Biomedical subjects

M J Kessler

Publications and source records attributed to M J Kessler.

At least 55 records · Page 3Linked to original sources

PubMed1986

Induction of experimental myasthenia gravis in rhesus monkeys: a model for the study of the human disease.

Experimental autoimmune myasthenia gravis (EAMG) was induced in rhesus monkeys using purified acetylcholine receptor (AChR) from Torpedo california. A single dose of 80 micrograms induced antibody formation two weeks after injection. Two subsequent doses at two-week intervals caused clinical signs (anorexia, fatigability, weight loss, ptosis and dysphagia) which initially responded to treatment with neostigmine. Histologic examination of post-mortem tissues revealed lesions characteristic of myasthenia gravis in man: muscular atrophy, fibrous degeneration and lymphocytic infiltration. Antibodies were quantitated in the sera of three other monkeys which received only 60 micrograms of purified AChR. Abnormally high titers persisted for two years (60-200 micrograms /ml versus 0-10 micrograms/ml for controls). A monkey injected with 60 micrograms AChR as part of reconstituted membrane vesicles had lower titers (30-50 micrograms/ml) than those which received purified receptor. Only those monkeys with antibody titers exceeding 800 micrograms/ml developed overt disease. These titers were 4-100 times higher than those reported for myasthenic humans. The antibody-antigen molar ratios were higher for monkeys with disease than for asymptomatic animals. These data suggest that the diversity of antibody molecules synthesized by the sensitized monkeys determined the appearance of clinical signs, and that the cross reaction of anti-torpedo antibodies with monkey receptor was primarily responsible for the development of EAMG.

Agglutination Tests↗

PubMed1985

Quantity of dengue virus required to infect rhesus monkeys.

As part of a dengue vaccine study, it was necessary to determine how much virus was required to infect rhesus monkeys. Serial dilutions of dengue 2 and 4 viruses were inoculated subcutaneously into groups of five monkeys and seroconversions determined on days 30 and 60 post-inoculation. The viruses were also titrated simultaneously in LLC-MK2 cells and mosquitoes. It was calculated that 9.5 mosquito infectious doses 50 (MID50) of dengue 2 virus and 22 MID50 of dengue 4 virus were required to infect 50% of the monkeys. The data suggest that 100 MID50 of dengue virus should be used as a challenge dose for monkeys previously immunized with dengue vaccine.

Animals↗

PubMed1985

Gestational diabetes mellitus and impaired glucose tolerance in an aged Macaca mulatta.

Gestational diabetes mellitus was diagnosed in an aged (21-year-old) pregnant rhesus monkey (Macaca mulatta); she was hyperglycemic and had minimal glucose clearance in an intravenous glucose tolerance test (iv-GTT). An overweight (840 g) dead full-term fetus was delivered by cesarean section. A second iv-GTT conducted 3 months later revealed impaired glucose tolerance. While pregnant, the monkey was hyperinsulinemic and showed minimal secretory response to the glucose load. When tested postpartum, the fasting insulin was only slightly elevated, but the insulin response to glucose was still lacking.

Aging↗

PubMed1985

Management of a harem breeding colony of rhesus monkeys to reduce trauma-related morbidity and mortality.

A management procedure was developed for a harem breeding colony of rhesus monkeys to reduce trauma-related injuries and deaths resulting from the periodic removal of pregnant monkeys for research and their subsequent return to the population. Lower morbidity and mortality rates, a reduced mean conception interval, and a higher mean conception rate occurred when monkeys were maintained in permanent harems to which returning females were reintroduced compared to new social groups formed from aggregates of unfamiliar animals.

Aggression↗

PubMed1985

Congenital cataracts in a free-ranging rhesus monkey.

This report documents the occurrence of congenital cataracts in a visually-impaired yearling rhesus monkey from the same matriline on Cayo Santiago in which a congenitally blind infant was born 2 years previously.

Animals↗

PubMed1984

Lack of viraemia and limited antibody response of dengue virus immune rhesus monkeys after vaccination with DEN-2/S-1 vaccine.

A dengue-2 live virus vaccine was tested in monkeys immune to heterologous dengue serotypes to determine if, as with wild DEN-2 virus, antibody-enhanced viraemia and seroconversion would occur. A low dose of 900 plaque-forming units (PFU) of the DEN-2/S-1 vaccine virus was inoculated subcutaneously into rhesus monkeys six months after they had received wild DEN-1, DEN-2 or DEN-3 viruses, and into non-immune monkeys. As previously reported for non-immune monkeys, there was little, if any, detectable vaccine viraemia in any of the groups of monkeys. There was no difference in seroconversion between the dengue heterologously immune (3/6) and non-immune (1/3) monkeys. These data indicated that (i) the vaccine virus may differ from the parent virus in the ability to complex with heterologous antibody and, thus, in the ability to infect Fc receptor bearing cells in monkeys; (ii) 10(3) PFU of vaccine virus is approximately the 50% infectious dose in monkeys as measured by seroconversion.

Animals↗

PubMed1984

Intestinal parasites of the free-ranging Cayo Santiago rhesus monkeys (Macaca mulatta).

Free-ranging rhesus macaques on the island of Cayo Santiago, Puerto Rico, were surveyed for intestinal parasites for the first time in over 40 years. Results were compared with the only previous study, and the relationships between the prevalence of Strongyloides and dominance rank, body weight, age, and matriline examined in the sampled population.

Age Factors↗

PubMed1984

Adult polycystic kidney disease in a rhesus monkey (Macaca mulatta).

Adult polycystic kidney disease was diagnosed at necropsy in a 16-year-old rhesus monkey dead from renal failure. Both kidneys were enlarged and contained multiple cysts ranging from 0.1 to 4.0 cm in diameter. The age of onset of the clinical signs, terminal uremia, and the gross and histologic findings in this macaque were consistent with adult (type III) polycystic kidney disease of man.

Animals↗

PubMed1984

Reproductive performance, population dynamics and anthropometrics of the free-ranging Cayo Santiago rhesus macaques.

This report summarizes demographic data collected on the Cayo Santiago colony of rhesus monkeys from 1976-1983 and compares the results with those from 1959-1964 [8,9]. For males and nonpregnant/nonlactating, pregnant, and lactating females mean (+/- 1 SD), body weights, crown-rump lengths, and ponderal indices are tabulated for each age on a large (n = 586) single sampling of this free-ranging population of macaques.

Animals↗

PubMed1984

Absence of naturally acquired tetanus antitoxin in the free-ranging Cayo Santiago rhesus monkeys (Macaca mulatta).

Tetanus is enzootic in the free-ranging rhesus monkey colony on Cayo Santiago. The disease accounts for 25% of all mortalities in the population. The high prevalence of tetanus provided a unique opportunity to study the potential roles of geophagia, wounding, and clinical tetanus infections on the development of naturally acquired tetanus antitoxin in rhesus macaques. Eighty-six unvaccinated monkeys, including six that recovered from tetanus, were serosurveyed using a mouse toxin neutralization test. None of the animals had detectable antitoxin titers (less than 0.001 AU/ml), suggesting that natural immunity to tetanus is either rare or nonexistent in the Cayo Santiago colony.

Animals↗

PubMed1983

Quantitation of radiolabeled biological molecules separated by high-performance liquid chromatography.

Several techniques are compared for the quantitation of radiolabeled molecules separated by high-performance liquid chromatography (HPLC). The first technique is the direct fraction collection of the HPLC eluent at pre-set times in individual tubes. Aliquots are removed from each tube, placed in scintillation vials, scintillation fluid is added and the radioactivity is counted in a liquid scintillation counter. The second technique is the direct interface (immediate analysis and plotting of data) of the eluent from the HPLC to a flow-through radioactivity detector. The third technique is to split the eluent from the HPLC with a microbore electronic stream splitter (flow/no flow) with a certain percentage directed to the flow-through radioactivity detector and the remainder collected in a fraction collector for further chemical characterization (gas chromatography-mass spectrometry, recrystallization, further purification). A direct comparison of the chromatograms, radioactivity counting efficiencies and sensitivities for these three techniques is presented.

Animals↗

PubMed1983

Virilizing adrenal adenoma in a 2-year-old girl.

A 2-year-old girl with virilization had an adrenal tumor that produced testosterone with little evidence of excessive urinary androgen excretion. Plasma testosterone concentration was 407 ng/dL and urinary 17-ketosteroid (17KS) levels were 3 and 2 mg/day. Excretion of 17KS decreased to 1.8 mg/day after suppression of dexamethasone therapy, but urinary 17-hydroxycorticosteroid excretion did not change from 1.0 to 0.7 mg/day after administration of dexamethasone. She had a blunted response to administration of metyrapone and insulin and a small diurnal variation in cortisol concentration suggesting suppression of corticotropin secretion, even though the plasma cortisol concentration was in the normal range and there were no clinical signs of cortisol excess. High-performance liquid chromatography was used to analyze the steroid content of tumor tissue. Those portions of the tumor that were rich in steroids contained predominantly testosterone.

Adenoma↗

PubMed1983

Congenital and hereditary anomalies in the rhesus monkeys (Macaca mulatta) of Cayo Santiago.

During seven annual birth seasons, from January 1976 to July 1982, 963 infants were born in the Cayo Santiago, Puerto Rico, colony of free-ranging rhesus monkeys (Macaca mulatta). The reproductive rate for mature females, 4 years of age and older, ranged between 74.1% and 84.7%, with a cumulative mean of 80.8% over 7 years. Live births comprised 95.3% of the total and the secondary sex ratio was 109 male to 100 female births. No twinning was observed. Aborted and stillborn monkeys represented 4.7% of all births. The percentage of stillborn females was greater than that of males (4.0% vs. 3.1%). Neonatal death, defined as mortality within 48 hours postpartum, occurred in 0.8% of the live births. Two cases of congenital abnormalities were observed. The first was an anencephalic, acranial female and the second a congenitally blind male. Both infants were born to matrilineally unrelated 7-and 8-year-old multiparous females with no prior history of delivering malformed offspring. The incidence of each defect, based on 963 births, was 0.10%, with a cumulative incidence of 0.20% for all teratisms seen during the study. Multiple occurrences of a rare, nonpathological and nonlethal hereditary anomaly were also seen. Five "golden" macaques were born into two genetically distinct social groups within the last 2 years of observation. The incidence of this phenotype, based on five cases, was 0.52%, 52 times the expected rate (.01%).

Animals↗

PubMed1983

Age- and pregnancy-related changes in serum total cholesterol and triglyceride levels in the Cayo Santiago rhesus macaques.

Ninety-six free-ranging rhesus monkeys were evaluated for age-, sex-, and pregnancy-related changes in total serum cholesterol and triglyceride levels and compared with previous studies. Our findings indicate that pregnancy depresses total cholesterol in females and that cholesterol levels tend to increase in males with age. Triglycerides decreased significantly with advancing age in males. The Cayo Santiago monkeys represent a unique opportunity to study the effects of age on population of nearly 1200 nonhuman primates on which there is accurate data on birth date, lineage, behavior, reproduction and post-mortem morphology (skeletons). Further gerontological studies are necessary to take full advantage of this resource and to increase the presently-scant body of information on aging in monkeys for comparative studies on humans and for the development of animal models of gerontological diseases of humans.

Aging↗

PubMed1983

The hemogram, serum biochemistry, and electrolyte profile of aged rhesus monkeys (Macaca mulatta).

The hemogram, serum biochemicals, and electrolytes of aged (15- to 28-year-old) rhesus monkeys were compared with values for younger adults (4-14 years old) maintained under identical conditions. Aged males had lower mean corpuscular volume, serum iron and magnesium, and higher percentages of eosinophils, globulins, and triglycerides than adult males. Aged females had lower mean corpuscular hemoglobin, total leukocyte count, percentage of neutrophils, alkaline phosphatase and magnesium, and higher percentages of lymphocytes and eosinophils, globulins, and uric acid than adult females.

Age Factors↗

PubMed1983

Blood values of free-ranging patas monkeys (Erythrocebus patas).

Free-ranging patas monkeys (Erythrocebus patas) from El Guayacán island, Puerto Rico, were surveyed to establish values for the hemogram, serum biochemicals, calcium, and phosphorus. Results were tabulated for males and nonpregnant/nonlactating, pregnant, and lactating females. A summary of blood values from previous studies on captive patas monkeys was also tabulated for comparison.

Age Factors↗

PubMed1982

Analysis of steroids from normal and tumor tissue by HPLC.

This paper presents a rapid method for the separation and quantitation of steroids obtained from normal and tumor tissue of the human adrenal and ovary. The tissues are initially extracted by organic solvent to separate the steroids from water-soluble compounds. The organically soluble steroids from the human tissues are chromatographed using a previously validated high performance liquid chromatography (HPLC) technique. This results in the rapid separation of progesterone, pregnenolone and corticosteroid pathway steroids. The steroids of the progesterone pathway (progesterone, testosterone, androstenedione, 17-hydroxyprogesterone) are directly quantitated by integration (using 254 nm absorbance) of the resultant peak areas. These direct quantitative results are compared to the results obtained by radioimmunoassay of the various steroids present in the sample. This use of HPLC results in the rapid separation and direct quantitation (in 40-50 min) of these steroids from human tissues.

Adrenal Gland Neoplasms↗

PubMed1982

Steroid metabolism by purified adult rat Leydig cells in primary culture.

To characterize Leydig cell steroidogensis, we examined the metabolism of [3H]pregnenolone (3 beta-hydroxy-5-pregnen-20-one) to androgens in the presence and absence of human chorionic gonadotropin (hCG) as a function of culture duration. Approximately 20-30% of the (3H)pregnenolone was converted to testosterone (17 beta-hydroxy-4-androsten-3-one) by purified Leydig cells at 0, 3 and 5 days (d) of culture. Androstenedione (4-androstene-3,17-dione) and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) were also produced while on day 5 of culture, significant amounts of progesterone (4-pregnene-3,20-dione) were isolated. The delta 5 intermediates, 17-hydroxypregnenolone (3 beta, 17-dihydroxy-5-pregnen-20-one) and dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), accounted for less than 1% of substrate conversion, indicating a clear preference for Leydig cells to metabolize (3H)pregnenolone via the delta 4 pathway. On day 0 of culture, unidentified metabolites considered of predominately polar steroids while on day 5 of culture, the unidentified metabolites consisted of predominately nonpolar steroids. In the presence of hCG, (3H-pregnenolone metabolism did not differ from basal on day 0 or 3 of culture. HCG increased the conversion of pregnenolone to progesterone and 17-hydroxyprogesterone (17-hydroxy-4-pregnene-3,20-dione) on 5d. This suggests that Leydig cells cultured for 5d have decreased C17-20 desmolase activity or that hCG acutely stimulates 3 beta-hydroxysteroid dehydrogenase and delta 5-delta 5 isomerase activities.

Androgens↗