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R J Fox

Publications and source records attributed to R J Fox.

30 records · Page 2Linked to original sources
PubMed1996

Anatomic details of intradural channels in the parasagittal dura: a possible pathway for flow of cerebrospinal fluid.

OBJECTIVE: The absorption of cerebrospinal fluid occurs primarily by means of arachnoid granulations (AG) in the superior sagittal sinus (SSS) and the lacunae laterales (LL) in the parasagittal dura. Previous descriptions of this region suggest a network of intradural channels, but finer details of extent and relationship between channels and AG were not addressed. Therefore, we undertook an anatomic study of cadaveric parasagittal dura. METHODS: The SSS and parasagittal dura of 20 formalin-fixed adult cadavers and 15 autopsy specimens from patients ranging in age from 18 weeks of gestation to 80 years were studied by use of a light microscope, a scanning electron microscope, and corrosion casting. Intradural injections into the parasagittal region were performed in two formalin-fixed and four autopsy specimens from adults by use of normal saline and corrosion casting. RESULTS: Extensive networks of intradural channels from 0.02 to 2.0 mm in diameter were noted in all of the specimens. Channels either were connected to the SSS at intervals along the side wall or drained directly into the LL, which extended up to 3 cm from midline. Channels lined with endothelium stained positive for Factor VIII, as did the endothelium of the LL and SSS. In some places, the network of channels seemed to coalesce to form LL. The underside of the dura was coarse and trabeculated where the channels were abundant, and AG were interdigitated between these trabeculae. In regions of the dura where channels were sparse or absent, the dural underside was smooth and lacked AG. Underlying cortical veins opened directly into the SSS and were unrelated to intradural channels. Intradural parasagittal injections from the epidural side accessed the SSS by way of channels using pressures between 0 and 20 cm H2O at 1.5 ml/min. CONCLUSION: These channels may represent a pathway for the flow of cerebrospinal fluid from AG to the SSS.

Adolescent↗
PubMed1996

PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease.

PCR-in situ hybridization (PCR-ISH) was developed and utilized to determine the distribution of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes (PBL) from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). PCR-ISH of HTLV-1 tax DNA in PBL from patients with HAM/TSP revealed that 1 in 5,000 to 1 in 10,000 PBL contained virus. PCR-ISH was sensitive, because a positive signal was consistently demonstrated from the HTLV-1-infected cell lines HUT-102 (which contains four to six copies of HTLV-1 proviral DNA per cell) and MT-1 (which contains one to three copies of HTLV-1 proviral DNA per cell). Also, intracellular amplification by PCR-ISH significantly increased sensitivity compared with conventional ISH and was shown to be specific for HTLV-1 tax DNA. These results are in contrast to solution-phase PCR amplification in which greater than 1% of cells were estimated to be infected. The discordance between these results is discussed and may indicate that more than one copy of HTLV-1 tax proviral DNA is present in an individual PBL.

Base Sequence↗
PubMed1996

Tumor necrosis factor alpha expression in the spinal cord of human T-cell lymphotrophic virus type I associated myelopathy/tropical spastic paraparesis patients.

HTLV-I Associated Myelopathy Tropical Spastic Paraparesis (HAM/TSP) is a chronic degenerative disease mainly affecting the spinal cord. The pathogenesis of HAM/TSP is unknown, but is thought to involve immunopathogenic mechanisms. Several reports have detected inflammatory cytokines such as tumor necrosis factor alpha (TNF alpha) in HAM/TSP patients. In this study, we used in situ hybridization (ISH) to examine the expression of TNF alpha RNA in spinal cord autopsy specimens from three chronic HAM/TSP patients with long-term disease (10-20 years duration). ISH identified many TNF alpha-expressing cells throughout all three patient's spinal cord tissues. Two patient's spinal cord tissue showed inflammatory cells, however double labeling by ISH for TNF alpha RNA with immunohisto-chemistry for CD45RO (a marker for memory T-cells) or CD-68 (a marker for microglia/macrophages) did not colocalize TNF alpha RNA with either CD45RO or CD-68 positive cells. Therefore, TNF alpha is expressed in the spinal cord of chronic HAM/TSP patients compared to normal controls and TNF alpha-expressing cells do not appear to be memory T-cells, microglia or macrophages.

Antigens, CD↗
PubMed1994

Bilateral lesions of the amygdala attenuate analgesia induced by diverse environmental challenges.

This study was designed to evaluate the role of the amygdala, particularly its central nucleus, in the induction of analgesia elicited by environmental challenges. Rats with large, radiofrequency lesions centered in the central nucleus were found to display significantly attenuated analgesic responses to three different challenges: cat exposure, acute footshock, and re-exposure to an environment associated with footshock. These findings show that the amygdala plays an important role in the elicitation of analgesia by each of the environmental challenges tested. Since the amygdala has been shown to play a critical role in fear, these findings suggest that the analgesia elicited by these challenges involves a substantial fear component. Moreover, the finding that amygdala lesions significantly reduced the analgesia elicited by a non-noxious unconditional stimulus (cat exposure) strongly suggests that these lesions disrupt the expression of analgesia rather than producing a learning impairment. And finally, the findings of this study support the suggestion that fear-elicited analgesia is triggered by activation of a projection from amygdala to periaqueductal gray which forms one component of an integrated 'defensive behavioral system.'

Amygdala↗
PubMed1994

Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response.

Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain in response to infection and by infiltrating mononuclear cells and their contributions to outcome of infection have not been identified. Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6 mRNAs were detected in uninfected mice before infection and were up-regulated within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice. LIF mRNA was occasionally detected in uninfected mice but increased in amounts only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs were not found in uninfected mice but were induced within 24 h and continued to rise through 7 days after infection with substantially higher levels in BALB/cJ than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4, IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data suggest a predominant type 2 cytokine response in the brain during SV encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had 100% mortality, whereas NSV-infected scid mice developed persistent nonfatal infection. Inflammation was more intense in NSV-infected mice, however, no substantial differences in cytokine mRNA levels were detected when compared with mice with nonfatal SV infection suggesting that the cytokines measured do not in and of themselves lead to fatal central nervous system disease.

Alphavirus Infections↗
PubMed1991

Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.

Imipramine is the prototypic tricyclic antidepressant utilized in the treatment of major depression and exerts its therapeutic efficacy only after prolonged administration. We report a study of the effects of short-term (2 wk) and long-term (8 wk) administration of imipramine on the expression of central nervous system genes among those thought to be dysregulated in imipramine-responsive major depression. As assessed by in situ hybridization, 8 wk of daily imipramine treatment (5 mg/kg, i.p.) in rats decreased corticotropin-releasing hormone (CRH) mRNA levels by 37% in the paraventricular nucleus (PVN) of the hypothalamus and decreased tyrosine hydroxylase (TH) mRNA levels by 40% in the locus coeruleus (LC). These changes were associated with a 70% increase in mRNA levels of the hippocampal mineralocorticoid receptor (MR, type I) that is thought to play an important role in mediating the negative feedback effects of low levels of steroids on the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine also decreased proopiomelanocortin (POMC) mRNA levels by 38% and glucocorticoid receptor (GR, type II) mRNA levels by 51% in the anterior pituitary. With the exception of a 20% decrease in TH mRNA in the LC after 2 wk of imipramine administration, none of these changes in gene expression were evident as a consequence of short-term administration of the drug. In the light of data that major depression is associated with an activation of brain CRH and LC-NE systems, the time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression.

Adrenal Glands↗
PubMed1990

Optimization of cRNA probe in situ hybridization methodology for localization of glucocorticoid receptor mRNA in rat brain: a detailed protocol.

1. We have described a general ribonucleotide probe in situ hybridization methodology for localization of mRNA in frozen, unfixed tissue sections of brain. 2. The most important steps in obtaining consistent and reproducible autoradiographs with ribonucleotide probes were tissue acetylation and application of the radiolabeled probe to tissue sections under unsealed, glass coverslips. 3. Variability of the hybridization signal in tissue sections has been minimized to achieve a high degree of reproducibility within a given experiment as determined by densitometric analysis of rat glucocorticoid and mineralocorticoid receptor mRNA hybridization autoradiographs. 4. Tissue quality has been optimized for high-resolution anatomical localization of mRNA species by nuclear track emulsion. 5. The protocol is amenable to rapid, batchwise processing of tissue samples.

Animals↗
PubMedDate not supplied

Do cigarette warnings warn? Understanding what it will take to develop more effective warnings.

Warnings in cigarette advertisements have been the principal method mandated by the federal government to educate consumers about the risks of smoking. Warnings have been required in all cigarette ads for 30 years and have remained largely unchanged during this time. The current warning program was neither developed nor implemented with specific communication goals in mind. Instead, it was negotiated by the government and tobacco industry representatives. The warning program has served the tobacco industry well by providing it with a key argument in tobacco litigation: "We warned you." It has, however, failed as a public health strategy, since much research has shown that the current warnings are ineffective communication devices. If Congress is to be effective in its efforts to educate consumers about the risks of smoking, it needs to rethink the warning strategy while making use of knowledge regarding how warnings work. The paper draws from current studies in order to develop realistic cigarette warning objectives and points out the considerations necessary to create such warnings. To be effective, warnings must be developed, targeted, tested, and revised over time.

Health Education↗
PubMedDate not supplied

A functional comparison of animal anterior cruciate ligament models to the human anterior cruciate ligament.

Many investigators have used animal models to clarify the role of the human anterior cruciate ligament (ACL). Because none of these models are anatomically and biomechanically identical to the human ACL, there exists a need for an objective comparison of these models. To do this, we used a universal force-moment sensor to measure and compare the in situ forces, including magnitude and direction, of the ACL and the anteromedial (AM) and posterolateral (PL) bundles of human, pig, goat, and sheep knees. An Instron was used to apply 50 and 100 N anterior tibial loads at 90 degrees of knee flexion, while a universal force-moment sensor was used to measure the forces applied by the ACL to the tibia, the in situ force of the ACL. We found significant differences between the magnitude of force experienced by the goat and sheep ACL and AM and PL bundles when compared with the human ACL and AM and PL bundles. Also, the direction of the in situ force in the ACL and AM bundles of the goat and sheep were different from the human. The pig knee differed from the human only in the magnitude and direction of the in situ force in the PL bundle in response under anterior tibial loading. A tally of the significant differences between the animal models and the human knees indicates that goat and sheep knees may have limitations in modeling the human ACL, while the pig knee may be the preferred model for experimental studies.

Aged↗
PubMedDate not supplied

Determination of the in situ forces in the human posterior cruciate ligament using robotic technology. A cadaveric study.

We examined the in situ forces in the posterior cruciate ligament as well as the force distribution between its anterolateral and posteromedial bundles. Using a robotic manipulator in conjunction with a universal force-moment sensor system, we applied posterior tibial loads from 22 to 110 N to the joint at 0 degrees to 90 degrees of knee flexion. The magnitude of the in situ force in the posterior cruciate ligament and its bundles was significantly affected by knee flexion angle and posterior tibial loading. In situ forces in the posterior cruciate ligament ranged from 6.1 +/- 6.0 N under a 22-N posterior tibial load at 0 degree of knee flexion to 112.3 +/- 28.5 N under a 110-N load at 90 degrees. The force in the posteromedial bundle reached a maximum of 67.9 +/- 31.5 N at 90 degrees of knee flexion, and the force in the anterolateral bundle reached a maximum of 47.8 +/- 23.0 N at 60 degrees of knee flexion under a 110-N load. No significant differences existed between the in situ forces in the two bundles at any knee flexion angle. This study provides insight into the knee flexion angle at which each bundle of the posterior cruciate ligament experiences the highest in situ forces under posterior tibial loading. This information can help guide us in more accurate graft placement, fixation, and tensioning, and serve as an assessment of graft performance.

Biomechanical Phenomena↗
PubMedDate not supplied

Orbital emphysema and diplopia following thoracotomy.

PURPOSE: To describe the clinical and radiological findings in a patient with diplopia and orbital emphysema following thoracotomy. METHODS: Reported is a 71-year-old woman who presented with diplopia several days following thoracotomy. RESULTS: Physical examination revealed diffuse subcutaneous emphysema and a right hypertropia. Head computed tomography revealed facial and palpebral subcutaneous emphysema extending into the infratemporal fossa and orbits bilaterally. A chest tube was replaced and her diplopia resolved. CONCLUSIONS: Subcutaneous emphysema can lead to diplopia and orbital emphysema in the absence of orbital trauma. Contrary to previously suggested mechanisms of orbital emphysema associated with subcutaneous emphysema, computed tomography imaging suggested that air entry into the orbit in this case was through the inferior orbital fissure.

Aged↗