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Biomedical subjects

J R Cook

Publications and source records attributed to J R Cook.

At least 91 records · Page 5Linked to original sources
PubMed1991

Congenital peripheral vestibular disease attributed to lymphocytic labyrinthitis in two related litters of Doberman pinscher pups.

Five Doberman Pinscher pups from a litter of 10 (litter A) and 3 of 9 pups from a subsequent mating of the same bitch (litter B) had clinical signs consistent with unilateral or bilateral peripheral vestibular disease. Results of CBC, serum biochemical analysis, urinalysis, ophthalmologic examination, deep otoscopic examination, and CSF analysis were normal in all affected pups. Bacteriologic culture results from CSF were negative and affected pups did not have canine distemper antibody titers in CSF. The most severely affected littermates were euthanatized and necropsied at the owner's request. Gross lesions were not found at necropsy, but marked lymphocytic labyrinthitis was discovered microscopically in decalcified sections of the labyrinthine system. The case history and histologic findings were suggestive of an infectious, most likely viral, cause, but organisms were not isolated from specimens of CNS tissue. The involvement of the same bitch in the 2 litters suggests heritable factors. One mildly affected pup apparently recovered or compensated for its vestibular dysfunction.

Animals↗
PubMed1991

Plasma and cerebrospinal fluid pharmacokinetics of cytosine arabinoside in dogs.

Cytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1 +/- 4.5 min and the mean elimination half-life was 69 +/- 28 min. The mean plasma clearance was 227 +/- 125 ml min-1 m-2. The peak concentration of ara-C in the CSF was 29 +/- 11 microM, which occurred at 57 +/- 13 min after the ara-C bolus. The CSF elimination half-life was 113 +/- 26 min. During a 12-h infusion of ara-C (50 mg m-2 h-1), the plasma steady-state concentration was 14.1 +/- 4.2 microM, the CSF steady-state concentration was 8.3 +/- 1.1 microM, and the CSF: plasma ratio was 0.62 +/- 0.14. The plasma elimination half-life was 64 +/- 19 min and the plasma clearance was 214 +/- 69 ml min-1 m-2. The CSF elimination half-life was 165 +/- 28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS.

Animals↗
PubMed1991

Effect of atenolol and diltiazem on heart period variability in normal persons.

Several time and frequency domain measures of heart period variability are reduced 1 to 2 weeks after myocardial infarction, and a reduced standard deviation of normal RR intervals over a 24 h period (SDNN) is associated with increased mortality. The predictive accuracy of heart period variability may be reduced by drugs used to treat patients after myocardial infarction. Accordingly, a randomized, three period, placebo-controlled, crossover (Latin square) design was used to determine the effect of atenolol and diltiazem on time and frequency measures of heart period variability calculated from 24 h continuous electrocardiographic recordings during treatment with atenolol, diltiazem and placebo in 18 normal volunteers. During atenolol treatment, the 24 h average normal RR (NN) interval increased 24% (p less than 0.001). The three measures of tonic vagal activity were significantly increased (p less than 0.001) during atenolol treatment: percent of successive normal RR intervals greater than 50 ms = 69%, root mean square successive difference of normal RR intervals = 61% and high frequency power in the heart period power spectrum = 84%. Low frequency power also increased 45% (p less than 0.01), indicating that this variable also is an indicator of tonic vagal activity over 24 h. Diltiazem had no significant effect on the 24 h average NN interval or on any measure of heart period variability. The decreased mortality rate after myocardial infarction associated with beta-adrenergic blocker but not calcium channel blocker therapy may be attributed in part to an increase in vagal tone caused by beta-blockers.

Adult↗
PubMed1991

Variability of electrocardiographic precordial lead placement: a method to improve accuracy and reliability.

Variability in precordial lead placement is a recognized source of electrocardiographic inaccuracy and lack of reproducibility. In an attempt to reduce error, we evaluated a new device to facilitate and guide precordial lead placement. This study involved three phases: (1) comparison of device-guided electrocardiogram with ECGs obtained by deliberate misplacement of precordial leads on the same patient; (2) electrocardiograms obtained by using the precordial lead device versus those obtained by standard technician methods; (3) reproducibility of precordial electrocardiographic leads between two technicians using the device to guide lead placement. Deliberate misplacement of precordial leads by 2 cm resulted in significant electrocardiographic interpretation changes in all patients. Comparing electrocardiograms obtained after device-guided precordial placement with those obtained after technician placement resulted in variations in 60% of patients including changes in R-wave amplitude, ST segments, Q waves, and transition zone. Significant Q-wave appearance/disappearance and/or significant ST-segment elevation/depression occurred in 19% of patients in Phase II. Sixteen percent of electrocardiograms showed significant changes when analyzed by an experienced electrocardiographer and 10% when interpreted by computer. Variable lead placements and resulting electrocardiographic alterations were not seen by either of two technicians when the device was used. This study confirms the widespread variability in precordial electrocardiograms secondary to lead misplacement. The use of a device to assist in the placement of precordial leads ensures accuracy and reproducibility of electrocardiography. Improved precision and quality control in this laboratory test have important implications in health care and its costs.

Electrocardiography↗
PubMed1991

Pudendal reflexes and effects of conditioning stimuli in cats.

Evaluation of pudendal reflexes and effects of pudendal branch conditioning on those reflexes was carried out in 2 studies. In the first study of pudendal reflexes, 20 adult male and female mixed-breed cats underwent surgical isolation of the anal branch, urethral branch, and distal trunk (consisting primarily of the dorsal nerve of the penis/clitoris) of the pudendal nerve. Reflexes were tested in all possible ipsilateral and contralateral test-response combinations. Latency values and effects of increasing stimulus rate on response amplitude were recorded. Reflexes were detected in all combinations, with response latencies between 6.3 and 13.0 ms. Response amplitudes were diminished at stimulus rates of 3 to 5 Hz, and responses were apparently abolished at 4 to 16 Hz, suggesting that pudendal reflexes are polysynaptic. In the second study of conditioning effects, 9 adult male and female mixed-breed cats underwent preparation similar to that for study 1. A train of conditioning stimuli was applied to branches of the pudendal nerve prior to attempting to induce reflex responses, as performed in study 1. Conditioning completely abolished reflex responses for a period of 70 to 130 ms. Reflex responses were diminished in amplitude, compared with those observed during preconditioning trials, for 180 to 300 ms after conditioning.

Anal Canal↗
PubMed1991

Comparison of genitoanal and bulbospongiosus reflexes and measurement of penile nerve conduction velocity in cats.

The bulbospongiosus reflex, genitoanal reflex, and nerve conduction velocity of the dorsal nerve of the penis were evaluated in cats. Seven adult sexually intact or castrated male mixed-breed cats underwent surgical isolation of the bulbospongiosus (analagous to bulbocavernosus) branch, anal branch, and distal trunk of the pudendal nerve. The bulbospongiosus and genitoanal reflexes were recorded from the bulbospongiosus and anal branches, respectively, by electrical stimulation, in turn, of the distal pudendal trunk and the penis itself. Nerve conduction velocity of the dorsal nerve of the penis was calculated by measuring response latency differences in the anal branch after stimulation of 2 sites on the extruded penis. The bulbospongiosus reflex had response latencies of 8.1 to 10.3 ms (distal trunk stimulation) and 11.0 to 13.0 ms (penile stimulation). The genitoanal reflex had latencies of 8.1 to 10.5 ms (distal trunk stimulation) and 11.2 to 13.2 ms (penile stimulation). Response amplitudes diminished at stimulus rates of 5 to 10 Hz; responses were abolished at rates of 12 to 15 Hz, suggesting that the reflexes are polysynaptic. There was no significant difference between latency values for the bulbospongiosus and genitoanal reflexes. Mean +/- SD nerve conduction velocity in the dorsal nerve of the penis was calculated to be 3.8 +/- 0.34 m/s, which was considerably slower than that found in human beings. This may represent technical difficulties in performing the test in cats, but could also indicate a difference between cats and human beings in the predominant population of cutaneous sensory fiber types of the penis.

Anal Canal↗
PubMed1991

Measurement of anal and genitoanal reflexes in cats.

Noninvasive determination of anal and genitoanal reflexes was evaluated in clinically normal cats. Thirty adult mixed-breed cats (15 sexually intact or castrated males, 15 sexually intact or spayed females) were sedated by IV administration of ketamine, acetylpromazine, and atropine. Anal reflexes were recorded from the anal sphincter muscle after ipsilateral and contralateral electrical stimulation of the perineal skin. Genitoanal reflexes were recorded from the anal sphincter muscle after electrical stimulation of the penis or clitoris. An anal sphincter response to tibial nerve stimulation was attempted. Anal reflexes from ipsilateral and contralateral stimulations and a genitoanal reflex were detected in all cats. Anal sphincter responses to tibial nerve stimulation were inconsistent (4/30) and were not included in any analyses. Anal reflexes had response latencies of 7.5 to 12.0 ms (ipsilateral stimulation) and 6.5 to 13 ms (contralateral stimulation). Genitoanal reflexes had latencies of 9.0 to 13.0 ms (males) and 6.5 to 9.0 ms (females). Anal reflex latencies were significantly (P less than 0.05) longer for contralateral, opposed to ipsilateral, stimulation and were significantly (P less than 0.05) longer in males than in females. Genitoanal reflex latencies were also significantly (P less than 0.05) longer in males than in females, reflecting the more peripheral stimulation site in males. Anal reflex responses could be recorded in 2 feline clinic patients with such severe perineal trauma that pudendal nerve function could not be manually evaluated A potentially favorable prognosis was given in each instance on the basis of detection of the response. One cat eventually recovered.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal Canal↗
PubMed1990

Fourteen internal transcribed spacers in the circular ribosomal DNA of Euglena gracilis.

Cytoplasmic ribosomes from Euglena gracilis contain 16 rRNA components. These include the typical 5 S, 5.8 S and 19 S rRNAs that are found in other eukaryotes as well as 13 discrete small RNAs that interact to form the equivalent of eukaryotic 25-28 S rRNA (accompanying paper). We have utilized DNA sequencing techniques to establish that genes for all of these RNAs, with the exception of 5 S rRNA, are encoded by the 11,500 base-pair circular rDNA of E. gracilis. We have determined the relative positions of the coding regions for the 19 S rRNA and the 14 components (including 5.8 S rRNA) of the large subunit rRNA, thereby establishing that the genes for each of these rRNAs are separated by internal transcribed spacers. We conclude that sequences corresponding to these spacers are removed post-transcriptionally from a high molecular weight pre-rRNA, resulting in a multiply fragmented large subunit rRNA. Internal transcribed spacers, in positions analogous to some of these additional Euglena rDNA spacers, have been found in the rDNA of other organisms and organelles. This finding supports the view that at least some internal transcribed spacers may have been present at an early stage in the evolution of rRNA genes.

Animals↗
PubMed1990

Acquired myasthenia gravis in a cat with thymoma.

A 4-year-old castrated Abyssinian cat was evaluated for profound neuromuscular weakness. Results of electromyography and repetitive nerve stimulation tests were normal. Thoracic radiography revealed a cranial mediastinal mass, which was excised and identified as a thymoma. Serum acetylcholine receptor antibodies were detected at high concentration, supporting a diagnosis of acquired myasthenia gravis. Clinical signs of disease responded to treatment with pyridostigmine and corticosteroids.

Animals↗
PubMed1990

Alpha-fetoprotein mRNA: variation of half-life in rat hepatoma cell lines and destabilization by sodium butyrate.

The half-life of alpha-fetoprotein (AFP) mRNA was determined in two rat hepatoma cell lines. In the 7777 cell line, AFP mRNA half-life is 30-35 h, consistent with earlier observations (Innis and Miller, 1979). However, the half-life in McA-RH8994 cells is only 14-16 h. Dexamethasone does not affect AFP mRNA half-life in either cell line, indicating that glucocorticoid-mediated alterations in AFP mRNA levels in these cells is at the transcriptional level. The naturally-occurring fatty acid sodium butyrate did, however, cause significantly more rapid degradation of AFP mRNA in McA-RH8994 cells, decreasing the half-life from 14-16 h to only 5-6 h. The ability of sodium butyrate to block glucocorticoid action on AFP gene expression in this cell line is therefore due to both transcriptional and post-transcriptional effects.

Animals↗
PubMed1990

The evaluation of chicken spermatozoa using fluorescent staining in a 96-well format.

An efficient method for the evaluation of spermatozoa using the fluorescent stains carboxyfluorescein diacetate and propidium iodide and an automated fluorescence concentration analyzer was adapted for chicken semen. Arbitrary fluorescence units representing either live or dead spermatozoa were strongly correlated with percentage of added dead spermatozoa and with the direct fluorescent microscope counts of live, dead, and damaged cells.

Animals↗
PubMed1990

Amplitude and latency characteristics of spinal cord motor-evoked potentials in dogs.

The motor-evoked potential can be reliably recorded in anesthetized dogs by use of percutaneous placement of active recording electrodes near the dorsal lamina of the vertebral column. Two types of responses were observed in this study; short (less than 5.5 ms at T9-10)- and long (greater than 5.8 ms at T9-10)-latency waves. Short-latency waves are larger in amplitude and appear with higher stimulus intensities than do long-latency waves. Short-latency waves are conducted at greater than 80 m/s and may not reflect pyramidal tract activation. The safety of using higher intensity stimuli to generate short-latency waves has not been determined.

Animals↗
PubMed1989

Microporosity of the substratum regulates differentiation of MDCK cells in vitro.

We have analyzed the ability of the physical substratum to modulate both the ultrastructural and protein synthetic characteristics of the Madin-Darby canine kidney (MDCK) renal cell line. When MDCK cells were seeded on Millipore Millicell CM microporous membrane cell culture inserts they demonstrated a more columnar organization with an increase in cell density sixfold greater than the same cells seeded on conventional plastic substrata. After 1 wk postseeding on the microporous membrane a partial basal lamina was noted, with a contiguous basement membrane being apparent after 2 wk. One-dimensional sodium dodecyl sulfate gel electrophoresis was used to analyze detergent-solubilized proteins from MDCK cells maintained on plastic substrata vs. microporous membranes. When proteins were pulse-labeled with [35S]methionine, a 55 kDa protein was evident in the cytosolic extract of cells grown on collagen, laminin, and nontreated plastic substrata; but this labeled protein was not evident in similar extracts from cells grown on collagen and laminin-coated microporous membranes. To test if the polarized, basement-membrane secreting phenotype of the MDCK cells could be generated on a microporous membrane without pretreatment with any extracellular matrix (ECM) components, cells were seeded on the Millipore Millicell HA (cellulosic) microporous membrane. This type of substrata does not need a coating of ECM components for cell attachment. A partial basement membrane was formed below cells where the basal surface of the cell was planar, but not in areas where the cell formed large cytoplasmic extensions into the filter. This led us to the conclusion that the microporous nature of the substrata can dictate both ultrastructural and protein synthetic activities of MDCK cells. Furthermore, we suggest that both the planar nature of the basal surface and the microporosity of the substrate are corequisites for the deposition of the basement membrane.

Animals↗
PubMed1988

Seizures as a manifestation of primary hyperparathyroidism in a dog.

Hypercalcemia caused by primary hyperparathyroidism was believed to be responsible for seizures in a dog. A diagnostic evaluation showed no primary causes of seizures. After surgical excision of the adenomatous parathyroid gland, phenobarbital treatment was discontinued, without recurrence of seizures.

Animals↗
PubMed1988

Enhancement of transformed cell growth in agar by serine protease inhibitors.

We investigated the effects of three serine protease inhibitors (leupeptin, soybean trypsin inhibitor, and aprotinin) on the serum-free growth of two transformed cell lines in soft agar. Aprotinin markedly enhanced the growth of rat embryo fibroblasts that had been transformed by polyoma middle T antigen (PyMLV-REF52), while having only a slight effect on the colonial growth of SV40 transformed Balb/c 3T3 cells (SV3T3-Aga). Leupeptin and soybean trypsin inhibitor, on the other hand, significantly enhanced the growth of SV3T3-Aga cells while having little effect on PyMLV-REF52 growth. We observed no stimulatory effect of any of the protease inhibitors on serum-free monolayer growth. Under conditions of excess aprotinin, PyMLV-REF52 cells were found to be unresponsive to epidermal growth factor (EGF) at a concentration that would normally stimulate agar colony growth. However, aprotinin was not capable of supporting colony formation with transforming growth factor-beta. These results indicate that aprotinin acts primarily as a protease inhibitor in spite of its structural homology to EGF and that EGF may promote the soft agar growth of these cell lines either by inhibiting proteolysis directly or by enhancing the synthesis of a serine protease inhibitor.

Antigens, Polyomavirus Transforming↗