Biomedical subjects

Lisa M Pierce

Publications and source records attributed to Lisa M Pierce.

8 recordsLinked to original sources

PubMed2006

Distribution and immunohistochemical characterization of primary afferent neurons innervating the levator ani muscle of the female squirrel monkey.

OBJECTIVE: This study was undertaken to examine the neurofilament and neurochemical composition of subpopulations of primary afferent neurons innervating the levator ani muscle by combining retrograde tracing and triple labeling immunofluorescence in the female squirrel monkey. STUDY DESIGN: Cholera toxin B subunit (CTB) was injected unilaterally into the levator ani muscle of 3 monkeys to identify primary sensory neurons in the dorsal root ganglia (DRG) and their central projections in the spinal cord. L7-S2 DRG were processed for dual or triple labeling immunofluorescence 3 days after injection to examine labeling of the 200 kD neurofilament marker RT97 (a marker of myelinated neurons), calcitonin gene-related peptide (CGRP; a marker of peptidergic neurons), isolectin B4 (IB4; a marker of small, unmyelinated neurons), and nerve growth factor receptor (TrkA) in CTB-positive neurons. RESULTS: RT97-negative (C-fiber) neurons were more numerous (74% of total CTB-labeled neurons) and smaller in size than RT97-positive (A-fiber) afferent neurons (26% of CTB-labeled neurons). IB4 labeling was almost exclusively found in RT97-negative afferent neurons. Approximately 43% of all CTB-labeled DRG neurons expressed CGRP, and the majority of these were small. The distribution and sizes of CTB-labeled TrkA-positive DRG neurons were similar to those of CTB-labeled CGRP-positive DRG neurons. CONCLUSION: The levator ani muscle is innervated by 3 major subpopulations of primary afferent neurons consisting of cells with large, neurofilament-rich soma and A fibers (putative proprioceptive neurons) and those with small, peptidergic or nonpeptidergic, neurofilament-poor soma and C fibers (putative nociceptive, mechanoreceptive, ergoreceptive, and thermoreceptive neurons). Future investigation is needed to elucidate the relationship between primary sensory neuron subpopulations and changes in neuropeptide and neurotrophin expression on experimental levator ani nerve damage, childbirth, and aging.

Animals↗

PubMed2006

Magnetic resonance imaging of the levator ani in the squirrel monkey: a comparison of muscle volume between a cohort with pelvic organ prolapse and matched normals.

OBJECTIVE: Magnetic resonance imaging was used to test whether squirrel monkeys with pelvic organ prolapse have reduced pelvic muscle volumes, compared with matched normals. STUDY DESIGN: Levator ani and obturator internus volumes obtained from T1-weighted axial scans of matched groups were measured. Muscle volumes and weights were compared for animals necropsied after magnetic resonance imaging. RESULTS: Two observers concurred on measures of levator ani and obturator internus (Kendal tau > or = 0.60 with P < .003). Levator ani volume was related to mass (R2 = 0.62, P = .0009). Animals with pelvic organ prolapse did not differ (P = .67, Wilks multivariate test) from those without pelvic organ prolapse in age, parity, and weight. Levator ani differed between groups (pelvic organ prolapse = 520 mm3 versus normals = 392 mm3, P = .015) and not sides (P = .80). The obturator internus did not differ between groups (P = .29) or sides (P = .72). CONCLUSION: Magnetic resonance imaging demonstrates that levator ani volumes in parous squirrel monkeys with pelvic organ prolapse were not reduced, suggesting that prolapse is not related to pelvic muscle size reduction in this species.

Abdominal Muscles↗

PubMed2005

Immunohistochemical evidence for the interaction between levator ani and pudendal motor neurons in the coordination of pelvic floor and visceral activity in the squirrel monkey.

OBJECTIVE: The purpose of this study was to characterize the spinal distribution of afferent and efferent pathways that innervate the levator ani (LA) muscle in the female squirrel monkey. STUDY DESIGN: Cholera toxin B (CTB) was injected unilaterally into the LA muscle of 5 monkeys to identify primary sensory neurons in the dorsal root ganglia (DRG) and motor neurons in the spinal cord that contribute fibers to the LA nerve. Fluoro-Gold (FG) was injected into the external anal sphincter of 2 of these animals to label pudendal motor neurons (1 of these animals underwent unilateral LA neurectomy before CTB injection). Spinal cord and DRG were processed for immunofluorescence 3 to 7 days after injections. RESULTS: Retrograde transport of CTB from the LA muscle labeled primary afferent neurons in the ipsilateral DRG, their central projections, and motor neurons in the medial portion of the ipsilateral ventral horn of the spinal cord (L7-S2 segments). Injection of FG into the external anal sphincter labeled cells in Onuf's nucleus, primarily in L7. Importantly, CTB-labeled LA motor neurons were virtually absent in Onuf's nucleus, where all pudendal motor neurons are located. CTB-labeled processes were observed within Onuf's nucleus, adjacent to FG-labeled pudendal motor neurons, and appeared to derive from dendrites of LA motor neurons that project into Onuf's nucleus. CONCLUSION: The LA muscle has a distinct innervation with very little or no contribution from the pudendal nerve. The intriguing labeling of LA neural elements within a nucleus that innervates the external urethral and anal sphincters (involved in pelvic visceral control) may represent a neuroanatomic substrate for physiologic integration of spinal and supraspinal inputs for the coordination of pelvic floor and visceral activity.

Afferent Pathways↗

PubMed2005

Evaluation of the aged female baboon as a model of pelvic organ prolapse and pelvic reconstructive surgery.

OBJECTIVE: This study examines the baboon as an animal model of pelvic organ prolapse (POP) by describing the pelvic floor anatomy and adapting human clinical assessment tools. STUDY DESIGN: The pelvic anatomy of an adult female baboon was observed at necropsy, and comparisons were made to the human and squirrel monkey. The pelvic organ prolapse quantification (POP-Q) system was used to assess vaginal support in 12 living adult baboons, including 6 young, reproductive-age, nulligravid females (4.8 +/- 0.5 years) and 6 older, multiparous females (23.0 +/- 0.5 years). RESULTS: The female baboon pelvic anatomy was found to have similar architecture to the human and squirrel monkey female. Six multiparous females with mean parity of 5 (range 2-8) showed no evidence of POP or differences in POP-Q measurements from 6 nulliparous females. CONCLUSION: The POP-Q system can be used to assess female baboon vaginal support. In a sample of baboons, pelvic support loss consistent with POP was not identified. As the pelvic anatomy is similar to the human female, the baboon may prove useful for evaluating surgical materials and for modeling pelvic floor reconstructive surgeries.

Aging↗

PubMed2003

Innervation of the levator ani muscles in the female squirrel monkey.

OBJECTIVE: The purpose of this study was to characterize the innervation of the levator ani muscles in the female squirrel monkey and to investigate its usefulness as an animal model of pelvic organ prolapse. STUDY DESIGN: Eleven nulliparous female squirrel monkeys with no pelvic organ prolapse were used in this study. Detailed pelvic dissections were conducted (n = 3), and the Koelle stain for acetylcholinesterase was used to identify the motor endplate zone in the levator ani muscles (n = 2). Unilateral levator ani (n = 4) and pudendal (n = 2) neurectomies were performed; changes in levator ani muscle mass and myocyte diameter were examined 14 days after neurectomy. Nerve biopsy specimens from each animal were processed for microscopy. RESULTS: The levator ani nerve originated from the S2 spinal root and entered the pelvic cavity adjacent to the pelvic nerve between the flexor caudalis brevis and iliocaudalis muscles. The levator ani nerve then projected caudally and bifurcated to penetrate the iliocaudalis and pubocaudalis. A single motor endplate zone in each muscle correlated with the point of levator ani nerve penetration. The pudendal nerve originated from the S1-S2 spinal roots to innervate the urethral and anal sphincters, clitoris, and perineum, but not the iliocaudalis or pubocaudalis. Significant atrophy and myocyte shrinkage occurred in the iliocaudalis and pubocaudalis ipsilateral to the levator ani nerve transection (P <.05). Pudendal neurectomy produced no levator ani muscle changes. CONCLUSION: Intrapelvic skeletal muscles in the female squirrel monkey are similar to humans and have distinct innervation with no contribution from the pudendal nerve. The squirrel monkey is likely to be a useful model of pelvic organ prolapse and warrants further study.

Animals↗

PubMed2002

Well-done red meat, metabolic phenotypes and colorectal cancer in Hawaii.

Heterocyclic amines (HAAs) and polycyclic hydrocarbons are suspected colorectal cancer (CRC) carcinogens that are found in well-done meat. They require metabolic activation by phase I enzymes, such as the smoking-inducible CYP1A isoenzymes. N-acetyltransferase 2 (NAT2) also play a role in the further activation of HAAs. We conducted a population-based case-control study in Hawaii to test the associations of preference for well-done red meat and HAA intake with colon and rectal cancers, as well as the modifying effects of NAT2 and CYP1A2. We interviewed 727 Japanese, Caucasian or Native Hawaiian cases and 727 controls matched on sex, age, and ethnicity. HAA intake was estimated based on consumption of meat and fish for each of several cooking methods and doneness levels. A subgroup of 349 cases and 467 controls was phenotyped for CYP1A2 by a caffeine test. We found that preference for well-done red meat was associated with a 8.8-fold increased risk of CRC (95% CI: 1.7-44.9) among ever-smokers with the NAT2 and CYP1A2 rapid phenotypes, compared to ever-smokers with low NAT2 and CYP1A2 activities and who preferred their red meat rare or medium. A dose-dependent association was also found between the HAA intake estimates and male rectal cancer, with a two- to three-fold increase in risk from the low (T(1)) to high (T(3)) tertile of intake for each HAA. This association was strongest for MeIQx. HAA intake was not associated with male colon cancer or colon or rectal cancer in women. These data provide support to the hypothesis that exposure to pyrolysis products through consumption of well-done meat increases the risk of CRC, particularly in individuals who smoke and are genetically susceptible (as determined by a rapid phenotype for both NAT2 and CYP1A2). An attempt to examine the risk associated with specific HAAs suggested that the main HAAs increase risk of rectal cancer in men and that they do not appreciably affect risk of rectal cancer in women or of colon cancer in either sex.

Adolescent↗

PubMed2002

Connexin 43 expression in normal versus dysfunctional labor.

OBJECTIVE: We sought to determine whether connexin 43 (Cx43), the major myometrial gap junction protein, is differentially expressed in normal versus dysfunctional labor. STUDY DESIGN: Myometrial biopsies were obtained from 28 patients undergoing cesarean section and grouped into the following categories: (1) no labor, (2) dysfunctional labor, and (3) normal labor. Northern and Western analyses were performed to determine Cx43 messenger RNA (mRNA) and protein expression, respectively. Localization of Cx43 protein was determined by immunohistochemistry. RESULTS: Labor was associated with increased Cx43 mRNA expression (P <.05). This association was not true for protein. There was no difference in mRNA or protein expression between patients with normal labor versus those with dysfunctional labor. The extent of Cx43 immunohistochemical staining was not significantly different among the groups (P >.05). CONCLUSION: Dysfunctional labor is not associated with aberrant Cx43 mRNA or protein expression or with a reduction in immunodetectable Cx43 gap junctions.

Adult↗

PubMed2002

The effect of fetal acidemia on fetal-placental vascular tone and production of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha.

OBJECTIVE: Our purpose was to determine the effects of fetal acidemia on placental vascular tone and production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). STUDY DESIGN: With use of an ex vivo placental perfusion model, the maternal and fetal circulation of two cotyledons from five human placentas were perfused for 4 hours. The fetal circulation of one cotyledon was perfused with acidemic (pH 6.90) Hanks' balanced salt solution (HBSS), whereas the fetal circulation of the other cotyledon was perfused with physiologic (pH 7.35) HBSS. Fetal venous effluents were collected hourly, and IL-6 and TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Cotyledon perfusion pressures were recorded every 10 minutes. Paired t tests were used to compare differences in cytokine production and perfusion pressure between the cotyledons. RESULTS: Fetal-placental vascular perfusion pressure was consistently reduced from baseline under acidemic, but not physiologic, conditions with statistical significance achieved from 20 minutes onward (P <.05). IL-6 and TNF-alpha increased exponentially over time for both conditions (P <.05). There was no difference in cytokine production when acidemic conditions were compared with physiologic conditions (P <.05). CONCLUSION: Fetal-placental vasodilation may be a compensatory mechanism to improve acidemic conditions. Unlike fetal hypoperfusion or fetal hyperoxia, fetal acidemia does not result in elevated placental cytokine levels.

Acids↗