the pH-dependent increase in thermal stability expected for the interaction of an aspartic acid with an alpha-helix dipole. Control mutants were also constructed to further characterize the nature of the interaction with the alpha-helix dipole. High-resolution crystal structure analysis was used to determine the nature of the interaction of the substituted amino acids with the end of the alpha-helix in both the primary and the control mutants. Control mutant S38N has stability essentially the same as that of wild-type lysozyme but hydrogen bonding similar to that of the stabilizing mutant S38D. This confirms that it is the electrostatic interaction between Asp 38 and the helix dipole, rather than a change in hydrogen-bonding geometry, that gives enhanced stability. Structural and thermodynamic analysis of mutant T109N provide a similar control for the stabilizing replacement T109D. In the case of mutant N116D, there was concern that the enhanced stability might be due to a favorable salt-bridge interaction between the introduced aspartate and Arg 119, rather than an interaction with the alpha-helix dipole. The additivity of the stabilities of N116D and R119M seen in the double mutant N116D/R119M indicates that favorable interactions are largely independent of residue 119. As a further control, Asp 92, a presumed helix-stabilizing residue in wild-type lysozyme, was replaced with Asn. This decreased the stability of the protein in the manner expected for the loss of a favorable helix dipole interaction. In total, five mutations have been identified that increase the thermostability of T4 lysozyme and appear to do so by favorable interactions with alpha-helix dipoles. As measured by the pH dependence of stability, the strength of the electrostatic interaction between the charged groups studied here and the helix dipole ranges from 0.6 to 1.3 kcal/mol in 150 mM KCl. In the case of mutants S38D and N144H, NMR titration was used to measure the pKa's of Asp 38 and His 144 in the folded structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1991

Effects of drink carbonation on the gastric emptying characteristics of water and flavored water.

The intent of this study was to determine whether adding carbonation to either water or a low calorie sport drink would affect gastric emptying (GE). Fifteen subjects rode for 20 minutes on a cycle ergometer at 55% of max VO2. After 5 minutes of exercise, the subjects ingested 5.5 ml/kg body weight of a test solution: water (W), carbonated water (CW), and a low calorie sport drink in both a carbonated (C2C) and noncarbonated (2C) form. At the end of each ride, the stomach was emptied through gastric aspiration. The results indicate that carbonation has no effect on GE. However, the type of drink did have an effect on GE, as both 2C and C2C emptied from the stomach at a slower rate than either W or CW. Subjective ratings of gastrointestinal comfort were similar for both carbonated and noncarbonated forms, and at no time did the subjects report discomfort. The results were independent of the exercise challenge, as exercise intensity, heart rate, and ratings of perceived exertion did not differ between experimental trials. It is concluded that carbonation does not affect the GE characteristics of a drink taken during submaximal exercise, but the flavoring system of the low calorie beverage decreased the rate of GE by as much as 25% when compared to water.

Adult↗
PubMed1991

Association between solar radiation and ocular squamous cell carcinoma in cattle.

The association between ocular squamous cell tumors and various measures of solar radiation was evaluated for 2,775 contemporaneous Hereford cattle. The animals were from 34 herds located in 21 states in the United States and in one Canadian province. Examinations and photographs were made of the eyes of all cows and heifers in a herd; 33 herds were examined between June and August 1957 and 1 herd was examined in 1958. Solar radiation was measured by altitude and mean annual hours of sunshine applying to an individual herd, and global radiation, a cloudiness index, and elevation of nearby National Weather Service stations. All measures of solar radiation provided evidence of a significant association between increasing risks of developing cancer eye and increasing levels of radiation; adjustments were made for possible confounding effects of age and corneoscleral pigmentation. Associations were evident whether affliction was defined as the occurrence of any type of tumor (ie, plaque, papilloma, or carcinoma), or as the occurrence of only papilloma or carcinoma. Average ages of affected cattle also tended to be lower at high radiation levels than at low levels, further supporting the hypothesis that solar radiation has an important role in the development of this disease. In view of the heritability of eye pigmentation and its inhibitory effect on lesions, cancer eye may be controlled by selective breeding for increased pigmentation in and around the eye to afford protection against the harmful effects of incident UV radiation.

Age Factors↗
PubMed1991

Genomic changes on the short arm of human chromosome 1 in breast cancer.

A total of 38 DNA sample pairs from normal and cancerous breasts were specifically examined for alterations on the short arm of chromosome 1 using probe pYNZ2. Of the pairs, 24 (63%) displayed changes at this locus including amplifications, deletions, gene rearrangements, and altered band intensities between heterozygous alleles. Due to technical considerations, this number is likely to be a conservative estimate of the frequency of alterations in this region. When data using a different probe from the short arm of chromosome 1 was added, the overall involvement of this region increased to 73%. The combined data indicate we have localized a region, likely to be less than 85 cm in size, that is involved in the development of breast cancer.

Breast Neoplasms↗
PubMed1990

pH-induced denaturation of proteins: a single salt bridge contributes 3-5 kcal/mol to the free energy of folding of T4 lysozyme.

The energetics of a salt bridge formed between the side chains of aspartic acid 70 (Asp70) and histidine 31 (His31) of T4 lysozyme have been examined by nuclear magnetic resonance techniques. The pKa values of the residues in the native state are perturbed from their values in the unfolded protein such that His31 has a pKa value of 9.1 in the native state and 6.8 in the unfolded state at 10 degrees C in moderate salt. Similarly, the aspartate pKa is shifted to a value of about 0.5 in the native state from its value of 3.5-4.0 in the unfolded state. These shifts in pKa show that the salt bridge is stabilized 3-5 kcal/mol. This implies that the salt bridge stabilizes the native state by 3-5 kcal/mol as compared to the unfolded state. This is reflected in the thermodynamic stability of mutants of the protein in which Asp70, His31, or both are replaced by asparagine. These observations and consideration of the thermodynamic coupling of protonation state to folding of proteins suggest a mechanism of acid denaturation in which the unfolded state is progressively stabilized by protonation of its acid residues as pH is lowered below pH 4. The unfolded state is stabilized only if acidic groups in the folded state have lower pKa values than in the unfolded state. When the pH is sufficiently low, the acid groups of both the native and unfolded states are fully protonated, and the apparent unfolding equilibrium constant becomes pH independent. Similar arguments apply to base-induced unfolding.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid↗
PubMed1990

Nocturnal hemodynamic patterns in dogs.

Several species which have a single daily wake-sleep cycle show a progressive fall in cardiac output and rise in total peripheral resistance during sleep, a cardiovascular response which may reflect a progressive decrease in plasma volume. The present study showed that no such progressive overnight changes in cardiac output or total peripheral resistance occur in the dog, a carnivore which tends to be awake and to drink intermittently during the night. Progressive overnight bradycardia (-12.7 +/- 3.1%) and compensatory increase in stroke volume (14.8 +/- 6.0%) were observed in this species, however. These findings are consistent with the view that differences between primates and carnivores in overnight hemodynamic function are related to species differences in sleep and ingestive behavior.

Animals↗