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1.
When a novel variant is found in a patient and not in a group of controls, it becomes a candidate for the disease-causing mutation in that patient. At present, no sampling theory exists for assessing the probability that the novel SNP might actually be a neutral variant. We have developed a population genetics-based method for calculating a P-value for a mutation-detection effort. Our method can be applied to a heterozygous patient, a homozygous patient, with or without inbreeding, or to a patient who is a compound heterozygote. Additionally, the method can be used to calculate the probability of finding a neutral variant at frequencies that differ between a group of patients and a group of controls, given some length of sequence examined. This method accounts for the multiple testing that is inherent in identification of variants through sequencing, to be used in subsequent case-control analyses. We show, for example, that for complete resequencing of 10 kb, the probability of finding a neutral variant in a patient and not in 50 controls is about 15%. Thus, discovery of a variant in a patient and not in a group of controls is, on its own, very weak evidence of involvement with disease.  相似文献   

2.
Genetic polymorphism of rabbit VHa region: a new allotype, a108   总被引:1,自引:0,他引:1  
We report a new rabbit IgVH allotype, designated a108, which was detected following studies of the progeny of a wild rabbit (Oryctolagus cuniculus) from Zembra Island (Tunisia). This allotype seems to be specific of this island, since it has not been detected in other wild rabbit populations (in Spain, Portugal or France). Its determinants are located on the Fd fragment of the immunoglobulin (Ig) heavy chain and it behaves like the product of an allele at the alpha locus. Allotype a108 was strongly related serologically to a1 and a107, and to a lesser extent to a101, a109 and a3 allotypes. We also detected determinants shared among the a1, a107, a108, a101 and a109 allotypes. These determinants were expressed by a large fraction of Ig molecules from rabbits of allotype a1, a107 and a108 and by a very small fraction of Ig from rabbits of allotype a101 and a109.  相似文献   

3.
Wnt-3a is a representative ligand that activates the beta-catenin-dependent pathway in Wnt signaling and is modified with glycans and palmitate. In this study, we analyzed the relationship between glycosylation and lipidation of Wnt-3a. Secretion of a Wnt-3a mutant that lacks glycosylation (Wnt-3a NQ) was impaired. Wnt-3a C77A, which lacks palmitoylation at Cys77, was secreted with similar efficiency to wild-type Wnt-3a (Wnt-3a WT), but did not induce the internalization of low-density lipoprotein receptor-related protein 6 (LRP6). Furthermore, removal of palmitate from Wnt-3a suppressed the ability to bind to its receptors Frizzled8 and LRP6. Wnt-3a C77A was glycosylated to an extent similar to Wnt-3a WT, while Wnt-3a NQ was not modified with palmitate. Expression of porcupine, which is a putative acyltransferase, enhanced palmitoylation of Wnt-3a WT greatly, but that of Wnt-3a NQ slightly. While Wnt-3a WT was present in both the endoplasmic reticulum (ER) and Golgi, Wnt-3a NQ was located to the ER only. Furthermore, Wnt-3a was not palmitoylated but was glycosylated in the cells treated with Brefeldin A, which inhibits transport of vesicles from the ER to the Golgi. These results indicate that glycosylation of Wnt-3a precedes palmitoylation and that both modifications are necessary for secretion of an active Wnt-3a.  相似文献   

4.
The present article is the fourth part of a comprehensive review of the arterial blood supply of the pancreas and completes the study of the arterial vascularization of the pancreatic head dealing with the anterior inferior and posterior inferior pancreaticoduodenal aa. and with some minor sources of blood supply not involving the classical system of the pancreaticoduodenal arches. The aim of this review is to summarise the anatomical studies, starting from Haller’s reports, and to supply, as far as possible with original material, angiographic evidence for the classic anatomical concepts. For this purpose, 1015 selective angiographs (celiac trunk and its branches, superior mesenteric a.) were taken from the angiographic archives of the Institutes of Radiology of Siena, Rome (Catholic University), and Perugia. These demonstrated the anterior inferior pancreaticoduodenal a., present in most instances, as arising from the inferior pancreaticoduodenal a., from a common trunk with the posterior inferior pancreaticoduodenal a. and the 1st jejunal a., from the 1st jejunal a. or from the superior mesenteric a.; on the other hand, the posterior inferior pancreaticoduodenal a. was more variable, originating from the inferior pancreaticoduodenal a., from a common trunk with the anterior inferior pancreaticoduodenal a. and the 1st jejunal a., from the superior mesenteric a., from the dorsal pancreatic a., or from a right accessory hepatic a. coming from the superior mesenteric a. In addition, minor branches to the head of the pancreas arose from the gastroduodenal a., the dorsal pancreatic a., the common hepatic a. and the inferior right phrenic a. Other origins of the inferior pancreaticoduodenal aa. previously reported, but not angiographically detectable with certainty, as well as further minor sources of blood supply to the head of the pancreas, have been listed. The differing opinions regarding the incidence of the various ways the inferior pancreaticoduodenal aa. arise are discussed and an attempt is made to explain the variability of the vascular anatomy of the pancreatic head on embryologic grounds.  相似文献   

5.
Summary The ultrastructure of the uterine secretion appearing locally at the site of a blastocyst or a blastocyst-like bead was compared to the ultrastructure of the secretion present in a sterile horn of similarly treated mice. The secretion consisted of a homogeneous substance with small vesicles. The secretion was sparse and only slightly electron dense in a sterile horn, while it was more abundant and denser in a horn with a luminal object. Around a blastocyst, the secretion appeared more dense than it did around a bead, while the small vesicles of the secretion were more frequently occurring around a bead than around a blastocyst. It is concluded that a luminal object like a blastocyst is capable of eliciting a local secretory activity in the uterine epithelium, and it is suggested that this secretion is rich in hydrolytic enzymes.  相似文献   

6.
So far, three subtypes of the F4 (K88) fimbrial antigen of porcine enterotoxigenic Escherichia coli, F4ab, F4ac, and F4ad, have been distinguished by using polyclonal antisera in agglutination and precipitation tests. The a factor represents one or more common epitopes, whereas each of the b, c, and d factors represents one or more subtype-specific epitopes. We further characterized the F4 antigen complex by using a panel of 40 F4-specific monoclonal antibodies (MAbs). The specificity of all MAbs was proven by enzyme-linked immunosorbent assays, agglutination and radioimmunoprecipitation tests, and immunoelectron microscopy. The MAbs either reacted with all F4 subtypes, reacted with two subtypes, or were subtype specific. Epitope analysis by competition enzyme-linked immunosorbent assays revealed at least 11 epitope clusters on the F4 antigen complex, designated a1 to a7, b1, b2, c, and d. The following antigenic formulas were found for the F4 subtypes: F4ab, a1a2a3a4a5a6b1b2; F4ac, a1a2a3(a4)a5a6a7c; and F4ad, a1a2a3a4a7d. All MAbs were directed against conformational epitopes located on the 27,500-dalton major fimbrial subunits. Consequences for the replacement of polyclonal antisera by MAbs in diagnostic tests are discussed.  相似文献   

7.
The ultrastructure of two types of sense receptors each is described for Gieysztoria and Rhinolasius. In Gieysztoria, one receptor possesses a number of long microvilli, a cilium with a cross-striated rootlet, a septate desmosome, and an electron-dense band apical to the desmosome. The band forms a complex reticulate extension into the base of the receptor. The second receptor is without microvilli, has a cilium with a long cross-striated rootlet, and a septate desmosome with a short basal electron-dense extension or extensions which do not form a complete ring. In Rhinolasius, one receptor possesses a short bulbous cilium without a rootlet, with a septate desmosome of the pleated sheet (comb) type and a weakly developed electron-dense band beneath it. The second receptor has a long cilium with cross-striated rootlet, and a septate desmosome with a weakly developed electron-dense band apical to it. Centrioles were found in nerve fibres of both species.  相似文献   

8.
A lipoblastoma is a rare benign tumor of immature white fat, and more than 90% of lipoblastomas occur before the age of 3 years. The diagnosis of a lipoblastoma is mostly dependent on a histopathological examination of a surgically excised specimen. However, an accurate preoperative diagnosis is essential for the planning of surgery, particularly for a lesion of the head and neck area. We experienced a case of a cervical lipoblastoma of a 23-month-old boy. A preoperative fine-needle aspiration biopsy showed the sample as moderately cellular and showed fragments of mature and immature adipose tissues containing a large number of capillary vessels. There were numerous lipoblast-looking cells with a multivacuolated cytoplasm, and the nuclei were small, compressed by vacuoles, and centrally located. According to the cytological findings, the lesion was diagnosed as a benign adipose tumor suggestive of a lipoblastoma. Subsequent surgical excision confirmed the diagnosis of the fine-needle aspiration biopsy. The cytologic features of lipoblastoma are not well known because of the rarity of the lesion. However, the fine-needle aspiration cytological features of a lipoblastoma are sufficiently characteristic to make a specific preoperative diagnosis.  相似文献   

9.
Earlier studies have shown that C5 fragments induce an inflammatory reaction when instilled into the rabbit lung. Because C5a is rapidly converted to C5a des Arg in vivo, experiments were performed to determine which fragment was most effective in producing pulmonary inflammation in this animal model. C5a des Arg consistently produced marked inflammation. This was characterized by neutrophil accumulation, edema, hemorrhage, fibrin formation, and damage to alveolar epithelium. The time course of the inflammatory reaction initiated by C5a des Arg showed pulmonary vascular sequestration of neutrophils with no intra-alveolar migration at 30 minutes after injection. By 2 hours, interstitial and alveolar neutrophils were numerous, with the accumulation of neutrophils in the alveoli increasing to a maximum at 6 hours. At 24 and 48 hours, the predominant cells were mononuclear (macrophages). By 120 hours, the lesions were resolving. In contrast, at all doses examined, a similar instillation of C5a induced either no inflammation or a milder, more focal response than C5a des Arg. This inability of C5a to initiate inflammation was not apparently due to the generation of inhibitors, since mixtures of C5a and C5a des Arg were phlogistic. A prolonged, intrapulmonary infusion of C5a (20 minutes), in contrast to a bolus instillation (1 minute), did initiate an inflammatory response, which may reflect the conversion of the C5a to C5a des Arg in the lung. This study points out the inflammatory potential of products of complement activation, particularly of the C5 fragment C5a des Arg, when applied to the airway side of the lungs. This inflammatory response raises the possibility that cleavage of intrapulmonary C5 may play an important role in the initiation of pulmonary inflammation.  相似文献   

10.
The rabbit is unique in having well-defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3' VH genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3' VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2-encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.  相似文献   

11.
Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events.  相似文献   

12.
A likelihood approach to HLA serology has been developed in which the aim is not to define a recognition set for a serum but to describe the serum's ability to react with each and every antigen in the test cells, this ability being quantified in terms of the probability of a positive reaction. For a given set of probabilities, one for each antigen, it is possible to derive the probability of the observed set of reactions (the likelihood of the set of probabilities). The maximum possible value of the likelihood for any possible combination of the probability set can then be sought, but this requires a maximization of likelihood with respect to 60-100 independent parameters. Theoretical considerations of the shape of the likelihood surface prove that, in this particular case, this is a feasible proposition. This approach allows the recognition of three groups of antigens: those for which there is considerable evidence of a specificity, those for which there is either no specificity or a very weak specificity, and those for which there is insufficient evidence on which to base a conclusion. The existence of a specificity can be tested using a log likelihood ratio as a statistic, but the usual assumption of a chi 2 distribution of this statistic cannot automatically be made in this situation. Therefore, the distribution is estimated by simulation. A serologist using this approach would receive considerably more information as to the serum's reaction patterns and valid statistics for the existence, or not, of a specificity.  相似文献   

13.
A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average flow rates and the average pressure head of the VAD. The conditions of the mock circulatory loop, including the pulse rate of the diaphragm pump, the fluid temperature, and the fluid viscosity were maintained. Eight VADs were tested with testing periods of 2 years, during which they were continuously in operation. The VAD performance factors, including the power consumption and the vibration characteristics, were kept almost constant. The long-term durability of the developed VAD was successfully demonstrated.  相似文献   

14.
We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.  相似文献   

15.
Using standard banding techniques, a within-arm intrachromosomal insertion can be mistakenly interpreted as a paracentric inversion. The need to correctly distinguish between these two types of chromosome rearrangements is emphasized by their different reproductive risks. For carriers of an intrachromosomal insertion, the empiric risk of having a liveborn child with a recombinant chromosome leading to a genetic imbalance is at least 15%, whereas the risk for a carrier of a paracentric inversion having a liveborn child with a recombinant chromosome leading to a genetic imbalance is thought to be practically negligible. We report a unique observation in which a paracentric inversion in the short arm of chromosome 5, 46,XX,inv(5)(p13.3p15.3), was identified in a women who had a daughter with an apparently terminal deletion in the distal short arm of chromosome 5, 46,XX,del(5)(p14.3), and the clinical diagnosis of cri-du-chat syndrome. We further characterized the rearrangement, and fluorescence in situ hybridization (FISH) and microsatellite analyses confirmed the paracentric inversion in the mother and showed the deletion in the daughter was maternal in origin. Therefore, this represents a case in which a confirmed paracentric inversion likely resulted in a viable terminal deletion. We propose a mechanism involving dicentric chromosome formation with subsequent breakage and telomere healing during meiosis. This illustrates a new genomic mechanism of chromosome rearrangement leading to cri-du-chat syndrome and should provide significant information for the medical management of patients with other terminal deletion syndromes.  相似文献   

16.
A rare case of an extragonadal teratoma, which occurred primarily in the uterus, is described. The tumor developed in the uterine cervix as a conventional cervical polyp, 3 months after an elective abortion in a 27-year-old woman. Microscopically, the solid 2.2 x 1.8 x 1.5 cm mass was a mature teratoma with exuberant lymphoid elements. It consisted of ectodermal, mesodermal and endodermal derivatives. The lymphoid elements may have been a lymphoid hyperplasia, a chronic inflammatory reaction or a component of the teratoma. However, as the lymphoid tissues had no spatial relation to the teratomatous components, the possibility of a teratomatous element was excluded. This could be regarded as a result of an immunological reaction to the tissues composing the tumor, rather than just a chronic inflammatory response because the lymphoid reaction was present in the tumor, the tumor-host interface and the perivascular areas. Because of the patient's history of an abortion and a lymphoid reaction, the possibility of fetal remnants implantation was raised, so DNA typing to compare the teratoma portion with a normal portion of the host was performed. We found the teratoma portions to be in accordance with that of the host, and hence ruled out fetal remnants implantation. This case showed that a mature teratoma of the uterine cervix may manifest as a feature of implanted fetal tissue. In addition, a real teratoma should be included in the differential diagnosis of uterine teratomatous lesion, even when detected in patients with a recent history of pregnancy and lymphoid hyperplasia.  相似文献   

17.
BACKGROUND. Compared with other clinical disciplines, academic general practice is in a difficult situation with respect to patient care. There are at least three different possible models of working arrangements for heads of departments of general practice: to work in a surgery in a medical school; to work in a surgery in the community, separate from a part-time university post; or to work part-time in a surgery in the community, separate from a university post. AIM. A study was undertaken to explore these models and to gain an understanding of academic teachers' organization of patient care in Europe. METHOD. A total of 77 heads of departments in universities in 12 European countries were sent a questionnaire enquiring about important characteristics of their department, the number of patients they treated per week and how they allocated their time. RESULTS. Sixty nine heads of department (90%) responded. Of respondents, 55% worked part-time in a surgery, separate from a university post, nearly one third worked mainly in a surgery, separate from a part-time university post, and 16% worked in a surgery in a medical school. Those working in a surgery with only a part-time university post spent most time in patient care compared with those working in other models (mean of 57%). Respondents working in a surgery in a medical school spent most time on administration (34%); they spent 22% of their time on patient care and 20% on education. Respondents working in a surgery in a medical school spent 25% of their time on research, those working in a surgery separate from a part-time university post spent 12% of their time on research, and those working mainly in a university with a part-time practice post spent 24% of their time on research. Those working mainly in a university post spent only 17% of their time in patient care. CONCLUSION. Working in a surgery in a medical school represented a well-balanced model of time allocation between patient care, research and education and seemed to be a good approach for the integration of general practice into medical schools. Working part-time in a surgery with a university post is an appropriate model for academic integration, but patient care seemed to be neglected. Those doctors working mainly in the community with a part-time university post were able to provide continuity of care and to come into close contact with the everyday problems of general practitioners. However, they might have to struggle for academic recognition.  相似文献   

18.
Cucumber mosaic virus (CMV, a cucumovirus) and Brome mosaic virus (BMV, a bromovirus) require the coat protein (CP) in addition to the 3a movement protein (MP) for cell-to-cell movement, while Cowpea chlorotic mottle virus (CCMV, a bromovirus) does not. Using bombardment-mediated transcomplementation assays, we investigated whether the movement functions encoded by these viruses potentiate cell-to-cell movement of movement-defective Tomato mosaic virus (ToMV, a tobamovirus) and Potato virus X (PVX, a potexvirus) mutants in Nicotiana benthamiana. Coexpression of CMV 3a and CP, but neither protein alone, complemented the defective movement of ToMV and PVX. A C-terminal deletion in CMV 3a (3a Delta C33) abolished the requirement of CP in transporting the ToMV genome. The action of 3a Delta C33 was inhibited by coexpression of wild-type 3a. These findings were confirmed in tobacco with ToMV-CMV chimeric viruses. Either BMV 3a or CCMV 3a alone efficiently complemented the movement-defective phenotype of the ToMV mutant. Therefore, every 3a protein examined intrinsically possesses the activity required to act as MP. In transcomplementation of the PVX mutant, the activities of BMV 3a, CCMV 3a, and CMV 3a Delta C33 were very low. The activities of the bromovirus 3a proteins were enhanced by coexpression of the cognate CP but the activity of CMV 3a Delta C33 was not. Based on these results, possible roles of cucumo- and bromovirus CPs in cell-to-cell movement are discussed.  相似文献   

19.
A slide centrifuge Gram stain procedure was performed to screen for bacteriuria 4161 urine specimens submitted in urine preservative tubes for routine culture. For slide centrifuge Gram staining, each urine sample was mixed well. Thereafter, 0.2 mL of each sample was placed, using a pipette, into a slide centrifuge chamber and centrifuged at 2,000 rpm for 5 minutes. The slides were heat fixed, Gram stained, and read by laboratory personnel who scanned 12 consecutive oil-immersion fields using a set pattern. The presence of the same organism in six or more fields was defined as a positive urine screen. Urine samples were cultured using a 0.001-mL loop and a comparison of culture growth with slide centrifuge screening was made. When growth of 100,000 or more colony-forming units per milliliter (CFU/mL) was the reference for comparison, the screen had a sensitivity rate of 98%, a specificity rate of 90%, a negative predictive value of 99%, and a positive predictive value of 65%. When a lower colony count of 10,000 or more CFU/mL was the reference for comparison, the screen had a sensitivity rate of 88%, a specificity rate of 95%, a negative predictive value of 96%, and a positive predictive value of 84%. The slide centrifuge Gram stain is a very sensitive screening method to detect bacteriuria in an adult male population.  相似文献   

20.
The goal of palliative care is the achievement of the best quality of life for patients and their families. Eyes are generally the first features of the face to be noticed. Loss of an eye is a traumatic event which has a crippling effect on the psychology of the patient. Several ocular and orbital disorders require surgical intervention that may result in ocular defects. An ocular prosthesis is fabricated to restore the structure, function, and cosmetics of the defects created by such conditions. Although an implant eye prosthesis has a superior outcome, due to economic factors it may not be a feasible option for all patients. Therefore, a custom-made ocular prosthesis is a good alternative. This case report presents a palliative treatment for a patient with an enucleated eye by fabricating a custom ocular prosthesis which improved his psychological, physical, social, functional, emotional and spiritual needs.  相似文献   

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