SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A magnetic tape-based archival system that provides for generation of computer-output microfiche has been developed. Data from magnetic tapes written on a turnkey laboratory system are used as the basis for generating the archival tapes. Programmed searches of the tapes allow retrieval directly by name or test(s). Accessing the computer-output microfiche allows retrieval by name and is being used to supplant a traditional file system.
In this study we investigated the acalculic condition of a patient, C.G., with the classical signs of Gerstmann's Syndrome: finger agnosia; right-left disorientation; a profound agraphia (but with an equally profound alexia) and a remarkably dense acalculia. Using a series of number processing and number knowledge tasks, a selective impairment for numbers was demonstrated. Within the category of numbers C.G. showed a largely preserved ability to deal with numbers below 4, in all tasks and in all modalities, while she was totally unable to deal with numbers above 4. The consistency of responses and the ineffectiveness of cueing indicated that numbers above 4 were lost, rather than hard to access. Further testing showed that this impairment did not result from a more general semantic memory problem, a difficulty in understanding quantities or a deficit in reasoning abilities thought to underlie the concept of numbers. Difficulty with some other ordinal structures was also present, but appeared unrelated to those affecting numbers.
Previous investigations into the genetic mechanism of fertility restoration in cytoplasmic male sterile Phaseolus vulgaris suggested that this is a particularly interesting system for the study of nuclear-mitochondrial interactions. This study was conducted to investigate the nature of nuclear-mitochondrial compatibility in fertile accession line G08063, the reported progenitor to the cytoplasmic male sterile line. Results from genetic analysis indicated that fertile line G08063 carried a sterility-inducing cytoplasm with a fertility restoring nuclear genotype. Mitochondrial DNA analysis indicated that the mechanism of fertility restoration by line G08063 was different from that conditioned by Fr, a previously described restorer gene. A mitochondrial DNA sequence associated with sterility and lost upon fertility restoration by nuclear gene Fr was present in the mitochondrial genome of fertile line G08063; this sequence was not carried within the mitochondrial genome of any other P. vulgaris accession line tested.
This paper reviews the literature of the past seven years concerning adolescent pregnancy. Social and motivational factors leading to pregnancy are discussed and weighed. Obstetric aspects of adolescent pregnancy are reviewed as well as the repercussions of this event. Goals and objectives are proposed, including: (1) assurance of health education, including family life and sex education, in all private and public schools, from elementary grades through high school; (2) assuring that family planning services are available, accessible, and acceptable to all school-aged individuals who desire such services; (3) assuring availability of inexpensive, or free, and easily accessible pregnancy testing, backed up by counseling about alternatives available to the pregnant school-aged woman; (4) assuring that pregnant adolescents have alternatives to childbirth, ie, abortion services, foster care services, adoption services; (5) assuring that pregnant adolescents receive optimal prenatal care, including social and other support services as well as medical care, and that their families are involved in the care process; (6) assuring that school-aged individuals and their families receive postnatal and follow-up care that includes social and other support services as well as medical care.
PURPOSE OF REVIEW: Inborn errors of immunity (IEIs), once considered rare disorders characterized primarily by recurrent infections, are now recognized as a rapidly expanding group of diseases encompassing autoimmunity, autoinflammation, allergy, malignancy, and immune dysregulation. Advances in next-generation sequencing, functional immunology, and systems biology have revealed overlap between traditionally distinct disease categories and highlighted the complexity of genotype-phenotype relationships. RECENT FINDINGS: While this evolution has led to the discovery of hundreds of previously unrecognized disorders, it has also challenged conventional diagnostic paradigms and demonstrated how patients may have care spread across multiple specialties, without a clear medical home. These discoveries have also highlighted ongoing challenges translating scientific findings to the clinic including difficulties in accessing genomic testing, interpretation of variants of uncertain significance, impacts of incomplete penetrance and somatic mosaicism, and limited availability of specialized functional assays. Emerging computational approaches, including artificial intelligence, offer opportunities to accelerate diagnosis but cannot replace comprehensive clinical evaluation or longitudinal physician-patient relationships. SUMMARY: This perspective examines how the diagnostic odyssey for immune dysregulatory disorders has evolved, side-by-side with the changing framework for diagnosing rare immune diseases. We propose an integrated approach combining clinical phenotyping, genomics, functional validation, and multidisciplinary expertise to unite ongoing discovery between clinicians and scientists, diagnostics, and patient outcomes.
Treatment of the reconstituted aspartate/glutamate carrier from mitochondria with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (Nbd-Cl) led to complete inactivation of carrier function. Inhibition could be attributed to chemical modification of one single cysteine in the active site. This residue was specifically protected in the presence of aspartate or glutamate, 50% substrate protection being observed at half-saturation of the external binding site. The bifunctional reagent 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) also modified the same cysteine and, in addition, an active-site lysine identified previously [Dierks, T., Stappen, R., Salentin, A. & Krämer, R. (1992) Biochim. Biophys. Acta 1103, 13-24]. The proximity of the cysteine [Cys(a)] and the lysine residue was confirmed by a mutual exclusion of the respective reagents when added consecutively. By using a variety of reagents a further cysteine [Cys(b)] and probably a histidine residue could be discriminated from Cys(a) and the lysine. The applied reagents were classified according to functional and structural criteria. Class A reagents, like Nbd-Cl, modified the active-site Cys(a) thereby inhibiting the antiport function. Class B reagents, like HgCl2, reacted with both Cys(a) and Cys(b) leading to a conversion of the carrier from antiport to uniport function [Dierks, T., Salentin, A., Heberger, C. & Krämer, R. (1990) Biochim. Biophys. Acta 1028, 268-280]. DIDS at relatively high concentration (60 microM) also acted as a uniport inducer. Class C reagents finally, like pyridoxal phosphate or diethyl pyrocarbonate, modified the active-site lysine or histidine, respectively, and blocked antiport and uniport activity. By testing the accessibility of the mentioned residues to the various reagents, when applied in different order, topological relationships could be elaborated indicating the location of these amino acids with respect to the exofacial active site of the carrier protein.
Background: There is a growing recognition that genetic predisposition contributes to the development of fibrotic interstitial lung disease. Adult onset monogenic disease is most commonly due to dysfunctional telomere maintenance, with a small proportion caused by surfactant biology disorders. These conditions can be associated with additional intrapulmonary and extrapulmonary features which themselves may require surveillance or treatment, making it important to make a genetic diagnosis. The recent introduction in England of a genetic testing panel accessible to respiratory physicians means that genetic information for these individuals is increasingly available but there is currently little standardisation of the subsequent management of patients and their relatives, which can be complex.Aims: This consensus considers the causes and clinical features of familial pulmonary fibrosis and provides a suggested framework for genetic investigation and clinical management of both patients and their relatives.Narrative: We suggest an initial workup that may help identify those with monogenic disease, with focus on key points in the history and examination that may identify features of a telomere or surfactant biology disorder. We highlight that clinical and radiological presentations are diverse and discuss the importance of making a genetic diagnosis to inform multidisciplinary management and facilitate screening of close family members. We also discuss the many outstanding uncertainties and challenges, including the investigation and management of non-monogenic familial pulmonary fibrosis and the management of asymptomatic family members who have inherited a potentially disease-causing genetic variant.Conclusions: We suggest a pathway for the workup and management of patients with familial pulmonary fibrosis, aiming to standardise clinical care for patients and their relatives and provide a framework for the development of a national database to facilitate disease phenotyping and clinical research to improve the evidence base for clinical practice.
Treatment of chromatin subunits (nucleosome monomers) with formaldehyde results in the formation of cross-links between DNA and histones and between histones and histones. Digestion of chromosomal proteins with proteinase K does not lower the protein/DNA weight ratio below 0.08 to 0.1 as determined by cesium chloride gradient centrifugation of the digestion product from formaldehyde-treated nucleosomes. In addition to proteinase K, formaldehyde-treated nucleosomes were tested for accessibility to trypsin and pronase. The CsCl gradient patterns show, that pronase digestion and proteinase K treatment yield similar results. Trypsin treatment of control and formaldehyde-treated nucleosomes shows, that the sites which are accessible for trypsin in native nucleosomes, are blocked after formaldehyde treatment. Analysis of the CsCl gradient peak fractions in polyacrylamide gels shows, that the reliability of DNA fragment size determinations depends on the completeness of deproteinization.
Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.
More than 5000 women infected with human immunodeficiency virus give birth annually in the United States. Many of these women are offered human immunodeficiency virus tests in prenatal settings. One of the incentives for them to be tested is access to medications that have been shown to prolong disease-free intervals in nonpregnant human immunodeficiency virus-infected individuals. However, the use of those medications during pregnancy has not been well studied and some have cautioned against their prenatal use. Thus consideration of these agents may be deferred by some clinicians until the postpartum period. In this article we argue that the availability of such agents should be disclosed to women who are seropositive for human immunodeficiency virus as part of the informed consent process.
Prenatal HIV education and testing requires access to many resources and is demanding of time and personnel. Properly trained sympathetic on-site counselors are essential. Such personnel may combine this role with other tasks but should have the time necessary to commit to individualized HIV counseling. High-quality laboratory facilities should be available. Ready access to psychiatric professionals, social service supports, clergy, internal medicine, pediatric primary care, and infectious disease consultation or referrals needs to be available and integrated into all prenatal screening programs. Obstetrician/gynecologists at all levels should seek access to and support for these necessary though resource-intensive programs and work toward extension of such programs to all women of childbearing age.
The onset of the AIDS epidemic has made evident how scanty our knowledge is about sexuality, not only in the developing world where behavioral science resources are limited, but in the developed world as well. That the findings of the Kinsey group of nearly half a century ago remain relevant to current scientific discussion is an important measure of the lack of a well-developed and active research tradition in the area of sexuality. As a result of a lack of support for sex research, except in a number of very limited areas, when the epidemic began, there was a lack of baseline data, accessible and tested research techniques, and trained personnel. There is evidence that some of these problems are being addressed as new research initiatives are being undertaken both nationally and internationally that are relevant to both AIDS and sexuality. At the same time, a majority of this research has been driven by a concern for the disease and has not taken into account the larger role of sexuality in the life of individuals in specific cultures and societies. Much of the research that has been undertaken is examining sexuality from the perspective of AIDS rather than AIDS in the perspective of sexuality. Perhaps it is well to understand that long after the AIDS epidemic is history, sexuality will remain with us as a source of pleasure and difficulty.
4-Thioflavins (oxygen at position 4 replaced by sulfur) have been studied as potential active site probes of flavoproteins. They react readily with thiol reagents, with large spectral changes, which should be useful for testing the accessibility of the flavin 4-position in flavoproteins. They have an oxidation-reduction potential at pH 7 of -0.055 V, approximately 0.15 V higher than that of native flavins. The spectral characteristics in the fully reduced state show two clear absorption bands, dependent on the ionization state (pK = 4.5). The lowest energy band of the neutral dihydroflavin has a maximum at approximately 485 nm while that of the anion is approximately 425 nm. This should be useful in defining the ionization state of the reduced flavin in flavoproteins. The spectral characteristics of the semiquinoid forms of 4-thioflavins have been determined bound to the apoproteins of flavodoxin and D-amino acid oxidase. The neutral radical has an absorption maximum at 730 nm, while the anion radical has an unusually sharp peak at 415 nm. The reduced forms of 4-thioflavins, free and enzyme bound, react with O2 to regenerate oxidized 4-thioflavin. Reduced 4-thio-FAD p-hydroxybenzoate hydroxylase, however, in its reaction with O2, undergoes a substantial conversion to the native FAD-enzyme. 4-Thioflavins are unusually susceptible to attack by nucleophiles such as hydroxylamine and amines to form the respective 4-hydroxyimino- and 4-aminoflavins, offering the possibility of forming stable covalent flavin-protein linkages with suitably positioned protein residues. Thiols also react with 4-thioflavins, promoting their conversion to the normal (4-oxo) flavin coenzymes. Such reactivity has been found with the apoenzymes of glucose oxidase and lactate oxidase, providing evidence for a thiol residue in the active site of these enzymes.
The purpose of this investigation was to determine how castable glass (Dicor) crowns would react to both cold testing and endodontic access intervention. Full crown preparations were made on six extracted maxillary teeth. The teeth were then forwarded to Dentsply International, York, Pa. Six castable glass crowns were fabricated to fit these teeth and returned to us. Subsequently the teeth were dried and the crowns were cemented. Scanning electron micrographs of the cemented crowns were made, and endodontic access openings were drilled. The teeth were also cold tested with standard methods. The teeth were then again subjected to scanning electron microscopy to determine any changes the crowns might have undergone. One crown cracked around the gingival collar as scanning electron microscopy was performed. The other crowns did not exhibit any problems such as cracking or crazing from either the access openings or the cold testing.
Genomic testing is a key component of precision oncology; however, Black patients receive genomic testing at lower rates. The purpose of this qualitative study was to identify individual and health system drivers of genomic testing disparities at a National Cancer Institute-designated comprehensive cancer center. We conducted interviews with 15 oncology providers and 11 Black cancer patients between September 2023 and October 2024. These patients were eligible for genomic testing based on National Comprehensive Cancer Network (NCCN) guidelines, being diagnosed within last 10 years (2014-2023), at least 18 years old, and English-speaking. Providers included oncologists and oncology patient navigators. Topics included motivators, barriers, and knowledge of genomic testing and factors influencing decision-making. The Penchansky and Thomas theoretical framework of healthcare access (e.g., availability, accessibility, accommodation, affordability, and acceptability) guided thematic analysis. Among patients eligible for genomic testing, most participants (n = 7) received genomic testing as part of their cancer treatment based on EMRs, however many patients (n = 7) could not recall discussing genomic testing with their oncologist. Most patients and all providers highlighted affordability as a challenge: patients were concerned about unexpected costs associated with testing, while providers were concerned about costs of matched molecular targeted therapy. Both patients and providers highlighted patient-centered communication to mitigate mistrust and promote patient engagement in care. Despite limited awareness, Black patients view genomic testing positively. Addressing multiple dimensions of access is key to improving system-level processes and ensuring that more patients benefit from lifesaving targeted therapy.
The authors present the results of studying the PHAT sensitivity in comparison with the neutralization test and the hemagglutination inhibition test in examination of 254 sera of revaccinated and 95 sera of primarily vaccinated children. It appeared that PHAT was characterized by a sufficiently high sensitivity, and reproducibility, in case the same batch of erythrocytic diagnostic agent was used; at the same time the test was simple, accessible, economic, and gave rapid results. This test can be used for assessment of the immunological efficacy of smallpox revaccination.
The allergic response to chymopapain intradiscal therapy has been well documented. The most serious of these reactions is anaphylactic shock, which may result in death. Various screening methods, including skin tests, have been proposed to identify susceptible patients. Anaphylactic shock occurred in a 40-year-old woman from application of the screening skin test. Appropriate therapeutic intervention should be readily accessible when this test is performed.
PURPOSE: The National Comprehensive Cancer Network (NCCN) recommends germline genetic testing for individuals at risk for hereditary ovarian cancer. We sought to determine the proportion and characteristics of individuals meeting testing criteria in a multicenter biobank who were appropriately offered testing. METHODS: In this retrospective cohort study, we identified Mass General Brigham Biobank participants meeting genetic testing criteria per NCCN guidelines. Logistic regression was used to analyze sociodemographic factors associated with which participants were offered testing, completed testing, and had a family history that matched their self-report documented in the electronic medical record. RESULTS: Most eligible participants (909/1441, 63.1%) were not offered genetic testing. Participants who were Black or Hispanic had a lower likelihood of being offered testing. Compared with self-report, 988 (68.6%) participants had a family history of ovarian cancer documented in their electronic medical record. Older age, Hispanic ethnicity, and public insurance use were associated with decreased likelihoods of accurate family history documentation. Correct documentation was associated with an increased likelihood of being offered testing. CONCLUSION: The majority of participants in this study did not receive NCCN-compliant care. Germline genetic testing for hereditary ovarian cancer screening is underutilized and access to this testing is currently inequitable.