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Biomedical subjects

D A Martin

Publications and source records attributed to D A Martin.

At least 19 recordsLinked to original sources

Effect of the dam strain on the spontaneous incidence of cleft lip and palate and intrauterine growth of CL/Fr mouse fetuses.

PURPOSE: The effects of dam strain on the spontaneous incidence of the cleft lip and palate (CLP) and the intrauterine growth of transferred CLP-susceptible CL/Fr embryos were examined with an embryo transfer technique. The CL/Fr strain of embryos at the early blastocyst stage was transferred to the same dam strain and also to the CLP-resistant C57BL dam strain. A laparotomy was done on the 18th gestational day at which time the number of fetuses, the resorption sites and the fetus weight were recorded. Each fetus was checked for the presence of CLP. Five criteria to assess the reproduction and fertility as well as the fetus weight were then compared between both dam strains. RESULTS: The dam pregnancy rate and the fetus survival rate in the CL/Fr dam strain were both significantly lower than those in the C57BL dam strain. The resorption rate in the CL/Fr dam strain was significantly higher than that in the C57BL dam strain. The spontaneous incidence rate of CLP in the CL/Fr dam strain was also significantly higher than that in the C57BL dam strain. The fetus weight of the CL/Fr fetuses developed in the CL/Fr dam strain was significantly lighter than that of the CL/Fr fetuses developed in the C57BL dam strain. CONCLUSION: The results indicated that the CLP-susceptible CL/Fr dam strain provided a less favorable uterine environment for the implantation, survival and intrauterine growth of the transferred CL/Fr embryos and also caused a higher spontaneous incidence rate of CLP. Thus, it can be concluded that the effect of the dam strain appears to play an important role on the spontaneous incidence of CLP and the intrauterine growth of the CL/Fr strain embryos transferred to both CL/Fr and C57BL dam strains.

Animals

Diet, not aging, causes skeletal muscle insulin resistance.

The purpose of this study was to compare the effects of raising female Fischer rats on a low-fat, high-complex-carbohydrate diet (LFCC) versus a high-fat, sucrose diet (HFS) on serum glucose and insulin as well as skeletal muscle glucose transport. No significant differences were observed between 6- and 24-month-old rats raised on the LFCC diet for serum glucose (3.6 +/- 0.1 vs. 3.7 +/- 0.2 mM) and insulin (88 +/- 6 vs. 98 +/- 10 pM) or for basal (35 +/- 3 vs. 39 +/- 6 pmol/mg protein/15 s) or insulin-stimulated (74.2 +/- 7.6 vs. 69.4 +/- 3.8 pmol/mg protein/15 s) glucose transport. These data indicate that aging per se does not lead to insulin resistance. When the 24-month-old animals raised on the HFS diet were compared with those on the LFCC diet, major differences were observed. Fasting serum insulin was significantly higher in the HFS group (437 +/- 118 vs. 98 +/- 10 pM) and insulin-stimulated glucose transport was significantly reduced (52.5 +/- 3.7 vs. 69.4 +/- 3.8 pmol/mg protein/15 s). Fasting glucose (3.7 +/- 0.2 vs. 3.6 +/- 0.1 mM) and basal glucose transport (38 +/- 6 vs. 39 +/- 6 pmol/mg protein/15 s) were unchanged. These results indicate that diet and not aging per se caused insulin resistance.

Aging

Effects of a high-fat, sucrose diet on serum insulin and related atherosclerotic risk factors in rats.

Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are all risk factors for atherosclerosis. The clustering of these risk factors in the same individual greatly increases the risk for atherosclerosis and has been termed 'Syndrome X' or 'The Deadly Quartet' The purpose of the present study was to investigate the effects of diet on these risk factors in inbred, female Fischer 344 rats. Animals were raised on ad lib diets consisting of high-fat, sucrose (HFS) or low-fat, complex-carbohydrate (LFCC). After 2 years, the HFS rats were obese (38% +/- 1% vs. 15% +/- 1% body fat), hypertensive (140 +/- 3 vs. 123 +/- 3 mmHg), hyperinsulinemic (439 +/- 118 vs. 98 +/- 10 pmol/l), and hypertriglyceridemic (1.1 +/- 0.2 vs. 0.4 +/- 0.07 mmol/l). The HFS rats also exhibited enhanced clotting and impaired fibrinolytic response to streptokinase. All these differences between the two groups were statistically significant (P < 0.05). Insulin was significantly correlated with body weight (r = 0.71), triglycerides (r = 0.48), and systolic blood pressure (r = 0.70). Total cholesterol was slightly, but not significantly higher, in the HFS group (2.8 +/- 0.3 vs 2.2 +/- 0.1 mmol/l) while HDL-cholesterol was unchanged. These results show that many risk factors for atherosclerosis can be induced in inbred rats by feeding a HFS diet. Aggregation of risk factors was found in the HFS group but not in the LFCC group. In fact, most of the rats on the LFCC diet developed no risk factors after 2 years, indicating that the development of risk factors is not an aging phenomenon.

Animals

Eastern equine encephalitis virus in Ohio during 1991.

During August and September of 1991, an epizootic of eastern equine encephalitis (EEE) virus in horses occurred in Wayne and Holmes countries, OH. This was the first recorded epizootic of EEE virus in the state. Twelve horses were confirmed positive for EEE virus through virus isolation or seroconversion, and seven additional horses with compatible symptoms were in close spatial and temporal proximity to the confirmed cases and were presumed to have died from EEE virus. The outbreak was centered around the Killbuck Wildlife Area, a 2,147-ha tract maintained by the state, half of which consists of wooded swamp and marsh. Mosquitoes were collected in upland areas before the epizootic and in the swamp basin at the end of the epizootic to identify the mosquito species involved in EEE virus transmission. We collected and tested 22,095 specimens for the presence of virus. EEE virus was isolated from one pool of the most likely epizootic vector, Coquillettidia perturbans (Walker). The minimum infection rate for EEE virus in this species was 0.1/1,000. Dense populations of Aedes vexans (Meigen) and Culex salinarius Coquillett occurred in the area, but their densities peaked after the epizootic. It is unlikely that these species were involved in epizootic transmission. IgM antibody to EEE virus was detected in three bird species collected in the swamp.

Animals

Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors.

Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of maturation and aging on the skeletal muscle glucose transport system.

Insulin resistance in old, compared with young, humans and animals has been well documented. The resistance is due primarily to defects in skeletal muscle. In the present study, skeletal muscle sarcolemmal membranes were purified from five age groups of female Fischer rats ranging from 2 to 24 mo. Basal specific D-glucose transport was not significantly different among any of the groups. Maximum insulin-stimulated transport was progressively decreased from 96.4 +/- 5.0 pmol.mg-1.15 s-1 in the 2-mo-old animals to 70.8 +/- 8.9 pmol.mg-1.15 s-1 in the 24-mo-old animals. Most of the decrease occurred during maturation, and in fact there was no significant difference in maximum transport among the 8-, 16-, and 24-mo-old rats. The decrease in insulin-stimulated transport in the 24-mo-old animals was due to a reduction in the number of glucose transporters translocated into the sarcolemma membrane (9.8 +/- 0.6 vs. 7.8 +/- 0.6 pmol/mg protein). The intracellular or microsomal pool of glucose transporters was not significantly different between the 2- and 24-mo-old animals (8.8 +/- 0.6 vs. 8.5 +/- 0.9/mg protein). Western blotting revealed no differences in the cellular GLUT-4 contents between the 2- and 24-mo-old rats. The number of insulin receptors (2.3 +/- 0.4 vs. 2.1 +/- 0.5 pmol/mg protein) was not significantly different. Tyrosine kinase activity of the insulin receptor was, however, significantly reduced in the 24-mo-old compared with the 2-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Effects of NIDDM on the glucose transport system in human skeletal muscle.

The purpose of this study was to investigate cellular changes in the glucose transport system in skeletal muscle of lean non-insulin-dependent diabetes mellitus (NIDDM) compared to lean nondiabetic control patients. NIDDM patients had significantly elevated fasting levels (means +/- SE) of serum glucose (10.1 +/- 1.3 vs. 5.4 +/- 0.4 mM, P less than 0.001) and serum insulin (110.8 +/- 31.1 vs. 35.9 +/- 3.6 pM, P less than 0.0025). Basal glucose transport (35.1 +/- 5.5 vs. 30.8 +/- 8.0 pM/mg protein) and cytochalasin-beta binding (3.5 +/- 1.2 vs 3.8 +/- 1.0 pM/mg protein) in isolated sarcolemmal vesicles were not significantly different between NIDDM and control groups. Insulin binding was reduced in NIDDM (0.82 +/- 0.03 vs. 1.63 +/- 0.18 pM/mg protein) as was the Kd (0.93 +/- 0.03 vs. 1.38 + 0.12 nM). Tyrosine kinase activity, as assessed from incorporation of [32P]ATP into Glu 4:Tyr 1, was significantly (P less than 0.005) reduced in NIDDM at insulin concentrations from 1-100 nM. Maximum kinase activity was depressed (1.88 +/- 0.04 vs. 2.97 +/- 0.07 fM 32P/fM insulin binding at 100 nM insulin). The number of glucose transporters in the low-density microsomes was not significantly different between NIDDM and control groups (7.01 +/- 1.40 vs. 7.65 +/- 0.90 pM cytochalasin-beta bound/mg protein). These results suggest that decreased insulin binding and diminished receptor tyrosine kinase activity play a substantial role in the development of skeletal muscle insulin resistance associated with NIDDM.

Adenosine Triphosphate

Induction of replicative competence ("priming") in normal liver.

We have used a system of nutritional manipulation to investigate whether hepatocytes of the normal liver can be primed for replication in vivo. In this system, rats that are denied protein for 3 days undergo a burst of hepatic DNA synthesis and mitosis when they are refed amino acids, while normally fed or starved rats do not respond. To determine if hepatocytes of protein deprived (PD) rats have been "primed" for replication, we examined changes in protooncogene expression in livers of PD rats to see if they would mimic the pattern of gene expression that is induced early after partial hepatectomy. c-jun, c-myc, and p53 mRNAs were elevated in livers of PD rats, while c-fos and c-ras genes were not expressed. The administration of amino acids to PD rats stimulated hepatic DNA synthesis in a shorter period than is required after partial hepatectomy and induced p53 and c-ras expression. In culture, hepatocytes from PD rats had higher levels of c-myc mRNA, underwent morphological changes more rapidly, and reached maximum rates of DNA synthesis earlier than normal hepatocytes. In both normal and primed hepatocyte cultures, transforming growth factor alpha stimulated DNA synthesis more effectively than epidermal growth factor. We conclude that hepatocytes pass through a priming stage before they proliferate and that replicative competence without DNA synthesis can be induced in hepatocytes in the normal liver.

Amino Acids

Auditory evoked potentials differ at 50 milliseconds in right- and left-handed listeners.

Left-handed individuals show a 4 ms later Wave Pb in the 45-60 ms latency range of the auditory middle latency response (MLR) than right-handed individuals. Examination of auditory evoked potentials in fifteen right-handed and fifteen left-handed normal hearing adults showed that this difference was not evident in time periods earlier or later than 45-60 ms. The isolation of this latency difference to a specific time period suggests that the source or sources of Wave Pb may be an independent physiological index which correlates with hand preference.

Acoustic Stimulation

Visual function in patients undergoing long-term total parenteral nutrition.

To evaluate the effects of long-term total parenteral nutrition (TPN) on eye function, 27 adults and 12 children in the UCLA Home TPN Clinic underwent ophthalmoscopic examination and visual-function testing. Direct inspection of the fundus showed a marked granularity of the retinal pigmented epithelium in some patients. About one-half of the children and one-third of the adults tested had at least one and usually two abnormalities in their electroretinogram. Determination of blood nutrients thought to affect vision revealed that zinc and vitamin E were within normal range. Vitamin A concentrations were above normal in 10 of 19 adults and selenium concentrations were below normal in 10 of 10 children and 17 of 21 adults tested. Linoleic and linolenic acid concentrations were low; plasma, platelet, and urine taurine concentrations were significantly lower than normal. Despite these diffuse nutrient abnormalities, only zinc and vitamin E concentrations correlated significantly with any index of visual function.

Adolescent

Effects of streptozotocin-induced diabetes on glucose transport in skeletal muscle.

Female Sprague-Dawley rats were injected with streptozotocin (45 mg/kg) to induce mild diabetes (glucose, greater than 13 mM). Half of the animals received daily insulin injections to reduce hyperglycemia. After 10 weeks, sarcolemmal membranes were isolated from hindlimb muscles to study glucose transport, and the number of glucose transporters was assessed by cytochalasin-beta binding. Both glucose transport (19.2 +/- 1.6 vs. 31.93 +/- 3.29 pmol/mg protein.15 sec) and cytochalasin-beta binding (3.06 +/- 0.28 vs. 6.14 +/- 0.59 pmol/mg protein) were significantly (P less than 0.05) reduced in the diabetic untreated rats compared to control values. Daily insulin injections restored both (P less than 0.05) basal transport (33.22 +/- 3.62 pmol/mg protein.15 sec) and cytochalasin-beta binding (5.52 +/- 0.66 pmol/mg protein) to control levels. Maximum insulin stimulation (1 U/kg, iv) significantly increased (P less than 0.05) both glucose transport (30.18 +/- 3.76 vs. 96.48 +/- 4.21 pmol/mg protein.15 sec) and cytochalasin-beta binding (4.38 +/- 0.29 vs. 9.40 +/- 0.42 pmol/mg protein) in the untreated diabetic and control rats. However, the stimulation in the untreated diabetic rats only reached basal control levels, which was significantly (P less than 0.05) below the insulin-stimulated value for the controls. In the rats receiving daily insulin injections, maximum insulin stimulation increased (P less than 0.05) both glucose transport (58.67 +/- 15.24 pmol/mg protein.15 sec) and cytochalasin-beta binding (6.4 +/- 0.7 pmol/mg protein), but both transport and binding were significantly (P less than 0.05) below insulin-stimulated values for the control rats. These data show that insulin deficiency adversely affected the glucose transport system in skeletal muscle. Both basal and maximum insulin-stimulated transport and the number of transport molecules were reduced. Daily insulin treatment corrected some of the defects, but maximum insulin stimulation was still significantly below values for control animals.

Animals

Dextromethorphan attenuates post-ischemic hypoperfusion following incomplete global ischemia in the anesthetized rat.

The effects of dextromethorphan (DM) were tested in an in vivo model of incomplete global cerebral ischemia. Anesthetized rats were divided into 4 groups: Group 1 (saline); Group 2 (DM pre-treatment, 20 mg/kg i.v. bolus followed by 10 mg/kg/h DM infusion); Group 3 (DM post-treatment, 2 mg/kg i.v. bolus followed by 10 mg/kg/h DM infusion at the onset of post-ischemic hypoperfusion); and Group 4 (sham-operated, drug-treated). Groups 1-3 underwent 15 min of 4-vessel occlusion followed by 3 h of reperfusion. Administration of DM in sham-operated animals (Group 4) had no effect on cerebral blood flow or electroencephalographic (EEG) activity. In contrast, when compared to the Group 1 saline controls, significant attenuation of post-ischemic hypoperfusion and EEG dysfunction was demonstrated in ischemic rats treated with DM (both pre- and post-treatment), suggesting an ability of DM to improve cerebral blood flow (CBF) and brain function in cerebral ischemia.

Animals

DNA content as a prognostic index in gestational trophoblastic neoplasia.

Hydatidiform mole will progress to malignant gestational trophoblastic neoplasia (GTN) in some cases. Aneuploidy and high proliferative activity are associated with malignant tumors. Molar pregnancy tissue was considered a precursor to malignant GTN, and was studied retrospectively using paraffin-embedded tissue to determine whether aneuploidy or proliferative rates measured on molar tissue could predict a malignant course. Tissues from 51 complete hydatidiform moles were analyzed for nuclear DNA content by flow cytometric techniques. A chart review identified the clinical course after evacuation of the mole. A satisfactory DNA histogram was generated in 40 cases. Of the 40 patients, 22 (55%) had spontaneous resolution, and 18 patients (45%) required treatment for persistent GTN. The molar tissue was found to be euploid in 27 cases and aneuploid in 13 cases. Eight of the twenty-seven euploid cases (30%) required treatment after evacuation, whereas 10 of the 13 aneuploid cases (77%) required treatment after molar evacuation. Proliferative index (PI) was compared with treatment requirements. Average PI was 0.11 +/- 0.10 for the treatment group and 0.08 +/- 0.06 for the spontaneous resolution group. The correlation of clinical course with ploidy was significant (P less than 0.01). The association with proliferative index was not (P greater than 0.05). Aneuploidy, therefore, identifies a high-risk group of molar pregnancies, and may represent those that have undergone one stage of malignant transformation.

DNA, Neoplasm

Calorimetric validation of the Caltrac accelerometer during level walking.

The primary purpose of this study was to compare the Caltrac accelerometer output with measured energy expenditure (Ee). Twenty-five volunteers (10 men, 15 women) walked on a level motor-driven treadmill at four different speeds (54, 81, 104, and 130 m.min-1) with the Caltrac device affixed to the waistline. Each of the four experimental trials lasted eight minutes, and the testing was completed within an hour. During the test, oxygen consumption (VO2) (in L.min-1 and in mL.kg-1.min-1) and nonprotein respiratory exchange ratio were monitored by the Beckman Horizon metabolic cart. The accelerometer output at the end of each exercise bout was also monitored and subsequently divided by 8 to convert the readings to counts.min-1. The mean VO2 (L.min-1) at steady state (ie, 6th-8th minutes of exercise) was converted to a caloric value. We obtained a moderate correlation coefficient (r) of .76 between the accelerometer output and the VO2 (mL.kg-1.min-1) and a high correlation coefficient of .92 between the Ee and the accelerometer readings. The Caltrac accelerometer output (counts.min-1) was significantly higher (p less than .01) than the Ee (kcal.min-1) at the four walking speeds. The difference between the accelerometer output and the Ee ranged from 13.3% to 52.9%. The data were further analyzed with linear, polynomial, multiple, and stepwise regression models. The results of the analyses revealed that the Caltrac accelerometer output is a valid predictor of Ee during level walking when the appropriate regression equation is used to adjust the values.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration

Autosomal dominant retinitis pigmentosa: a log quotient analysis of the photopic and scotopic b-wave amplitude.

The relationship of the photopic and the scotopic b-wave amplitudes of the electroretinogram was studied in 85 normal subjects and 25 patients with autosomal dominant retinitis pigmentosa, in which one amplitude was at least 20 microvolts. The log quotient of their b-wave amplitudes--that is log of the photopic b-wave amplitude divided by the scotopic b-wave amplitude--was considered to represent the activity of cones relative to rods. The log quotient values had a normal gaussian distribution in the normal control eyes, while they formed two groups in the patients with autosomal dominant retinitis pigmentosa. In the first group (type 1), the scotopic b-wave was non-recordable while the photopic b-wave amplitude was larger than 20 microvolts in all cases, indicating that the log quotient is larger than 0.5 and that the rod system is much more severely affected than the cone system. The second group (type 2) had a log quotient smaller than 0.5 and its distribution almost overlapped the normal one, indicating more symmetrical damage in the cone and rod systems. The mean final rod threshold at 45 minutes for type 1 was significantly higher than that for type 2. The log quotient proved to be a useful index for analysing the cone and rod involvement and consequently provides a better understanding of autosomal dominant retinitis pigmentosa.

Adolescent

Nurses' involvement in ethical decision-making with severely ill newborns.

This study was an exploratory investigation of the extent and nature of nurses' reported participation in the resolution of treatment dilemmas for infants with severe congenital anomalies. Participants in the study were 83 registered nurses from neonatal intensive care units in five large urban hospitals in the Southwest. Data were collected through the use of intensive semi-structured interviews with each participant and nurse responses to an investigator designed case study instrument, The Nursing Ethical Decision-Making Scale. Results indicated that a majority (85%) of the nurses in the study do not participate in a substantial way in decisions to initiate or forego life-sustaining treatment for their infant patients, yet they bear the major responsibility for implementing those decisions. The lack of participation in the decision-making process was cited by 70% of the nurses as being a major source of occupational stress and ethical anguish. Nurses with graduate educational preparation or advanced clinical practitioner education tended to take a more active role in decision-making. Other factors that appeared to promote participation in decision-making included nurse perceptions of administrative support for involvement, the existence of internal mechanisms for communication about treatment dilemmas (including infant care review committees), and hospital affiliation with a medical school. Eighty-seven percent of the nurses identified themselves as the infant's primary advocate, but only 20% of that group reported that they would pursue decisions through the chain of command outside the neonatal unit if they believed that an infant was not receiving appropriate treatment.

Adult