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991.
Andresen BS; Bross P; Udvari S; Kirk J; Gray G; Kmoch S; Chamoles N; Knudsen I; Winter V; Wilcken B; Yokota I; Hart K; Packman S; Harpey JP; Saudubray JM; Hale DE; Bolund L; Kolvraa S; Gregersen N 《Human molecular genetics》1997,6(5):695-707
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most commonly
recognized defect of mitochondrial beta-oxidation. It is potentially fatal,
but shows a wide clinical spectrum. The aim of the present study was to
investigate whether any correlation exists between MCAD genotype and
disease phenotype. We determined the prevalence of the 14 known and seven
previously unknown non-G985 mutations in 52 families with MCAD deficiency
not caused by homozygosity for the prevalent G985 mutation. This showed
that none of the non-G985 mutations are prevalent, and led to the
identification of both disease- causing mutations in 14 families in whom
both mutations had not previously been reported. We then evaluated the
severity of the mutations identified in these 14 families. Using expression
of mutant MCAD in Escherichia coli with or without co-overexpression of the
molecular chaperonins GroESL we showed that five of the missense mutations
affect the folding and/or stability of the protein, and that the residual
enzyme activity of some of them could be modulated to a different extent
depending on the amounts of available chaperonins. Thus, some of the
missense mutations may result in relatively high levels of residual enzyme
activity, whereas the mutations leading to premature stop codons will
result in no residual enzyme activity. By correlating the observed types of
mutations identified to the clinical/biochemical data in the 14 patients in
whom we identified both disease-causing mutations, we show that a
genotype/phenotype correlation in MCAD deficiency is not straightforward.
Different mutations may contribute with different susceptibilities for
disease precipitation, when the patient is subjected to metabolic stress,
but other genetic and environmental factors may play an equally important
role.
相似文献
992.
Tim J T Sutherland D Robin Taylor Malcolm R Sears Jan O Cowan Christene R McLachlan Susan Filsell Avis Williamson Justina M Greene Richie Poulton Robert J Hancox 《Annals of allergy, asthma & immunology》2007,99(6):534-539
BACKGROUND: Asthma is an inflammatory condition of the airways, and there is some evidence to suggest that it is associated with a systemic inflammatory response, as measured by C-reactive protein (CRP) and fibrinogen. Exhaled nitric oxide is a noninvasive measure of asthmatic airway inflammation. OBJECTIVE: To determine if there is an association between exhaled nitric oxide and these systemic inflammatory markers. METHODS: The Dunedin Multidisciplinary Health and Development Study is a birth cohort of approximately 1,000 individuals born between April 1, 1972, and March 31, 1973. At the age of 32 years, study members were assessed for diagnosis of asthma, atopy by skin prick testing, smoking, body mass index, exhaled nitric oxide, high-sensitivity serum CRP, and plasma fibrinogen level. RESULTS: There was no significant association between exhaled nitric oxide and CRP (P = .99). There was a trend to an inverse association between exhaled nitric oxide and fibrinogen (P = .049), but this was not significant after adjusting for smoking and use of corticosteroids or after further adjustment for body mass index and atopy (P = .71). CONCLUSION: In this population-based sample of young adults, there was no association between airway inflammation, as measured by exhaled nitric oxide, and systemic inflammation, as measured by either CRP or fibrinogen. 相似文献
993.
The distribution of gamma-tubulin as a marker of microtubule organizing
centres (MTOC) was studied during spermiogenesis in rodents and in rabbit,
monkey and man. A polyclonal antibody directed against human gamma-tubulin
was used both for indirect immunofluorescence (IIF) and post-embedding
immunogold procedures. In all species, gamma-tubulin was detected in the
proximal and distal centrioles of round spermatids. In elongating
spermatids, gamma-tubulin was predominantly found in the pericentriolar
material (PCM) of both centrioles and particularly around the adjunct of
the proximal centriole. At this level, some labelling was also associated
with manchette microtubules, but other parts of the manchette and the
nuclear ring were never labelled. We propose a role for distal centriole
gamma-tubulin in axoneme nucleation and centriolar adjunct gamma-tubulin in
manchette nucleation. The disappearance of gamma-tubulin in mature
spermatozoa indicates that sperm aster nucleation should be dependent on
oocyte gamma-tubulin. Remnants of gamma-tubulin in some human spermatozoa
suggest that paternal gamma-tubulin also could contribute to sperm aster
formation.
相似文献
994.
Renshaw AA Richie JP Loughlin KR Jiroutek M Chung A D'Amico AV 《American journal of clinical pathology》1999,111(5):641-644
The amount of tumor in radical prostatectomy specimens can be determined with several techniques. Maximum tumor diameter correlates well with total tumor volume and can readily be obtained in incompletely submitted specimens. Initial results in a small series suggested that this measure also may predict for prostate-specific antigen (PSA) failure. We studied whether maximum tumor diameter was an independent predictor of PSA failure in a series of 434 men who underwent radical prostatectomy because of prostatic adenocarcinoma; 118 (27.2%) had PSA failure. Preoperative PSA, Gleason score, pathologic stage, margin status, and largest tumor diameter were determined, and multivariate logistic modeling was performed on the outcome of PSA failure. Maximum tumor diameter was an independent risk factor for PSA failure, along with preoperative serum PSA level, and Gleason score > or = 8. Only 15% of men with tumor with maximum diameter < 1 cm had PSA failure, compared with 73% of men with tumor with maximum diameter > 2. Maximum tumor diameter of prostatic carcinoma is a simple, inexpensive, and independent predictor of PSA failure that can be obtained readily from partially submitted radical prostatectomy specimens. 相似文献
995.
Heather L. Poetschke David B. Klug Dawn Walker Ellen R. Richie 《Clinical & developmental immunology》1996,5(1):1-15
Although it is generally agreed that TCR ligation is a minimal requirement for negative
selection in the CD+8+ double-positive (DP) thymocyte subset, the costimulatory requirements
and specific signaling events necessary to induce apoptosis are not well defined. We
have explored the consequences of cross-linking CD3/TCR complexes on thymocytes from
H-Y TCR transgenic (Tg) mice. In agreement with previous reports, we demonstrate that
culturing DP thymocytes with plate-bound anti-TCR antibody induces downregulation of
CD4 and CD8 and upregulation of CD69 expression. Nevertheless, the activated cells did
not undergo apoptosis, as determined by viable cell recoveries and by quantitation of DNA
fragmentation using the TUNEL assay. However, specific depletion of the DP subset occurred
within 24 hr when thymocytes were incubated in the presence of both anti-TCR and
the immunosuppressant cyclosporin A (CsA). CsA also induced depletion of anti-CD3
stimulated normal DP thymocytes. Using mice homozygous for the lpr or gld mutation, we
also have shown that Fas/Fas ligand interactions are not involved in the CsA-induced
death of TCR-stimulated DP thymocytes. These data verify that TCR cross-linking alone
is insufficient to induce apoptosis of DP thymocytes and further suggest that TCR stimulation
activates a CsA-sensitive protective pathway that interferes with signaling events
leading to apoptosis in DP thymocytes. 相似文献
996.
A. B. Blair A. Dwarakanath A. Mehta H. Liang X. Hui C. Wyman JP P. Ouanes H. T. Nguyen 《Hernia》2017,21(6):895-900
Purpose
Inguinal hernia repair is a common general surgery procedure with low morbidity. However, postoperative urinary retention (PUR) occurs in up to 22% of patients, resulting in further extraneous treatments.This single institution series investigates whether patient comorbidities, surgical approaches, and anesthesia methods are associated with developing PUR after inguinal hernia repairs.Methods
This is a single institution retrospective review of inguinal hernia from 2012 to 2015. PUR was defined as patients without a postoperative urinary catheter who subsequently required bladder decompression due to an inability to void. Univariate and multivariate logistic regressions were performed to quantify the associations between patient, surgical, and anesthetic factors with PUR. Stratification analysis was conducted at age of 50 years.Results
445 patients were included (42.9% laparoscopic and 57.1% open). Overall rate of PUR was 11.2% (12% laparoscopic, 10.6% open, and p = 0.64). In univariate analysis, PUR was significantly associated with patient age >50 and history of benign prostatic hyperplasia (BPH). Risk stratification for age >50 revealed in this cohort a 2.49 times increased PUR risk with lack of intraoperative bladder decompression (p = 0.013).Conclusions
At our institution, we found that patient age, history of BPH, and bilateral repair were associated with PUR after inguinal hernia repair. No association was found with PUR and laparoscopic vs open approach. Older males may be at higher risk without intraoperative bladder decompression, and therefore, catheter placement should be considered in this population, regardless of surgical approach.997.
998.
RT Chen JW Glasser PH Rhodes RL Davis WE Barlow RS Thompson JP Mullooly SB Black HR Shinefield CM Vadheim SM Marcy JI Ward RP Wise SG Wassilak SC Hadler 《Pediatrics》1997,99(6):765-773
OBJECTIVE: To fill the large "gaps and limitations" in current scientific knowledge of rare vaccine adverse events identified in recent reviews of the Institute of Medicine. METHODS: Computerized information on immunization, medical outcomes, and potential confounders on more than 500 000 children 0 to 6 years of age is linked annually at several health maintenance organizations to create a large cohort for multiple epidemiologic studies of vaccine safety. RESULTS: Analysis of 3 years of follow-up data shows that 549 488 doses of diphtheria-tetanus-pertussis (DTP) and 310 618 doses of measles-mumps-rubella (MMR) vaccines have been administered to children in the study cohort. Analyses for associations between vaccines and 34 medical outcomes are underway. Screening of automated data shows that seizures are associated with receipt of DTP on the same day (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1 to 4.0) and 8 to 14 days after receipt of MMR (RR, 3.0; 95% CI, 2.1 to 4.2). The diversity of vaccination exposures in this large cohort permits us to show that an apparent association of seizures 8 to 14 days after Haemophilus influenzae type b vaccine (RR, 1.6; 95% CI, 1.2 to 2.1) was attributable to confounding by simultaneous MMR vaccination; the association disappears with appropriate adjustment (RR, 1.0; 95% CI, 0.7 to 1.4). CONCLUSION: Preliminary design, data collection, and analytic capability of the Vaccine Safety Datalink project has been validated by replication of previous known associations between seizures and DTP and MMR vaccines. The diversity in vaccine administration schedules permits potential disentangling of effects of simultaneous and combined vaccinations. The project provides a model of public health-managed care collaborations in addition to an excellent infrastructure for safety and other studies of vaccines. 相似文献
999.
Thermoregulation in newborn infant differs from that of adult. Comparisons between sleep stages show that, during rapid eye movements (REM) sleep, the impairment of thermoregulatory responses in adult is not observed in newborn. Both behavioral and autonomic temperature regulations are always operative in the range of air temperatures usually imposed. The interaction between sleep and thermoregulation seems to be less important in newborns than in adults, suggesting that sleep processes are well protected, reducing the probability of occurrence of central dysfunction. According to the model describing thermoregulation during sleep on the basis of changes in the hierarchical dominance of brain structures, either the influence of diencephalic structures is never depressed in REM sleep or the functional autonomy of the rhombencephalon is still relevant in the immature encephalon of the newborn. The thermoregulatory model also allows understanding of inter-individual differences in thermoregulation and levels of thermoneutrality. An attempt has also been made to learn the role of heat stroke in the production of sudden infant death syndrome when body heat loss is hampered.
Résumé
La régulation thermique du nouveau-né est différente de celle de l'adulte. Les comparaisons entre les stades de sommeil montrent que les mécanismes autonomes et comportementaux de la thermorégulation ne sont pas déprimés en sommeil paradoxal, contrairement à l'adulte. Ainsi les interactions entre le sommeil et la thermorégulation semblent moins importantes chez le nouveau-né, ce qui suggère que le sommeil est bien protégé et qu 'un dysfonctionnement du système nerveux central est moins probable. Selon le modèle décrivant les processus thermorégulateurs selon une hiérarchie de dominances fonctionnelles de structures cérébrales, variable selon le stade de sommeil, il semble que l'influence diencéphalique persiste au cours du sommeil paradoxal du nouveau-né ou que l'autonomie fonctionnelle du rhombencéphale reste intacte dans le cerveau en maturation. Le modèle des dominances fonctionnelles hiérarchiques permet d'expliquer les différences interindividuelles de températures de neutralité et de réponse thermorégulatrice au chaud et au froid. Cette revue de la littérature tente également de montrer les influences du stress thermique sur la mort subite du nourrisson lorsque les pertes de chaleur de l'enfant sont réduites. 相似文献1000.
Kumar S Duque JL Guimaraes KC Dicanzio J Loughlin KR Richie JP 《The Journal of urology》1999,162(6):1927-1929
PURPOSE: A thoracoabdominal incision provides optimal exposure for radical nephrectomy, especially for large tumors. Intuitively it is perceived that the morbidity of a thoracoabdominal incision far exceeds that of a flank incision. We compare the morbidity of thoracoabdominal and flank incisions, which to our knowledge has not been reported previously. MATERIALS AND METHODS: A questionnaire assessing postoperative pain, use of pain medications and return to activities was sent to the last 100 renal donors who underwent nephrectomy at our institution through the 11th rib (flank incision, group 1) and the last 100 patients who underwent radical nephrectomy through the 8th to 10th rib (thoracoabdominal incision, group 2). A total of 52 group 1 and 42 group 2 questionnaires were returned. Pain was assessed at 4 periods using a visual analog scale. RESULTS: Length of stay was the same in both groups. There were no differences between groups in terms of pain severity on postoperative day 1, on day of discharge home, 1 month postoperatively and at the time of study (p >0.05). There were no significant differences between groups in times following surgery when pain completely disappeared, when pain medications were discontinued, and when the patient returned to daily activities and work (p >0.05). CONCLUSIONS: Morbidity was comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge home and return to normal activities. 相似文献