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Biomedical subjects

C S Carlson

Publications and source records attributed to C S Carlson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Diabetes mellitus and islet amyloidosis in cynomolgus monkeys.

Six 15- to 20-year-old obese cynomolgus monkeys were determined to have diabetes mellitus. These monkeys were hyperglycemic and hypertriglyceridemic, yet remained nonketotic for several years before requiring clinical intervention. A significant decrease in glucose disappearance and an increased area under the glucose disappearance curve were found in response to intravenous glucose tolerance testing. Basal hyperinsulinemia was found in three animals that, in response to glucose stimulation, had a blunted insulin response, resulting in an overall decrease in the area under the insulin curve. Two animals died during the study and had extensive amyloid infiltration of pancreatic islets. The combined findings of old age, obesity, hyperinsulinemia, improvement in response to caloric restriction, and islet amyloidosis are consistent with type 2 diabetes mellitus.

Adipose Tissue↗
PubMed1995

Osteoarthritis in cynomolgus macaques. II. Detection of modulated proteoglycan epitopes in cartilage and synovial fluid.

The purpose of the present study was to determine the usefulness of the monoclonal antibodies 7-D-4 and 3-B-3 as biomarkers of severity of naturally occurring osteoarthritis in the knee joints of adult cynomolgus macaques. The antibodies were used to immunolocate chondroitin sulfate proteoglycan epitopes in articular cartilage or synovial fluid from knee joints with a range in severity of osteoarthritis. The joints were examined radiographically, grossly, microradiographically, and histologically to characterize the severity of disease, and the results of three different methods of proteoglycan analysis (immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analysis) were compared. Subjectively, the degree of positive immunostaining for 7-D-4 was minimal in normal sites and increased as damage to articular cartilage increased. The scores for 7-D-4 immunostaining in the medial tibial plateau (the site most severely involved in this model) were correlated significantly with severity of damage to articular cartilage (p < 0.05, r2 = 0.50), thus supporting the subjective observations. The ratio of 7-D-4 to sulfated glycosaminoglycans in synovial fluid also was correlated with the score for 7-D-4 immunostaining in the medial tibial plateau (p < 0.05, r2 = 0.54) and with the score for 3-B-3 immunostaining in the medial femoral condyle (p < 0.05, r2 = 0.65). There were no significant correlations among scores for 3-B-3 immunostaining, severity scores, and the ratios of 3-B-3 to sulfated glycosaminoglycans in the synovial fluid. By Western blot analysis, both epitopes were sensitive markers of early cartilage damage in young adult monkeys but were less sensitive in older monkeys. This work provides evidence that measurement of the epitope recognized by 7-D-4 in synovial fluid or, by immunohistochemical or Western blot methods, in articular cartilage has potential use as a marker of severity of naturally occurring osteoarthritis.

Animals↗
PubMed1995

Cartilage oligomeric matrix protein: isolation and characterization from human articular cartilage.

Cartilage oligomeric matrix protein was purified in a native form from normal adult human articular cartilage. The key steps in the purification scheme were selective extraction with buffer containing EDTA, wheat germ agglutinin affinity chromatography, and removal of the related protein thrombospondin by heparin affinity chromatography. Particles of cartilage oligomeric matrix protein viewed by electron microscopy after rotary shadowing revealed structures similar to the prototype molecule purified from Swarm rat chondrosarcoma. The protein demonstrated a bouquet-like five-armed structure, with peripheral globular domains connected by thin flexible strands to a central assembly domain. Immunohistochemistry revealed age-dependent differences in the protein's distribution in cartilage. In normal human adult articular cartilage, there was a relatively uniform distribution throughout the interterritorial extracellular matrix, whereas in fetal articular cartilage, immunostaining was localized to the extracellular matrix directly adjacent to the chondrocytes. The isolation and characterization of human cartilage oligomeric matrix protein will facilitate its study in pathological conditions of human cartilage.

Adult↗
PubMed1995

Expression of beta 1 integrins by cultured articular chondrocytes and in osteoarthritic cartilage.

Expression of beta 1 integrins was studied in vitro as articular chondrocytes reestablished a matrix in culture and in situ in a nonhuman primate model of osteoarthritis in order to investigate a potential role for integrins in mediating cell-extracellular matrix interactions in cartilage. Chondrocytes were found to express alpha 1 beta 1, alpha 3 beta 1, and alpha 5 beta 1 integrins both in vitro and in situ. Cell surface expression of beta 1 integrins increased as chondrocytes were maintained in cultured from 3 to 7 days. Increased beta 1 integrin expression was also observed in osteoarthritic cartilage compared with normal cartilage. The greatest relative increase in both systems was noted for the alpha 1 beta 1 integrin. The increase in chondrocyte beta 1 integrin expression in vitro was noted in both monolayer and alginate cultures and occurred prior to detectable changes in the differentiated phenotype of the chondrocyte. Disruption of the cytoskeleton with the drug dihydrocytochalasin B inhibited the cell culture induced increase in integrin expression, while treatment of cultured cells with TGF-beta resulted in increased expression of the alpha 5 beta 1 integrin. The modulation of beta 1 integrin expression noted in vitro and in situ indicates that chondrocytes are capable of regulated expression of beta 1 integrins and suggests that beta 1 integrins may play an important role in mediating chondrocyte-extracellular matrix interactions in cartilage.

Animals↗
PubMed1995

Osteochondrosis of the articular-epiphyseal cartilage complex in young horses: evidence for a defect in cartilage canal blood supply.

The objectives of this study were to determine in horses 1) the ages at which viable cartilage canal vessels are present in the articular-epiphyseal cartilage complex of three predilection sites and one nonpredilection site of osteochondrosis (OC), 2) the prevalence of lesions of OC in these sites, and 3) whether there was an association of lesions of OC with necrotic cartilage canal blood vessels. The medial femoral condyle, lateral femoral trochlear ridge, and distal ends of the tibia and proximal phalanx were examined grossly, microradiographically, and histologically in 35 horses 18 months old or younger. Cartilage canals containing patent blood vessels were present in all sites examined in foals less than 3 weeks old and were absent from all sites by 7 months of age. The overall prevalence of lesions of OC at one or more of the sites examined was 12/35 (34%). Prevalence increased to 11/22 (50%) in horses 2 months old and older. These lesions occurred primarily in the medial condyle of the femur (n = 5) and the intermediate ridge of the distal tibia (n = 5). All lesions seen in horses between 3 weeks and 5 months of age were associated with necrotic cartilage canal blood vessels. In horses 7 months of age and older, lesions of OC were considered chronic because of extensive involvement of the subchondral bone and bone marrow. These results suggest that OC lesions develop prior to 7 months of age and that ischemic necrosis of cartilage secondary to a defect in vascular supply is an important factor in the pathogenesis of this disease in horses.

Aging↗
PubMed1994

Bone functional changes in intact, ovariectomized, and ovariectomized, hormone-supplemented adult cynomolgus monkeys (Macaca fascicularis) evaluated by serum markers and dynamic histomorphometry.

Several parameters of bone mass and function were investigated in three experiments involving intact, ovariectomized, or hormone-supplemented ovariectomized female cynomolgus monkeys. Ovariectomized animals had increased serum levels of alkaline phosphatase and acid phosphatase compared with intact and hormone-supplemented animals. Vertebral bone mass measured ex vivo by dual-photon absorptiometry was reduced by 11-19% in ovariectomized animals compared with intact and hormone-supplemented animals. The most dramatic effects observed with ovariectomy were markedly increased (30-60%) bone formation rates in vertebral cancellous bone, primarily caused by higher activation frequency of basic multicellular units of bone. In addition, combined resorption and reversal periods were decreased and formation period increased in untreated ovariectomized animals. Changes in static histomorphometry parameters were less dramatic, cancellous bone volume being 1-14% lower in ovariectomized animals compared with intact or ovariectomized hormone-supplemented animals. The data indicate that changes in bone resorption are primarily responsible for the lower bone mass of estrogen deficiency and increased bone mass in hormone-supplemented animals. Bone changes in ovariectomized cynomolgus monkeys resemble those in women after menopause and similarly respond positively to hormone supplementation. As such, cynomolgus monkeys are an excellent model for studying the basic mechanisms of osteoporosis and for the development of suitable therapeutic regimens.

Acid Phosphatase↗
PubMed1994

Osteoarthritis in cynomolgus macaques: a primate model of naturally occurring disease.

The objective of the present study was to determine if naturally occurring osteoarthritis of the knee joints that is similar to the condition in humans develops in cynomolgus macaques. Knee joints from 58 young adult (mean age, 7.4 years) female cynomolgus macaques were studied with x-ray densitometry, high-detail radiography, and histology. The animals studied were subjects in a triad designed to examine the effects of the administration of sex steroids on atherosclerosis; except for a control group, the monkeys had been either ovariectomized or treated with sex steroids for 2 years. Therefore, the data were analyzed to determine if these treatments, both of which can influence bone density, affected the severity of osteoarthritis. There was a high prevalence of osteoarthritic lesions, morphologically similar to those seen in humans. Bone changes were more common and severe than cartilage changes and morphologically appeared to precede the cartilage changes. Treatment with testosterone resulted in increased body weight, body mass index, and bone mineral content in the femur and tibia but did not affect the severity of osteoarthritis. These data indicate that naturally occurring osteoarthritis developed in the knee joints of cynomolgus macaques; these animals may be a useful model for the study of osteoarthritis in humans.

Animals↗
PubMed1994

Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. A paradigm of human B19 parvovirus infection.

Although human B19 parvovirus infection has been clearly associated with a number of distinct syndromes (including severe anemia, abortion, and arthritis), detailed knowledge of its pathogenesis has been hindered by the lack of a suitable animal model. We have identified a novel simian parvovirus in cynomolgus monkeys with severe anemia. Sequencing of a 723-bp fragment of cloned viral DNA extracted from serum revealed that the simian parvovirus has 65% homology at the DNA level with the human B19 parvovirus but little homology with other known parvoviruses. Light microscopic examination of bone marrow from infected animals showed intranuclear inclusion bodies, and ultrastructural studies showed viral arrays characteristic of parvoviruses. Another striking feature was the presence of marked dyserythropoiesis in cells of the erythroid lineage, raising the possibility that B19 parvovirus infection may underlie related dyserythropoietic syndromes in human beings. Affected animals had concurrent infection with the immunosuppressive type D simian retrovirus, analogous to HIV patients who develop severe anemia because of infection with B19 parvovirus. The remarkable similarities between the simian and B19 parvoviruses suggest that experimentally infected cynomolgus monkeys may serve as a useful animal model of human B19 infection.

Amino Acid Sequence↗
PubMed1993

Immunolocalization of noncollagenous bone matrix proteins in lumbar vertebrae from intact and surgically menopausal cynomolgus monkeys.

The noncollagenous matrix proteins, composing about 10% of the organic matrix of bone, are considered important for cell matrix organization and regulation of mineralization in bone. In the present study, seven of the major noncollagenous bone matrix proteins were localized immunohistochemically in serial sections of lumbar vertebrae from 24 (12 intact and 12 ovariectomized) adult female cynomolgus monkeys (Macaca fascicularis). Osteocalcin was the only protein restricted to bone cells and mineralized bone matrix. Bone sialoprotein was present in both bone and calcified cartilage, and all the other proteins were distributed in soft tissues as well as bone. Staining for both osteocalcin and bone sialoprotein was present diffusely throughout the bone matrix, but osteonectin, osteopontin, matrix gla protein, decorin, and biglycan staining was concentrated along bone surfaces. Osteoid was negative for osteocalcin and bone sialoprotein, but all other proteins had areas of positive immunostaining within osteoid. All proteins except biglycan exhibited strong immunostaining of a subset of active osteoblasts, suggesting that they may be markers of osteoblast maturity or state of activation. The pattern of immunostaining in intact and surgically menopausal monkeys was similar, except that staining for matrix proteins concentrated along bone surfaces appeared to be more widely distributed in the surgically menopausal monkeys, probably due to the higher rate of bone formation in these animals.

Animals↗
PubMed1992

Articular-cartilage matrix gamma-carboxyglutamic acid-containing protein. Characterization and immunolocalization.

Matrix gamma-carboxyglutamic acid (Gla)-containing protein (MGP) was found to be present in articular cartilage by Western-blot analysis of guanidinium chloride extracts of human and bovine cartilage and was further localized by immunohistochemical studies on human and monkey specimens. In newborn articular cartilage MGP was present diffusely throughout the matrix, whereas in growth-plate cartilage it was seen mainly in late hypertrophic and calcifying-zone chondrocytes. In adult articular cartilage MGP was present primarily in chondrocytes and the pericellular matrix. Immunoelectron microscopy studies revealed an association between MGP and vesicular structures with an appearance consistent with matrix vesicles. MGP may be an important regulator of cartilage calcification because of its localization in cartilage and the known affinity of Gla-containing proteins for Ca2+ and hydroxyapatite.

1-Carboxyglutamic Acid↗
PubMed1991

Ischemic necrosis of cartilage in spontaneous and experimental lesions of osteochondrosis.

This study was designed to examine the association of spontaneous lesions of osteochondrosis with vascular supply to epiphyseal cartilage, and to determine whether similar lesions could be experimentally reproduced by selective interruption of cartilage canal blood supply. The vascular supply to the articular-epiphyseal cartilage complex of the distal end of the femur was studied in 27 microfil- or barium-injected and cleared specimens and 24 serially sectioned microangiographic specimens from 27 clinically normal female swine (3.6 to 71.0 kg). Blood vessels supplying the articular-epiphyseal cartilage complex were consistently restricted to the epiphyseal region and the number of vessels decreased as the pigs increased in weight (p less than 0.001). Spontaneous lesions of osteochondrosis (i.e., cartilage necrosis) were initially seen in the first areas of epiphyseal cartilage to become avascular and were associated with necrotic blood vessels. The number and size of foci of necrotic cartilage increased as the pigs increased in weight (p less than 0.001). Blood supply to epiphyseal cartilage from cartilage canal vessels was surgically interrupted in a highly vascular area of the medial femoral condyle in eight additional 23-kg female swine. This procedure resulted in necrosis of blood vessels within cartilage canals followed by necrosis of surrounding cartilage, lesions that appeared to be identical to early spontaneous lesions of osteochondrosis. These results suggest that the viability of epiphyseal cartilage in the articular-epiphyseal cartilage complex is highly dependent on an adequate blood supply from cartilage canal vessels, and strongly implicates a defect in blood supply in the pathogenesis of osteochondrosis.

Animals↗
PubMed1991

Accuracy and precision of lumbar bone mineral content by dual-energy X-ray absorptiometry in live female monkeys.

Dual-energy X-ray absorptiometry (DXA) was used to determine the in vivo bone mineral content (BMC) of lumbar vertebrae in 20 feral adult female cynomolgus macaques (Macaca fascicularis). The ash weight of the third lumbar vertebra (L3) was compared to the measured L3BMC of the in vivo DXA analyses. Correlation between the estimated L3BMC by DXA and the actual ash weight was significant (r = 0.965, P less than 0.01); however, DXA methodology underestimated ash weight on the average of 6.2%. Correlation was significant between two sequential in vivo DXA scans (r = 0.988, P less than 0.001). Noninvasive in vivo DXA was a fast, precise, and effective method for measuring the lumbar BMC in female cynomolgus macaques.

Absorptiometry, Photon↗
PubMed1990

Vascular permeability and coagulation during Rickettsia rickettsii infection in dogs.

The vascular permeability of the ocular fundus, alterations in the coagulation system, and plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in dogs following intradermal inoculation with 5 x 10(5) TCID50 of Rickettsia rickettsii. Twenty-four to 48 hours after the onset of fever and rickettsemia, multifocal areas of retinal vasculitis were evident, which corresponded to areas of altered vascular permeability demonstrated by fluorescein angiography. The number and intensity of retinal vessels with sodium fluorescein leakage peaked during the second week after inoculation, and retinal vascular permeability remained altered during the third week of infection, well past the phase of clinical and clinicopathologic recovery. Development of retinal vasculitic foci was associated with thrombocytopenia, increased concentrations of circulating fibrinogen, and slight prolongation of activated partial thromboplastin time. Increased concentrations of fibrin/fibrinogen degradation products were detected in 4 of 9 dogs. Despite the degree of vascular endothelial damage evident on fluorescein angiographic and histologic studies in these dogs, plasma TXB2 and 6-keto-PGF1 alpha concentrations were not increased.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effect of Nd:YAG laser energy on articular cartilage healing in the dog.

The effect of low dose neodymium:yttrium aluminum garnet (Nd:YAG) laser therapy on cartilage healing was studied. Partial- and full-thickness cartilage defects were surgically created in the femoral condyles of 20 adult dogs. The cartilage defects in one limb of each dog were exposed to 30 J of Nd:YAG laser energy. The dogs were euthanatized 1 week (n = 6), 1 month (n = 7), and 6 months (n = 7) after surgery. Plastic-embedded, undecalcified histologic sections of each cartilage defect were examined for evidence of cartilage healing. Special stains were used to determine the type of repair tissue present, and morphometric measurements of repair tissue were made. No effect of Nd:YAG laser therapy on cartilage healing was noted.

Animals↗
PubMed1989

Degeneration of cartilage canal vessels associated with lesions of osteochondrosis in swine.

Articular-epiphyseal cartilage complexes from the distal femur and humerus of five 3-month-old pigs were collected and preserved using either a conventional or a ruthenium hexammine trichloride (RHT)-supplemented fixation technique. Lesions were similar regardless of the fixation technique. Areas of necrosis were in epiphyseal but not articular cartilage from both sites of all pigs. Cartilage canals were confined to epiphyseal cartilage and contained vessels which had endothelial cells in varying stages of degeneration and necrosis. Areas of necrotic cartilage often were adjacent to or surrounded degenerate cartilage canals. Lipid emboli (up to 40.0 micron in diameter) were infrequently located in vessels within cartilage canals. Associated with the lipid emboli were leukocytes, erythrocytes, necrotic cell remnants, and flocculent material. Restriction of necrosis to epiphyseal cartilage and the association of these necrotic areas with degenerating vessels in cartilage canals strongly implicate a defect in cartilage canal blood supply in the pathogenesis of osteochondrosis. The RHT fixation technique resulted in excellent cellular detail at the light microscopic level, but ultrastructurally there was marked vacuolation of chondrocytes and matrix. The conventional technique caused shrinkage of all chondrocytes, resulting in a wide halo of pericellular matrix surrounding each cell.

Animals↗
PubMed1988

Effect of reduced growth rate on the prevalence and severity of osteochondrosis in gilts.

Ninety-six recently weaned gilts were assigned to 3 groups. Group-1 gilts were fed a corn-soybean meal diet ad libitum and were killed when they weighed 110 kg. Gilts in groups 2 and 3 were fed 70% of the feed consumed by group-1 gilts. Group-2 gilts were killed when they weighed 110 kg, and group-3 gilts were killed at the same age as group-1 gilts. At slaughter, the right pelvic and thoracic limbs from all gilts were removed, and the distal end of each femur and humerus was sectioned serially at 5-mm intervals. Articular-epiphyseal cartilage complexes from these sites were examined grossly, radiographically, and histologically. Effects of treatment (ad libitum vs limited energy intake) and average daily gain on the prevalence and severity of lesions were analyzed statistically, using chi 2 analysis, a categoric-modeling technique, analysis of variance, and correlation coefficients. Of humeri and femora, 49 and 70%, respectively, had lesions of osteochondrosis, and 86% of the gilts had a lesion at one or both sites. Group-2 gilts (killed at 110 kg, but approx 70 days older than group-1 gilts) had significantly lower prevalence (P = 0.009) and severity (P = 0.002) of osteochondrosis of the distal end of the femur than did gilts in groups 1 and 3. When each group was evaluated individually, gilts that had a higher average daily gain had an increased prevalence and severity of lesions.

Animal Feed↗