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Biomedical subjects

S Black

Publications and source records attributed to S Black.

At least 19 recordsLinked to original sources

Over-expression of Candida albicans mitochondrial ribosomal protein S9 (MrpS9p) disturbs mitochondrial function in Saccharomyces cerevisiae.

A Candida albicans mitochondrial ribosomal protein S9 (MRPS9) cDNA was identified in a screen for sequences whose expression induce galactose lethality in Saccharomyces cerevisiae. MRPS9 appears to encode a protein of 346 amino acids with an N-terminal mitochondrial targeting sequence and an internal S9 signature that is conserved amongst eukaryotic mitochondrial and prokaryotic ribosomal protein S9 sequences. Expression of a GAL1-CaMRPS9 fusion in S. cerevisiae caused the slow development of a galactose-negative phenotype upon repeated subculturing, and this correlated with an increased frequency of petite mutant formation. Therefore, over-expression of CaMRPS9 interferes with S. cerevisiae mitochondrial function, which accounts for the inhibition of growth on galactose.

Amino Acid Sequence

Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers.

OBJECTIVES: The objectives of this study were (1) to determine the safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate (PNCRM7) vaccine in infants and (2) to determine the effect of concurrent hepatitis B immunization during the primary series and the effect of concurrent diphtheria and tetanus toxoid and acellular pertussis [DTaP (ACEL-IMUNE)] and conjugate CRM197 Haemophilus influenzae type b [HbOC (HibTITER) immunization at time of the booster dose on the safety and immunogenicity of PNCRM7and these other concurrently administered vaccines. METHODS: This was a randomized double-blinded study in 302 healthy infants in the Northern California Kaiser Permanente (NCKP) Health Plan. Infants received either PNCRM7 vaccine or meningococcal group C conjugate vaccine as a control at 2, 4 and 6 months of age and a booster at 12 to 15 months of age. Study design permitted the evaluation of immunology and safety of concurrent administration of routine vaccines. Antibody titers were determined on blood samples drawn before and 1 month after the primary series and the booster dose. RESULTS: After the third dose of PNCRM7 geometric mean concentrations (GMCs) ranged from 1.01 for serotype 9V to 3.72 microg/ml for serotype 14. More than 90% of all subjects had a post-third dose titer of > or =0.15 microg/ml for all serotypes, and the percentage of infants with a post-third dose titer of > or =1.0 microg/ml ranged from 51% for type 9V to 89% for type 14. After the PNCRM7 booster dose, the GMCs of all seven serotypes increased significantly over both post-Dose 3 and pre-Dose 4 antibody levels. In the primary series there were no significant differences in GMCs of pneumococcal antibodies between the subjects given PN-CRM7 alone or concurrently with hepatitis B vaccine. At the toddler dose concurrent administration of PNCRM7 and DTaP and HbOC resulted in a near conventional threshold for statistical significance of a post-Dose 4 GMC for serotype 23F [alone 6.75 mirog/ml vs. concurrent 4.11 microg/ml (P = 0.057)] as well as significantly lower antibody GMCs for H. influenza polyribosylribitol phosphate, diphtheria toxoid, pertussis toxin and filamentous hemagglutinin. For all antigens there were no differences between study groups in defined antibody titers that are considered protective. CONCLUSION: We conclude that PNCRM7 vaccine was safe and immunogenic. When this vaccine was administered concurrently at the booster dose with DTaP and HbOC vaccines, lower antibody titers were noted for some of the antigens when compared with the antibody response when PNCRM7 was given separately. Because the GMCs of the booster responses were all generally high and all subjects achieved similar percentages above predefined antibody titers, these differences are probably not clinically significant.

Antibodies, Bacterial

Blood loss and transfusion practice in the perioperative management of craniosynostosis repair.

During the past 5 years, the surgical repair for sagittal synostosis has been modified to a more complex and involved procedure. This led to a retrospective evaluation of the current transfusion practice in a large series of craniosynostosis repairs. The charts of 76 patients (81 surgical procedures) undergoing craniosynostosis repair from January 1990 to November 1996 were examined. The calculated volume of blood loss (BL) was determined for each surgical procedure and related to the estimated blood volume (EBV) and acceptable blood loss (ABL). The anesthesiologist's ability to estimate BL was compared with the calculated blood loss (CBL). In most surgical procedures for craniosynostosis, especially in the complex sagittal repairs, CBL was underestimated and exceeded ABL. Packed red blood cell transfusion occurred in 96.3% of the patients and was appropriate for most procedures based on ABL. Thus, transfusion for craniosynostosis repair is almost inevitable, and the preventive preparation of blood on the order of the mean estimated blood loss (EBL) plus 2 SD is appropriate. With the increased complexity of sagittal repair and its performance in a younger population, the cosmetic benefit of surgical repair has major implications for management of blood and fluids.

Age Factors

Comparative safety of two recombinant hepatitis B vaccines in children: data from the Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink (VSD).

BACKGROUND: Preliminary review of data from the Vaccine Adverse Event Reporting System (VAERS), 1991-1994, revealed that more serious adverse events were reported in children who received a specific brand of recombinant hepatitis B (HepB) vaccine. OBJECTIVE: To compare the post-marketing safety experience of the two recombinant HepB vaccines licensed for use in infants and children in the United States. DESIGN: Review of a case series derived from passive surveillance data in the national VAERS. A retrospective cohort study using data from one health maintenance organization participating in Vaccine Safety Datalink (VSD), a computerized record linkage system. POPULATIONS STUDIED: U.S. children, ages birth-10 years for whom adverse events after HepB vaccine were reported to VAERS, 1991-1994. Children, ages birth-6 years, who received HepB vaccine at Kaiser Permanente Medical Care Program, Northern California, 1991-1994. MAIN OUTCOME MEASURES: VAERS reporting rates for each vaccine by manufacturer were calculated from the numbers of reported events occurring within 30 days of HepB vaccination and the number of doses distributed by the manufacturers. VSD event rates for each vaccine were calculated from the numbers of hospitalization or emergency room visits within 30 days of HepB vaccination and the number of vaccine doses administered to the cohort. RESULTS: In VAERS, higher rates of serious events (i.e., life threatening or resulting in hospitalization or permanent disability) were reported in children who received Vaccine A vs. Vaccine B (relative risk [RR]: 3.13-8.18, P < 0.01), particularly by those vaccinated in the private (RR: 7.62-28.58, P < 0.01), but not public sector (RR: 2.12, P = 0.19). Similar types of events were reported in recipients of both vaccines. In contrast, analysis of VSD data showed no significant difference in rates of hospitalization or ER visits in children who received either HepB vaccine (RR: 0.96-1.25, P > 0.05). CONCLUSIONS: Our investigation reveals that it is unlikely there is a true difference between rates of serious events temporally associated with the two HepB vaccines in children. This study demonstrates the dual roles played by VAERS and VSD in providing a more complete picture of the post-marketing safety profile of childhood vaccines, and underscores the importance of using other analytic studies to evaluate findings from passive surveillance systems of adverse events.

Adverse Drug Reaction Reporting Systems

Ocular search during line bisection. The effects of hemi-neglect and hemianopia.

We examined ocular fixations during line bisection in five patients with left hemianopia, two patients with right hemianopia, nine patients with left hemi-neglect and nine normal control subjects. Compared with measures in control subjects, the median fixation, and left- and rightmost fixations were shifted contralaterally in patients with hemianopia alone and ipsilaterally in patients with hemi-neglect. The fixation with the longest duration and the bisection point were also shifted contralaterally with hemianopia and ipsilaterally with hemi-neglect. However, the number of fixations and the spatial range spanned by fixations did not differ between the groups, showing that ocular exploration was not truncated in any group. Only some patients showed a previously reported directional search bias. Overall, there was no directional bias in saccadic number or amplitude. The distribution of fixations was most dense at the centre of the line in normal subjects, while hemianopic patients fixated most frequently at the ends of lines in their contralateral (blind) hemispace and at a central locus that was biased slightly contralaterally, as was their bisection judgement. This contralateral bias may reflect either an adaptive contralateral attentional gradient or a non-veridical spatial representation within the remaining normal hemifield. Hemi-neglect patients had a broad distribution of fixation peaks in the ipsilateral hemispace. Of two hemi-neglect patients with many fixations, one clustered fixations at a position right of centre, as if a normal fixation pattern was shifted rightward, while the other had two fixation peaks: one to the far right and the other near the centre of the line, reminiscent of the dual peaks of activity seen in some recent hemi-neglect models. These data reveal a heterogeneity in the routes by which right-biased judgements of spatial centre are reached by hemi-neglect patients.

Adult

Failure to awaken after general anesthesia due to cerebrovascular events.

Failure to awaken after general anesthesia is a rare complication that may be caused by residual drug effect, systemic abnormalities, or neurologic injury. Failure to awaken often is initially attributed to residual drug effect, potentially delaying correct diagnosis. Three cases of failure to awaken because of neurologic injury are reviewed. Differential diagnosis of failure to awaken is discussed, and the importance of distinguishing pathologic causes from residual anesthetic is stressed.

Aged

Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.

OBJECTIVE: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. METHODS: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. RESULTS: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. CONCLUSIONS: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.

Dementia

Risk of chronic arthropathy among women after rubella vaccination. Vaccine Safety Datalink Team.

CONTEXT: A review by the Institute of Medicine found a possible relationship between rubella vaccination and chronic arthritis among women. OBJECTIVE: To evaluate the risk of persistent joint and neurologic symptoms in rubella seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. DESIGN: Retrospective cohort study based on computerized laboratory data and medical record review. Records were reviewed for symptoms occurring within 2 years before and after the date of serological testing and to identify vaccinees. Possible cases were evaluated by a rheumatologist blinded to serological findings and vaccination status. SETTING: Large health maintenance organization in northern California. PATIENTS: Women aged 15 to 59 years serotested for rubella during 1990 with continuous health plan membership for 2 years before and after the date of their serological test. Seronegative women immunized within 1 year of serotesting (n=971) were defined as exposed. Primary comparison groups included all unvaccinated, seronegative women (n=924) and randomly selected seropositive, unvaccinated women (n=2421) matched to exposed subjects on serological test date and age (+/-3 years). MAIN OUTCOME MEASURES: Prevalence and incidence of chronic joint and neurologic symptoms during 1-year follow-up period stratified by age and serological findings, immunization, and postpartum status. RESULTS: No significantly increased risk was associated with receipt of rubella vaccine for any outcome except for prevalence of carpal tunnel syndrome in vaccinated women at least 30 years old compared with seropositive, unvaccinated women (2.9% vs 1.4%; P=.03). A total of 34 women had onset of conditions within the 1-year follow-up period; 9 of these were in the group of seronegative, immunized women, of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6 women, symptoms included transient arthritis or arthralgias (<6 weeks duration) in 4 women, arthralgia of indeterminate chronicity in 1 woman, and carpal tunnel syndrome in 1 woman. Postpartum women across all groups were less likely to be seen for nontraumatic arthropathies than nonpostpartum women (4.5% vs 7.2%, P=.08 in vaccinated women; 4.8% vs 8.1%, P=.09 in seronegative controls; and 4.8% vs 10.0%, P=.01 in seropositive controls). CONCLUSIONS: In this large retrospective cohort analysis there was no evidence of any increased risk of new onset chronic arthropathies or neurologic conditions in women receiving the RA 27/3 rubella vaccine. These data support the continued vaccination of rubella-susceptible women to reduce the risk of congenital rubella syndrome.

Adolescent

Regulated exocytosis and sequential construction of the extracellular matrix surrounding the sea urchin zygote.

After fertilization most eggs become surrounded by a complex extracellular matrix. This study examines those matrix assembly processes that are triggered by fertilization of the sea urchin egg. The study uses antibodies that identify five different storage compartments in the egg. These compartments release their protein contents in a highly regulated fashion to assemble and modify the extraembryonic layers. The exocytosis sequence begins with a fertilization wave that progresses from the site of sperm entry and elevates the fertilization envelope above a water-filled perivitelline space. The immediate surface of the zygote then becomes covered by a newly secreted hyaline layer. Prior to fertilization some of the antigens are localized to cortical granules. Others are found in "basal laminar vesicles" that are released in a wave beginning at about 30 sec, or roughly at the same time as cortical granule exocytosis. The remaining antigens are exocytosed with a rather precise timing, but with a delay of several to tens of minutes relative to the first wave of exocytosis. "Apical vesicles," so named because antigens from this class are preferentially exocytosed toward the apical cell surface of polarized cells, include antigens that are exocytosed beginning at about 5 min postfertilization. The fourth compartment, named "echinonectin vesicles" release echinonectin, a protein that is deposited to the inner side of the hyaline layer. Surface staining of echinonectin is first detected about 10-15 min following sperm contact. Finally, maternal cadherin, which is stored in yet a fifth distinct compartment, is not detected on the surface until at least 30 min following fertilization. The data are also consistent with the notion that the tightly regulated timing of exocytosis contributes to the ordered assembly of the hyaline layer and elevation of the fertilization envelope. Finally, two of the vesicle classes continue to exocytose after the cells become polarized. In polarized cells apical and basal laminar antigens are trafficked toward opposite sides of the same cell after passing through the same trans-Golgi network-like compartment.

Animals

Venous air embolism and selective denervation for torticollis.

Selective denervation to relieve severe torticollis requires surgery with the patient in the sitting position. Nerve stimulation is used to guide the procedure; therefore, patients undergo general anesthesia without muscle relaxation. Because of the risk of venous air embolism (VAE), monitoring with precordial Doppler and a multiorifice right atrial catheter has been recommended. To document the incidence of VAE and, thus, the effectiveness of monitors to detect it, consecutive patients who underwent selective peripheral denervation for torticollis between June 1993 and July 1994 were studied retrospectively, and those who underwent the procedure between August 1994 and February 1996 were studied prospectively. No VAE was documented in the retrospective group (n = 31). In the prospective group (n = 69), precordial Doppler detected one episode of VAE that lasted < 20 s and had no clinical sequelae. The incidence of complications from right atrial catheter insertion was 8% (carotid puncture, hematoma, inability to cannulate) but with no permanent sequelae. We conclude that VAE is infrequent and self-limited in association with selective denervation for torticollis. While monitoring with precordial Doppler for patients undergoing denervation for torticollis is indicated, the use of a right atrial catheter is of limited value because of associated complications and increased operating room time and cost.

Adult

Epidemiology of pertussis.

Throughout this century infants and young children have remained most susceptible to pertussis-related morbidity and mortality. In recent years infants younger than 6 months who are not old enough to have received three doses of the diphtheria-tetanus-pertussis vaccine and under-vaccinated preschool children have been at highest risk for pertussis-associated complications. Pertussis infection rates dropped dramatically after the whole cell pertussis vaccine came into widespread use, and an all-time low in reported cases in the United States was reached in 1976. Just as widespread immunization helped control the incidence of pertussis, it has probably been the primary factor in reducing pertussis-related mortality. Despite a stable or increasing vaccination rate in the United States since 1962, pertussis infection rates have been rising since the early 1980s. In 1993 the number of cases of pertussis reported represented an 82% increase over reported cases during the previous year and the highest incidence of pertussis since 1967. In 1993 pertussis became the most commonly reported vaccine-preventable disease among children in the United States younger than 5 years old. Growth of a susceptible adult population appears to be the primary factor contributing to the resurgence of pertussis in the United States; widespread immunization has reduced the potential for individuals to acquire exposure-induced immunity. It has been suggested that the majority of patients now infected with Bordetella pertussis are adults. Several studies have confirmed the importance of pertussis as the cause of persistent cough among teenagers and adults. As the diagnosis of pertussis goes unrecognized in these older patients and treatment is delayed or administered only partially, adolescents and adults have become an important source for transmission of B. pertussis infection to other household members, particularly infants and young children who are not adequately immunized.

Adolescent

Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project.

OBJECTIVE: To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population. STUDY DESIGN: A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case. RESULTS: The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses). CONCLUSION: Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.

Case-Control Studies

MMR2 immunization at 4 to 5 years and 10 to 12 years of age: a comparison of adverse clinical events after immunization in the Vaccine Safety Datalink project. The Vaccine Safety Datalink Team.

BACKGROUND: The Advisory Committee on Immunization Practices recommends a second dose of measles, mumps, and rubella vaccine (MMR2) at age 4 to 5 years of age, whereas the American Academy of Pediatrics suggests MMR2 immunization at age 11 to 12 years of age. Because there is little information on whether the rate of adverse reactions to MMR2 immunization varies among these two age groups, we took advantage of differing immunization policies at two large HMOs to compare the frequency of clinical events after, and possibly related to, MMR2 immunization. METHODS: Information was collected on clinical events plausibly associated to MMR immunization (seizures, pyrexia, malaise/fatigue, nervous/musculoskeletal symptoms, rash, edema, induration/ecchymoses, lymphadenopathy, thrombocytopenia, aseptic meningitis, and joint pain) in two cohorts. At three facilities at Northern California Kaiser (Oakland, CA), 8514 children received MMR2 immunization at age 4 to 6 years of age; at Group Health Cooperative (Seattle, WA) 18 036 children received MMR2 immunization at age 10 to 12 years of age. To account for age-related differences in health care use, within each HMO, clinical events in a 30-day period after immunization were compared with a 30-day period before vaccination. RESULTS: Children 10 to 12 years of age were 50% more likely to have a clinical event after MMR2 immunization than in the period before immunization (odds ratio, 1.45; 95% confidence interval: 1.00,2.10). Children 4 to 6 years of age were less likely to have a visit for an event after immunization compared with the period before immunization (odds ratio, 0.64; 95% confidence interval: 0.40,1.01). CONCLUSIONS: These results suggest that the risk for clinical events after MMR2 immunizations is greater in the 10- to 12-year age group.

Adolescent

Semantic satiation in healthy young and older adults.

In four experiments, semantic satiation was investigated in young and old adults. In the first two experiments, subjects were repeatedly presented a word (e.g., DOG) and then were presented a pair of words (e.g., DOG-CAT or DOG-CHAIR) for a relatedness decision. The results of both experiments indicated that for the young adults, the relatedness effect (the difference between response latency on related and unrelated trials) decreased as a function of the number of times the satiated word was repeated, whereas for the older adults, there was no evidence of a decrease in the relatedness effect across repetitions of the satiated word. In the third experiment, we investigated whether phonological codes are also susceptible to satiation. This experiment was similar to the first two experiments with the exception that subjects made rhyme decisions (SAME-CLAIM VS. SAME-DIME) instead of semantic relatedness decisions. The results of this experiment did not yield any evidence of satiation for either the young adults or the older adults. The final experiment eliminated a simple decrease in attentional alertness or fatigue account of the semantic satiation effects found in the first two experiments. In this experiment, the repeated word was always unrelated to the pair of words presented for the relatedness decision. The results of this experiment did not yield any evidence of semantic satiation for either the young or the older adults. The discussion focuses on the mechanisms underlying semantic satiation and the implications of age-related changes in these mechanisms.

Adolescent

Immunization tracking systems: experience of the CDC Vaccine Safety Datalink sites.

Recognizing the potential of large databases within HMOs for the evaluation of vaccine safety, the Centers for Disease Control and Prevention (CDC) funded the Vaccine Safety Datalink project, linking outcome and vaccine exposure information at Group Health Cooperative of Puget Sound, Kaiser Permanente Northwest, Kaiser Permanente Medical Care Program Northern California, and Southern California Kaiser Permanente. Integral to the Vaccine Safety Datalink Project was the development of Immunization Tracking Systems at each site; this report describes the effort required to establish these tracking systems. Essential requirements are the methods used to insure data quality and to educate system users. Tracking systems can be a valuable means for assessing vaccine coverage, evaluating barriers to complete immunization, and studying the effectiveness of interventions design to improve immunization coverage. Finally, we report on recent efforts to link HMO Immunization Tracking Systems with developing regional tracking systems.

California

Chemical shift assignments and secondary structure of the Grb2 SH2 domain by heteronuclear NMR spectroscopy.

The growth factor receptor-bound protein-2 (Grb-2) is an adaptor protein that mediates signal transduction pathways. Chemical shift assignments were obtained for the SH2 domain of Grb2 by heteronuclear NMR spectroscopy, employing the uniformly 13C-/15N-enriched protein as well as the protein containing selectively 15N-enriched amino acids. Using the Chemical Shift Index (CSI) method, the chemical shift indices of four nuclei, 1H alpha, 13C alpha, 13C beta and 13CO, were used to derive the secondary structure of the protein. Nuclear Overhauser enhancements (NOEs) were then employed to confirm the secondary structure. The CSI results were compared to the secondary structural elements predicted for the Grb2 SH2 domain from a sequence alignment [Lee et al. (1994) Structure, 2, 423-438]. The core structure of the SH2 domain contains an antiparallel beta-sheet and two alpha-helices. In general, the secondary structural elements determined from the CSI method agree well with those predicted from the sequence alignment.

Adaptor Proteins, Signal Transducing