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Biomedical subjects

R D Park

Publications and source records attributed to R D Park.

At least 37 records · Page 2Linked to original sources

An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy.

A mitochondrial DNA mutation at nucleotide position 14,484 was found in 14 independent probands with Leber hereditary optic neuropathy and in 0/250 controls. The 14,484 mutation, which changes methionine-64 to valine in a conserved domain of the ND-6 gene, occurred in association with a mitochondrial DNA haplotype that includes the 13,708 secondary mutation in 10/14 probands. An associated mutation at nucleotide position 3,394, which changes conserved tyrosine-30 to histidine in the ND-1 gene, was observed in 5/14 probands positive for the 14,484 mutation, all of whom harbored the same mitochondrial DNA haplotype. Multiple mitochondrial DNA mutations may interact in the pathogenesis of Leber hereditary optic neuropathy and the 13,708 secondary mutation appears to play a central role in this process.

Base Sequence↗

Role of vesicular traffic in the transport of surface transferrin receptor to the Golgi complex in cultured human cells.

We have previously shown that transferrin receptor (TfR) recycles from the cell surface through the Golgi complex in K562 human leukemia cells. However, little is known about the transport pathway that carries these receptors to the Golgi complex. To learn more about this transport, we studied the effects of treatments that block specific types of vesicular traffic. K562 cells were cultured in test media and the transport of surface TfR to the Golgi complex was assessed by measuring the entry of asialo-TfR into the sialyltransferase compartment of the Golgi complex. Depletion of cellular potassium, which blocks formation of coated vesicles at the cell surface, stimulated asialo-TfR resialylation by 60% over controls, suggesting that coated vesicle formation is not the rate-limiting step in cell surface-to-Golgi transport. Similarly, culture in sodium-free medium, which blocks transport from endosomes to lysosomes, increased asialo-TfR resialylation by 40%, arguing that lysosomes do not lie on the transport pathway. In contrast, incubation of cells in hypertonic medium, which blocks many vesicular transport steps, inhibited TfR resialylation by 40%, confirming the importance of vesicular traffic in transport of asialo-TfR from the cell surface to the Golgi complex. These results are consistent with two possible pathways for cell surface-to-Golgi transport. Receptor could be transported via an endosomal intermediate, with the rate-limiting step occurring at a post-endosomal site. Alternatively, receptor could be transported directly to the Golgi via a pathway that does not involve endosomes.

Biological Transport↗

Female pseudohermaphroditism in three sibling greyhounds.

Three 18-month-old Greyhound siblings were found to have female pseudohermaphroditism. The disorder in sexual differentiation likely developed because the dam received testosterone proprionate for estrus prevention. All 3 siblings had a prepuce (no penis), vagina, uterus, and ovaries.

Abnormalities, Drug-Induced↗

Ureteral injury following experimental intraoperative radiation.

Beagle dogs were randomized to receive a range of total dose delivered in three different protocols. Sixteen dogs received external beam radiation therapy (EBRT), 32 dogs received intraoperative irradiation (IORT), and 32 dogs received combinations of external beam radiation therapy and intraoperative irradiation. A sublumbar field was irradiated which always included the left ureter. Dogs were observed for 5 years; sequential excretory urograms were done at 6 months, and 1 and 5 years. Morphometric analysis of tissues were also done. The canine ureter tolerated 17.5 Gy intraoperative irradiation with no evidence of injury and 25 Gy intraoperative irradiation with a low probability of injury. The ED50 for radiographic abnormalities was 32.9 Gy. When 50 Gy external beam radiation therapy was given prior to intraoperative irradiation, the ureter tolerated 10 Gy intraoperative irradiation with no evidence of injury and 17.5 Gy with a low probability of injury. The ED50 was 29 Gy intraoperative irradiation after EBRT. The external beam radiation therapy had little effect on the ureter when given alone or prior to intraoperative irradiation. Clinical signs of renal disease occurred only in dogs who had received bilateral ureteral irradiation intraoperatively at doses of 32.5 Gy intraoperative irradiation and 25 Gy intraoperative irradiation after external beam radiation therapy. Histologic evidence suggests that the chronic injury of the ureter expressed at 5 years is of vascular etiology. The early injury may be due to ulceration of the epithelium.

Animals↗

Response of aorta and branch arteries to experimental intraoperative irradiation.

Injury to the aorta was evaluated in dogs 2 and 5 years after fractionated irradiation (EBRT), intraoperative irradiation (IORT) or a combination. Doses greater than 20 Gy IORT combined with 50 Gy EBRT given in 2 Gy fractions or 30 Gy IORT alone were accompanied by a significant risk of aneurysms or large thrombi as determined at necropsy 4 to 5 years following irradiation. Narrowing of the aorta as detected by aortography occurred at 5 years but was not detected earlier. The ED50 for aortic narrowing was 38.8 Gy IORT and 31 Gy IORT plus 50 Gy EBRT. The ED50 for branch artery injury was 24.8 Gy IORT alone and 19.4 Gy IORT plus 50 Gy EBRT. The difference in ED50s for IORT alone and IORT plus EBRT indicates that the contribution of the EBRT dose in terms of an IORT dose for aortic narrowing was 7.8 Gy and for branch artery injury was 5.4 Gy. The ED50 for incidence of small thrombi in the aorta was about 29 Gy for IORT alone and 23.5 Gy for IORT combined with EBRT. Fibrous thickening of the adventitia was measured and the effect of the 50 Gy EBRT component of a combination of EBRT and IORT was determined to be equivalent to 10 to 12 Gy IORT. Based on the various estimates, IORT doses of 10-15 Gy have an effect of 5 times or greater the amount given in 2 Gy fractions. At all EBRT doses and at lower IORT doses the intima was greatly thickened. At IORT doses of 20 Gy or above there was a dose related decrease in intimal thickness to near normal values. This was probably due to cell killing or inhibition of intimal proliferation that predominated at higher doses. Although the risk of serious vascular complications appears low following IORT of humans, this may be due to short observation times and the fact that IORT doses currently used are usually 20 Gy or less; this may be near the tolerance for late response of larger arteries. Only one dog in this study had complete rupture of the aorta causing death. Five other dogs at high IORT doses had near ruptures of the aorta but were clinically normal.

Aortic Dissection↗

Radiographic examination of the equine foot.

A complete radiographic examination of the equine foot consists of properly exposed, processed, and positioned radiographs. For radiographic interpretation, in addition to knowing radiographic signs of disease, a knowledge of normal radiographic anatomy and possible insignificant anatomic variations is necessary.

Animals↗

Ultrasonographic features of splenic lymphosarcoma in dogs: 12 cases (1980-1986).

The ultrasonographic appearance of the spleen and adjacent organs in 12 dogs with splenic lymphosarcoma was reviewed. Poorly marginated hypoechoic to anechoic nodules (4 mm to 3 cm in diameter) were found in all dogs. The anechoic nodules did not result in reflective shadowing or acoustic enhancement of the underlying tissues. The remainder of the splenic parenchyma appeared relatively hypoechoic when compared with the liver or renal cortices in 9 dogs. Recognition of this ultrasonographic pattern appears to be a useful diagnostic tool. Needle aspiration guided ultrasonographically will then enable histologic confirmation of lymphosarcoma.

Animals↗

Ultrasonographic features of splenic hemangiosarcoma in dogs: 18 cases (1980-1986).

The medical records of 18 dogs in which ultrasonography was useful in making a diagnosis of splenic hemangiosarcoma were reviewed. Splenic ultrasonography revealed masses with echo patterns that ranged from anechoic fluid to hyperechoic tissue. In 7 dogs, metastasis was detected ultrasonographically as anechoic to hypoechoic lesions in the liver.

Animals↗

Hypertonic sucrose inhibition of endocytic transport suggests multiple early endocytic compartments.

Incubation of animal cells with hypertonic sucrose and polyethylene glycol (PEG) 1,000 renders endosomes sensitive in situ to hypotonic shock (Okada and Rechsteiner, 1982). We found that: 1) in vitro endosomes were osmotically insensitive; and 2) hypertonic sucrose inhibited transport from very early endosomes to lysosomes. Endocytic vesicles were labeled by incubating Chinese hamster ovary (CHO) cells for 1-10 min at 37 degrees C with horseradish peroxidase (HRP) and/or fluorescein isothiocyanate-conjugated dextran (FITC-dextran). Cell fractions prepared in 0.25 M sucrose were hypotonically shocked by dilution with 5 mM Na phosphate buffer, pH 6.7, to a final sucrose concentration of 0.05 M. After hypotonic shock, endocytized HRP and FITC-dextran pelleted with membrane while lysosomal hydrolases did not. The HRP activity in the pellet was latent, suggesting that endosomes were resistant to osmotic shock. Uptake in the presence of hypertonic sucrose had little effect on the subsequent osmotic sensitivity of the endosomes. Uptake in the presence of hypertonic sucrose and PEG 1,000 rendered endosomes fragile to cell homogenization. Unexpectedly, the inclusion of hypertonic sucrose in the uptake and chase media inhibited the appearance of HRP in lysosomes. HRP internalized during a 10-min uptake appeared as if it were present in two physically distinct compartments, one accessible to transport inhibition by exogenous sucrose ("very early" endosomes) and the other not ("early" endosomes). After a brief uptake (1-3 min), postincubation of CHO cells in 0.25 M sucrose-containing media completely blocked transport of internalized HRP to lysosomes. This blockage could be partially relieved by cointernalization of invertase with HRP. These results suggest that transport between multiple early endosome populations is sensitive to intraorganellar osmotic conditions.

Animals↗

Ultrasonographic diagnosis of portacaval shunts in young dogs.

Ultrasonography was performed on 21 young dogs with portacaval shunts. Initial ultrasonography revealed a small hypovascular liver in all dogs. Eight portacaval shunts (4 intrahepatic, 4 extrahepatic) were detected. Supplementary ultrasonography of dogs under general anesthesia and subjected to positive-pressure ventilation identified 6 additional intrahepatic portacaval shunts.

Animals↗

Chinese hamster ovary cell lysosomes rapidly exchange contents.

We have used cell fusion to address the question of whether macromolecules are rapidly exchanged between lysosomes. Donor cell lysosomes were labeled by the long-term internalization of the fluid-phase pinocytic markers, invertase (sucrase), Lucifer Yellow, FITC-conjugated dextran, or Texas red-conjugated dextran. Recipient cells contained lysosomes swollen by long-term internalization of dilute sucrose or marked by an overnight FITC-dextran uptake. Cells were incubated for 1 or 2 h in marker-free media before cell fusion to clear any marker from an endosomal compartment. Recipient cells were infected with vesicular stomatitis virus as a fusogen. Donor and recipient cells were co-cultured for 1 or 2 h and then fused by a brief exposure to pH 5. In all cases, extensive exchange of content between donor and recipient cell lysosomes was observed at 37 degrees C. Incubation of cell syncytia at 17 degrees C blocked lysosome/lysosome exchange, although a "priming" process(es) appeared to occur at 17 degrees C. The kinetics of lysosome/lysosome exchange in fusions between cells containing invertase-positive lysosomes and sucrose-positive lysosomes indicated that lysosome/lysosome exchange was as rapid, if not more rapid, than endosome/lysosome exchange. These experiments suggest that in vivo the lysosome is a rapidly intermixing organellar compartment.

Acid Phosphatase↗

Oxidation of indole-3-acetic Acid-amino Acid conjugates by horseradish peroxidase.

The stability of 21 amino acid conjugates of indole-3-acetic acid (IAA) toward horseradish peroxidase (HRP) was studied. The IAA conjugates of Arg, Ile, Leu, Tyr, and Val were oxidized readily by peroxidase. Those of Ala, beta-Ala, Asp, Cys, Gln, Glu, Gly, and Lys were not degraded and their recovery was above 92% after 1 hour incubation with HRP. A correlation between the stability of IAA conjugates toward peroxidase-catalyzed oxidation and the hydrophobicity of the amino acid moiety conjugated to IAA was demonstrated. Polar amino acid conjugates of IAA are more resistant to HRP-catalyzed oxidation.

Journal Article↗

Comparison of radiography and ultrasonography in the evaluation of renal lesions in the dog.

Survey abdominal radiographs, excretory urograms, and nephrosonograms were obtained from 14 dogs with renal lesions. Renal enlargement was suspected on survey radiographs and confirmed by excretory urography in 13 dogs. Radiographic differentiation between a solid and cystic renal lesion was not possible in 9 dogs. Ultrasonography determined the presence of solid masses in 12 dogs, established the presence of a renal cyst in the opposite kidney in 1 dog, and revealed hydronephrosis in 2 dogs. Ultrasonography appeared to be more sensitive than radiography in differentiating the internal characteristics of renal lesions.

Animals↗

Periosteal transection and stripping for treatment of angular limb deformities in foals: clinical observations.

Correction was attempted in 27 foals (41 limbs) with angular deformities at the carpal region (35 limbs), metatarsophalangeal region (5 limbs) and distal end of the tibia (1 limb) by hemicircumferential transection of the periosteum (HCTP) and periosteal stripping (PS). Successful outcome was determined by straight limbs and soundness, which was achieved in 81.5% of the cases, with 60% of the horses in performance training. Follow-up evaluation for all foals was completed at various times after physiologic closure of the physes. In none of the limbs was the deformity overcorrected. Owners of foals with carpal region deviations corrected by means of HCTP and PS were satisfied with the result. The cosmetic appearance of the surgical site was excellent. The HCTP and PS adequately corrected greater degrees of carpal region deformity and greater degrees of deformity in older foals than previously reported with this or other surgical techniques.

Animals↗

Periosteal transection and stripping for treatment of angular limb deformities in foals: radiographic observations.

Radiographs of 23 foals (35 forelimbs) with carpal region angular limb deformities, which later were corrected by hemicircumferential transection of the periosteum and periosteal stripping, were evaluated as to geometric and morphologic abnormalities. Geometric evaluation included deviation angle and deviation pivot point. Morphologic abnormalities were categorized as: asymmetric width of the distal radial physis; asymmetric width of the distal radial epiphysis; carpal bone collapse or fracture; carpal bone hypoplasia; carpal bone displacement; and metacarpal bone displacement. Fifty-seven percent of limbs had radiographic lesions in the carpal joints and 20% had lesions in the metacarpus. Of all the limbs, 48% had carpal or metacarpal bone hypoplasia, 26% had carpal or metacarpal bone displacement, and 12% had carpal bone collapse or fragmentation. On long-term followup (5 months to 2 years), 83% of the foals were sound and had straight limbs, regardless of the deviation angle, deviation pivot point, or morphologic carpal bone changes. Sixty percent of the foals were in performance training. About 50% of these foals in performance training had carpal bone hypoplasia before correction of the deviation. It was concluded that geometric and morphologic radiographic interpretation should be performed before surgical correction of carpal angular limb deformities with hemicircumferential transection of the periosteum and periosteal stripping, but that epiphyseal, carpal bone, or metacarpal bone changes, severe deviation angle (20 to 29 degrees) or distal location of the pivot point should not discourage attempted surgical correction.

Animals↗

Patent ductus arteriosus with pulmonary hypertension in the dog.

The clinical, physiologic, and pathologic manifestations of patent ductus arteriosus (PDA) with pulmonary hypertension (right to left type PDA) were studied in 5 dogs. Cyanosis, hindlimb collapse, low-intensity heart murmurs, and splitting of the 2nd heart sound were prominent clinical findings. Secondary polycythemia was a feature in 3 dogs. Electrocardiography revealed marked frontal plane right axis deviation in all dogs. Radiographic findings in all dogs consisted of an enlarged right ventricle and main pulmonary artery segment, with a hypovascular pulmonary pattern. A wide descending aorta was evident in 4 dogs. Pulmonary arteriography revealed blunt, tortuous secondary and tertiary vessels. Blood flow through the PDA was from right to left in 4 dogs and bidirectional in 1. Necropsy of 1 dog revealed extensive pulmonary arterial disease characterized by fibromuscular intimal proliferation. Surgical correction was contraindicated, and medical therapy was not required in the 4 dogs retained by the owners as pets. Due to the persisting congenital heart defect and the real and potential sequelae, the prognosis is guarded.

Animals↗

Osteochondrosis in feedlot cattle.

Beginning in summer 1977 and continuing through four consecutive seasons, we examined lame limb joints from 106 partially fattened cattle and 28,235 pairs of occipital condyles from fully fattened cattle for osteochondrosis. Of the 106 lame cattle, nine (8.5%) had characteristic lesions, usually in their stifle joints, and of the 28,235 atlanto-occipital joints, 1063 (3.8%) had lesions on their condyles. Slices of affected articular cartilage and subjacent bone were studied radiographically and histologically. Radiographs showed subchondral defects and epiphyseal "cyst-like" lesions, and histologic sections showed disarrayed and degenerated chondrocytes. Splits occurred along osteochondral junctions or in adjacent cartilage or bone. Some bone trabeculae had been replaced by fibrous tissue that, in some areas, extended deep into epiphyses.

Animals↗

Limb arthropathies and periarticular injuries in feedlot cattle.

Beginning summer 1977 and continuing through 4 consecutive seasons, we examined samples of at least 25, and a total of 106, lame limbs or joints from slaughtered beef cattle. Of this number about 64 (60%) were articular and 42 (40%) periarticular lesions. Fifty-three were caused by trauma and 9 by osteochondrosis. Stifle joints (40) and digital joints (19) were the most frequently affected articulations, and the humerus and femur were the most frequently fractured bones. Twenty joints, mostly stifles, had fibrinous arthritis, and Mycoplasma spp. were isolated from 11.

Animals↗