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1.
Early Pregnancy Factor: An Unresolved Molecule 总被引:1,自引:0,他引:1
2.
R W Lash R K Desai C A Zimmerman M R Flack T Yoshida F E Wondisford B D Weintraub 《Journal of endocrinological investigation》1992,15(4):255-263
In recent studies, site-directed mutagenesis has been used to alter the tripeptide glycosylation recognition sequences of glycoprotein hormone subunits, thereby affecting their structure and function. However, it is not known whether these effects result from changes in glycosylation status, amino acid sequence, or both. We therefore studied the synthesis of wild-type and mutant recombinant human thyrotropins produced by transient transfection of a human cell line. Mutating the TSH-beta subunit glycosylation recognition sequence, Asn-Thr-Thr (codons 23-25), to either Gln-Thr-Thr or Asn-Thr-Tyr abolished subunit glycosylation, as demonstrated by the inability to incorporate 3H-carbohydrates. However, a third mutation (Asn-Thr-Ser) contained an intact glycosylation recognition sequence site, and was shown to retain glycosylation. The mutations that abolished TSH-beta subunit glycosylation resulted in greater than 90% decreases in TSH synthesis. However, the glycosylation recognition sequence mutant that retained beta subunit glycosylation exhibited a 70% decrease in TSH production. These decreases were not attributable to the intracellular accumulation of TSH or its free beta subunit. We also engineered two TSH-beta subunit mutations that did not alter the glycosylation recognition sequence. A glycine to arginine mutation adjacent to the glycosylation recognition sequence, in a region thought to be critical for heterodimer formation, abolished TSH production. In contrast, shortening the TSH-beta subunit carboxyterminus by six amino acids increased TSH synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model. 相似文献
5.
乳腺管状小叶癌(Tubulolobular carcinoma,TLC)最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征,并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁(中位年龄60岁)。1例双侧乳腺受累,5例病变为多灶性。肿瘤直径0.5-2.5cm,色灰褐,质硬。组织学观察:TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂,且两者比例相当(统称为管状小叶模式)。 相似文献
6.
C. L. Mills O. Ariyo K. M. Yamada J. W. Lash Ruth Bellairs 《Anatomy and embryology》1990,182(5):425-434
Summary In the chick embryo the paraxial mesoderm forms about 50–53 pairs of somites, the precise number depending on the extent to which segmentation proceeds along the tail. However, the terminal mesoderm of the tail fails to segment despite the fact that it appears to contain a reservoir of potential somites. Why does this mesoderm not segment? Some clues can be obtained by comparing this non-segmenting region with the segmental plate in the trunk. We and others have shown that in the trunk region of the chick, cell adhesion plays a major role in somitogenesis and that this increased cell adhesion is associated with compaction of segments of mesoderm immediately prior to segmentation. This compaction can be brought about prematurely by fibronectin and by the specific adhesion peptide GRGDS. The terminal mesoderm in the tail resembles the segmental plate mesoderm in the trunk in undergoing compaction in response to fibronectin and GRGDS. The tail mesoderm differs from the segmental plate mesoderm in that it can also respond to peptides closely related to GRGDS. The response suggests that, whereas the integrin receptors for fibronectin and GRGDS appear to be specific in the presomitic trunk mesoderm, responding only to the specific adhesion-peptide GRGDS, the tail mesoderm may contain more heterogeneous sets of receptors within the integrin/VLA family that respond to a wider variety of ligands. Coincident with these differences is the phenomenon of regional cell death in the tail bud mesoderm. All of these factors are thought to play a role in the extent of segmentation in the paraxial mesoderm of the embryonic chick. 相似文献
7.
Hugues JN Soussis J Calderon I Balasch J Anderson RA Romeu A;Recombinant LH Study Group 《Human reproduction (Oxford, England)》2005,20(3):629-635
BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort. 相似文献
8.
Amyn A. Malik Neel R. Gandhi Timothy L. Lash Lisa M. Cranmer Saad B. Omer Junaid F. Ahmed Sara Siddiqui Farhana Amanullah Aamir J. Khan Salmaan Keshavjee Hamidah Hussain Mercedes C. Becerra 《Emerging infectious diseases》2021,27(3):805
In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%. 相似文献
9.
Kelly R. Stiegel Matthew T. Valentine Jonathan G. Lash Justin M. Cardenas Melvyn A. Harrington David M. Green 《The Journal of arthroplasty》2021,36(5):1478-1483
BackgroundTotal joint arthroplasty is the most common elective orthopedic procedure in the Veterans Affairs hospital system. In 2019, physical medicine and rehabilitation began screening patients before surgery to select candidates for direct transfer to acute rehab after surgery. The primary outcome of this study was to demonstrate that the accelerated program was successful in decreasing inpatient costs and length of stay (LOS). The secondary outcome was to show that there was no increase in complication, reoperation, and readmission rates.MethodsA retrospective review of total joint arthroplasty patients was conducted with three cohorts: 1) control (n = 193), 2) transfer to rehab orders on postop day #1 (n = 178), and 3) direct transfers to rehab (n = 173). To assess for demographic disparities between cohorts, multiple analysis of variance tests followed by a Bonferroni P-value correction were used. Differences between test groups regarding primary outcomes were assessed with analysis of variance tests followed by pairwise t-tests with Bonferroni P-value corrections.ResultsThere were no significant differences between the cohort demographics or comorbidities. The mean total LOS decreased from 7.0 days in the first cohort, to 6.9 in the second, and 6.0 in the third (P = .00034). The mean decrease in cost per patient was $14,006 between cohorts 1 and 3, equating to over $5.6 million in savings annually. There was no significant change in preintervention and postintervention short-term complications (P = .295).ConclusionsSignificant cost savings and decrease in total LOS was observed. In the current health care climate focused on value-based care, a similar intervention could be applied nationwide to improve Veterans Affair services. 相似文献
10.
OBJECTIVES: To compare patient interview-based and medical-record based measures of comorbidity and their relation to primary tumor therapy, all cause mortality, self-reported upper body function, and overall physical function. METHODS: Three-hundred and three breast cancer patients (> or = 55 years) who were diagnosed in 1 of 5 Boston hospitals were enrolled. Patient interviews and medical record abstracts provided the information necessary to construct the Charlson index, Satariano index, and a new interview-based index of cardiopulmonary comorbidity. Those indices were used alone and in combination to predict the patient outcomes. RESULTS: The indices of comorbidity corresponded well with one another. No index of comorbidity predicted mortality or receipt of definitive primary therapy. The new interview-based index of cardiopulmonary comorbidity was a better predictor of upper body function and overall physical function than was the interview-based or medical record-based Charlson or Satariano indices of comorbidity. CONCLUSION: Older breast cancer patients are able to provide information about their diseases and related symptoms that correlates well with medical record-based measures of comorbidity and displays similar patterns of predictive power. A new self-reported measure of cardiopulmonary comorbidity performs better than the medical record-based measures for predicting patient related functional outcomes. 相似文献