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21.
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
22.
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
23.
24.
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献
25.
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
26.
27.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
28.
Marcus Wei Ping Tan Stacy Wei Ling Ng Jerry Yongqiang Chen Ming Han Lincoln Liow Ngai Nung Lo Seng Jin Yeo 《The Journal of arthroplasty》2021,36(4):1269-1276
BackgroundThe aim of this study is to compare the long-term functional outcome and quality of life between total knee arthroplasty (TKA) and fixed-bearing unicompartmental knee arthroplasty (UKA) for the treatment of isolated medial compartment osteoarthritis.MethodsBetween 2000 and 2008, a total of 218 patients underwent primary UKA at our tertiary hospital. A TKA group was matched through 1:1 propensity score matching and adjusted for age, gender, body mass index, preoperative knee flexion, and function scores. All patients had medial compartment osteoarthritis. The patients were assessed with the range of motion, Knee Society Knee Score and Knee Society Function Score, Oxford Knee Score, Short Form-36 physical component score (PCS) and mental component score preoperatively, at 6 months, 2 years, and 10 years. Patients’ satisfaction, expectation fulfillment, and minimal clinically important difference were analyzed.ResultsThere were no differences in baseline characteristics between groups after propensity score matching (P > .05). UKA had greater knee flexion at all time points. Although the Knee Society Function Score was superior in UKA by 5.5, 3, and 4.3 points at 6 months, 2 years, and 10 years, respectively (P < .001), these differences did not exceed the minimal clinically important difference (Knee Society Knee Score 6.1). There were no significant differences in the Oxford Knee Score and Short Form-36 physical component score/mental component score. At 10 years, similar proportions of UKA and TKA were satisfied (90.8% vs 89.9%, P = .44) and had expectation fulfillment (89.4% vs 88.5%, P = .46). Between 2 and 10 years, all function scores deteriorated significantly for both groups (P < .01).ConclusionUKA and TKA are excellent treatment modalities for isolated medial compartment osteoarthritis, with similar functional outcomes, quality of life, and satisfaction at 10 years. 相似文献
29.
Yong Zhi Khow Graham S. Goh Jerry Yongqiang Chen Ngai Nung Lo Seng Jin Yeo Ming Han Lincoln Liow 《The Journal of arthroplasty》2021,36(6):1974-1979
BackgroundPrevious studies evaluating weight changes following total knee arthroplasty (TKA) were performed on heterogenous cohorts. However, no study has evaluated weight changes in a cohort of simultaneous-bilateral TKA (SB-TKA) patients. This study aimed to evaluate the prevalence of patients who lost or gained weight, determine if postoperative weight change influences functional outcome, and identify predictors of weight change after SB-TKA.MethodsProspectively collected registry data of 560 patients who underwent SB-TKA were reviewed. Patients were assessed preoperatively, at 6 months, and 2 years using the Knee Society Score, Oxford Knee Score, Short-Form 36, and range of motion. Change in body mass index (BMI) >5% was used to categorize patients into 3 groups: lost, maintained, or gained weight. Analysis of variance, Kruskal-Wallis test, and chi-squared test were used to compare functional outcomes between groups. Multivariable logistic regression evaluated predictors for postoperative weight changes.ResultsAt 2 years, 59% of patients maintained weight, 28% of patients gained weight, and 13% of patients lost weight. All groups experienced similar improvements in functional outcomes, rates of minimal clinically important difference attainment, and patient satisfaction (P > .05). Older patients were more likely to gain weight (P < .05). Patients with higher preoperative BMI were more likely to gain weight (P < .05) and less likely to lose weight (P < .05). Patients with greater preoperative comorbidities were less likely to lose weight (P < .05).ConclusionUp to 41% of patients experience significant weight changes after SB-TKA. Older patients with higher preoperative BMI were more likely to gain weight, while higher preoperative BMI with more comorbidities were less likely to lose weight following SB-TKA; however, postoperative weight changes do not appear to affect functional outcomes.Level of EvidenceIII, therapeutic study. 相似文献
30.
JS Tsang Chi Chung Foo Jeremy Yip Hok Kwok Choi Wai Lun Law Oswens Siu Hung Lo 《The surgeon》2021,19(3):150-155
IntroductionThe difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery.MethodWe conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated.ResultsIn total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6).ConclusionRight colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease. 相似文献