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Biomedical subjects

R Kurtz

Publications and source records attributed to R Kurtz.

At least 19 recordsLinked to original sources

Synaptic transfer of dynamic motion information between identified neurons in the visual system of the blowfly.

Synaptic transmission is usually studied in vitro with electrical stimulation replacing the natural input of the system. In contrast, we analyzed in vivo transfer of visual motion information from graded-potential presynaptic to spiking postsynaptic neurons in the fly. Motion in the null direction leads to hyperpolarization of the presynaptic neuron but does not much influence the postsynaptic cell, because its firing rate is already low during rest, giving only little scope for further reductions. In contrast, preferred-direction motion leads to presynaptic depolarizations and increases the postsynaptic spike rate. Signal transfer to the postsynaptic cell is linear and reliable for presynaptic graded membrane potential fluctuations of up to approximately 10 Hz. This frequency range covers the dynamic range of velocities that is encoded with a high gain by visual motion-sensitive neurons. Hence, information about preferred-direction motion is transmitted largely undistorted ensuring a consistent dependency of neuronal signals on stimulus parameters, such as motion velocity. Postsynaptic spikes are often elicited by rapid presynaptic spike-like depolarizations which superimpose the graded membrane potential. Although the timing of most of these spike-like depolarizations is set by noise and not by the motion stimulus, it is preserved at the synapse with millisecond precision.

Action Potentials↗

Transfer of visual motion information via graded synapses operates linearly in the natural activity range.

Synaptic transmission between a graded potential neuron and a spiking neuron was investigated in vivo using sensory stimulation instead of artificial excitation of the presynaptic neuron. During visual motion stimulation, individual presynaptic and postsynaptic neurons in the brain of the fly were electrophysiologically recorded together with concentration changes of presynaptic calcium (Delta[Ca(2+)](pre)). Preferred-direction motion leads to depolarization of the presynaptic neuron. It also produces pronounced increases in [Ca(2+)](pre) and the postsynaptic spike rate. Motion in the opposite direction was associated with hyperpolarization of the presynaptic cell but only a weak reduction in [Ca(2+)](pre) and the postsynaptic spike rate. Apart from this rectification, the relationships between presynaptic depolarizations, Delta[Ca(2+)](pre), and postsynaptic spike rates are, on average, linear over the entire range of activity levels that can be elicited by sensory stimulation. Thus, the inevitably limited range in which the gain of overall synaptic signal transfer is constant appears to be adjusted to sensory input strengths.

Action Potentials↗

Two classes of visual motion sensitive interneurons differ in direction and velocity dependency of in vivo calcium dynamics.

Neurons exploit both membrane biophysics and biochemical pathways of the cytoplasm for dendritic integration of synaptic input. Here we quantify the tuning discrepancy of electrical and chemical response properties in two kinds of neurons using in vivo visual stimulation. Dendritic calcium concentration changes and membrane potential of visual interneurons of the fly were measured in response to visual motion stimuli. Two classes of tangential cells of the lobula plate were compared, HS-cells and CH-cells. Both neuronal classes are known to receive retinotopic input with similar properties, yet they differ in morphology, physiology, and computational context. Velocity tuning and directional selectivity of the electrical and calcium responses were investigated. In both cell classes, motion-induced calcium accumulation did not follow the early transient of the membrane potential. Rather, the amplitude of the calcium signal seemed to be related to the late component of the depolarization, where it was close to a steady state. Electrical and calcium responses differed with respect to their velocity tuning in CH-cells, but not in HS-cells. Furthermore, velocity tuning of the calcium response, but not of the electrical response differed between neuronal classes. While null-direction motion caused hyperpolarization in both classes, this led to a calcium decrement in CH-cells, but had no effect on the calcium signal in HS-cells, not even when calcium levels had been raised by a preceding excitatory motion stimulus. Finally, the voltage-[Ca2+]i-relationship for motion-induced, transient potential changes was steeper and less rectifying in CH-cells than in HS-cells. These results represent an example of dendritic information processing in vivo, where two neuronal classes respond to identical stimuli with a similar electrical response, but differing calcium response. This highlights the capacity of neurons to segregate two response components.

Animals↗

Ultra-short pulse (femtosecond) laser surgery: initial use in LASIK flap creation.

The highly localized tissue effects of low energy femtosecond duration (ultrashort) laser pulses may be used to create three-dimensional intrastromal resections with micron precision and minimized collateral tissue damage. A surgical laser system that produces and delivers such pulses has been developed and tested clinically for creation of a corneal flap in LASIK. Expanded evaluation of this technology in this and additional keratorefractive applications is currently underway.

Corneal Stroma↗

Dendritic calcium accumulation associated with direction-selective adaptation in visual motion-sensitive neurons in vivo.

Motion adaptation in directionally selective tangential cells (TC) of the fly visual system has previously been explained as a presynaptic mechanism. Based on the observation that adaptation is in part direction selective, which is not accounted for by the former models of motion adaptation, we investigated whether physiological changes located in the TC dendrite can contribute to motion adaptation. Visual motion in the neuron's preferred direction (PD) induced stronger adaptation than motion in the opposite direction and was followed by an afterhyperpolarization (AHP). The AHP subsides in the same time as adaptation recovers. By combining in vivo calcium fluorescence imaging with intracellular recording, we show that dendritic calcium accumulation following motion in the PD is correlated with the AHP. These results are consistent with a calcium-dependent physiological change in TCs underlying adaptation during continuous stimulation with PD motion, expressing itself as an AHP after the stimulus stops. However, direction selectivity of adaptation is probably not solely related to a calcium-dependent mechanism because direction-selective effects can also be observed for fast moving stimuli, which do not induce sizeable calcium accumulation. In addition, a comparison of two classes of TCs revealed differences in the relationship of calcium accumulation and AHP when the stimulus velocity was varied. Thus the potential role of calcium in motion adaptation depends on stimulation parameters and cell class.

Adaptation, Physiological↗

Maturation and myotonia influence the abundance of cation channels KDR, KIR and CIR differently: a patch-clamp study on mouse interosseus muscle fibres.

To detect cation channels, the expression of which is dependent on the physiological state of muscle, single-channel activities of dissociated fibres of the mouse interosseus muscle were recorded using the patch-clamp technique in the cell-attached mode. Fibres were prepared from juvenile and adult wild-type (WT), from chloride channel-deficient myotonic and from denervated adult WT muscles. In all cases delayed-rectifier K+ channels (KDR) with a unitary conductance of 11 pS were recorded in more than 95% of sarcolemmal patches, but with a low, steady-state open probability. Inwards-rectifying K+ channels (KIR) with a conductance of 31 pS in 140 mM [K+]o were active in about 50% of the membrane patches from WT and in more than 90% of those from myotonic fibres. A hitherto undescribed, inwards-rectifying, cation channel, provisionally termed CIR, with fast kinetics and a unitary conductance of 36 pS, was active in nearly every membrane patch from juvenile mice, both WT and myotonic. The abundance of CIR decreased during development, but was not changed 7 days after denervation of adult WT muscle. Ca(2+)-dependent K+ channels were seen sporadically. Channels with the characteristics of adenosine 5'-triphosphate (ATP)-sensitive K+ channels were recorded frequently upon excision of membrane patches, but remained inactive in most cell-attached recordings. In conclusion, of the investigated ion channels, only KIR was responsive to the activity pattern of adult muscle, whereas CIR was down-regulated during muscle maturation.

Aging↗

Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice.

Diphosphoryl lipid A (DPLA) obtained from the nontoxic lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides ATCC 17023 did not induce interleukin-1 release by murine peritoneal macrophages. However, it blocked this induction by toxic deep-rough chemotype LPS (ReLPS) from Escherichia coli D31m4. Previously, we obtained similar results on the induction of tumor necrosis factor (TNF) by macrophages. These results showed that DPLA is able to block in vitro the induction of two important mediators of gram-negative bacterial sepsis. We then wanted to determine whether DPLA could also block the induction of TNF by LPS in animals. Mice were treated with 100 micrograms of R. sphaeroides DPLA and challenged 60 min later with 1.0 micrograms of ReLPS from E. coli. The serum TNF level was measured after 60 min. Treatment of mice with this DPLA blocked the rapid and transient rise of TNF caused by ReLPS. This result suggested that R. sphaeroides DPLA might be able to protect animals against endotoxin shock caused by gram-negative bacterial infection.

Animals↗

Effects of betaxolol/timolol on epinephrine stimulated cyclic-AMP levels in human trabecular meshwork cells.

The effects of timolol and betaxolol were compared for blocking beta agonist stimulation of cyclic-AMP in cultured human trabecular meshwork cells. Epinephrine (10(-5) M) produced a large and rapid increase in HTM cyclic-AMP; timolol (10(-6) M), at concentrations readily achieved in the aqueous humor after 0.5% eyedrops, completely blocked this effect. Recovery from timolol treatment appeared to be relatively slow, with only a 30-40% recovery observed by 9 hours. In comparison, betaxolol (10(-6) M) produced a smaller blockade of the epinephrine effects; a rapid recovery from the betaxolol effects was observed, with a greater than half-maximal response to epinephrine observed 15 minutes after removal of this beta blocker. These findings may help to explain the clinical observations of an outflow facility effect of epinephrine when used in combination protocols with betaxolol, but not with timolol.

Betaxolol↗

The formalin test and the opioid nature of stress-induced analgesia.

Exposure to electric shock produces an analgesic reaction (SIA) that is reversed by opiate antagonists ("opioid" SIA) under some conditions but not under other conditions ("nonopioid" SIA). A number of studies using tail-flick to radiant heat as the measure of pain sensitivity have found that a small number of shocks lead to nonopioid SIA, while a large number of shocks produce opioid SIA. In contrast, a small number of shocks have been reported to produce opioid SIA when the Formalin test was used to measure pain reactivity. However, the Formalin test involves administering a chronic pain stimulus (injection of Formalin into the paw) for an extended period before the shocks. Here it is reported that this "preexperimental" stress is sufficient to convert the SIA after a small number of shocks measured by tail-flick to the opioid form.

Afferent Pathways↗

Small-cell carcinoma of the esophagus: treatment by chemotherapy alone.

Small-cell carcinoma of the esophagus is a rare tumor. In most reported cases, surgery has been the major mode of therapy. Most patients have relapsed rapidly with disseminated disease. We treated a patient with small-cell carcinoma of the esophagus with a multi-drug regimen being used in small cell-carcinoma of the lung. Within two months of beginning therapy, the primary lesion, as evaluated by barium esophogram, had completely resolved. Residual disease was seen on panendoscopy. The patient was considered to be in partial remission. She relapsed nine months after starting therapy and died with widespread metastases. Small-cell carcinoma of the esophagus should not be treated surgically but rather in the same fashion as is small-cell carcinoma of the lung, i.e., with multi-drug chemotherapy and radiation therapy.

Aged↗

Peritonitis in patients with liver disease and ascites. Use of Candida albicans as a microbiological clue in differential diagnosis.

Peritonitis in patients with pre-existing liver disease and ascites may be secondary to a local abdominal condition which potentially requires surgery for cure, or alternatively, may be spontaneous in origin. For the latter, antimicrobials are therapeutic while surgery is contraindicated. An easily accessible and important clue for distinguishing these forms of peritonitis may be found in the microbiology of ascitic fluid. Visualization on gram stain smear or recovery on culture of multiple organisms and/or anaerobes favors local abdominal disease over spontaneous peritonitis. The presence of Candida species in the ascitic fluid of such patients, although less common, is highly significant. In the absence of peritoneal dialysis, recent abdominal surgery, or risk factors for disseminated candidiasis, the isolation of Candida suggests specifically gastrointestinal perforation.

Aged↗

Cutaneous manifestation of internal malignancies (I). Acanthosis nigricans.

Skin changes may be the first clue to a neoplastic process at a stage when it still is treatable (Such as the development of Acanthosis Nigrican (AN) in an otherwise healthy adult). Ninety percent of the neoplasm responsible for the development of AN originate in the abdomen. The tumor, even in a subclinical state, seems to possess unidentified properties that activate the dermatosis.

Acanthosis Nigricans↗