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Robert D Wurster

Publications and source records attributed to Robert D Wurster.

10 recordsLinked to original sources
PubMed2006

T-type calcium channels and tumor proliferation.

The role of T-type Ca2+ channels in proliferation of tumor cells is reviewed. Intracellular Ca2+ is important in controlling proliferation as evidenced by pulses, or oscillations, of intracellular Ca2+ which occur in a cell cycle-dependent manner in many tumor cells. Voltage-gated calcium channels, such as the T-type Ca2+ channel, are well suited to participate in such oscillations due to their unique activation/inactivation properties. Expression of the T-type Ca2+ channels has been reported in numerous types of tumors, and has been shown to be cell cycle-dependent. Overexpression of the alpha1 subunit of T-type Ca2+ channels in human astrocytoma, neuroblastoma and renal tumor cell lines enhanced proliferation of these cells. In contrast, targeting of the alpha1 subunit of the T-type calcium channel via siRNA decreased proliferation of these cells. A Ca2+ oscillatory model is proposed involving potassium channels, Ca2+ stores and Ca2+ exchangers/transporters. A review of T-type channel blockers is presented, with a focus on mibefradil-induced inhibition of proliferation. The development of newer blockers with higher selectivity and less potential side effects are discussed. The conclusion reached is that calcium channel blockers serve as a potential therapeutic approach for tumors whose proliferation depends on T-type calcium channel expression.

Animals↗
PubMed2005

Variation of T-type calcium channel protein expression affects cell division of cultured tumor cells.

In this study we investigated the T-type calcium channel and its involvement in the cell division of U87MG cultured glioma cells and N1E-115 neuroblastoma cells. Using Western blot analysis, we found that expression of both alpha1G and alpha1H subunits of the T-type calcium channel decreased during conditions associated with a decrease in proliferation as evidenced by increased expression of cyclin D1, a marker for non-proliferating cells. Both serum starvation and application of mibefradil, a selective T-type calcium channel antagonist, resulted in a 50% decrease in the expression of alpha1G and alpha1H and a 700-900% increase in levels of cyclin D1 in U87MG and N1E-115 cells, respectively. Furthermore, overexpression of the alpha1H subunit resulted in a two-fold increase in cell proliferation compared to control cultures or cultures receiving an empty vector. In contrast, blocking expression of the alpha1G subunit using antisense oligonucleotides lead to a 70% decrease in proliferation of U87MG and N1E-115 cells compared to control cultures or cultures receiving a scrambled oligonucleotide. Our findings suggest that proliferation of U87MG glioma cells and N1E-115 is regulated by T-type calcium channel expression.

Animals↗
PubMed2005

Chronic instrumentation with model microstimulators in an animal model of the lower urinary tract.

BACKGROUND: Microstimulators are a new type of neuroprosthetic device that should be considered for applications such as micturition control after spinal cord injury (SCI). These devices are small (less than 25 mm by 5 mm) and the electrodes are located on the ends of the stimulator. The aim of the current study was to develop methods for chronic implantation of model microstimulators (M-Micro) on the bladder wall and pelvic plexus of female cats. A postmortem evaluation of the effects of 3 months of implantation is reported. METHODS: Techniques to produce the M-Micro are described. Four of these devices were implanted in 4 female cats and maintained after the initial instrumentation surgery and a second survival surgery for SCI (at T10). Using a single suture tied around the M-Micro, these devices were secured to the bladder wall or the fat pads adjacent to the pelvic plexus. Additional instrumentation was implanted, including 2 catheters in the bladder, 1 abdominal balloon, and electromyography electrodes in the urethral and anal sphincters. Postmortem observations of the location of the M-Micro on the bladder wall were conducted after fixation. RESULTS: The animals' conditions were good. One animal was sacrificed early because of a skin infection. A single suture was sufficient to anchor the M-Micro. However, during the surgical implantation the pelvic plexus M-Micro ended up close to the bladder neck. Extensive fibrous connective tissue formed around the M-Micro and implanted catheters on the bladder wall. This appeared to result, in part, from multiple devices implanted on or near the bladder wall. CONCLUSIONS: These pilot studies showed that the M-Micro could be easily constructed and secured to the bladder wall or fat pads close to the pelvic plexus. There was a concern that the pelvic plexus location for the M-Micro ended near the bladder neck during the surgical implantation; however, these devices did not appear to migrate over this short, 3-month implantation period. The extensive connective tissue responses of the bladder wall to the tubes, wires, and M-Micro was a major concern. The M-Micro appears to be a good device to assess the potential of commercial microstimulators for use in micturition control.

Animals↗
PubMed2005

A spinal cord injured animal model of lower urinary tract function: observations using direct bladder and pelvic plexus stimulation with model microstimulators.

BACKGROUND: Microstimulators are new devices that should be considered for management of lower urinary tract problems following spinal cord injury (SCI) such as urinary retention. These devices are small (less than 25 mm by 5 mm) with the electrodes located on the ends of the stimulator. However, it is not known whether the small electrodes on these devices would be effective in stimulating the plexus of nerves that innervate the bladder. The aim of the present study was to provide preliminary observations with model microstimulators (M-Micro) for inducing bladder contractions in an SCI animal model. Bladder wall and pelvic plexus stimulation sites were compared. Additional investigations evaluated parameters such as stimulation polarity, frequency, and period as well as bladder filling volume. METHODS: In an initial survival surgery, bilateral M-Micros were implanted on the bladder wall and the pelvic plexus along the urethra in 3 female cats. A second survival surgery was conducted 3 to 5 weeks later to produce a T1 0 SCI. Studies are reported following the second survival surgery. These studies included the effects of stimulation and bladder filling. RESULTS: The postmortem location of the implanted pelvic plexus M-Micro was previously described as near the bladder neck. Therefore, the pelvic plexus location is described in this report as "pelvic plexus (bladder neck)" stimulation. The observations showed effective stimulation with pelvic plexus (bladder neck) stimulation and voiding in some cases. Stimulation was limited by side effects of increased abdominal pressure and leg movement. Other factors also affected the response to stimulation, including the initial bladder volume and stimulating parameters. Fluoroscopy showed that when stimulation did not induce voiding the striated urethral sphincter was closed. CONCLUSIONS: This case series of 3 SCI animals showed that the small electrodes on the M-Micro could be used to stimulate the bladder with contractions and voiding in some cases. The pelvic plexus (bladder neck) location for the M-Micro may be a better location than higher on the bladder wall. Limiting side effects of stimulation included leg movement and increased abdominal pressure. Additional important factors included the stimulation parameters, initial bladder volume, and the function of the skeletal urethral sphincter.

Animals↗
PubMed2003

Attenuation of baroreflex sensitivity after domoic acid lesion of the nucleus ambiguus of rats.

The nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX) innervate distinct populations of cardiac ganglionic principal neurons. This anatomic evidence suggests that these two nuclei play different roles (Cheng Z and Powley TL, Soc Neurosci Abstr 26: 1189, 2000). However, lesion of the DmnX does not attenuate baroreflex sensitivity (Cheng Z, Guo SZ, Lipton AJ, and Gozal D, J Neurosci 22: 3215-3226, 2002). The present study tested the functional role of the NA in baroreflex control of heart rate (HR). Domoic acid (DA) was injected into the left NA of Sprague-Dawley rats to lesion the NA. The neuronal loss was assessed using retrograde labeling and confocal microscopy. HR changes induced by phenylephrine and sodium nitroprusside administration and after electrical stimulation of the left vagal trunk were measured at 15 days, and HR responses to left NA microinjection of L-glutamate were determined at 180 days postlesion. Compared with vehicle injections, DA lesions significantly reduced the population of NA motor neurons by approximately 68% (P < 0.01) and attenuated baroreflex sensitivity by approximately 83% (P < 0.01) at 15 days. Similarly, electrical stimulation of the vagal trunk of DA-lesioned animals led to attenuated decreases in HR responses. NA neuronal counts were reduced by approximately 81% (P < 0.01) and mean HR responses to l-glutamate injection into the lesioned NA were attenuated by approximately 65% (P < 0.01) at 180 days. Therefore, the NA plays a major role in baroreflex control of HR, and the integrity of the NA is critically important for the normal baroreflex control. In addition, NA lesions produce long-term anatomic and functional dysfunction of the nucleus, and thus it may provide an useful model for functional assessment of respective roles of the NA and DmnX.

Animals↗
PubMed2003

Preliminary observations of a synergistic bladder-sphincter relationship following spinal cord injury in a quadruped animal.

BACKGROUND/OBJECTIVES: High urethral resistance or detrusor-sphincter dyssynergia (DSD) is characterized by obstructed voiding during bladder contractions. DSD is caused by an exaggerated pelvic floor reflex resulting from sensory input from elevated pressure in the bladder that produces reflex constriction of the urethral sphincter. The objective of this study was to determine whether sensory input from the bladder produced synergistic or dyssynergic pelvic floor reflexes following SCI in an animal model. METHODS: A pelvic floor reflex that shares the same motor pathway with DSD is the bulbocavernosus (BC) reflex. The BC reflex was elicited with electrical stimulation in 4 male cats with T1 spinal injury, and recorded as an anal sphincter contraction. Recordings were obtained during control and elevated bladder pressures. Increased bladder pressure was induced with either manual pressure (Crede procedure) or spontaneous contractions resulting from bladder filling. RESULTS: During the control period, the BC reflex indicated by the peak anal pressure response was 23 +/- 6 cmH2O. During elevated bladder pressure of 34 +/- 18 cmH2O, the BC response decreased to 10 +/- 3 cmH2O (not significant), showing a synergistic relationship. Anal sphincter tone between BC reflex tests showed a dyssynergic response. All 4 animals showed increased tone during elevated bladder pressures that averaged 9 +/- 5 cmH2O. Because abdominal pressure was not recorded, the significance is not clear. However, there was further support of a dyssynergic relationship based on increases in the anal and urethral electromyography recordings and some pelvic floor spasms during the elevated bladder pressure. CONCLUSIONS: Because 2 different pelvic floor activities were observed during increased bladder pressures, this animal model may be described best as a mixed model. This model shows both synergistic and dyssynergic relationships between the bladder and the BC contractions. Although observed changes were not significant, the unique observations of synergistic bladder-sphincter activity shown by the inhibited BC reflex is in marked contrast to the strictly dyssynergic bladder-sphincter relationship seen in SCI patients.

Anal Canal↗
PubMed2002

Mitogen activated protein kinase activation and oxidant signaling in astrocytoma cells.

Presence of increased reactive oxygen species (ROS) has been observed in most high risk factors for brain tumor development. Our past study demonstrated that ROS could induce increased brain tumor cell proliferation. Growth effects of ROS may involve modifications of cellular proteins such as mitogen-activated protein kinases (MAPKs), which regulate cell proliferation. Here, we report effects of a ROS (hydrogen peroxide, H2O2) and an antioxidant (N-acetylcysteine, NAC) on MAPK activation in astrocytoma (U373-MG) cells. MAPKs are activated by phosphorylation that can be detected by Western blot analysis. The unphosphorylated/inactivated form of MAPK exhibits slower mobility on SDS-PAGE compared to the phosphorylated/activated form. Densitometric analysis was used to measure MAPK activation. Results indicate that H2O2 caused a dose and time-dependent increase in MAPK activation in astrocytoma cells. Furthermore, ROS-induced activation was almost completely suppressed by NAC. NAC also inhibited serum-induced MAPK activation indicating there may be an oxidant-sensitive component to serum-induced growth signaling. Modifications of MAPKs by H2O2 demonstrate that ROS-induced proliferation is via biochemical pathways similar to other known growth stimuli. Understanding of processes that link a proliferation signal (ROS) to cell proliferation can aid in the selection of therapy used to suppress brain tumor growth.

Antioxidants↗
PubMed2002

Silver nitrate injury in the rat sciatic nerve: a model of facial nerve injury.

BACKGROUND: An unpublished communication of a permanent facial paralysis secondary to silver nitrate application in a postoperative mastoid cavity with a dehiscent facial nerve raises concern regarding its neurotoxicity. This study was performed to examine functional neural injury and the morphology of nerve injury due to silver nitrate contact with a peripheral motor nerve. METHODS: Sprague-Dawley male rats were assigned to a sham surgery group or to a group where silver nitrate was applied directly to a surgically exposed sciatic nerve for 1, 5, or 10 seconds. Individual walking track data were collected on postoperative days (POD) 1, 4, 7, and 14, and the Sciatic Functional Index (SFI) was calculated to assess neural function. On POD 14, the cauterized nerve was harvested, and the histologic axon loss of each specimen was graded. RESULTS: In all experimental groups, the most severe functional loss was noted on POD 1. At POD 14 the greatest neural recovery was observed in the 1-second group, whereas the 5- and 10-second cautery groups demonstrated a significantly worse deficit. A moderate or greater degree of axon loss was observed in 50% of animals injured for 1 second and nearly all animals injured for 5 or 10 seconds. CONCLUSION: Functional and neuropathologic data demonstrate that silver nitrate causes significant injury to the rat sciatic nerve. A 5-second cautery causes greater functional impairment and more severe axonal loss than a 1-second injury.

Animals↗
PubMedDate not supplied

Bladder-wall and pelvic-plexus stimulation with model microstimulators: Preliminary observations.

Severe urinary retention is not a common condition, but may occur following some pelvic surgeries or other medical conditions. Electrical stimulation of the bladder has been examined as a means of managing this difficult problem. We conducted preliminary investigations in cats to prove the hypothesis that pelvic-plexus (bladder-neck) stimulation would produce greater micturition response with reduced side effects, such as animal movement or discomfort, than bladder-wall stimulation with electrodes implanted higher on the bladder wall. We used model microstimulators that mimic the look and function of commercial microstimulators, but that we constructed. We instrumented four female cats during a survival surgery. Animals recovered well and studies were conducted over a 1-month period in the conscious animal and under anesthesia. We performed a variety of studies with different stimulation parameters and electrode locations to evaluate our hypothesis. In the active animal, we supplied only low currents, but two animals responded to stimulation with bladder contractions and voiding. Following anesthesia, higher stimulating currents resulted in greater bladder contractions during stimulation in two of the three animals. In two cases, pelvic-plexus (bladder-neck) stimulation induced greater micturition responses than direct bladder-wall stimulation. In conclusion, we learned from these preliminary observations that stimulation at the pelvic plexus (bladder neck) may induce a better micturition response than stimulation higher on the bladder-wall. Newly available commercial microstimulators should be further studied for the treatment of urinary retention.

Animals↗