Biomedical subjects

F Parker

Publications and source records attributed to F Parker.

At least 19 recordsLinked to original sources

PubMed1999

Upregulation of the RAS-GTPase activating protein (GAP)-binding protein (G3BP) in proliferating RPE cells.

Cultured human retinal pigment epithelial (RPE) cells of different passages (P0 and P3) were used as a model system to examine changes in gene expression in proliferating RPE cells by polymerase chain reaction (PCR)-based differential expressed mRNA analysis (DEmRNA-PCR). DEmRNA-PCR showed enhanced expression of a specific RNA in P3 compared with P0. Sequence alignment displayed its identity with the 3'-end of the coding sequence of the human RAS-GTPase activating protein (GAP)-binding protein (G3BP). Confirmation of the induced expression of G3BP was performed by gene-specific reverse transcription-polymerase chain reaction (RT-PCR) of freshly prepared human RPE cells and of cultured cells of P0, P3 and P8 and by immunohistochemistry of cultivated retinal pigment epithelial cells in an artificial lesion assay. The expression of G3BP mRNA increased with the number of passages. G3BP protein expression increased in cells repopulating the artificial lesion. DEmRNA-PCR in RPE cells with subsequent sequence analysis led to the characterization of dedifferentiation- and proliferation-dependent expression of a previously undetected gene product in cultured RPE cells with a possible role in modifying signal transduction responses that may have implications on the treatment of proliferative vitreoretinopathy.

Aged↗

PubMed1999

A novel apolipoprotein A-1 variant, Arg173Pro, associated with cardiac and cutaneous amyloidosis.

An American kindred was found to have hereditary amyloidosis with cutaneous and cardiac involvement. Characterization of fibrils isolated from skin identified the amyloid protein as the N-terminal 90 to 100 residues of apolipoprotein A-1. Sequence of the apolipoprotein A-1 gene was normal except for a G/C transversion at position 1638 which predicts an Arg to Pro substitution at residue 173. This mutation, unlike previously described amyloidogenic mutations is not in the N-terminal fragment which is incorporated into the fibril. The mutation is at the same residue as in apolipoprotein A-1 Milano (Arg173Cys) which does not result in amyloid formation. Decreased plasma HDL cholesterol levels in carriers of the Arg173Pro mutation suggest an increased rate of catabolism as has been shown for the amyloidogenic Gly26Arg mutation. This suggests that altered metabolism caused by the mutation may be a significant factor in apolipoprotein A-1 fibrillogenesis.

Adult↗

PubMed1999

Paraganglioma of the cauda equina region--report of two cases and review of the literature.

A paraganglioma of cauda equina region is extremely rare and except for secreting tumour, the pre-operative diagnosis of paraganglioma is very difficult. Two cases of non-functional paragangliomas of the cauda equina region are reported, one was attached to the filum terminale and the other to a rootlet looking very much like a vascular neurinoma. Both were successfully removed by surgery. An extensive review of the literature permits one to find 77 other cases. The clinical, radiological, pathological (ultrastructural and immunohistochemical) features and surgical findings of all theses cases are discussed. Surgery remains the treatment of choice. No effect of radiotherapy on recurrence prevention has ever been demonstrated.

Adult↗

PubMed1999

Presurgical contribution of quantitative stereotactic positron emission tomography in temporo limbic epilepsy.

BACKGROUND: We quantified the interictal metabolic changes associated with temporal lobe epilepsy by using an accurate stereotactic method. METHODS: We selected 16 patients who had proven unilateral focal or regional temporal onset defined by SEEG criteria. Each patient underwent stereotactic MRI and stereotactic [18 fluoro] fluorodeoxyglucose positron emission tomography (PET). RESULTS: Asymmetries (mean, +/- SD) were found in mesio-temporal structures: amygdala (-0.033+/-0.027, p = 0.0002), hippocampus (-0.035+/-0.032, p = 0.0006), and superior temporal gyrus (-0.036+/-0.032, p = 0.0004). Four of the sixteen patients had previously had unlocalized qualitative nonstereotactic PET analysis. CONCLUSIONS: The quantitative stereotactical PET method allows a higher resolution study of mesio-temporal structures.

Adolescent↗

PubMed1999

[The place of MRI in the study of cerebrospinal fluid fistulas].

Results of CT and MRI explorations in 8 patients with cerebrospinal fluid (CSF) fistulae are reported and compared with surgical findings in 7. Sensitivity of MRI (CISS and fast T2 spin-echo sequences) was excellent giving perfect correlations with surgical findings in 7/7 cases. CT and MRI were found to provide complementary information suggesting they should be used in combination as first intention explorations of suspected CSF fistulae. Computerized cisternography should be used if MRI is contraindicated or if a clinically and biologically proven CSF fistulae is not visualized by CT or MRI.

Adolescent↗

PubMed1999

[Syringomyelia and Chiari abnormality in the adult. Analysis of the results of a cooperative series of 285 cases].

This chapter discusses the retrospective data found in 285 patients with syringomyelia associated with Chiari abnormality and collected from 18 neurosurgical departments. A pre and postoperative MRI study and a minimum follow up of at least 2 years were required. A scale of severity was fixed and tested before and after treatment. The size of the cyst, the degree of the foraminal obstruction were analyzed. The mean age at diagnosis was about 39 years and the duration of symptoms about 6.7 years. Sensory disorders were present in 91% of cases, pain in 66% and motor deficit in about 60%. According to our functional classification, the majority of our patients were moderately disabled and only 10.8% showed a severe impotence. Results of the two major surgical procedures, foramen magnum decompression (FMD) (88% of cases) and cyst shunting procedures (SP) (32% of cases) were evaluated with a mean follow-up period of 6.7 years (ranged from 2 to 14 years). Better clinical and morphological results (87% of stabilization or improvement for FMD versus 71% for SP) were obtained by FMD procedure comparing to SP, with the same rate of complications.

Adult↗

PubMed1999

[Non-traumatic arachnoiditis and syringomyelia. A series of 32 cases].

We conducted a retrospective study of 32 patients treated for syringomyelia associated with non-traumatic arachnoid scarring. We selected the cases with documented history of arachnoiditis with pre and post-operative clinical evaluation of the neurological status and anatomical study on MRI with a minimal follow-up of one year. Extensive arachnoid scarring (Group I) was noted in 18 cases, after spinal meningitis in 15 cases (tuberculosis in 9 cases, listeria in 3 cases, pyogenic meningitis in 3 cases), subarachnoid hemorrhage in 3 cases. Focal arachnoid scarring (Group II) occurred in 10 cases, related to spinal surgery in 5 cases (meningiomas: 2, neurinomas: 2, thoracic discectomy: 1), to peridural anesthesia in 1 case, thoracic disc herniation in 1 case, Pott's disease in 1 case, no obvious cause in 2 cases. Basal arachnoid scarring without hindbrain herniation (Group III) was associated with birth injuries in 4 cases. Shunting of the syrinx to the subarachnoid or peritoneal cavity was associated with a recurrence rate of 60% whereas microsurgical dissection of the arachnoid scar and decompression of the subarachnoid space with a recurrence rate of 33%, with a mean follow-up period of 28 months. Successful long-term management of the syrinx was associated with basal or focal spinal arachnoid scarring, no history of spinal meningitis, microsurgical dissection of the arachnoid scar and decompression of the subarachnoid space.

Adult↗

PubMed1999

[Characterization of sensation disorders and neuropathic pain related to syringomyelia. A prospective study].

The present prospective study aimed to perform quantitative sensory testing (QST) in patients with painful or painless syringomyelia before and after surgical treatment of their syrinx (at 3 and 9 months). Eighteen consecutive patients with cervical or dorso-lumbar syringomyelia completed the study and 9 underwent surgery. Twelve patients had central neuropathic pain (of whom 6 were followed up). Spontaneous pain and brush-evoked allodynia were assessed. Von Frey hairs, vibrameter and a thermotest device were used to determine the mechanical-, vibratory-, thermal-detection thresholds, and the mechanical and thermal pain thresholds. Results showed evidence of deficits in temperature and pain sensibility in 17 cases, often associated with deficits in vibration and touch sensitivity (11 cases). Magnetic resonance scan, including axial images, demonstrated good correlation between paramedian extension of the syrinx and the laterality of thermal deficits. Somatosensory evoked potentials (11 patients) were abnormal in 9 cases at level, and showed good correlation with deficits in vibration. The magnitude of the thermal and tactile deficit was similar between areas of spontaneous pain and adjacent non painful areas. Surgery induced a significant decrease of tactile deficits, and to a lesser extent, of thermal deficits. Effects on neuropathic pain were positive in 3 patients (total disappearance of pain) and negligible or negative in 3 patients, despite collapse of the syrinx (in 2 cases). These results confirm that QST are useful in clinical practice to quantify the clinical results of surgery in patients with syringomyelia, and allow some hypotheses about the mechanisms of neuropathic pain in these patients.

Adult↗

PubMed1999

[Dynamic MRI in the evaluation of syringomyelic cysts].

We report the results of a MR velocity study of the cerebrospinal fluid including 36 patients with syringomyelic cysts (25 with a foraminal syringomyelia, 7 with a post-traumatic cyst, 2 with a tumoral spinal cord cyst, 2 with a spinal arachnoiditis). Velocity measurements were performed in the cysts and in the pericystic subarachnoid spaces and compared with clinical data, evolutive pattern of the disease, cyst volume, degree of stenosis of the cranio-cervical junction (in patients with Chiari I) or of the spinal canal (in post-traumatic cases), and with the extension of the cyst (post-traumatic cases). Cyst velocities correlated in the pre operative course with the clinical status of the patients and with the volume of the cyst. Correlation with the degree of foraminal stenosis was uncertain and no correlation was found with the duration of the disease course. In the post-operative course cyst velocity decreased and velocity of the subarachnoid spaces increased. Onset of the systolic peak occurred sooner in the cyst than in the subarachnoid spaces. We believe that this point may be important in the pathogenesis of the disease. We consider that systolic and diastolic cyst velocities respectively greater than 2.3 cm/s and 1.5 cm/s in the post-operative course may characterize aggressive cysts. In the future comparison of velocity measurements in patients with Chiari I without syrinx and patients with Chiari I related syringomyelia may be helpful for a better understanding of the natural history of the syringomyelia.

Adult↗

PubMed1999

[History, controversy and pathogenesis].

In this paper, we discuss the historical and pathophysiological aspects of syringomyelia. Defined as fluid cavities extending beyond several segments within the spinal cord this pathological entity is a condition with many possible causes. Hindbrain herniation is the commonest foramen magnum abnormality associated with the so called "hindbrain related syringomyelia". A history of birth injury, a small posterior fossa, an arachnoid scarring of the basal cisterna, a segmentation abnormality of the superior cervical vertebrae, a hydrocephalus or arachnoid cyst of the posterior fossa are often present in this context. Previous theories of the origin and the mechanism of syringomyelia progression have been controversly proposed. Gardner and colleagues postulated that the primary event is the incomplete embryonic opening of the outlets of the fourth ventricle. The fluid arrived in the syrinx along the embryologically natural route down the central canal. Their hydrodynamic theory states that with each arterial pulse, the outflow of CSF is transmitted from the fourth ventricle down to the syrinx via the central canal. Most patients have patent fourth ventricle foramina and evidence of communication between the ventricle and the syrinx is rare. Williams then proposed his "cranio-spinal pressure dissociation theory". Significant pressure differential occur daily during activities that increase intrathoracic pressure such as sneezing, coughing and could be transmitted to the spinal fluid from the epidural spinal veins. The progression of the cavity is better understood and analyzed with dynamic MR imaging and quantitative analysis. The CSF flow from the cranial to the spinal subarachnoid space results from the expansile motion of the brain during the cardiac cycle. The progression of the cavity is based on pressure acting on the surface of the cord and does not require any communication of the fourth ventricle with the central canal and the syrinx. The origin of fluid cavity remain questionable. Aboulker but also Ball and Dayan pointed out the role of the perivascular spaces and the DREZ which are involved in the communication between the perimedullar CSF, the spinal cord extracellular spaces and the central canal. Other causes of syringomylia include acquired conditions which could be grouped under the heading of "non-hindbrain related syringomyelia". Arachnoid scarring is related in many case to spinal trauma or occurs after spinal meningitis, spinal intradural surgery, peridural anesthesia, subarachnoid hemorrhage. Rarely an extra medullary compression is discussed. The mechanism involved is here again an alteration of the CSF flow at the spinal level.

History, 18th Century↗

PubMed1998

Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor.

Epidermal growth factor (EGF) receptor was shown to be involved in the activation pathway of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) cascade not only by EGF, but also by UV radiation or osmotic stress. This paper describes a specific interaction between the COOH-terminal SH3 domain of Grb2 and the NH2-terminal regulatory domain of MEKK1 in ER22 cells overexpressing the EGF receptor. This interaction results in the formation of a constitutive complex between Grb2 and MEKK1 in both proliferating and resting cells. EGF stimulation causes this complex to be rapidly and transiently recruited by Shc proteins. The subsequent release of the Grb2-MEKK1 complex from Shc proteins correlates with JNK activation. Transfection of the NH2-terminal regulatory domain of MEKK1 specifically inhibits EGF-dependent JNK activation indicating that Grb2 is involved in MEKK1 activation. Thus, adaptor proteins have a new role in the regulation of the SAPK/JNK cascade after EGF stimulation.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Differential interactions of the growth factor receptor-bound protein 2 N-SH3 domain with son of sevenless and dynamin. Potential role in the Ras-dependent signaling pathway.

In this paper, we show that the 36-45 surface-exposed sequence WYKAELNGKD of growth factor receptor-bound protein 2 (Grb2) N-SH3 domain inhibits the interaction between Grb2 and a 97-kDa protein identified as dynamin. Moreover, the peptide GPPPQVPSRPNR from dynamin also blocks the binding of dynamin to the proline-rich recognition platform of Grb2. Mutations in the 36-45 motif show that Glu-40 is critical for dynamin recognition. These observations were confirmed by immunoprecipitation experiments, carried out using ER 22 cells. It was also observed that the proline-rich peptide from dynamin was unable to dissociate the Grb2.Sos complex, whereas the proline-rich peptide from Son of sevenless (Sos) inhibited Grb2. dynamin interaction. A time-dependent stimulation of epidermal growth factor receptor overexpressing clone 22 (ER 22) cells by epidermal growth factor resulted in an immediate increase of the Grb2.Sos complex and a concomitant decrease in Grb2.dynamin. This suggests that the recruitment of Grb2.Sos to the membrane, triggered by epidermal growth factor stimulation, activates the Ras-dependent signaling and simultaneously enhances free dynamin levels, leading to both receptor internalization and endocytotic processes.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Topical metronidazole maintains remissions of rosacea.

BACKGROUND: Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred. OBJECTIVE: To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea. DESIGN: A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study). SETTING: Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers. SUBJECTS: One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel. INTERVENTIONS: Subjects were evaluated monthly for up to 6 months to determine relapse rates. MAIN OUTCOME MEASURES: Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed. RESULTS: In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%). CONCLUSION: In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel.

Administration, Cutaneous↗

PubMed1998

Haemangioblastoma of the central nervous system in von Hippel-Lindau disease. French VHL Study Group.

Haemangioblastoma of the central nervous system (CNS) is the most characteristic lesion and the most common presenting manifestation of von Hippel-Lindau (VHL) disease and has a striking tendency to multiple occurrence. Its sites of predilection are the posterior fossa (cerebellum++), and the spinal cord. Haemangioblastoma may cause increased intracranial pressure and/or neurological deficits and remains the main cause of morbidity and mortality in VHL. Treatment of symptomatic haemangioblastoma remains neurosurgical and is often in emergency. Haemangioblastoma appears to be more commonly associated with VHL than previously reported and suggests that all patients with 'sporadic' haemangioblastoma should be investigated for evidence of VHL disease. From a fundamental point of view, haemangioblastoma is a benign neoplastic entity with a double, vascular and cellular differentiation. Mutational inactivation of both copies of the VHL gene plays a major role in the pathogenesis of haemangioblastoma. Over-expression of vascular endothelial growth factor (VEGF) and VEGF-receptors has been recently demonstrated in these tumours, raising the possibility of angioblastic origin, and is of very great interest in view of the direct implication of the VHL gene in negative regulation of VEGF.

Central Nervous System Neoplasms↗

PubMed1998

A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a potential link between signal transduction and RNA stability.

A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src homology 3 [SH3] binding protein), was previously identified based on its ability to bind the SH3 domain of RasGAP. Here we show that G3BP colocalizes and physically interacts with RasGAP at the plasma membrane of serum-stimulated but not quiescent Chinese hamster lung fibroblasts. In quiescent cells, G3BP was hyperphosphorylated on serine residues, and this modification was essential for its activity. Indeed, G3BP harbors a phosphorylation-dependent RNase activity which specifically cleaves the 3'-untranslated region of human c-myc mRNA. The endoribonuclease activity of G3BP can initiate mRNA degradation and therefore represents a link between a RasGAP-mediated signaling pathway and RNA turnover.

Animals↗

PubMed1998

Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study.

Anticonvulsants are widely used in the treatment of neuropathic pain, and are assumed to act preferentially on lancinating, shooting pain. In the present study, the effects of gabapentin, a novel anticonvulsant, were evaluated systematically on both spontaneous and evoked pain in 18 patients with peripheral nerve injuries or central lesions. Gabapentin was administered orally in gradually increasing doses up to a maximum of 2,400 mg/day. Evaluations of spontaneous ongoing and paroxysmal pain, allodynia and hyperalgesia were performed at the beginning of the study ('baseline') and 6 weeks after the steady-state dose had been reached. Quantitative sensory tests were used to measure detection and pain thresholds to mechanical and thermal stimuli and the responses to suprathreshold stimuli. Gabapentin induced a moderate and statistically significant relief of ongoing spontaneous pain and was particularly effective in reducing paroxysmal pain. A striking finding was the significant effect on brush-induced and cold allodynia. In contrast, no effects were observed on detection and pain thresholds to static mechanical and hot stimuli. Side effects were generally minor and did not interfere with everyday activities. The present study suggests that gabapentin has preferential antihyperalgesic and/or antiallodynic effects, and is equally effective in pain due to peripheral nerve injuries and central lesions.

Acetates↗

PubMed1998

Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity.

Fotemustine is a chloroethylnitrosourea with antitumor activity in disseminated melanoma and adult primary brain tumors. Because new drugs are required for the treatment of medulloblastoma in children, we evaluated the preclinical antitumor activity of fotemustine in four s.c. medulloblastoma xenografts, in comparison with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Both drugs were administered as a single i.p. injection to nude mice bearing advanced-stage tumor. Fotemustine displayed significant antitumor activity in three of four medulloblastoma xenografts; two, IGRM34 and IGRM57, were highly sensitive, with 37 and 100% tumor-free survivors, respectively, more than 120 days after treatment at the highest nontoxic dose (50 mg/kg). Fotemustine was also highly active in a malignant glioma xenograft (IGRG88; five of six tumor-free survivors on day 177). Fotemustine proved to be significantly more active than BCNU in IGRM34 and the glioma xenograft IGRG88. The DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) was detected in all tumor xenografts, ranging in activity from 6 to 892 fmol/mg protein. The high in vivo sensitivity to fotemustine and BCNU observed in three xenografts was clearly associated with a low ATase activity (> 20 fmol/mg), whereas the two poorly sensitive or refractory medulloblastoma xenografts showed high ATase activity (> 500 fmol/mg). Alkylpurine-DNA N-glycosylase activity was detected in all tumor xenografts but at levels ranging only from 513 to 1105 fmol/mg/h; no consistent relationship was found between alkylpurine-DNA N-glycosylase activity and the in vivo sensitivity to the two chloroethylnitrosoureas. The improved activity and tolerance of fotemustine in comparison with BCNU in pediatric medulloblastoma xenografts strongly support the clinical development of this agent in children with brain tumors, in which ATase should be examined as a potential prognostic indicator.

Animals↗

PubMed1998

Squamous and basal cell carcinoma in heart transplant recipients.

BACKGROUND: Cutaneous malignancies are frequent in organ transplant recipients. We retrospectively reviewed a large series of heart transplant recipients and report on the prevalence and risk factors for development of cutaneous squamous and basal cell carcinoma. METHODS: Between Dec. 4, 1985, and Dec. 27, 1996, 299 heart transplantations were performed at the Oregon Health Sciences University. Heart transplant recipients with more than 6 months survival or follow-up were investigated for squamous and basal cell carcinoma (n = 248). RESULTS: Forty-one patients (17%) were found to have 192 squamous or basal cell carcinomas. Squamous cell carcinoma was the predominate skin malignancy, constituting 172 (90%) of the lesions. The mean number of skin malignancies per patient was 4.7 +/- 0.81 (range 125). Patients with development of a skin malignancy were 8 years older on average, with a male-to-female ratio of 19.5:1. The predominant skin type and eye color were fair (59%) and blue (59%), respectively. Cumulative risk, based on actuarial survival analysis for development of a squamous or basal cell carcinoma at 1 year, was 3% and increased to 21% and 35% at 5 and 10 years, respectively. In addition, cumulative risk increased in patients who received treatment with OKT3. CONCLUSION: Cumulative risk of development of a skin malignancy increased with time and use of OKT3. Additional patient risk factors included older age, male sex, fair skin, and blue eyes.

Actuarial Analysis↗