Biomedical subjects

S Arnold

Publications and source records attributed to S Arnold.

At least 55 records · Page 3Linked to original sources

PubMed2001

Identification of focal adenomyosis as a uterine lesion in two dogs.

A focal uterine adenomyosis is described in two bitches. In both cases, the uterus showed knobbly enlargements of 4 to 8 cm in diameter, which resulted in distinct clinical symptoms. Other pathological changes of the uterus were not present. One bitch was presented because of a history of vaginal discharge of several months' duration. Radiographs, as well as ultrasonography, revealed a soft tissue lesion at the cervix. The other bitch showed a marked reduction in its general condition and a sudden onset of a tense abdomen. Radiologically, a lesion of soft tissue opacity was observed in the mid-abdomen and was seen to originate from the left uterine horn during exploratory laparotomy. A torsion of the lesion was present, which explained the clinical signs in this second case.

Animals↗

PubMed2001

New control of mitochondrial membrane potential and ROS formation--a hypothesis.

A new control of mitochondrial membrane potential delta(psi)m and formation of reactive oxygen species (ROS) is presented, based on allosteric ATP-inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP ratios. Since the rate of ATP synthesis by the ATP synthase is already maximal at low membrane potentials (100-120 mV), the ATP/ADP ratio will also be maximal at this delta(psi)m (at constant rate of ATP consumption). Therefore the control of respiration by the ATP/ADP-ratio keeps delta(psi)m low. In contrast, the known 'respiratory control' leads to an inhibition of respiration only at high delta(psi)m values (150-200 mV) which cause ROS formation. ATP-inhibition of cytochrome c oxidase is switched on and off by reversible phosphorylation (via cAMP and calcium, respectively). We propose that 'stress hormones' which increase intracellular [Ca2+] also increase delta(psi)m and ROS formation, which promote degenerative diseases and accelerate aging.

Adenosine Triphosphate↗

PubMed2001

Immunogenetic markers and seropositivity predict radiological progression in early rheumatoid arthritis independent of disease activity.

OBJECTIVE: A prospective clinical study of patients with recent onset rheumatoid arthritis (RA) to examine the relationship between inflammatory disease activity and joint destruction in a 4 year followup, and to evaluate prognostic markers for severe joint erosions early in the disease. METHODS: Eighty-seven patients with RA according to the American College of Rheumatology criteria and a disease duration < 2 years were followed for an observation time of 2 to 4 years (mean 3.1 yrs). Variables of clinical and laboratory disease activity were monitored, and HLA-DRB1 alleles were determined. Hand and foot radiographs were taken every 6 months. RESULTS: Multivariate analysis of independent contributions of covariates to progression of joint destruction resulted in a mixed effect regression model with significant influences for the presence of a shared epitope (SE) positive DR4 allele (SE+ DR4+; p = 0.007), rheumatoid factor (RF) IgA (p = 0.01), and sex (p = 0.059), but not for clinical variables or acute phase reactants. The odds ratio to reach a Larsen score above 32 during the observation period of 4 years was increased in patients positive for RF IgM (OR 2.7, p = 0.019), for the shared epitope on a DR4 allele (OR 8.6, p < 0.005), and in patients with erosions already at study entry (OR 11.9, p = 0.001). The highest sensitivity and specificity for the prediction of severe bone destruction (84% and 79%) were found when the presence of either a SE+ DR4 allele or of early erosions was used as a prognostic marker (OR 20.4, p < 0.0001). CONCLUSION: Our results show the pace of joint destruction in RA to be influenced by the presence of SE+ DR4 alleles, RF production, and sex and by the presence of erosive disease at presentation. Those prognostic markers exert their influence independently from the inflammatory disease activity.

Adult↗

PubMed2001

Lhermitte-Duclos disease: assessment with MR imaging, positron emission tomography, single-photon emission CT, and MR spectroscopy.

SUMMARY: Lhermitte-Duclos disease (LDD) is a rare cerebellar lesion with features of both malformation and benign neoplasm. However, the fundamental nature of the entity, its pathogenesis, and the exact genetic alterations remain unknown. We describe MR findings (including perfusion- and diffusion-weighted images) in two patients with LDD, as well as findings from single-photon emission CT (SPECT), MR spectroscopy (MRS), and fluorodeoxyglucose (FDG) positron emission tomography (PET) that give additional information about tumor pathophysiology. MR imaging usually distinguishes the LDD by its characteristic "tiger-striped" appearance. The regions of increased regional cerebral blood volume (rCBV) within the lesion correlated closely to the regions of FDG-hypermetabolism and high thallium (201-Tl) uptake. Proton MRS revealed an increased level of lactate and decreased level of myo-inositiol and N-acetyl-aspartate, as observed in low-grade gliomas, but decreased levels of choline. Our cases indicate that the functional investigations give additional information about tumor pathophysiology and reflect the histopathologic controversial entity with both characteristics found in low-grade gliomas and characteristics not typical for tumors.

Adult↗

PubMed2001

The relationship of urinary incontinence to early spaying in bitches.

It is still controversial whether a bitch should be spayed before or after the first oestrus. It would be desirable to spay bitches at an age that would minimize the side effects of neutering. With regard to the risk of mammary tumours, early spaying must be recommended because the incidence of tumours is reduced considerably. The aim of the present study was to determine whether early spaying also reduces the risk of urinary incontinence. The owners of 206 bitches that had been spayed before their first oestrus and for at least 3 years were questioned on the occurrence of urinary incontinence as a result of spaying. At the time of the enquiry the average age of the bitches was 6.5 years, and the average age at the time of surgery was 7.1 months. Urinary incontinence after spaying occurred in 9.7% of bitches. This incidence is approximately half that of spaying after the first oestrus. Urinary incontinence affected 12.5% of bitches that were of a large body weight (> 20 kg body weight) and 5.1% of bitches that were of a small body weight (< 20 kg body weight). The surgical procedure (ovariectomy versus ovariohysterectomy) had no influence on the incidence, or on the period between spaying and the occurrence of urinary incontinence. Urinary incontinence occurred on average at 2 years and 10 months after surgery and occurred each day, while the animals were awake or during sleep. However, compared with late spaying the clinical signs of urinary incontinence were more distinct after early spaying.

Aging↗

PubMed2001

A male to female sex-reversed dog with a reciprocal translocation.

A registered female Yorkshire terrier aged 3 years was diagnosed as intersex. Molecular and cytogenetic studies were carried out to determine whether chromosomal abnormalities were involved in the development of this condition. Analysis of the testicular tissue in the gonads and PCR amplification of three canine Y chromosome-specific DNA sequences from the genomic DNA of this animal indicated that the dog had a genetic complement with a Y chromosome. An analysis of > 100 banded metaphase chromosome spreads of this intersex dog showed uniformly a 78,XY chromosome complement and confirmed that the animal might be a male to female sex-reversed dog. However, two different types of X chromosome were observed. A whole chromosome painting probe was developed by microdissection of ten X chromosomes from the intersex dog and used for fluorescence in situ hybridization experiments on metaphase chromosome spreads from a normal male dog. Hybridization signals were detected on the X chromosome and on an autosome (not yet internationally standardized) indicating that a reciprocal translocation event had occurred. The karyotype of this mosaic sex-reversed dog was designated tentatively as 78,XY/78,XYrcp (X; autosome). This is believed to be the first report of a canine intersex dog showing male to female sex reversal. Further investigations should identify the autosome and the breaking points of the chromosomal rearrangement. These investigations potentially add to our knowledge of autosomal and X-linked loci involved in sexual differentiation of mammals.

Animals↗

PubMed2000

A switch mechanism for G beta gamma activation of I(KACh).

G protein-gated inwardly rectifying potassium (GIRK) channels are a family of K(+)-selective ion channels that slow the firing rate of neurons and cardiac myocytes. GIRK channels are directly bound and activated by the G protein G beta gamma subunit. As heterotetramers, they comprise the GIRK1 and the GIRK2, -3, or -4 subunits. Here we show that GIRK1 but not the GIRK4 subunit is phosphorylated when heterologously expressed. We found also that phosphatase PP2A dephosphorylation of a protein in the excised patch abrogates channel activation by G beta gamma. Experiments with the truncated molecule demonstrated that the GIRK1 C-terminal is critical for both channel phosphorylation and channel regulation by protein phosphorylation, but the critical phosphorylation sites were not located on the C terminus. These data provide evidence for a novel switch mechanism in which protein phosphorylation enables G beta gamma gating of the channel complex.

Amino Acid Sequence↗

PubMed2000

A multicenter investigation with D-FISH BCR/ABL1 probes.

Twenty-eight laboratories evaluated a new fluorescence in situ hybridization (FISH) strategy for chronic myeloid leukemia. In a three-part study, bcr/abl1 D-FISH probes were used to study bone marrow specimens. First, laboratories familiarized themselves with the strategy by applying it to known normal and abnormal specimens. Then, collectively the laboratories studied 20 normal and 20 abnormal specimens blindly and measured workload. Finally, each laboratory and two experts studied six serial dilutions with 98-0% abnormal nuclei. Using the reported normal cutoff of < 1% abnormal nuclei, participants reported no false-negative cases and 15 false-positive cases (1-6.6% abnormal nuclei). Results provided by participants for serial dilutions approximated the expected percentages of abnormal nuclei, but those from the experts exhibited greater precision. The clinical sensitivity, precision, nomenclature, workload, recommendations for training, and quality assurance in methods using D-FISH in clinical practice are discussed.

Bone Marrow↗

PubMed2000

Massive cerebral embolization: successful treatment with retrograde perfusion.

Stroke is an unpredictable and morbid complication of cardiac operations. We report a patient who suffered massive bilateral cerebral embolization during aortic cannulation for coronary bypass. This was treated successfully with hypothermic circulatory arrest and high flow retrograde cerebral perfusion. The patient suffered only minimal neurologic impairment and improved rapidly. She was discharged home on postoperative day 7 neurologically intact.

Aged↗

PubMed2000

Mitochondrial energy metabolism is regulated via nuclear-coded subunits of cytochrome c oxidase.

A new mechanism on regulation of mitochondrial energy metabolism is proposed on the basis of reversible control of respiration by the intramitochondrial ATP/ADP ratio and slip of proton pumping (decreased H+/e- stoichiometry) in cytochrome c oxidase (COX) at high proton motive force delta p. cAMP-dependent phosphorylation of COX switches on and Ca2+-dependent dephosphorylation switches off the allosteric ATP-inhibition of COX (nucleotides bind to subunit IV). Control of respiration via phosphorylated COX by the ATP/ADP ratio keeps delta p (mainly delta psi(m)) low. Hormone induced Ca2+-dependent dephosphorylation results in loss of ATP-inhibition, increase of respiration and delta p with consequent slip in proton pumping. Slip in COX increases the free energy of reaction, resulting in increased rates of respiration, thermogenesis and ATP-synthesis. Increased delta psi(m) stimulates production of reactive oxygen species (ROS), mutations of mitochondrial DNA and accelerates aging. Slip of proton pumping without dephosphorylation and increase of delta p is found permanently in the liver-type isozyme of COX (subunit VIaL) and at high intramitochondrial ATP/ADP ratios in the heart-type isozyme (subunit VIaH). High substrate pressure (sigmoidal v/s kinetics), palmitate and 3,5-diiodothyronine (binding to subunit Va) increase also delta p, ROS production and slip but without dephosphorylation of COX.

Animals↗

PubMed2000

Turkey cytochrome c oxidase contains subunit VIa of the liver type associated with low efficiency of energy transduction.

Cytochrome c oxidase was isolated from turkey liver, heart and breast skeletal muscle and separated by SDS/PAGE. The N-terminal amino-acid sequence of subunit VIa from all tissues and internal sequences from the skeletal muscle enzyme show homology to the mammalian liver-type subunit VIaL, which was verified by isolation and sequencing of the cDNA of turkey subunit VIa. No cDNA corresponding to subunit VIaH (mammalian heart-type) could be found by RACE-PCR with mRNA from all turkey tissues. Measurement of proton translocation with the reconstituted enzymes from turkey liver and heart revealed H+/e- ratios below 0.5 that were independent of the intraliposomal ATP/ADP ratio, as previously found with the bovine liver enzyme. Under identical conditions, the bovine heart enzyme revealed H+/e- ratios of 0.85 at low and 0.48 at high intraliposomal ATP/ADP ratios. The results suggest that in birds the lower H+/e-ratio of cytochrome c oxidase participates in elevated resting metabolic rate and thermogenesis.

Adenosine Diphosphate↗

PubMed2000

Response to steroid therapy in autism secondary to autoimmune lymphoproliferative syndrome.

We report a child who developed autoimmune lymphoproliferative syndrome (ALPS) secondary to a heterozygous dominant negative mutation in the death domain of the Fas receptor. Previously developmentally normal, he had symptoms of autism with rapid regression in developmental milestones coincident with the onset of lymphoproliferation and autoimmune hemolytic anemia. Low-dose steroid therapy induced early and complete remission in the ALPS phenotype. There was subjective improvement, followed by objective improvement in speech and developmental milestones. We propose that autism may be part of the autoimmune disease spectrum of ALPS in this child, and this case represents a novel manifestation and target organ involvement in this disease.

Apoptosis↗

PubMed2000

The significance of preformed aprotinin-specific antibodies in cardiosurgical patients.

UNLABELLED: Acute hypersensitivity reactions are serious complications of reexposure to aprotinin. Previous contact via infusions or fibrin tissue adhesives can induce specific antibodies. In this study, we aimed to elucidate the preoperative prevalence of aprotinin-specific antibodies in patients scheduled for cardiac operations. Sera of 520 consecutive cardiosurgical patients were collected preoperatively and screened retrospectively for aprotinin-specific IgG using a standard enzyme-linked immunosorbent assay (ELISA). Positive sera were analyzed also for aprotinin-specific IgA (ELISA) and IgE (fluorescence enzyme immunoassay). The histories of all patients were reviewed with focus on aprotinin preexposure. Of 520 patients, 22 (4%) had specific IgG. Only three of these had a documented aprotinin preexposure. Of 448 patients exposed to aprotinin intraoperatively, 15 had preformed specific antibodies. The only patient presenting with severe anaphylaxis was positive for both IgG and IgE, and had a recent IV preexposure in cardiovascular surgery. The presence of aprotinin-specific IgG alone seems not to induce adverse reactions on exposure. Exposure history alone is not sensitive enough to identify patients with aprotinin-specific antibodies. IMPLICATIONS: Anaphylaxis on IV reexposure to aprotinin is a medical emergency. The clinical significance of preformed aprotinin-specific IgG remains questionable, whereas preformed IgE was present in the only patient who suffered from severe anaphylaxis on reexposure to aprotinin. Preformed antibodies are not reliably predicted by exposure history.

Aged↗

PubMed2000

Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia.

PURPOSE: Comparison of regional reduction of GABA receptor binding and seizure onset zone in patients with extratemporal epilepsy due to focal cortical dysplasia. METHODS: Two patients with frontal lobe epilepsy who remained seizure free after partial frontal lobe resection were investigated with magnetic resonance imaging, positron emission tomography (PET) with 18F-fluoro-deoxy-glucose (FDG) and 11C-flumazenil, subdural EEG-video recordings, and postoperative benzodiazepine (BDZ)-receptor autoradiography. RESULTS: The area of reduced BDZ-receptor binding as documented by preoperative flumazenil-PET and postoperative BDZ-receptor autoradiography corresponded to the seizure onset zone and was smaller than the interictal hypometabolism documented by FDG-PET. CONCLUSION: Flumazenil-PET is a useful tool for localization of the epileptogenic zone in patients with extratemporal epilepsy caused by focal cortical dysplasia. Neuronal distribution of BDZ-receptor density confirms in vivo flumazenil-PET findings. The regional reduction of BDZ-receptor binding in focal cortical dysplasia seems to be confined to the seizure onset zone and not to the extent of dysplastic cortex.

Adolescent↗

PubMed2000

Tonic seizures: their significance for lateralization and frequency in different focal epileptic syndromes.

PURPOSE: To determine whether the clinical features of tonic seizures (TSZ) are useful for lateralization of epileptic syndromes and the differential diagnosis of focal epileptic syndromes. METHODS: From a group of 481 patients, 123 patients with TSZ (44 females; mean age, 22.9 years; mean age at onset, 7 years; mean duration of epilepsy, 16 years) were selected. A total of 1595 epileptic seizures, documented during videoelectroencephalographic monitoring, were analyzed. Patients who had had surgery for epilepsy previously were excluded. Seizures were classified using a semiological seizure classification. Epilepsy syndromes were classified using all test data (electroencephalography, magnetic resonance imaging, computed tomography, positron emission tomography, and single-photon emission tomography). Data were compared using chi2 analysis or the Fisher exact test. RESULTS: More patients with TSZ had extratemporal than temporal lobe epilepsies (79% vs. 1.7%; p < 0.0001) among those with an epilepsy localized to one lobe (n = 306). In the 123 patients, TSZ were part of 170 different seizure evolutions. Seizure evolutions began with TSZ as the first seizure type more often in patients with frontal lobe epilepsy (FLE) compared with patients with parieto-occipital lobe epilepsy (POLE) (40% in POLE vs. 67% in FLE; p < 0.05). In contrast, TSZ in POLE were more likely to be preceded by auras (50% in POLE vs. 26% in FLE; p < 0.05). TSZ were bilateral in 129 (76%) and unilateral in 41 (24%) seizure evolutions. Unilateral TSZ correctly lateralized the epilepsy syndrome to the contralateral hemisphere. CONCLUSION: Analysis of seizure semiology and evolution in patients with TSZ is helpful for differentiating between focal epilepsies of temporal, frontal, and parieto-occipital origin. Unilateral TSZ provide useful information for the lateralization of the epileptic syndrome.

Adult↗

PubMed2000

Palmoplantar hyperkeratosis in Irish terriers: evidence of autosomal recessive inheritance.

An abnormal development of the epidermis of the footpad was observed in Irish terriers. At the age of six months, the affected animals developed smooth parchment-like footpads. The pad epidermis then hardened and grew lateral cone-like protrusions of up to 5 mm in diameter. Fissures and cracks developed and these predisposed the animal to secondary infection. The repeated occurrence in subsequent generations led to the assumption of a hereditary form of hyperkeratosis. Evidence for an autosomal recessive mode of inheritance was derived from a retrospective analysis of the breeder's records. The clinical, histopathological and ultrastructural features of the disease are presented and the genetic transmission and its implications discussed.

Animals↗

PubMed2000

Studies of interaural attenuation to investigate the validity of a dichotic difference tone response recorded from the inferior colliculus in the chinchilla.

In a previous paper (Arnold and Burkard, 1998) a dichotic f2-f1 difference tone (DT) auditory evoked potential from the chinchilla inferior colliculus (IC) was measured while presenting f1 (2000 Hz) to one ear and f2 (2100 Hz) to the other ear. This measurement paradigm could be used as a means to study binaural processing in an unanesthetized animal model. However, it is possible that this response is actually generated peripherally, as a result of acoustic crossover. The purpose of the present set of experiments was to investigate whether the dichotic DT is a true binaural phenomenon. Recordings were made from chronically implanted IC electrodes in unanesthetized, monaural chinchillas (left cochlea destroyed). In experiment 1, interaural attenuation (IA) was measured in two ways. First, IA was measured by comparing IC evoked potential thresholds obtained when stimulating the normal right ear and the dead left ear, using tone bursts (0.5-8 kHz). Mean values of interaural attenuation ranged from 50-65 dB across frequency (55 dB at 2000 Hz). Next, the DT was measured monaurally using f1 = 2000 and f2 = 2100 (L1 = L2). By comparing the mean DT input/output functions for monaural stimulation of the right and left ears, a mean value of IA for the tonal pair was estimated (approximately 69 dB). In experiment 2, the DT was measured with right monaural stimulation, while varying the relative levels of the primaries. A small DT could be seen with primary levels up to 30 dB apart, but not for greater level differences. Differences substantially greater than 30 dB would be expected in the crossover situation based upon IA. In experiment 3, the stimuli were presented dichotically (f1 to right ear, f2 to left ear and vice versa, L1 = L2) to determine whether acoustic crosstalk to the normal right ear would generate a DT. No DT was reliably observed in this condition. Taken together, these results suggest that the dichotic DT is a true binaural phenomenon, and not simply attributable to acoustic crossover.

Animals↗

PubMed2000

Childhood sexual abuse and dating experiences of undergraduate women.

Child sexual abuse is a prevalent social problem with a variety of negative consequences for adult survivors. Whereas most studies have focused on intrapersonal effects including depressive symptomatology and post-traumatic stress disorder, recent work has begun to call attention to interpersonal results as well. The current study examined the relationship between the experience of childhood sexual abuse and being a victim of psychological aggression, physical violence, or sexual coercion in a dating relationship in the past year. Participants were 219 female college undergraduates. Child sexual abuse was significantly related to having experienced both physical and psychological dating aggression even after controlling for the presence of conflict in the family of origin. Child sexual abuse was not significantly related to sexual coercion or reports of silencing oneself in relationships.

Adolescent↗