HIV and infertility: time to treat. There's no justification for denying treatment to parents who are HIV positive.
Explore the source record for details and available documents.
Female↗
Biomedical subjects
J R Smith
Publications and source records attributed to J R Smith.
Characterization of a novel zinc finger gene with increased expression in nondividing normal human cells.
We report here the cloning and characterization of a novel KRAB zinc finger gene, ZFQR, which has eight tandemly repeated zinc fingers, a complete KRAB box at the N-terminal region, and a unique C-terminal sequence. It is expressed in a variety of human tissues, and mRNA levels are upregulated in nondividing senescent and quiescent human fibroblasts. Overexpression of the protein in quiescent cells stimulated with serum growth factors results in inhibition of entry into the cell cycle. The latter activity is lost when the N-terminal KRAB domain is deleted. The KRAB domain is also required for the transcriptional repression activity of ZFQR and in maintaining association of the protein with the nuclear matrix. The gene has been mapped to human chromosome 19q13.4. The association of ZFQR with the nuclear matrix, transcriptional repression activity, increased expression in senescent and quiescent cells, and the ability to inhibit quiescent cells stimulated with growth factors from entering the cell cycle suggests a role for ZFQR in the maintenance of the nondividing state of normal human cells.
Amino Acid Sequence↗
Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease.
OBJECTIVE: To evaluate the clinical usefulness of tumor necrosis factor (TNF) inhibitors in patients with inflammatory eye disease that is resistant to conventional immunosuppressive therapies. METHODS: Sixteen patients (4 males and 12 females aged 7 to 78 years) who received etanercept (n = 14) or infliximab (n = 2) for either inflammatory eye disease or associated joint disease were studied retrospectively to determine the effect of these medications on their ocular inflammation. RESULTS: Nine cases of uveitis and 7 cases of scleritis were treated. Systemic diagnoses included rheumatoid arthritis (n = 8), juvenile rheumatoid arthritis (n = 3), ankylosing spondylitis (n = 1), and psoriatic spondylarthropathy (n = 1). Three patients had uveitis without associated systemic disease. Although 12 of 12 patients with active articular inflammation (100%) experienced improvement in joint disease, only 6 of 16 with ocular inflammation (38%) experienced improvement in eye disease. Five patients developed inflammatory eye disease for the first time while taking a TNF inhibitor. No patient discontinued treatment because of adverse drug effects. CONCLUSION: TNF inhibitors are well tolerated immunosuppressive medications that may benefit certain subgroups of patients with inflammatory eye disease, but they appear to be more effective in controlling associated inflammatory arthritis.
Adolescent↗
Analysis of the degradation compounds of chemical warfare agents using liquid chromatography/mass spectrometry.
The analysis of the degradation products of chemical warfare (CW) agents has been a challenge to analysts. The low volatility of these compounds makes them unsuitable for direct gas chromatography analysis without prior derivatization. Lack of a chromophore causes difficulties with classic detection methods after liquid chromatography separation. With the recent development of various interfaces that allow for the introduction of a liquid solvent stream into the mass spectrometer, the task of directly analyzing these compounds has become easier. For this report, we examined three different liquid chromatography/mass spectrometry (LC/MS) interfaces for their suitability for the analysis of CW degradation compounds. The interface types examined were particle beam electron impact ionization (PBI), electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). Several alkylphosphonates and thiodiglycol analogs that are produced from the degradation of organophosphorus nerve agents and sulfur mustard, respectively, were analyzed using each of the three techniques. Electron impact ionization following gas chromatography or particle beam introduction typically generates very reproducible, library-searchable mass spectra. Most of the CW breakdown compounds examined using the PBI interface did not produce a molecular ion. Despite the lack of a molecular ion, the mass spectra of the various compounds contained enough different structural information from fragment ions for the positive identification of each. The mass spectra generated using ESI are generally limited to protonated molecular ions with little or no fragmentation. For positive identification and confirmation, tandem mass spectrometry techniques quite often must be used. Many of the compounds in this study were characterized by prominent sodiated adducts along with the protonated molecular ion. Methylphosphonic acid produced protonated dimers, trimers, etc. Although the various adduct ions can be used for additional confirmation of the molecular weight of a compound, the adducts also can result in suppression of ionization of the compound and thus reduce sensitivity. Another 'soft' ionization technique that results in abundant protonated molecular ions is APCI. The mass spectra of the breakdown compounds produced using APCI were characterized generally by either a prominent protonated molecular ion or a dehydrated form of it. In addition, a number of structurally significant fragment ions were observed and their relative abundances could be adjusted by altering the APCI conditions. The data presented here indicate that each of the three techniques can be used successfully for direct liquid introduction and analysis of the non-volatile compounds produced from the degradation of CW agents. The mass spectra produced using each technique are quite different and could be utilized as additional confirmation of compound identity.
Chemical Warfare Agents↗
Army medical laboratory telemedicine: role of mass spectrometry in telediagnosis for chemical and biological defense.
An army medical field laboratory presently has the capability of performing standard protocols developed at the US Army Medical Research Institute of Chemical Defense for verification of nerve agent or sulfur mustard exposure. The protocols analyze hydrolysis products of chemical warfare agents using gas chromatography/mass spectrometry. Additionally, chemical warfare agents can produce alkylated or phosphorylated proteins following human exposure that have long biological half-lives and can be used as diagnostic biomarkers of chemical agent exposure. An analytical technique known as matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) currently is being examined for its potential to analyze these biomarkers. The technique is capable of detecting large biomolecules and modifications made to them. Its fast analysis time makes MALDI-TOF/MS technology suitable for screening casualties from chemical or biological attacks. Basic operation requires minimal training and the instrument has the potential to become field-portable. The limitation of the technique is that the generated data may require considerable expertise from knowledgeable personnel for consultation to ensure correct interpretation. The interaction between research scientists and field personnel in the acquisition of data and its interpretation via advanced digital telecommunication technologies can enhance rapid diagnosis and subsequently improve patient care in remote areas.
Biomarkers↗
Linkage of prostate cancer susceptibility loci to chromosome 1.
Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24-25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42-43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease.
Chromosome Mapping↗
Pregnancy subsequent to uterine artery embolization.
Explore the source record for details and available documents.
Adult↗
Improved student learning in ophthalmology with computer-aided instruction.
PURPOSE: Recent changes in the medical school curriculum and in teaching styles have stimulated the development of novel learning resources. We investigated the impact of computer-aided learning in the field of ophthalmology at a large Australian undergraduate medical school. METHODS: Clinical case studies describing common ophthalmic conditions were incorporated into a computing program which uses a problem-solving format. The program was made available to 85 medical students for a 2 week period. A control group of 20 medical students did not have access to this material. Acquisition of new knowledge was assessed as the improvement in score on a knowledge-based multiple-choice examination which students took both before and following the learning interval. RESULTS: Students in the control group showed no improvement over the test period, whilst the students who had access to the computer significantly increased their knowledge base, both for material provided on the program (p = 0.0001) and in related areas (p = 0.0015). CONCLUSIONS: Suitably constructed material on the computer is a useful aid in teaching ophthalmology to medical undergraduates. The material and the medium may also act as a stimulus for further learning.
Computer-Assisted Instruction↗
Reduced herpes simplex virus type 1 latency in Flt-3 ligand-treated mice is associated with enhanced numbers of natural killer and dendritic cells.
We have investigated the effect of Flt-3 ligand (Flt-3L) on the resistance to herpes simplex virus type-1 (HSV-1) infection in BALB/c mice which are normally highly susceptible to challenge with this virus. We have confirmed data by others that in vivo treatment with Flt-3L causes an increase in dendritic cells (DC) and natural killer (NK) cells in lymphoid tissue. Increasing doses of Flt-3L caused a corresponding increase in liver and spleen CD11c+ DC which were increased up to 20-fold compared with control levels. A significant expansion of NK cells was seen in the spleen of Flt-3L-treated mice where the number of DX5+ cells was increased by up to fivefold. We subsequently tested the hypothesis that Flt-3L treatment, at the time of viral infection, might lead to enhanced immunity and protection against viral pathogenesis. Two murine models of HSV-1 (SC16) infection were used. In the first model, mice were injected with Flt-3L daily for 9 days. Control mice received mouse serum albumin (MSA). On day 7 of the Flt-3L treatment 106 plaque-forming units (PFU) of SC16 was inoculated into the ear pinna. Flt-3L treatment significantly reduced mortality following virus inoculation, with 80% survivors in this group compared with 20% survivors in the MSA-treated group. In the second model, Flt-3L-treated mice were scarified with 104 PFU of SC16. In this case there was 60% survival in the Flt-3L-treated group of mice compared with 10% survival in the MSA-treated group. Assessment by in situ hybridization for latency-associated transcripts showed that Flt-3L treatment reduced the amount of latent virus within infected neurons. These studies show that in vivo treatment with Flt-3L results in protection against challenge with live HSV-1, which may be a consequence of enhanced numbers of DC and/or NK.
Animals↗
Microscopical investigations on the epicuticle of mammalian keratin fibres.
The existence of a thin chemically resistant layer, the epicuticle, close to the surfaces of all undamaged mammalian keratin fibres has been known since 1916. The identification of such a specific structure within the fibre cuticle has remained elusive. Now, through transmission electron microscope investigations of stained transverse sections of hairs from various animal species, the epicuticle has been tentatively identified as a sharply defined and continuous layer approximately 13 nm thick covering the entire outwardly facing intracellular surface of every cuticle cell. The staining behaviour of the epicuticle leads one to suppose that it is rich in cystine and that thioester-bound lipids might be present within its bulk. With the atomic force microscope it was established that the undamaged outer surface of all mammalian keratin fibres, even including those from the monotremes, were longitudinally striated. The lateral spacing of the striations was always in the range 0.29-0.39 microm. Striations only occurred on the freely exposed outer surfaces of the original undamaged fibres; evidently arising by some, as yet undefined, interaction in the follicle with the cuticle of the inner root sheath. By stripping off fatty acids known to be covalently attached to the fibre's outer surface, the striations were shown to reflect a corresponding irregularity of the epicuticle's surface.
Animals↗
Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.
AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.
Adult↗
Calcium signaling mechanisms in dedifferentiated cardiac myocytes: comparison with neonatal and adult cardiomyocytes.
Our studies focused on calcium sparking and calcium transients in cultured adult rat cardiomyocytes and compared these findings to those in cultured neonatal and freshly isolated adult cardiomyocytes. Using deconvolution fluorescence microscopy and spec trophotometric image capture, sequence acquisitions were examined for calcium spark intensities, calcium concentrations and whether sparks gave rise to cell contraction events. Observations showed that the preparation of dedifferentiated cardiomyocytes resulted in stellate, neonatal-like cells that exhibited some aspects of calcium transient origination and proliferation similar to events seen in both neonatal and adult myocytes. Ryanodine treatment in freshly isolated adult myocytes blocked the calcium waves, indicating that calcium release at the level of the sarcoplasmic reticulum and t-tubule complex was the initiating factor, and this effect of ryanodine treatment was also seen in cultured-dedifferentiated adult myocytes. However, experiments revealed that in both neonatal and cultured adult myocytes, the inositol triphosphate pathway (IP3) was a major mechanism in the control of intracellular calcium concentrations. In neonatal myocytes, the nucleus and regions adjacent to the plasma membrane we re major sites of calcium release and flux. We conclude: (1) culturing of adult cardiomyocytes leads them to develop mechanisms of calcium homeostasis similar in some aspects to those seen in neonatal cardiomyocytes; (2) neonatal myocytes rely on both extracellular and nuclear calcium for contractile function; and (3) freshly isolated adult myocytes use sarcoplasmic reticulum calcium stores for the initiation of contractile function.
Age Factors↗
Uterine transplantation, abdominal trachelectomy, and other reproductive options for cancer patients.
More and more women with cancer issues are now raising fertility concerns as survival improves and childbearing is delayed. Pregnancy is no longer contraindicated in cancer patients including breast and endometrial cancer survivors. In fact, survival in patients treated for breast cancer who subsequently become pregnant is actually higher than that in patients who do not become pregnant. "Therapeutic" abortions are no longer recommended. Assisted reproductive technology (ART) have been associated with ovarian neoplasms, but the association is probably not causal. Neither ART nor hormone replacement is contraindicated in cancer patients. Our institution is very supportive of patients and the difficult decisions cancer survivors face. Using a program of counseling and close collaboration between oncologists, perinatologists, and reproductive endocrinologists, informed patients are offered every possible option, including ART and uterine transplantation, to achieve their family planning objectives.
Breast Neoplasms↗
Molecular basis for impaired muscle differentiation in myotonic dystrophy.
Differentiation of skeletal muscle is affected in myotonic dystrophy (DM) patients. Analysis of cultured myoblasts from DM patients shows that DM myoblasts lose the capability to withdraw from the cell cycle during differentiation. Our data demonstrate that the expression and activity of the proteins responsible for cell cycle withdrawal are altered in DM muscle cells. Skeletal muscle cells from DM patients fail to induce cytoplasmic levels of a CUG RNA binding protein, CUGBP1, while normal differentiated cells accumulate CUGBP1 in the cytoplasm. In cells from normal patients, CUGBP1 up-regulates p21 protein during differentiation. Several lines of evidence show that CUGBP1 induces the translation of p21 via binding to a GC-rich sequence located within the 5' region of p21 mRNA. Failure of DM cells to accumulate CUGBP1 in the cytoplasm leads to a significant reduction of p21 and to alterations of other proteins responsible for the cell cycle withdrawal. The activity of cdk4 declines during differentiation of cells from control patients, while in DM cells cdk4 is highly active during all stages of differentiation. In addition, DM cells do not form Rb/E2F repressor complexes that are abundant in differentiated cells from normal patients. Our data provide evidence for an impaired cell cycle withdrawal in DM muscle cells and suggest that alterations in the activity of CUGBP1 causes disruption of p21-dependent control of cell cycle arrest.
Base Sequence↗
A role for methotrexate in the management of non-infectious orbital inflammatory disease.
AIM: To evaluate the clinical usefulness of methotrexate for patients with non-infectious orbital inflammatory disease who fail to respond to systemic corticosteroids and/or orbital irradiation. METHODS: The medical records of patients with non-infectious orbital inflammatory disease who were treated with methotrexate at Oregon Health Sciences University between June 1993 and June 2000 were examined. Methotrexate was administered at a median maximum dose of 20 mg per week (range 15-25 mg per week) in conjunction with folate supplementation. Patients were followed with regular ophthalmic examinations, as well as serum liver enzyme levels and blood cell counts. Clinical signs of regression of the orbital inflammation, visual acuity, dosage and duration of methotrexate therapy, requirement for concurrent corticosteroid administration, and adverse drug reactions were recorded. RESULTS: The study cohort included 14 patients (24 eyes) with diagnoses including non-specific orbital inflammation (n=7), Tolosa-Hunt syndrome (n=1), thyroid orbitopathy (n=3), Wegener's granulomatosis (n=1), sarcoidosis (n=1), and Erdheim-Chester disease (n=1). In all cases, methotrexate was commenced as a corticosteroid sparing agent. 10 patients (71%) completed a 4 month therapeutic trial of methotrexate. Median duration of treatment for the nine (64%) patients who experienced clinical benefit was 25 months (range 10-47 months). Six responders were ultimately able to cease methotrexate, including the single patient who required concurrent long term corticosteroid therapy. Complications included fatigue, gastrointestinal disturbance, hair thinning and mild, reversible serum liver enzyme elevation. Two patients (14%) discontinued treatment because of adverse effects. CONCLUSION: Methotrexate is a well tolerated immunosuppressive medication which may benefit patients with recalcitrant non-infectious orbital inflammatory disease.
Adult↗
Effects of combining public assistance and employment on mothers and their young children.
One goal of recent welfare reform legislation is to move welfare-dependent mothers with young children into the paid labor force. However, prior to the new legislation, many welfare-dependent women were already engaged in employment activities. In this paper we examine whether child or maternal well-being is influenced by a mother's strategy of combining work and public assistance receipt in the late 1980s. Measures of well-being include children's cognitive test scores and behavior problems, parenting behavior, and maternal mental health, social support, and coping strategies collected when children were 2 1/2 to 3 years of age. Data from the Infant Health and Development Program (a sample of low birthweight, premature infants born in 8 sites in 1985) were used to identify low-income families (incomes under 200% of the poverty threshold; N = 525). Comparisons were made among mothers in the following groups: (a) Work Only, (b) Some Work-Some Welfare, (c) Some Work-No Welfare, (d) No Work-No Welfare, and (e) Welfare Only. Mothers in the Some Work-Some Welfare group had children with cognitive and behavioral scores similar to children whose mothers were in the Work Only group; these two groups also had similar mental health, social support, and coping scores. However, not working and receiving welfare (Welfare Only) was associated with negative cognitive and behavioral outcomes for children, with less stimulating home learning environments, lower maternal mental health, less social support, and more avoidant coping strategies. We discuss the proposition that welfare and work may be complementary rather than opposing strategies, in terms of putting together a family income package.
Adaptation, Psychological↗
Prospective comparison between laparoscopic preperitoneal herniorrhaphy and open mesh herniorrhaphy.
Controversy persists regarding the most effective inguinal hernia repair. The purpose of this study is to compare the complications, charges, patient satisfaction, and recovery time between laparoscopic (LH) and open mesh herniorrhaphy (OH). A nonrandomized prospective analysis of 233 consecutive inguinal hernia repairs was performed over a 12-month period by 27 surgeons. The type of repair was determined by surgeon preference. Cost analysis was performed using anesthesia records and hospital cost. Patient satisfaction and recovery time were evaluated by third-party interview. A total of 113 OHs and 120 LHs were performed; 11 OHs and 42 LHs were bilateral. Patient demographics were equivalent for the two groups. No statistical difference was noted when comparing anesthesia/operating room time between the two groups. The LHs accrued an additional charge of $2254 per case. Complication rates were 4.4 per cent for the OHs and 8.3 per cent for the LHs. All complications were considered minor. No infectious complications or recurrences were noted in either group. Satisfaction rates and pain indices were nearly identical for both OHs and LHs. The LHs had a shorter recovery time by 5.5 days. We conclude that LH is associated with a higher complication rate and cost than OH. Pain indices are similar, but LH has a shorter recovery time.
Cohort Studies↗
Case reports and small case series: scleritis occurring in association with Takayasu disease.
Explore the source record for details and available documents.
Adult↗