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D M Bowden

Publications and source records attributed to D M Bowden.

At least 37 records · Page 2Linked to original sources
PubMed1990

Constructing an instrument to measure the rate of aging in female pigtailed macaques (Macaca nemestrina).

To develop a battery of innocuous tests measuring individual differences in the rate of biological aging, longitudinal data were gathered on 28 biochemical, physiological, and morphological characteristics of 40 adult female pigtailed macaques. The change in each variable over time, i.e., the beta coefficient of linear regression, was calculated for each animal, and a matrix of correlations among the variables was constructed. Eight variables correlated well with the first principal component of the matrix. These variables (rate of fingernail growth, blood lymphocytes, mean corpuscular hemoglobin, immunoglobulin A, and serum sodium, chloride, total protein, and creatinine) represented the best subset of the potential biomarkers analyzed to produce an index covering a range of morphologic and functional systems that change with age. A similar set representing a wider range of systems and measured over a larger fraction of the life span should provide a valid index of an individual's rate of biological aging.

Aging↗
PubMed1990

Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation.

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week. Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. Thirty-three live born infants were assessed for abnormalities of physical and behavioral development. Ocular pathology, neuropathologic and neurochemical assessements were done on 31 animals at 6 months postnatal age. Microphthalmia was noted in three of the 26 animals exposed to ethanol. Retinal ganglion cell loss was significantly associated with intra-uterine ethanol exposure. Microphthalmia and retinal ganglion cell loss was observed in both the delayed and full-gestational exposed animals. No structural anomalies were found in the brains via gross inspection or light microscopy. Chemical abnormalities in the striatal nuclei were identified. Striatal dopamine concentrations increased with increasing MPPEC exposure (0-249 mg/dl) among animals exposed weekly to ethanol throughout gestation. Striatal dopamine concentrations decreased with increasing MPPEC exposure (260-540 mg/dl) among animals whose weekly exposure to ethanol was delayed until the 5th week of gestation. The same pattern of association was also noted between MPPEC and ultrastructural alterations in the caudate nucleus. The extent of ultrastructural alterations increased with increasing MPPEC among the full-gestational exposed animals and decreased with increasing MPPEC among the delayed-dose animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The major histocompatibility complex, MnLA, of pigtailed macaques: definition of fifteen specificities.

The major histocompatibility complex (MHC) of pigtailed macaques (Macaca nemestrina, Mn) is defined and designated as MnLA. Twenty-nine alloantisera were generated by fullsib alloimmunization and tested against a panel of 220 unrelated animals. The reactivities of different alloantisera were analyzed statistically in pairwise comparisons. Using 2 X 2 contingency tables, we calculated chi 2 independence, chi 2 allelism, and correlation coefficient values. Initially, specificities were defined by significant associations of certain sera, but some sera defined specificities individually. In all, 15 specificities were defined, and by family studies and negative correlation coefficients, a two-locus model was evident. Genetic analyses, together with statistical applications, revealed that the behavior of these specificities is consistent with the nature of MHC in other primate species, including man.

Alleles↗
PubMed1989

Ovarian cyclicity, hormones, and behavior as markers of aging in female pigtailed macaques (Macaca nemestrina).

Age-related differences in reproductive function were studied to identify variables suitable for a battery of noninvasive tests used to measure aging rate. Twenty-seven adult female pigtailed macaques, ranging in age from 8 to 31 years, were studied in a cross-sectional design. Perineal tumescence, menses, and activity in the home environment were recorded daily. Sexual behavior, when paired with unfamiliar males of three age groups, was observed six times in the early follicular phase of two ovarian cycles. Estradiol, LH, and FSH were measured twice during the same time period. Of the behavioral measures, mount, present, and activity were found to be lower in old than in young females. Of the physiological measures, ovarian cyclicity was less regular, estradiol was lower, and FSH and LH were higher in old compared to young females. Correlations between measures suggested two dimensions of reproductive function, a behavioral dimension and a physiological dimension.

Aging↗
PubMed1988

Primate research and "psychological well-being".

In Mark Crawford's News & Comment article "Superconductor funds flat" (4 Mar., p. 1089), Robert J. Birgeneau was reported to have had his grant cut to $4.4 million. That National Science Foundation grant actually covers the Massachusetts Institute of Technology's Materials Research Laboratory and supports 40 faculty members. Birgeneau's personal grant was reduced from $125,000 in 1987 to $122,000 for this year.

Animal Welfare↗
PubMed1988

Physical anomalies and developmental delays in nonhuman primate infants exposed to weekly doses of ethanol during gestation.

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3, or 4.1 gm/kg from the 5th week. Mean maternal mean peak plasma ethanol concentrations (MPPEC) ranged from 24 +/- 6 mg/dl at the 0.3 gm/kg dose to 549 +/- 71 mg/dl at the 4.1 gm/kg dose. Thirty-three viable infants were followed from birth to 6 months of age and assessed for growth, health, congenital anomalies and developmental rate. Facial anomalies, growth deficiency, or central nervous system dysfunction were found in 57% of the alcohol-exposed animals. No animal showed all the features of the human fetal alcohol syndrome. Ten of the twelve animals (83%) with mean MPPEC above 140 mg/dl had evidence of a teratogenic impact. The animals with full gestational exposure to ethanol and mean MPPEC between 140 and 249 mg/dl had much more severe and consistent cognitive abnormalities than the animals with delayed gestational exposures, even though the latter were exposed to mean MPPEC between 260 and 540 mg/dl. Conclusions from this study included: 1) ethanol-related behavioral teratogenesis occurred without accompanying physical anomalies, 2) measurable teratogenic effects from weekly exposures occurred only at intoxicating doses of ethanol, and 3) early gestational exposure to ethanol appeared to be more damaging to cognitive function than later and considerably greater alcohol exposure.

Animals↗
PubMed1988

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome in Macaca fascicularis: which midbrain dopaminergic neurons are lost?

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces, in both human and non-human primates, a syndrome very similar to idiopathic Parkinson's disease. The syndrome is associated with degeneration of the dopamine-containing neurons in the substantia nigra, many of which project to the neostriatum. The purpose of the present study was to quantify the regional distribution of midbrain dopamine neurons remaining after MPTP administration to the monkey (Macaca fascicularis) and to develop alternative procedures for maintaining the normal nutrition in MPTP-treated animals. Three monkeys were treated with MPTP and three served as controls. Representative sections were examined from rostral to caudal through the midbrain dopamine cell nuclei and the location of every tyrosine hydroxylase-containing cell was entered into a computer. Midbrain dopamine neuronal cell loss ranged from 36-78%, being most extensive in the two monkeys which exhibited the most severe parkinsonian syndrome. The greatest cell loss (46-93%) occurred in the substantia nigra pars compacta, or nucleus A9, and the loss was primarily in the ventral portion of the nucleus. Contrary to most previous reports, however, there was also a loss of cells in the ventral tegmental area (28-57%) and ventral reticular formation (33-87%), corresponding to nuclei A10 and A8, respectively. Since neuroanatomical tracing studies have shown that the dorsal and lateral portions of the striatum (areas showing the greatest dopamine depletion after MPTP) receive input from cells in the ventral A9 and from cells in the A8 and A10 areas, the present data suggest that MPTP preferentially destroys dopamine cells that project to the striatum (i.e. the mesostriatal cells).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence.

We have detected, in monkey caudate nucleus and putamen, neuronal cell bodies containing tyrosine hydroxylase-like immunoreactivity, as revealed by peroxidase-antiperoxidase immunohistochemistry. Many of these cells are distributed in an outer rim of 1-2 mm throughout the anterior-posterior extent of the neostriatum near its borders with the corona radiata; others are embedded in the adjacent white matter, especially near the ventral putamen and nucleus accumbens. Light and electron microscopy indicate that they are small (8-12 micron), bipolar cells with large nuclei. Such neostriatal neurons, containing tyrosine hydroxylase-like immunoreactivity, number in the tens of thousands.

Animals↗
PubMed1987

Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque (Macaca nemestrina).

Ethanol was orally administered once per week to gravid pig-tailed macaques (Macaca nemestrina) in doses of 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg. A control group received a sucrose solution, isocaloric and isovolemic to the highest ethanol dose. Pregnancy was followed after 116 possible conceptions in 54 females. Peak plasma ethanol concentrations (PPECs) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. An increased rate of spontaneous abortion was related to ethanol exposure at and above 1.8 g/kg (mean PPEC = 205 mg/dl). Pregnancy failure in the first 30 days of gestation increased at doses above 2.5 g/kg. The effect on pregnancy outcome of weekly exposure to ethanol in this nonhuman primate is comparable to available data on humans. The methodology of this study represents an effective model for studying ethanol teratogenesis in a nonhuman primate.

Abortion, Spontaneous↗
PubMed1987

Cross-sectional evaluation of potential biological markers of aging in pigtailed macaques: effects of age, sex, and diet.

The objective of our research was to establish a useful battery of innocuous tests suitable for detecting individual differences in biological aging rate in pigtailed macaques. Data were gathered from more than 60 animals of three age groups (8 to 9, 12 to 17, and 18 to 28 years olds) fed two diets differing in lipid, cholesterol, complex carbohydrate, refined sugar, and sodium chloride content. Candidate variables for an aging battery were identified in a cross-sectional analysis by performing a three-way analysis of variance (ANOVA) for the effects of age, sex, and diet on each of 72 variables. Twenty-eight variables were found to be influenced by age. By examining patterns of differences among means, 20 variables were identified that show promise of being useful, including, for example, rectal body temperature, blood albumin, immunoglobulin A, fingernail growth rate, bone thickness, and blood calcium. The set of variables used to estimate biological aging might not be identical for all age-sex classes.

Aging↗
PubMed1986

Pharmacokinetics of ethanol in pigtailed macaques: intersubject variability and effect of subchronic administration.

The pharmacokinetics of IV ethanol (0.6 g/kg) were examined in 11 male colony-bred pigtailed macaques (Macaca nemestrina) aged 3 to 13 years. The animals were either chaired during blood sampling (4 hr) or connected to a tether system that allowed injections and blood sampling while the animal moved freely about its cage. In all instances, ethanol pharmacokinetics could be described by a single Michaelis-Menten function; inclusion of a parallel first-order rate constant to account for non-alcohol dehydrogenase elimination of ethanol did not improve the fit. Volume of distribution was 0.802 +/- 0.054 L/kg (mean +/- SD), Km (the apparent in vivo Michaelis constant) was 0.063 +/- 0.022 micrograms/ml, and Vmax was 0.199 +/- 0.039 g/kg/hr. The pharmacokinetic parameter values of chaired and tethered monkeys did not differ. Three of the tethered monkeys received 3 g/kg of ethanol daily for two weeks by IV infusion (subchronic administration). Ethanol pharmacokinetics, determined on five occasions before and five occasions after subchronic ethanol administration, showed that the treatment did not alter the volume of distribution or Km in any of the three monkeys. The value of Vmax increased approximately 23% in one of the three monkeys that received subchronic ethanol; this increase may have been due to a single, inadvertent administration of a 4.5-g/kg dose over a 20-min period. Vmax did not change in the other two monkeys.

Animals↗
PubMed1986

Effects of food, mild stress, and distributed intake on the absorption and plasma concentration-time profile of orally ingested ethanol in pigtailed macaques.

To evaluate the possibility of estimating ethanol plasma level from a record of voluntary intake, the effects of food, mild stress, and distributed dosing on the fraction of ethanol absorbed and the relative exposure to circulating blood ethanol were determined in four adult male pigtailed macaques (Macaca nemestrina). The animals received 0.6 g/kg ethanol IV and orally after an 18-hour fast, after a small meal, and under mild stress; distributed dosing was evaluated for the oral route only. The concentration-time profile for the oral/fasting condition was very similar to that following an IV dose. The dose was completely absorbed and peak plasma level occurred about 30 min after ingestion. Peak plasma concentration was reduced by 42% following a small meal, 29% following mild stress, and 18% following distribution of the dose over 60 min. The time to peak concentration was more than doubled by distributed dosing. Relative exposure was reduced by 18 to 27% by all conditions of oral administration except feeding, which caused a 52% reduction. The fraction of ethanol absorbed was influenced only by feeding, which caused a reduction of 20%. The magnitude of changes in concentration-time profile produced by such factors precludes accurate estimation of blood levels from records of voluntary intake. Furthermore, the effects of social factors on voluntary ethanol consumption may be mediated by centrally controlled changes in gastrointestinal function that alter the rate and extent of absorption of the drug.

Animals↗
PubMed1985

Techniques for improving stereotaxic accuracy in Macaca fascicularis.

Sources of stereotaxic variability in long-tailed macaques (Macaca fascicularis) were examined by X-ray techniques. Accuracy in the vertical dimension can be improved significantly by measuring from the top of the brain rather than from the Frankfurt plane established by external bony landmarks. Even greater accuracy in both the vertical and anterior-posterior dimensions can be attained by rotating the cranium in the stereotaxic instrument to bring the intercommissural line, as defined by ventriculography, into a plane parallel to the horizontal stereotaxic plane, thus approximating the orientation of the brain as represented in both of the brain atlases currently available for this species. An adjustable eyebar spacer, which allows the cranium to be rotated in the stereotaxic instrument, is described.

Animals↗
PubMed1985

Fetal alcohol syndrome: an examination of craniofacial dysmorphology in Macaca nemestrina.

The purpose of this investigation was to evaluate the craniofacial features in nonhuman primate models exposed in utero to moderate and high weekly binge doses of ethanol. While the high-dosed animal did have unusual craniofacial dysmorphology, she did not exhibit the typical facial pattern seen in human fetal alcohol syndrome. The high-dosed specimen displayed a scaphocephalic head shape secondary to synostosis of the sagittal suture. The brain of this monkey was grossly abnormal and microcephalic.

Animals↗