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41.
Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from
mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has
revealed some general genotype-phenotype correlations. Severe disease has
been associated with mutations that produce a premature termination while
more mild disease has been associated with missense mutations. Here, we
provide experimental proof for these genotype-phenotype correlations by
demonstrating that nonsense mutations fail to produce stable merlin protein
while missense mutations result in the generation of merlin proteins
defective in negative growth regulation. This inability to suppress cell
growth may result from defects in the function of merlin at several levels,
including failure to form an intramolecular complex. Based on these
findings, we propose a model for merlin growth suppression that provides a
framework for analyzing NF2 patient mutations and merlin function.
相似文献
42.
JS Pooni Dr DWL Hukins PF Harris RC Hilton KE Davies 《Surgical and radiologic anatomy : SRA》1986,8(3):175-182
Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc. 相似文献
43.
K. Kovacs E. Horvath B. Corenblum A. M. T. Sirek G. Penz C. Ezrin 《Virchows Archiv : an international journal of pathology》1975,366(2):113-123
Summary Morphologic studies of pituitary neoplasms removed by surgery from 36 human patients revealed 8 chromophobe adenomas which differed clearly from the remaining tumors. The cytoplasm of the adenoma cells failed to stain with PAS, aniline blue, aldehyde fuchsin, aldehyde thionin, orange G or light green, but positively stained granules were found by using erythrosine or carmoisine. Immunoperoxidase technique disclosed the presence of prolactin in the cytoplasm of some adenoma cells. The adenoma cells exhibited distinct ultrastructural features such as well developed rough surfaced endoplasmic reticulum with Nebenkern formation, prominence of Golgi apparatus, presence of misplaced exocytosis as well as pleomorphism of secretory granules with a considerable variation of size ranging from 130 to 500 nm in diameter. Thus, by electron microscopy the adenoma cells showed a close resemblance to prolactin cells of the non-tumorous pituitary glands except for the reduced size and number of secretory granules.These chromophobe adenomas are regarded as representing a distinct pathological entity clearly distinguishable from other forms of pituitary neoplasms. In view of the morphologic findings and the elevation of blood prolactin level (measured in 3 patients) the term, sparsely granulated prolactin producing pituitary adenoma, appears to be the most appropriate one to designate these tumors.The authors wish to thank Dr. H. Friesen for providing the anti-human prolactin and Dr. L. A. Sternberger for the peroxidase-anti-peroxidase complex. The excellent technical assistance of Mrs. Gezina Ilse and Miss Nancy Macphail and the valuable secretarial help of Mrs. Maureen Rowling are appreciated.The work was supported in part by MA-552 grant of the Medical Research Council of Canada and by the St. Michael's Hospital Research Society. 相似文献
44.
Charles Frèche Francisque Leynadier Friedrich Horak David Hide Fernando Duce Gracia Manfred Goos Claus Bachert Attila Horvath Eva Antosova Muriel Verrecchia Paul Ben Soussen 《Annals of allergy, asthma & immunology》2002,89(3):304-310
BACKGROUND: Mizolastine is a nonsedating H1 histamine receptor antagonist with additional antiallergic properties currently marketed in Europe for the treatment of seasonal and perennial allergic rhinitis (PAR) and urticaria. OBJECTIVE: This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of mizolastine in PAR compared with loratadine and placebo. METHODS: After a 1-week placebo run-in period, 428 adult PAR patients received placebo (146 of 428), mizolastine 10 mg (141 of 428), or loratadine 10 mg (141 of 428) once daily for 28 days. Symptoms were evaluated by patients and physicians using a total nasal score, evaluating itching, rhinorrhea, nasal blockade, and sneezing severity. RESULTS: Mizolastine treatment resulted in a significantly greater decrease in patient-rated total nasal score than placebo after 2 weeks (D14; -42%, P < 0.001) and at the end of the treatment period (-46%, P = 0.01), and significantly greater than that observed with loratadine at D14 (P = 0.031). No significant difference in change in total nasal score was observed between loratadine and placebo at 2- and 4-week visits. The global safety was satisfactory and the incidence of adverse events was similar in the three treatment groups. CONCLUSIONS: Mizolastine provides effective symptom relief in PAR together with a satisfactory safety profile. Improvement with mizolastine was significantly greater than placebo throughout the study despite a large placebo effect. Also mizolastine's effects were greater those observed with loratadine after 2 weeks of treatment. 相似文献
45.
Ochiai Y Golding LA Massiello AL Medvedev AL Horvath DJ Gerhart RL Chen JF Krogulecki AY Takagaki M Doi K Howard MW Fukamachi K 《ASAIO journal (American Society for Artificial Internal Organs : 1992)》2002,48(3):249-252
The Cleveland Clinic CorAide left ventricular assist system consists of a permanently implantable centrifugal pump in which the rotating assembly is completely suspended and noncontacting. A series of chronic animal in vivo studies were conducted to evaluate the biologic effects of CorAide circulatory support without the use of anticoagulation therapy. The CorAide pump was implanted in six calves (five calves for 21 to 32 days and one calf for 95 days). The first five calves received intravenous heparin during the early postoperative periods (2-7 days). Heparin administration was then discontinued and no other anticoagulant drugs were used for the duration of the experiments. The last calf did not receive any anticoagulant except for a bolus dose of heparin (200 U/kg) during surgery. Hemodynamics were stable in all six calves, with a mean pump flow of 5.6+/-1.2 L/min and mean arterial pressure of 100+/-4 mm Hg. The blood pump surfaces were clean of thrombus in all six calves. Significant findings at autopsy were limited to one case of renal infarction. There was no incidence of mechanical failure, bleeding, or device infection. The CorAide pump can be safely run with minimal or no anticoagulant therapy. 相似文献
46.
Ectopic pituitary adenoma (EPA) is rare and, to the authors’ knowledge, its association with peliosis has not yet been described.
The case of a 38-yr-old woman with clinical and biochemical evidence of Cushing’s syndrome is reported. Magnetic resonance
imaging (MRI) disclosed a normal pituitary and a separate mass in the sphenoid sinus. The surgically remove’s hyaline change
in the corticotrophs, indicating exposure to glucocorticoid excess. By histology, the mass in the sphenoid sinus was a congested,
chromophobic, partly basophilic, periodic acid-Schiff (PAS)-positive pituitary adenoma composed of pleomorphic, adrenocorticotropic
hormone (ACTH)-positive, corticotrophs. There was focal immunopositivity for MIB-1 and proliferating cell nuclear antigen
(PCNA). Electron microscopy confirmed the diagnosis of corticotroph adenoma. A striking finding, consistent with the diagnosis
of peliosis, was the presence of multiple large blood-filled spaces lacking an endothelial lining. The capillaries were dilated,
but often appeared empty and the fenestrated endothelium exhibited discontinuities. The cause of peliosis is obscure. It may
be that the venous outflow was impaired in this case leading to capillary dilation, congestion, hyperpermeability, rupture,
and accumulation of blood in extravascular spaces. 相似文献
47.
Deodhare SS Bilbao JM Kovacs K Horvath E Nomikos P Buchfelder M Reschke K Lehnert H 《Endocrine pathology》1999,10(3):237-241
We report a case of xanthomatous hypophysitis, a recently described entity of obscure etiology affecting the pituitary gland,
in a 43-yr-old women. Histologically it is characterized by infiltration of the anterior pituitary by foamy histiocytes which
are strongly immunoreactive for CD68 (histiocytic marker) and are immunonegative for S100 and CD1a. Electron microscopy revealed
histiocytes with abundant cytoplasmic lipid droplets and membrane bound vacuoles. Fragments of intact anterior pituitary with
preserved vascular and reticulin networks are seen. Xanthomatous hypophysitis resembles neoplasm on clinical and radiologic
grounds. 相似文献
48.
Albert Beckers Kalman Kovacs Eva Horvath Roger Abs Michel Reznik Achille Stevenaert 《Endocrine pathology》1991,2(3):123-131
Twenty-four acromegalic patients were treated with octreotide subcutaneously for periods of 3 to 6 weeks (group I, 12 cases)
or 6 months (group II, 12 cases) before transsphenoidal surgery. Radiological studies performed in 19 patients before and
at the end of this treatment period revealed no changes in 8 cases. In 8 other cases, a slight reduction in tumorsize was observed, and in 3 cases an important shrinkage was documented. At surgery, the adenomatous tissue appeared softer than
in nonpretreated patients, facilitating the operation. Pathological examination revealed widening of perivascular spaces with
accumulation of fibrous tissue and more crinophagy than in nonpretreated patients but failed to reveal morphologically pronounced
cell involution as observed in prolactin-producing adenomas treated with dopamine agonists. No significant difference in frequency
or extent of cellular changes was noted between the two groups. These morphological findings seem to be more consistent with
a functional inhibition of growth hormone release than with cellular alterations induced by octreotide. 相似文献
49.
50.
Detecting pre-ovulatory luteinizing hormone surges in urine 总被引:2,自引:1,他引:2
Kesner JS; Knecht EA; Krieg EF Jr; Wilcox AJ; O'Connor JF 《Human reproduction (Oxford, England)》1998,13(1):15-21
The study objectives were to determine (i) if pre-ovulatory luteinizing
hormone (LH) surges, undetected in urine by two immunoradiometric assays
(IRMA), were detectable by an ultrasensitive immunofluorometric assay
(IFMA) and (ii) the influence of creatinine adjustment on the detection and
timing of the urinary LH surges. Daily urine specimens were contributed by
healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for
an epidemiological study conducted in 1983-1985. Specimens were selected as
having been previously assayed by two IRMA without consistently detecting
LH surges. These urine specimens were remeasured using an IFMA and adjusted
for creatinine concentration. IFMA measurements revealed unambiguous LH
surges in all cycles. Adjusting IRMA urinary LH values for creatinine
concentrations revealed previously undetected LH surges in four of eight
cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH
surges by 1-5 days. These results demonstrate an IFMA that detects pre-
ovulatory LH surges in unpreserved, frozen urine from cycles where such
surges were previously undetectable. Further, creatinine adjustment can
markedly affect detection and timing of the onset and peak of the urinary
LH surge. While our analysis suggests that this adjustment improves the
validity of the LH measure, this requires further investigation.
相似文献