Hereditary canine spinal muscular atrophy: genetics, neurophysiology, and pathology.
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Animals↗
Biomedical subjects
S L Green
Publications and source records attributed to S L Green.
Cyclin-dependent protein kinase 5 activity increases in rat brain following ischemia.
Cyclin-dependent kinase 5 (CDK5) is the 34 kDa catalytic subunit of a recently characterized neuronal cdc2-like protein kinase which appears to be involved in regulation of the neurocytoskeleton. Using the rat postdecapitative model, the effect of brain ischemia on histone H1 and tau protein CDK5 phosphorylating activity was examined. Histone H1 kinase activity increased in both cytosolic and particulate fractions of the hippocampus and neocortex after 5 min and 15 min of ischemia, then declined to control levels. CDK5 tau protein phosphorylating activity increased after 15 min ischemia; however, no electrophoretic shifts or changes in radiodensity of the tau bands were observed autoradiographically. On Western blot analysis, the CDK5 protein band did not change after 25 min ischemia, despite the increase and subsequent decline in enzyme activity. These data demonstrate a postischemic increase in CDK5 activity, an associated increase in CDK5 tau phosphorylating activity and a decline in activity in the absence of massive proteolysis. CDK5 appears to play a role in the events associated with neuronal response to ischemic injury.
Animals↗
Rabies.
Equine rabies is a sporadic but highly fatal zoonotic disease. The disease persists in wildlife populations throughout the United States, Canada, Mexico, and other parts of the world. It remains a threat to all domestic species, including the horse. This article reports recent advances in the molecular virology of the rabies virus and its pathogenesis, and it also reviews the history, clinical signs, diagnostic tests, vaccination protocols, and postexposure management recommendations for the equine species.
Animals↗
Differences in the prevalence of a TaqI RFLP in the 3' flanking region of the alpha 1-proteinase inhibitor gene between asthmatic and non-asthmatic black and white South Africans.
The prevalence of the Taq I(-) allele in variants of alpha 1-proteinase inhibitor (alpha 1PI) was investigated in a group of 28 black asthmatic patients and 32 black control individuals, and was compared to 43 white asthmatic patients and 32 white control individuals. The plasma concentration of alpha 1PI was determined in eight black and 14 white asthmatics without the Taq I(-) allele, and compared to seven black and three white asthmatics with the Taq I(-) allele. Alpha-1-PI concentration was also determined in 10 black and 29 white control individuals without the Taq I(-) allele and compared to seven black and three white controls with the Taq I(-) allele. There was a highly significant difference in the frequency of the Taq I(-) allele between black South Africans (24.1%) and white South Africans (6%) (p < 0.00001) and a significant difference in the frequency of the Taq I(-) allele between black asthmatics and white asthmatics (p = 0.0004) and between black controls and white controls (p = 0.011). The Taq I(-) allele was significantly associated with the M1 (Val213) variant as compared to the M1 (Ala213) of alpha 1PI (p = 0.0042). There was no difference in the concentration of alpha 1PI between the asthmatics (black and white) lacking the Taq I(-) allele and the asthmatics (black and white) with the allele. However, a significant increase in plasma alpha 1PI concentration was found in the asthmatics compared to the controls (p = 0.011). The Taq I(-) allele did not seem to interfere with the basal expression of alpha 1PI in the groups of asthmatic patients in this study.
Adolescent↗
The tactual horizontal-vertical illusion depends on radial motion of the entire arm.
We sought to clarify the causes of the tactual horizontal-vertical illusion, where vertical lines are overestimated as compared with horizontals in L and inverted-T figures. Experiment 1 did not use L or inverted-T figures, but examined continuous or bisected horizontal and vertical lines. It was expected that bisected lines would be perceived as shorter than continuous lines, as in the inverted-T figure in the horizontal-vertical illusion. Experiment 1 showed that the illusion could not be explained solely by bisection, since illusory effects were similar for continuous and bisected vertical and horizontal lines. Experiments 2 and 3 showed that the illusory effects were dependent upon stimulus size and scanning strategy. Overestimation of the vertical was minimal or absent for the smallest patterns, where it was proposed that stimuli were explored by finger movement, with flexion at the wrist. Larger stimuli induce whole-arm motions, and illusory effects were found in conditions requiring radial arm motion. The illusion was weakened or eliminated in Experiment 4 when subjects were forced to examine stimuli with finger-and-hand motion alone, that is, their elbows were kept down on the table surface, and they were prevented from making radial arm motions. Whole-arm motion damaged performance and induced perceptual error. The experiments support the hypothesis that overestimation of the vertical in the tactual horizontal-vertical illusion derives from radial scanning by the entire arm.
Adolescent↗
The DNA damage response in DNA-dependent protein kinase-deficient SCID mouse cells: replication protein A hyperphosphorylation and p53 induction.
Severe combined immunodeficient (SCID) mice display an increased sensitivity to ionizing radiation compared with the parental, C.B-17, strain due to a deficiency in DNA double-strand break repair. The catalytic subunit of DNA-dependent protein kinase (DNA-PKCS) has previously been identified as a strong candidate for the SCID gene. DNA-PK phosphorylates many proteins in vitro, including p53 and replication protein A (RPA), two proteins involved in the response of cells of DNA damage. To determine whether p53 and RPA are also substrates of DNA-PK in vivo following DNA damage, we compared the response of SCID and MO59J (human DNA-PKcs-deficient glioblastoma) cells with their respective wild-type parents following ionizing radiation. Our findings indicate that (i) p53 levels are increased in SCID cells following ionizing radiation, and (ii) RPA p34 is hyperphosphorylated in both SCID cells and MO59J cells following ionizing radiation. The hyperphosphorylation of RPA p34 in vivo is concordant with a decrease in the binding of RPA to single-stranded DNA in crude extracts derived from both C.B-17 and SCID cells. These results suggest that DNA-PK is not the only kinase capable of phosphorylating RPA. We conclude that the DNA damage response involving p53 and RPA is not associated with the defect in DNA repair in SCID cells and that the physiological substrate(s) for DNA-PK essential for DNA repair has not yet been identified.
Animals↗
Iron deprivation inhibits cyclin-dependent kinase activity and decreases cyclin D/CDK4 protein levels in asynchronous MDA-MB-453 human breast cancer cells.
Iron chelation, known to block progression through the cell cycle, was examined for effects on the activity and subunit levels of the cyclin-dependent protein kinases (cdk). Treatment of asynchronous MDA-MB-453 cells with the iron chelators mimosine or desferrioxamine (DFO) for 24 h stopped cell division, but did not produce a single, synchronous block. DNA content analysis demonstrated that although a majority of the cells were blocked in G1 (87.3%), an unexpectedly large fraction of the cells were blocked in S phase (11.5%). Western blot analysis of the treated lysates demonstrated the presence of cyclin B, confirming that part of the cell population was blocked in S phase. After release from mimosine treatment, 84% of the cell population remained in G1 up to 8 h. Treating breast cancer cells with 400 microM mimosine for 24 h inhibited cyclin E- and cyclin A-associated kinase activity by 85% or more, although immunoblots using anti-cyclin A, cyclin E, cdc2, and cdk2 antibodies showed that these key subunits were still present in the cells at pretreatment levels. Interestingly, Western blot analysis also demonstrated that iron chelation decreased the protein levels of the cyclin D and cdk4 subunits as compared to control and produced a change in retinoblastoma protein phosphorylation. These results indicate that iron deprivation effects the activity and protein levels of the cyclin-dependent kinases, and ultimately, the pathways that control cell division.
Breast Neoplasms↗
Perceived non-dextrality. A marker for schizophrenia?
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Adult↗
Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.
OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.
AIDS-Related Complex↗
Efficacy of oral fleroxacin in bone and joint infections.
Bone and joint infections have traditionally required long-term parenteral antimicrobial therapy, which is often expensive and inconvenient. Because of their excellent absorption and tissue penetration, oral quinolones may provide an alternative to parenteral therapy. This multicenter study was designed to evaluate the efficacy and safety of oral fleroxacin in osteomyelitis and septic arthritis. A total of 96 patients with either septic arthritis or acute or chronic osteomyelitis from 17 U.S. centers were enrolled in a noncomparative study using oral fleroxacin 400 mg per day. Patients with implantable devices were excluded. Proof of infection for evaluability required clinical findings in addition to bacteriologic recovery of a susceptible organism from synovial fluid or bone. Treatment lasted 2-12 weeks. Clinical and bacteriologic outcomes were judged at the conclusion of therapy and in the 6-week follow-up period. A total of 30 patients qualified for efficacy analysis (26 osteomyelitis, 4 septic arthritis). Bacteriologic cure was achieved in 77% of the osteomyelitis group and 50% of the septic arthritis group. Clinical cures were reported in 54% of the osteomyelitis group and 50% of the septic arthritis group. Staphylococcus aureus was the most frequently recovered pathogen (62% evaluable cases). Safety was evaluated in 96 patients. The most common side effects were nausea, vomiting, and skin reactions. Oral fleroxacin may be a safe, effective, and certainly less expensive alternative to standard intravenous antimicrobial therapy in patients with bone and joint infections.
Administration, Oral↗
Equine rabies.
With the continued increase in the number of wildlife rabies cases reported across the United States and Canada, this disease will remain a threat to the horse as the potential for exposure to infected wildlife and other domestic animals is likely to also increase. Because there are no rapid, definitive antemortem diagnostic tests, the tentative diagnosis is based upon the variable and sometimes nonspecific clinical signs. Although the CSF analysis may be helpful in some cases, it may not be abnormal. Nor is collection of the specimen always practical in the field situation. The FAT on neural tissue remains the most accurate diagnostic test; therefore, the diagnosis of rabies can be definitively made only at necropsy. Vaccination of horses with the inactivated rabies vaccines is thought to be safe and effective and may be advised for horses in endemic areas. Practitioners should consult with state or provincial authorities regarding the need for vaccination in their area. Veterinary technicians, veterinarians, and other animal health workers should be vaccinated against rabies.
Animals↗
Vesicular stomatitis in the horse.
Vesicular stomatitis (VS) is a viral disease of livestock that results in vesicles and ulcerations on the teats, oral mucosa, tongue, and coronary bands. All three main serotypes of the VS virus can infect the horse. Although VS does not have a major impact on the equine industry, it is clinically identical to the other more economically devastating vesicular diseases of cattle and swine and can produce influenza-like symptoms in humans. VS in horses is reportable, as are all vesicular diseases of livestock.
Animals↗
Adult respiratory distress syndrome with or without systemic disease associated with infections due to Mycoplasma fermentans.
An unusual but typical clinicopathological presentation was noted among several groups of previously healthy, human immunodeficiency virus-negative patients who had an apparent fulminant infectious disease but had no etiologic agent identified. The clinical courses were characterized by rapid progression and development of adult respiratory distress syndrome with or without systemic disease. Histopathological changes in the diseases tissues (other than lung) obtained by biopsy or at autopsy ranged from extensive necrosis with only minimal inflammatory reaction to prominent lymphohistiocytic infiltrate with focal areas of acute inflammation. This report focuses on pulmonary changes in three patients. The alveolar epithelial (type I) cells and type II pneumocytes are diffusely damaged. There is interstitial edema and thickened septa. An eosinophilic alveolar membrane may form, and the alveolar space may fill with foamy macrophages. Immunohistochemical studies identified Mycoplasma fermentans infection in the patients' lungs and liver. Mycoplasma-like particles could also be identified by electron microscopy. There is a previously unrecognized form of fulminant disease in humans that is associated with M. fermentans infections.
Adult↗
Clinical pharmacokinetics of amikacin in hypoxic premature foals.
The pharmacokinetics of amikacin, administered iv at 7 mg/kg, every 8 h, were evaluated over the first 48 h of hospitalisation in 7 critically ill hypoxic premature foals and compared with those in 8 full-term nonhypoxic critically ill neonatal foals. The pharmacokinetic data were used to calculate dosage schedules that would maintain the plasma amikacin concentrations in individual foals within a target range of > or = 15 micrograms/ml but < 30 micrograms/ml for peak values and < or = 3 micrograms/ml for trough values. The results indicated a statistically significant increase in the amikacin serum half-life (5.39 +/- 3.46 h) and smaller elimination rate constant (0.17 +/- 0.09 h-1) in premature foals. The pharmacokinetic derangements required increasing the dose to 8.5-10.5 mg/kg bwt in 6 of 7 premature foals and an increase in the dosage interval to 12-24 h in all 7 foals. Overall, the total dosage of amikacin was decreased in the hypoxic, premature foals so that target peaks and troughs could be maintained. Our findings suggest that prematurity and hypoxia are variables related to a prolonged serum half-life of amikacin in hypoxic, premature foals. Although there was no evidence of amikacin-induced nephrotoxicity in any of these foals, daily monitoring and tailoring of the dose schedule to the individual foal are strongly advised.
Amikacin↗
Diagnosis and prediction of cervical vertebral malformation in thoroughbred foals based on semi-quantitative radiographic indicators.
Over a period of 5 years on a central Kentucky Thoroughbred stud farm 132 foals were evaluated for the presence of cervical vertebral malformation (CVM). Lateral cervical vertebral radiographs were obtained on 70 standing foals. These radiographs were evaluated semi-quantitatively and scored numerically for the presence of stenosis of the vertebral canal, enlarged physeal growth plates, caudal extension of the dorsal border of the orifice of the vertebral canal, angular fixation, delayed ossification of bone and degenerative joint disease. From these scores a total CVM score was given for each set of radiographs. All foals were repeatedly examined for clinical signs of neurological disease. Foals with no clinical signs of CVM had maximal total CVM scores (mean +/- sd) of 5.7 +/- 2.8 and foals affected with CVM had maximal total CVM scores of 17.0 +/- 2.8. Determination of the total CVM score was non-invasive, inexpensive and a very accurate procedure for predicting and diagnosing the presence of CVM in Thoroughbred foals up to 1 year of age.
Animals↗
Postanesthetic recumbency associated with hyperkalemic periodic paralysis in a quarter horse.
Anesthesia and surgery in a Quarter Horse affected with hyperkalemic periodic paralysis resulted in euthanasia after 7 days of postoperative recumbency. Initial recovery was uneventful after extensive sinus surgery, but within 2 hours, the horse had severe muscle weakness. Plasma electrolyte concentrations were within the normal range during the period of recumbency. There was no clinical or laboratory evidence of severe muscle damage. Despite treatment with acetazolamide, isoproterenol, and intensive nursing, the horse was unable to stand for more than a few seconds and developed severe decubital ulcers. Ultrastructural examination revealed nemaline rods and swollen mitochondria in disrupted myofibers.
Anesthesia, General↗
Meningitis in neonatal calves: 32 cases (1983-1990).
Case records of 32 neonatal calves with the antemortem diagnosis of meningitis were reviewed. Mean age at admission was 6 days (range, 11 hours to 30 days), and the most common concurrent clinical problem was diarrhea (16/32). Twenty-seven of the calves were available for necropsy. At postmortem, there was evidence of septicemia in 22 (81%) of these calves. Escherichia coli was the organism most frequently isolated (11/16; 69%) from the CNS. The major clinical signs of CNS disturbance observed over the course of hospitalization were lethargy, recumbency, anorexia, loss of suckle reflex, and coma. Leukocytosis and a left shift was evident in 11 of 15 (73%) calves. Concurrent metabolic problems that could have aggravated the CNS disturbance included hyperkalemia and respiratory acidosis. Analysis cerebrospinal of fluid from 22 of the calves, revealed pleocytosis, xanthochromia, turbidity, and high total protein concentration. Cytologically, neutrophils predominated in the CSF in calves with acute disease. Mononuclear cells dominated in calves with chronic disease. Microscopically, bacteria were evident in 10 of 22 (45%) of the antemortem CSF samples and bacteria were isolated from slightly more than half (11/19) of the specimens subjected to microbial culturing. Escherichia coli was the agent most frequently isolated from the CSF. Two of the 9 E coli isolates were resistant to trimethoprim potentiated sulfonamide drugs and all (4/4) of the CSF E coli isolates tested for susceptibility to triple-sulfonamide drugs were resistant. Twenty-seven of the 32 calves died or were euthanatized within 2.43 days after hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Rabies in horses: 21 cases (1970-1990).
The records of 21 horses with rabies were reviewed. Results of fluorescent antibody testing for rabies antigen in brain tissue were positive in each case. According to the histories, 5 of the horses had been vaccinated for rabies between 4 to 24 months prior to the onset of the clinical signs. Bite wounds were not observed on any of the horses, and exposure to a suspected rabid animal was witnessed in only 5 cases. Clinical signs of disease at the time of initial examination included ataxia and paresis of the hindquarters (9/21, 43%), lameness (5/21, 24%), recumbency (3/21, 14%), pharyngeal paralysis (2/21, 10%), and colic (2/21, 10%). The major clinical signs observed over the course of hospitalization included recumbency (21/21; 100%), hyperesthesia (17/21; 81%), loss of tail and anal sphincter tone (12/21; 57%), fever (11/21; 52%), and ataxia and paresis of the hindquarters (11/21; 52%). Mean survival time after the onset of clinical signs was 4.47 days (range, 1 to 7 days). Supportive treatment, given to 9 horses, had no effect on survival time and did not correlate with the detection of negri bodies at necropsy. Cerebrospinal fluid (CSF) was obtained from 6 horses and was determined to be abnormal in 5. The most common abnormality was a slightly high total cell count (5/6), with a predominance of lymphocytes (4/6). The CSF total protein concentration was high in only 2 horses. At necropsy, there was gross evidence of diffuse brain edema, meningeal congestion, and focal areas of hemorrhage in 5 horses (24%).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗