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Biomedical subjects

T Falk

Publications and source records attributed to T Falk.

17 recordsLinked to original sources
PubMed2006

Herpes folliculitis: clinical, histopathological, and molecular pathologic observations.

BACKGROUND: Herpes folliculitis is a rare manifestation of herpes virus infection and it is often misdiagnosed. Diagnostic criteria are not well established, only 24 patients being reported in the literature. Recently it has been suggested that herpetic folliculitis is more common in infections with varicella zoster (VZV) than in those with herpes simplex viruses (HSV-1 and -2). OBJECTIVES: To refine diagnostic criteria for folliculitis caused by VZV, HSV-1 and HSV-2, and to study whether follicular involvement enables morphological differentiation between VZV and HSV infections. PATIENTS AND METHODS: Twenty-one patients with herpetic infection of follicular epithelium were assessed clinically and histopathologically. Polymerase chain reaction (PCR) studies for specific DNA of herpes viruses were performed on paraffin-embedded biopsy specimens. RESULTS: In 17 of our cases PCR was positive for VZV, four were positive for HSV-1, none for HSV-2. The clinical presentation of herpes folliculitis often lacked vesicles or pustules (14/21). Histopathological features were often devoid of ballooning (12/21), multinucleated giant cells (12/21) and keratinocytes with steel grey nuclei (15/21). The most consistent findings were lymphocytic folliculitis and perifolliculitis (20/21) and necrotic keratinocytes in follicular epithelium (12/21). In zoster, but not in varicella eruption or HSV infections, follicular involvement was unaccompanied by marked changes in the epidermal surface. CONCLUSIONS: In biopsy specimens taken from herpes virus infections, involvement of follicular units is more commonly encountered in VZV infections compared with HSV infections. Early in the course, herpes folliculitis presents as lymphocytic folliculitis devoid of epithelial changes considered to be diagnostic of herpes virus infections. Exclusive involvement of follicles is rather typical of zoster.

Biopsy↗
PubMed2004

Intramyocardial arterial narrowing in dogs with subaortic stenosis.

Earlier studies have described intramyocardial arterial narrowing based on hyperplasia and hypertrophy of the vessel wall in dogs with subaortic stenosis (SAS). In theory, such changes might increase the risk of sudden death, as they seem to do in heart disease in other species. This retrospective pathological study describes and quantifies intramyocardial arterial narrowing in 44 dogs with naturally occurring SAS and in eight control dogs. The majority of the dogs with SAS died suddenly (n=27); nine had died or been euthanased with signs of heart failure and eight were euthanased without clinical signs. Dogs with SAS had significantly narrower intramyocardial arteries (P<0.001) and more myocardial fibrosis (P<0.001) than control dogs. Male dogs and those with more severe hypertrophy had more vessel narrowing (P=0.02 and P=0.02, respectively), whereas dogs with dilated hearts had slightly less pronounced arterial thickening (P=0.01). Arterial narrowing was not related to age, but fibrosis increased with age (P=0.047). Dogs that died suddenly did not have a greater number of arterial changes than other dogs with SAS. This study suggests that most dogs with SAS have intramyocardial arterial narrowing and that the risk of dying suddenly is not significantly related to the overall degree of vessel obliteration.

Age Factors↗
PubMed2003

Effect of thyroid hormone supplementation on survival of euthyroid dogs with congestive heart failure due to systolic myocardial dysfunction: a double-blind, placebo-controlled trial.

Nineteen euthyroid dogs of 12 breeds with echocardiographic signs of dilated cardiomyopathy (DCM) and radiographic and clinical signs of congestive heart failure (CHF) were evaluated in a randomised, double-blind, and placebo-controlled study. The dogs received either thyroxine or placebo as an adjunct to digoxin, furosemide and propranolol. The group assignment of individual dogs and serum concentrations of thyroid hormones remained unknown to owners and investigators during the entire study period. Dogs were evaluated clinically and with electrocardiography (ECG), thoracic radiography, echocardiography and measurement of total thyroxine (tT4) and thyroid stimulating hormone (TSH) before beginning of the trial, and then one week, 2 months, 6 months and yearly after initial examination, and, when applicable, at the time of euthanasia. End-point of the study was euthanasia (n = 17) due to severe congestive heart failure or sudden death (n = 2). Survival times ranged from 17 to 1030 days (median 187 days) in the placebo group, and from 18 to 1000 days (median 73 days) in the treatment group. There was no statistically significant difference in survival times between the treatment group and the placebo group (p = 0.46). Post mortem and histopathologic examinations revealed the attenuated wavy fiber type of DCM in 11 dogs, and myocardial infarcts, arteriosclerosis and chronic valvular disease in one dog. In conclusion, there was a wide range in survival times of dogs treated with digoxin, furosemide and propranolol. Adding thyroid hormones to the treatment did not significantly influence survival.

Animals↗
PubMed2003

Developmental regulation of the A-type potassium-channel current in hippocampal neurons: role of the Kvbeta 1.1 subunit.

The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvbeta 1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA. Whole-cell patch clamp recordings of rat hippocampal pyramidal neurons in primary culture showed a developmental decrease in the time constant of inactivation (tau(in)) of voltage-gated K+ currents: 17.9+/-1.5 ms in young neurons (5-7 days in vitro; n=53, mean+/-S.E.M.); 9.9+/-1.0 ms in mature neurons (12-15 days in vitro; n=72, mean+/-S.E.M., P<0.01). During the same developmental time, the level of Kvbeta 1.1 transcript increased more than two-fold in vitro and in vivo, determined by semi-quantitative reverse transcriptase-polymerase chain reaction for hippocampus. The hypothesis that up-regulation of Kvbeta 1.1 led to the changes in tau(in) was tested in vitro, using antisense knockdown. Kvbeta 1.1-specific antisense DNA was introduced with a modified herpes virus co-expressing enhanced green fluorescent protein and knockdown of Kvbeta 1.1 was verified by immunocytochemistry. Following transduction with the antisense virus, mature neurons reverted to tau(in) values characteristic of young neurons: 18.3+/-2.4 ms (n=20). The effect of antisense knockdown on electrical excitability was tested using current-clamp protocols to induce repetitive firing. Treatment with the antisense virus increased the interspike interval over a range of membrane depolarization (baseline membrane potential=-40 to +20 mV). This effect was most pronounced at -40 mV, where the ISI of the first pair of action potentials was nearly doubled. These data indicate that Kvbeta 1.1 contributes to the developmental control of IA in hippocampal neurons and that the magnitude of effect is sufficient to regulate electrical excitability. Viral-mediated antisense knockdown of Kvbeta 1.1 is capable of decreasing the electrical excitability of post-mitotic hippocampal neurons, suggesting this approach has applicability to gene therapy of neurological diseases associated with hyperexcitability.

Analysis of Variance↗
PubMed2001

Biochemical genetic markers to identify two morphologically similar South African Mastomys species (Rodentia: Muridae).

The two common southern African mice species (Mastomys coucha and M. natalensis) are morphologically almost identical, making field identification impossible at present. Specimens from two localities were collected and tissue and blood samples taken. The habitat type of each locality was studied, and a distribution map compiled. A definite correlation between biome-type and species range was found to be present. Three isozyme markers were identified: glucose phosphate isomerase in liver, and two general (non-specific) protein coding loci in muscle. In addition, we also identified species characteristic haemoglobin components in both species. This is the first study to report genetic variation within, and differentiation between these species. Our results are of medical importance because Mastomys coucha carries bubonic plague and M. natalensis carries Lassa Fever.

Journal Article↗
PubMed2001

Viral vector-mediated expression of K+ channels regulates electrical excitability in skeletal muscle.

Modification of K+ currents by exogenous gene expression may lead to therapeutic interventions in skeletal muscle diseases characterized by alterations in electrical excitability. In order to study the specific effects of increasing outward K+ currents, we expressed a modified voltage-dependent K+ channel in primary cultured rat skeletal muscle cells. The rat Kv1.4 channel was expressed as an N-terminal fusion protein containing a bioluminescent marker (green fluorescent protein). Transgene expression was carried out using the helper-dependent herpes simplex 1 amplicon system. Transduced myoballs, identified using fluorescein optics and studied electrophysiologically with single-cell patch clamp, exhibited a greater than two-fold increase in K+ conductance by 20-30 h after infection. This increase in K+ current led to a decrease in membrane resistance and a 10-fold increase in the current threshold for action potential generation. Electrical hyperexcitability induced by the Na+ channel toxin anemone toxin II (1 microM) was effectively counteracted by overexpression of Kv1.4 at 30-32 h after transduction. Thus, virally induced overexpression of a voltage-gated K+ channel in skeletal muscle has a powerful effect in reducing electrical excitability.

Action Potentials↗
PubMed2000

Ischaemic heart disease in the dog: a review of 65 cases.

Sixty-five dogs are reviewed with histopathologically confirmed intramural arteriosclerosis. Clinical data (clinical signs, electrocardiographic findings and ultrasound parameters) on these animals were collected from nine small animal clinics in Sweden: 16 dogs had died suddenly, with few or no previous clinical signs; 13 dogs died or were euthanased during or shortly after general anaesthesia or sedation; 30 dogs developed acute (14) or chronic (16) congestive heart failure; and six dogs died or were euthanased for causes unrelated to cardiac disease. Electrocardiography of 23 of the dogs revealed several types of arrhythmias, with atrial fibrillation and sinus tachycardia being most commonly detected. Ultrasonographic examinations of 24 dogs found a relatively high number (19) with decreased indices of contractility. Dogs that had died suddenly and in relation to general anaesthesia or sedation had a higher incidence (25 of 29) of purely arteriosclerotic changes in the myocardial vessels, whereas just over half the dogs with congestive heart failure (16 of 30) had other concomitant heart lesions (in most cases endocardiosis). The incidence of myocardial infarcts was high (51 of 65 cases). It is postulated that arteriosclerosis in the dog may be an important reason for sudden death and death during general anaesthesia. Coronary arterial disease should also be a consideration in the clinical evaluation of dilated cardiomyopathy and may contribute to the decreased myocardial contractility when it is present in dogs with mitral regurgitation.

Anesthesia, General↗
PubMed1999

Expression of Niemann-Pick type C transcript in rodent cerebellum in vivo and in vitro.

This study assesses the developmental expression of the Niemann-Pick type C mRNA in vivo and in vitro in rat cerebellum. NPC is an autosomal recessive neurovisceral lipid storage disease associated with an alteration in cholesterol trafficking. In the mouse model of NPC and in the early onset form of human NPC, Purkinje neurons are among the first neurological targets, suffering stunted growth during postnatal development and dying, leading to ataxia. Recently, the genes responsible for human (NPC1) and mouse (Npc1) NPC disease have been cloned. Based on a highly homologous domain, we designed primers to look for levels of Npc1 mRNA with a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) approach using cyclophilin as an internal standard. Total RNA was isolated from various postnatal developmental stages of the rat cerebellum as template for the analyses. Npc1 transcripts were observed at postnatal day 0 and at later stages of development, both in vivo and in vitro from primary cerebellar cultures. To identify the location of Npc1 inside the cerebellum, we performed immunostaining with an anti-Npc1 antibody in primary rat cerebellar cultures identifying reactive Purkinje neurons by double-labeling with the Purkinje specific marker calbindin and sub-populations of glial cells. In summary, Npc1 is expressed in rat cerebellum in vivo and in vitro and is expressed during early postnatal development as well as in the adult cerebellum. Since Npc1 is expressed at similar levels throughout development, the vulnerability of Purkinje neurons to this disease is likely to involve disruption of an interaction with other developmentally-regulated proteins.

Amino Acid Sequence↗
PubMed1999

Differential expression of three classes of voltage-gated Ca(2+) channels during maturation of the rat cerebellum in vitro.

Voltage-gated Ca(2+) channels provide a mode of Ca(2+) influx that is essential for intracellular signaling in many cells. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the relative amounts of mRNAs encoding three classes of Ca(2+) channels (alpha1A, alpha1B and alpha1E) during development, in cultures established from prenatal rat cerebellar cortex. Ca(2+) channel transcript levels were standardized to a constitutive marker (cyclophilin). For all three classes of Ca(2+) channels, transcript levels were highest at early stages (4-10 days in vitro) and declined with age. This developmental pattern was differentially regulated by a depolarizing agent, tetraethylammonium chloride (TEA, 1 mM). Chronic depolarization yielded a significant elevation in transcript levels for alpha1B (N-type) and alpha1E (R-type) Ca(2+) channels during neuronal maturation (10-21 days in vitro), but dramatically suppressed transcript levels for the alpha1A (P-type) Ca(2+) channel at all stages of development. The effects of TEA on alpha1A, alpha1B and alpha1E transcript levels were mimicked by increasing external K(+) (from 5 to 10 mM). The regulatory effects of depolarization on transcript levels were dependent on extracellular Ca(2+) for alpha1E but not for alpha1A. For alpha1B, transcript levels depended on extracellular Ca(2+) only for increased K(+) as the depolarizing stimulus, but not for TEA. These results suggest that levels of Ca(2+) channel transcripts in rat cerebellum are developmentally regulated in vitro and can be influenced differentially by transmembrane signaling via chronic depolarization and Ca(2+) entry. Dynamic regulation of Ca(2+) channel expression may be relevant to the different functional roles of Ca(2+) channels and their regional localization within neurons.

Animals↗
PubMed1999

The middle ear bioelectronic microphone for a totally implantable cochlear hearing device for profound and total hearing loss.

BACKGROUND: A bioelectronic middle ear microphone (BMEM) has been developed in a laboratory bench model and successfully tested in fresh human temporal bones. A transducer actually has been bench-tested in our laboratory; it was implanted in chronic animal experiments (cats) as well as in humans for a period of 1 year as a driver of a semi-implantable electromagnetic middle ear hearing device (IDE, FDA approved). This BMEM is the result of the use of this same electromagnetic transducer used in a reverse mode. The applicability of the BMEM is for the development of a totally implantable cochlear implant using the eardrum as a diaphragm that transmits vibrations to a magnet cemented to the ossicles. This BMEM is to be powered by a lithium-ion implantable, rechargeable battery. MATERIALS AND METHODS: To test the efficacy of this BMEM, the experiment was divided into two parts: (1) bench model, and (2) fresh human temporal bones, using an air-core electromagnetic (EM) coil and a ferrite core EM coil for comparison. RESULTS: In the bench model, the average displacement at 3 kHz was 0.95 microns (peak) for 4 V p-p and 1.65 microns (peak) for 10 V p-p. At 5 kHz, the measurements were somewhat higher. In fresh human temporal bones, with sound source in the ear canal (60 dB HL and 90 dB HL), the result was better with the magnet implanted on the head of the malleus with the incus removed. The ferrite core EM coil with the magnet implanted on the malleus with the incus removed was compared with the air-core EM coil. At 60 dB HL, the ferrite core EM coil yielded more than four times the amplitude of the EM coil. At 90 dB HL, the ferrite core EM coil produced more than five times the amplitude compared with the air-core coil. CONCLUSION: This BMEM using an EM ferrite coil and a permanent magnet on the head of the malleus is more efficient when compared with an EM air-core coil. This BMEM may be applicable to the construction of a totally implantable cochlear implant. Further research is necessary to integrate this BMEM with the other components of the design concept of the totally implantable cochlear implant.

Animals↗
PubMed1996

An endogenous inactivating inward-rectifying potassium current in oocytes of Xenopus laevis.

An endogenous inward-rectifying K+ current is described, which is present in native oocytes of some Xenopus laevis donors. Experiments were performed using defolliculated oocytes from donor frogs obtained from two different suppliers. In all oocytes from animals from one source, an inward-rectifying K+ current could be elicited with negative pulses from a holding potential of -20 mV in external solutions with a high K+ concentration. Increasing external K+ concentrations increased the amplitude of this current and shifted the reversal potential towards more positive potentials. In 118 mM KCl, the inward-rectifying K+ current partially inactivated between -20 and -80 mV and completely inactivated at more negative membrane potentials; 50% steady-state inactivation occurred near -50 mV. The time course of inactivation of the inward-rectifying current could be well fitted with two exponentials. The slow time constant had values of about 500 ms and was voltage independent. In contrast, the fast time constant and the time to reach the peak inward current decreased with more negative membrane potentials. Ba2+, Cs+, quinine (all 5 mM) and 50 mM tetraethylammonium partially blocked the inward-rectifying K+ current, whereas 10 mM 4-aminopyridine was without blocking effect. The oxidant chloramine-T blocked the inward-rectifying K+ current without slowing its inactivation.

Animals↗
PubMed1995

Cloning, functional expression and mRNA distribution of an inwardly rectifying potassium channel protein.

In GH3/B6 cells at least two different inward K+ currents are observed that are regulated by thyrotropin-releasing hormone and somatostatin, respectively. Using a polymerase chain reaction based approach a cDNA was isolated and functionally expressed in human embryonic kidney cells that encodes an inward rectifier K+ channel, rIRK3, with a predicted molecular mass of 49.7 kDa. Corresponding transcripts of 2.6 kb have been detected in rat brain, pituitary and GH3/B6 cells. In situ hybridization revealed that rIRK3 mRNA is distributed throughout the brain and occurs predominantly in the piriform cortex, indusium griseum, supraoptic nucleus, facial nucleus and cerebellar Purkinje cells.

Amino Acid Sequence↗
PubMed1995

Contactless semi-implantable electromagnetic middle ear device for the treatment of sensorineural hearing loss. Short-term and long-term animal experiments.

A contactless electromagnetic hearing device has been designed following basic science experiments, improvement of electronics, and precision micromechanics. Different prototypes have been developed and tested in the laboratory, fresh human temporal bones, and acute and chronic animal experimentation. A conductive hearing loss model was first developed in the cat using samarium cobalt as the target magnet. Later, a highly efficient electromagnetic air-core coil was selected to vibrate a neodymium iron boron magnet cemented to the body of the incus and tested in acute and chronic experiments using the cat as the model. In this group of animals, the ossicular chain was left intact. There was no failure of the target magnet, driving coil, or implanted electronics. The only problem encountered in this evaluation was a malfunction of the receiving antenna that had to be redesigned and retrofitted into the implanted units. This system would be suitable for the treatment of moderate to severe sensorineural hearing loss. Planning to begin human clinical trials is ongoing.

Animals↗
PubMed1994

A contactless electromagnetic implantable middle ear device for sensorineural hearing loss.

Following basic science experiments, improvement of precision micromechanics and electronics design, and development of different prototypes, a contactless electromagnetic hearing device has been successfully implanted in cats (acute experiments). Chronic animal experiments using the cat as well as the rabbit are ongoing to test the components of the device. A highly efficient air core coil is used to vibrate a neodymium-iron-boron magnet cemented to the body of the incus. The parts of the system, including implanted electronics (hybrid circuit, solid state), are laser welded and hermetically sealed. The system allows for the generation of enough force which vibrates the magnet implanted on the incus. It would be suitable for the treatment of moderate to severe sensorineural hearing loss.

Animals↗
PubMedDate not supplied

Auscultation in mild mitral regurgitation in dogs: observer variation, effects of physical maneuvers, and agreement with color Doppler echocardiography and phonocardiography.

Observer variation in diagnosing mild mitral regurgitation in dogs by cardiac auscultation was assessed by having 6 veterinarians with different levels of experience examine 57 Cavalier King Charles Spaniels. Comparisons with color Doppler echocardiography and phonocardiography were made, and the effects of 2 physical maneuvers on the auscultatory findings were evaluated. Using mildly diseased dogs, interobserver agreement in diagnosing the presence or absence of left-sided murmurs ranged from 63% to 88%. The agreement with phonocardiography (range, 53-91%) increased with the amount of observer experience. The 2 most experienced observers could discern soft ejection murmurs from regurgitant murmurs and were able to diagnose 89% of the dogs with regurgitant jets larger than 30% of the left atrial area. In general, less experienced observers diagnosed most jets larger than 50%. In many dogs with small jets, no murmur was found by auscultation and phonocardiography. The audibility of mild regurgitation was significantly reduced in dogs that were difficult to auscultate. Early systolic murmurs were typical of mild regurgitation, whereas holosystolic murmurs typified severe regurgitation. In a few dogs, late systolic murmurs alternated with holosystolic murmurs. Systolic clicks were found phonocardiographically in 18 dogs with mild to moderate regurgitation, but the audibility apparently was low. In many mildly affected dogs, physical maneuvers increased murmur intensity. Thus, some form of dynamic auscultation might facilitate the diagnosis of mild regurgitation. Auscultatory findings in mild regurgitation appear to depend on observer experience, circulatory status, and how difficult the dog is to auscultate.

Animals↗