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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 145 records · Page 8Linked to original sources
PubMed1999

Lymphocyte activation during acute simian/human immunodeficiency virus SHIV(89.6PD) infection in macaques.

Host-virus interactions control disease progression in human immunodeficiency virus-infected human beings and in nonhuman primates infected with simian or simian/human immunodeficiency viruses (SHIV). These interactions evolve rapidly during acute infection and are key to the mechanisms of viral persistence and AIDS. SHIV(89.6PD) infection in rhesus macaques can deplete CD4(+) T cells from the peripheral blood, spleen, and lymph nodes within 2 weeks after exposure and is a model for virulent, acute infection. Lymphocytes isolated from blood and tissues during the interval of acute SHIV(89.6PD) infection have lost the capacity to proliferate in response to phytohemagglutinin (PHA). T-cell unresponsiveness to mitogen occurred within 1 week after mucosal inoculation yet prior to massive CD4(+) T-cell depletion and extensive virus dissemination. The lack of mitogen response was due to apoptosis in vitro, and increased activation marker expression on circulating T cells in vivo coincided with the appearance of PHA-induced apoptosis in vitro. Inappropriately high immune stimulation associated with rapid loss of mature CD4(+) T cells suggested that activation-induced cell death is a mechanism for helper T-cell depletion in the brief period before widespread virus dissemination. Elevated levels of lymphocyte activation likely enhance SHIV(89.6PD) replication, thus increasing the loss of CD4(+) T cells and diminishing the levels of virus-specific immunity that remain after acute infection. The level of surviving immunity may dictate the capacity to control virus replication and disease progression. We describe this level of immune competence as the host set point to show its pivotal role in AIDS pathogenesis.

Animals↗
PubMed1999

Characterization of a novel simian immunodeficiency virus (SIV) from L'Hoest monkeys (Cercopithecus l'hoesti): implications for the origins of SIVmnd and other primate lentiviruses.

The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) appear to have originated by cross-species transmission of simian immunodeficiency virus (SIV) from asymptomatically infected African primates. Few of the SIVs characterized to date efficiently infect human primary lymphocytes. Interesting, two of the three identified to infect such cultures (SIVsm and SIVcpz) have appeared in human populations as genetically related HIVs. In the present study, we characterized a novel SIV isolate from an East African monkey of the Cercopithecus genus, the l'hoest monkey (C. l'hoesti), which we designated SIVlhoest. This SIV isolate efficiently infected both human and macaque lymphocytes and resulted in a persistent infection of macaques, characterized by high primary virus load and a progressive decline in circulating CD4 lymphocytes, consistent with progression to AIDS. Phylogenetic analyses showed that SIVlhoest is genetically distinct from other previously characterized primate lentiviruses but clusters in the same major lineage as SIV from mandrills (SIVmnd), a West African primate species. Given the geographic distance between the ranges of l'hoest monkeys and mandrills, this may indicate that SIVmnd arose through cross-species transmission from close relatives of l'hoest monkeys that are sympatric with mandrills. These observations lend support to the hypothesis that the primate lentiviruses originated and coevolved within monkeys of the Cercopithecus genus. Regarded in this light, lentivirus infections of primates not belonging to the Cercopithecus genus may have resulted from cross-species transmission in the not-too-distant past.

Amino Acid Sequence↗
PubMed1999

The neural circuitry involved in the reading of German words and pseudowords: A PET study.

Silent reading and reading aloud of German words and pseudowords were used in a PET study using (15O)butanol to examine the neural correlates of reading and of the phonological conversion of legal letter strings, with or without meaning. The results of 11 healthy, right-handed volunteers in the age range of 25 to 30 years showed activation of the lingual gyri during silent reading in comparison with viewing a fixation cross. Comparisons between the reading of words and pseudowords suggest the involvement of the middle temporal gyri in retrieving both the phonological and semantic code for words. The reading of pseudowords activates the left inferior frontal gyrus, including the ventral part of Broca's area, to a larger extent than the reading of words. This suggests that this area might be involved in the sublexical conversion of orthographic input strings into phonological output codes. (Pre)motor areas were found to be activated during both silent reading and reading aloud. On the basis of the obtained activation patterns, it is hypothesized that the articulation of high-frequency syllables requires the retrieval of their concomitant articulatory gestures from the SMA and that the articulation of low-frequency syllables recruits the left medial premotor cortex.

Adult↗
PubMed1999

Ultrastructure of phospholipid mixtures reconstituted with surfactant proteins B and D.

Surfactant protein (SP)-D is secreted from pulmonary alveolar type II cells into the alveolar lumen where potential interactions with surfactant lipids might occur. SP-D binds phosphatidylinositol (PI), a component of mammalian surfactants that is increased in a variety of injury states. We investigated the ultrastructure and properties of lipid protein recombinants that included SP-D, PI, and SP-B and compared these with recombinants based on SP-A. SP-D had a profound effect on the organization of phospholipid vesicles containing PI and SP-B, promoting the formation of atypical but highly ordered and surface-active tubular aggregates distinct in their dimensions and shape from the classical tubular myelin formed by SP-A. We also found both types of tubules in the secretions of type II cells maintained in long-term culture. These results suggest that surface atypical tubules can be formed with SP-D in vitro and in vivo.

Animals↗
PubMed1999

Anxiety disorders among African-American and white primary medical care patients.

The prevalence of current anxiety disorders and associated clinical patterns was examined in a sample of 125 African American and 120 white primary medical care patients between ages 18 and 64. Patients who indicated they had at least one mood or anxiety symptom in response to a screening questionnaire were interviewed to determine the presence of a DSM-IV anxiety, mood, or possible alcohol abuse disorder. Demographic data and data on mental- and physical-health-related functioning and health service utilization were also collected. The authors found no racial differences in the proportions of patients who met DSM-IV criteria for the disorders, nor in their symptom patterns, level of functional disability, or rates of health and mental health service utilization.

Adult↗
PubMed1999

Speech perception of young children using nucleus 22-channel or CLARION cochlear implants.

This study compares the auditory perceptual skill development of 23 congenitally deaf children who received the Nucleus 22-channel cochlear implant with the SPEAK speech coding strategy, and 20 children who received the CLARION Multi-Strategy Cochlear Implant with the Continuous Interleaved Sampler (CIS) speech coding strategy. All were under 5 years old at implantation. Preimplantation, there were no significant differences between the groups in age, length of hearing aid use, or communication mode. Auditory skills were assessed at 6 months and 12 months after implantation. Postimplantation, the mean scores on all speech perception tests were higher for the Clarion group. These differences were statistically significant for the pattern perception and monosyllable subtests of the Early Speech Perception battery at 6 months, and for the Glendonald Auditory Screening Procedure at 12 months. Multiple regression analysis revealed that device type accounted for the greatest variance in performance after 12 months of implant use. We conclude that children using the CIS strategy implemented in the Clarion implant may develop better auditory perceptual skills during the first year postimplantation than children using the SPEAK strategy with the Nucleus device.

Child, Preschool↗
PubMed1999

Speech production results in children implanted with the CLARION implant.

Speech production changes were examined in 24 profoundly hearing-impaired children following implantation with the CLARION Multi-Strategy Cochlear Implant. All study participants were implanted below the age of 6, and with 1 exception, the children were congenitally deaf, with little or no auditory experience prior to implantation. A within-subjects design was used in which the children's preoperative speech skills with hearing aids were compared to postoperative performance with the Clarion after 3 and 6 months of implant use. Production skills were evaluated with a measure designed specifically to assess hearing-impaired children's spontaneous use of early developing phonological patterns in words. The results revealed significant improvement over time in 8 of the 9 speech features examined. The greatest improvement occurred between the 3- and 6-month postoperative intervals, with more limited improvement evident between the preimplant and 3-month time periods. The results demonstrate that significant improvements occur in speech production skills in very young children with congenital deafness after they have used current implant technology for a relatively limited amount of time.

Child, Preschool↗
PubMed1999

Abdominal compartment syndrome: does intra-cystic pressure reflect actual intra-abdominal pressure? A prospective study in surgical patients.

BACKGROUND: Abdominal compartment syndrome is defined as the adverse physiologic effects of increased intra-abdominal pressure. Prolonged, unrelieved pressure may lead to respiratory compromise, renal impairment, cardiac failure, shock, and death. Abdominal compartment syndrome is diagnosed by measuring intra-cystic pressure as a reflection of intra-abdominal pressure. To examine the validity of the technique, we conducted a prospective study in surgical patients by directly measuring bladder and abdominal pressures simultaneously during laparoscopic cholecystectomy using a previously described technique. RESULTS: In the present model, the bladder had higher baseline pressures than did the abdomen. Measurements across the bladder wall were not identical, but had high positive correlation coefficient when evaluated on an individual basis. Global analysis of the data for all patients showed a weak correlation coefficient. CONCLUSION: In the present study model, intra-cystic pressure did not reflect actual intra-abdominal pressure. In spite of some limitations in the study design, we feel that further research is warranted to identify other possible variables that may play a role in the relationship between the urinary bladder and the abdominal cavity pressures, providing better means for diagnosis of abdominal compartment syndrome.

Journal Article↗
PubMed1999

LSD use and flashbacks in alcoholic patients.

Lysergic Acid Diethylamide (LSD) is a hallucinogenic drug that received considerable attention in the 1960's and early 1970's. It produced a wide variety of psychological phenomena, including a variety of perceptual disturbances which would manifest among some users long after the drug had left the system. These phenomena were commonly referred to as "flashbacks" and may have been largely responsible for the drug falling out of favor among recreational drug users. This report describes histories of LSD use among alcoholism treatment facility inpatients and reports specific characteristics of flashbacks and the degree of subjective distress experienced during flashbacks. Findings indicate a statistically significant relationship between number of doses and incidence of flashbacks.

Adolescent↗
PubMed1999

Pathogenesis of Newcastle disease in chickens experimentally infected with viruses of different virulence.

Groups of 4-week-old White Rock chickens were inoculated intraconjunctivally with nine isolates of Newcastle disease virus representing all pathotypes. Birds were monitored clinically and euthanatized sequentially, with collection of tissues for histopathologic examination and in situ hybridization using an anti-sense digoxigenin-labeled riboprobe corresponding to the sequence of the gene coding for the matrix protein. Disease was most severe with velogenic viscerotropic pathotypes and was characterized by acute systemic illness with extensive necrosis of lymphoid areas in the spleen and intestine. Viral nucleic acid was detected in multiple tissues but most prominently in macrophages associated with lymphoid tissue. Velogenic neurotropic isolates caused central nervous system disease despite minimal amounts of viral nucleic acid detected in neural tissue. Mesogenic and lentogenic pathotypes caused no overt disease; however, viral nucleic acid was present in myocardium and air sac epithelium following infection with these isolates. Compromise of air sac and myocardium may predispose mesogen- and lentogen-infected chickens to secondary infection and/or decreased meat and egg production.

Air Sacs↗
PubMed1999

Improved antibody responses to delayed pneumococcal vaccination in splenectomized rats.

Pneumococcal vaccination following splenectomy is widely used as prophylaxis against overwhelming postsplenectomy infection. There remains controversy however, over the timing of vaccination. We hypothesized that delaying vaccination would increase the antibody response. Pneumococcal vaccinations were given at designated intervals to rats that had undergone either a sham abdominal surgery or splenectomy. Sixty male Sprague-Dawley rats, 250 to 400 g, were divided into three groups for vaccination: I, 1 day postoperatively; II, 7 days postoperatively; and III, 28 days postsplenectomy/sham. Serum antibody levels were then determined by enzyme-linked immunosorbent assay at 5 and 21 days after vaccination. Immunoglobulin (Ig) levels after delayed vaccination at 1 week postoperatively and 1 month postoperatively were significantly higher than levels from rats vaccinated 1 day postoperatively. IgM levels after vaccinations 1 week and 1 month postoperatively were also significantly higher than levels of rats vaccinated 1 day postoperatively (P < 0.05 for both IgG and IgM). On the basis of these results, we conclude that delaying vaccination after splenectomy enhances antibody responses.

Animals↗
PubMed1999

Predicting Binding Regions within Disordered Proteins.

Disordered regions are sequences within proteins that fail to fold into a fixed tertiary structure and have been shown to be involved in a variety of biological functions. We recently applied neural network predictors of disorder developed from X-ray data to several protein sequences characterized as disordered by NMR (Garner, Cannon, Romero, Obradovic and Dunker, Genome Informatics, 9:201-213, 1998). A few predictions on the NMR-characterized disordered regions were noted to contain false negative indications of order that correlated with regions of function. These and additional examples are examined in more detail here. Overall, 8 of 9 functional segments in 5 disordered proteins were identified or partially identified by this approach. The functions of these regions appear to involve binding to DNA, RNA, and proteins. These regions are known to undergo disorder-to-order transitions upon binding. This apparent ability of the predictors to identify functional regions in disordered proteins could be due to the existence of different flavors, or sub-classes of disorder, originating from the sequence of the disordered regions and perhaps owing to local inclinations toward order. These different flavors may be a characteristic that could be used to identify binding regions within proteins that are difficult to characterize structurally.

Journal Article↗
PubMed1998

High-level expression of secreted glycoproteins in transformed lepidopteran insect cells using a novel expression vector.

An expression cassette for continuous high-level expression of secreted glycoproteins by transformed lepidopteran insect cells has been developed as an alternative to baculovirus and mammalian cell expression systems. The expression cassette utilizes the promoter of the silkmoth cytoplasmic actin gene to drive expression from foreign gene sequences, and also contains the ie-1 transactivator gene and the HR3 enhancer region of BmNPV to stimulate gene expression. Using an antibiotic-resistance selection scheme, we have cloned a Bm5 (silkmoth) cell line overexpressing the secreted glycoprotein juvenile hormone esterase (JHE-KK) at levels of 190 mg/L in batch suspension cultures. A baculovirus (AcNPV) expressing the same gene under the control of the p10 promoter of AcNPV produced only 4 mg/L active JHE in static cultures of infected Sf21 cells. A cloned Bm5 cell line overexpressing a soluble isoform of the alpha-subunit of the granulocyte-macrophage colony stimulating factor receptor (solGMRalpha) was also generated and produced five times more solGMRalpha in static cultures than a cloned BHK cell line obtained by transformation with a recombinant expression cassette utilizing the human cytomegalovirus (CMV) enhancer-promoter system. Finally, we show that recombinant protein expression levels in transformed Bm5 cells remain high in serum-free media, that expression is stable even in the absence of antibiotic selection, and that lepidopteran cells other than Bm5 may be used equally efficiently with this new expression cassette for producing recombinant proteins.

Animals↗