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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 325 records · Page 18Linked to original sources

In vitro modulation of platelet sodium, potassium adenosine triphosphatase enzyme activity by antiallergy drugs.

Previous studies have documented decreased levels of platelet sodium, potassium adenosine triphosphatase (Na+, K+ ATPase) enzyme activity in allergic subjects. The purpose of this study was to determine the effect of several drugs used to treat allergy and asthma on platelet Na+,K+ ATPase activity. Platelets from five allergic and five nonallergic subjects were incubated at 37 degrees C for 30 minutes with cortisol (1.0 to 3.6 micrograms/ml), theophylline (10 to 40 micrograms/ml), cromolyn (0.5 to 2.0 micrograms/ml), albuterol (3 to 24 ng/ml), chlorpheniramine (2.5 to 20 micrograms/ml), or diluent. The platelets were then rinsed, sonicated, serially centrifuged, and assayed for Na+,K+ ATPase activity nmol/min x micrograms protein by spectrophotometry. Mean activity (+/- 1 SEM) for the diluent incubation was 5.55 +/- 1.27 nmol/min x micrograms protein and 0.91 +/- 0.32 nmol/min x micrograms protein for the nonallergic and allergic subjects, respectively. The enzyme activity of allergic platelets (same units as above) increased after incubation with the following drugs: cortisol, 6.07 +/- 1.75 (p < 0.025) at 1.0 micrograms/ml, 7.55 +/- 1.36 (p < 0.005) at 1.4 micrograms/ml, and 5.95 +/- 0.91 (p < 0.025) at 1.8 micrograms/ml; cromolyn, 5.79 +/- 1.68 (p < 0.050) at 1.0 micrograms/ml; and albuterol, 4.43 +/- 1.61 (p < 0.05) at 12 ng/ml. Theophylline and chlorpheniramine did not have a similar effect on Na+,K+ ATPase activity. These data show that some of the drugs commonly used to treat allergic patients, especially anti-inflammatory agents, can increase the depressed platelet levels of Na+,K+ ATPase activity observed in allergic subjects. Modulation of Na+,K+ ATPase is a possible mechanism of action for these drugs in vivo.

Adult↗

Serratia marcescens endocarditis in a horse.

Serratia marcescens was the causative agent of bacterial endocarditis in a 2-year-old Arabian stallion. The horse was treated with broad-spectrum antibiotics for 1 month. The horse died several months after treatment was discontinued. To our knowledge, Serratia marcescens has not been reported as the cause of bacterial endocarditis in horses; however, multiple cases of bacterial endocarditis attributable to Serratia marcescens have been documented in human beings. The bacteria is most commonly isolated in immune-compromised patients.

Animals↗

A glycine250--> aspartate substitution in the alpha-subunit of hexosaminidase A causes juvenile-onset Tay-Sachs disease in a Lebanese-Canadian family.

The mutation causing juvenile Tay-Sachs disease (TSD) in two sibs of Lebanese-Maronite origin is described. An mRNA-containing extract of cultured fibroblasts obtained from one of the probands was used as a template to amplify the coding sequence of the hexosaminidase A (Hex A) alpha-subunit. Sequencing of amplified cDNA fragments revealed a single alteration, guanine to adenine at nt 749 creating a G250D mutation. The mutation introduces a new recognition site for the restriction enzyme Eco RV, permitting identification of heterozygotes for this allele following PCR amplification and Eco RV digestion of exon 7 sequences from genomic DNA templates. In order to test the effect of this substitution, an in vitro mutagenized cDNA construct was introduced into a mammalian expression vector and transfected into monkey Cos-1 cells separately or along with a beta-cDNA expression vector. When the mutant alpha-cDNA was the only gene introduced into COS cells no enzymatic activity above endogenous COS cell activity was detected. Cotransfection of normal alpha-cDNA and beta-cDNA followed by immunoprecipitation of human Hex A resulted in 20-fold increase in the ratio between positive and negative (mock transfection) control values. This allowed the detection of some residual activity (12% of the positive control) when the mutant alpha-cDNA replaced its wild-type counterpart. The predicted protein environment in which the mutation occurs is compared to that of the adult-onset Tay-Sachs disease mutation caused by a Gly269-->Ser substitution in exon 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

An unidentified Toxoplasma-like tissue cyst-forming coccidium in a cat (Felis catus).

An unidentified coccidium was found in the brain and the heart of a 6-year-old female cat. Tissue cysts measured 40-130 x 40-112 microns and contained hundreds of bradyzoites measuring 4.2-5.2 x 1.2-1.8 microns. The cyst wall was 0.26-0.53 microns thick. Tissue cysts reacted positively with anti-Toxoplasma gondii serum but not with anti-Neospora caninum serum in an immunohistochemical test. Ultrastructurally, the cyst was aseptate and contained banana-shaped bradyzoites. Micronemes and rhoptries in bradyzoites were unlike those found in T. gondii bradyzoites. In the unidentified coccidium, the micronemes were arranged in rows and the rhoptries extended from the anterior tip to the posterior end.

Animals↗

Age-associated changes and sex differences in urinary 6-sulphatoxymelatonin circadian rhythm in the rat.

The circadian rhythm of 6-sulphatoxymelatonin (aMT6s) excretion has been determined in male and female rats at 3 weeks and at 2, 8, 14 and 20 months of age. All animals have a pronounced circadian pattern of aMT6s excretion under a 12 hour dark: 12 hour light cycle. A significant increase in aMT6s excretion is observed from 3 weeks to 14 months followed by a decrease at 20 months. There is a highly significant correlation between aMT6s excretion and body weight (r = 0.73 for female rats and r = 0.74 for male rats; p values are all less than 0.001). Thus, a decrease in aMT6s excretion associated with increasing age occurs when body weight is taken into consideration. aMT6s excretion is higher in males at 3 weeks and at 2 and 8 months of ages. Urinary testosterone in male rats and estradiol in female rats increase from 3 weeks to 8 months and decrease at older ages. These data suggest that increase of body weight from 3 weeks to 14 months is an important factor responsible for the age-related alteration. The sex differences in aMT6s excretion in younger rats may be associated with their sex hormonal milieu.

Age Factors↗

Do different fluorochrome labels give equivalent histomorphometric information?

Substances that bind calcium are given to determine where and how fast bone is forming. Several vital dyes are used (tetracycline, calcein, alizarin, xylenol), but it is not known whether the histomorphometric results they provide are equivalent. This work tests whether different fluorochrome labels give the same results when they are quantitatively measured. Twelve-week-old rats (n = 58) were divided into six groups and given double labels IP of calcein, tetracycline HCl, alizarin complexone, or xylenol using a 1-7-1 scheme. Two other groups received either calcein followed by tetracycline, or tetracycline followed by calcein. Our results show that (a) tetracycline hydrochloride leads to a significant underestimation of mineralizing surface when given as the second label, probably because of its weak fluorescence; (b) there were no differences among any of the non-tetracycline labels for any of the histomorphometric measurements; (c) there was no evidence of osteoblast suppression with any label; and (d) there was no evidence that tetracycline caused increased osteoblast resting periods.

Animals↗

Engaging patients with alcohol problems in treatment: the first consultation.

This paper considers the impact of the first consultation at a specialist alcohol clinic on patients' perceptions of their drink problem and on their expectations of help from three sources: an alcohol clinic, general practitioners and Alcoholics Anonymous. At intake, males had higher expectations than females of help from the alcohol clinic while people in manual occupations and those in the 'less heavy' drinking category had higher expectations of general practitioner help than other patients. Change was found to occur during the first clinic consultation so that by the end of the session patients had raised their rating of problem severity and their expectations of help from the three sources examined. Overall, patient perceptions of the clinic assessment session were positive. The study highlights the importance of obtaining a full understanding of the process of engagement in treatment and indicates the potential of a clinical assessment to effect change in patient attitudes.

Adult↗

The use of services for alcohol problems: general practitioner and specialist alcohol clinic.

A sample of 40 patients referred to a specialist alcohol clinic were given a full assessment by a clinician and then randomly allocated to one of two groups. The first group received continuing care from the clinic. The second group were returned to the management of their general practitioners who were offered specialist support in caring for their patients. Patients and general practitioners were followed-up 6 months after the clinic assessment. This paper reports on the uptake of clinic and general practice services by patients and examines the possible factors associated with continuing attendance, including patient attributes, service activity, patients' self-assessments of their drink problem and their expectations of help from services. Qualitative data is used to examine patients' perceptions and experiences of clinic and general practice-based care for drinking problems. The findings highlight some of the difficulties reported by patients in receiving help for their problems particularly from general practitioners.

Adult↗

DNA probe technology: implications for service planning in Britain.

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.

Adolescent↗

Persistent diarrhea associated with AIDS.

Chronic diarrhea and wasting are very common manifestations of AIDS in adults in developing countries. Etiologic studies show that protozoa (including Cryptosporidium parvum, Isospora belli, and Enterocytozoon bieniusi) and Mycobacterium avium-intracellulara are the most frequently identified pathogens. Limited data in children suggest that common enteric pathogens are equally as likely in HIV+ and HIV- babies. Preliminary analysis of an ongoing longitudinal study of 469 babies born to mothers with known HIV serostatus in Kinshasa, Zaire, reveals progression of acute to persistent diarrhea is six times greater in HIV+ compared to HIV- babies, and 3.5 times greater in HIV- babies born of HIV+ mothers in comparison to HIV- babies with HIV- mothers. HIV+ babies were also at greater risk than HIV- babies to have recurrent episodes of diarrhea (RR = 2.3). Fifty percent of the deaths were due to acute or persistent diarrhea, and were strongly associated with HIV infection. Efforts to improve child survival in AIDS infected populations will need to address HIV infections in both mothers and infants.

Acquired Immunodeficiency Syndrome↗

Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire.

Because little was known about the prevalence of neurological complications of human immunodeficiency virus type 1 (HIV-1) infection in Africa, we conducted a cross-sectional study among consecutive admissions to the internal medicine wards of Mama Yemo Hospital in Kinshasa, Zaire. Of the 196 patients studied, 104 (53%) were HIV-1 seropositive, of whom 50 (48%) had stage 3 and 49 (47%) had stage 4 HIV-1 infection according to the provisional WHO staging criteria for HIV infection. Neuropsychiatric abnormalities were present in 43 (41%) of 104 HIV-1-seropositive patients. Of the HIV-1-seropositive patients, 9 (8.7%; 95% confidence interval, 4-16%) were diagnosed as having possible HIV-1-associated dementia complex, 1 (1%) as having possible HIV-1 myelopathy, and 3 (2.7%) as having possible HIV-1-associated minor cognitive/motor disorder. Definitive diagnoses could not be made because there were no facilities for neuroimaging and neuropathology. Meningitis caused by cryptococcus was diagnosed in six (5.6%) and by Mycobacterium avium in two (2%) of the HIV-1 seropositive patients. Acute onset hemiplegia, believed to be due to stroke, was present in four (4%) of the HIV-1-seropositive patients. The prevalence of other central nervous system opportunistic infections and mass lesions, especially toxoplasmic encephalitis, could not be assessed. In this population of Zairian inpatients, the prevalence of neurological complications of HIV-1 infection was similar to that observed in industrialized countries among patients with advanced HIV disease.

Adult↗

Scombroid fish poisoning. Underreporting and prevention among noncommercial recreational fishers.

Food-borne diseases, including those caused by seafood products, are common and greatly underreported sources of morbidity. In this article we review the epidemiology of scombroid fish poisoning and its possible relationship to the noncommercial and recreational catch and sale of fish. More than 20% of all fish sold in the United States is caught by sport fishers, and outbreaks of scombroid fish poisoning have involved improperly handled fish from private catches. We report an outbreak of scombroid fish poisoning among recreational fishers in California. The unregulated sale of recreationally caught fish for consumption and the prevention of scombrotoxism are discussed from the perspectives of public health agencies, clinicians, and the fishing public. Scientific and policy issues that require further attention are high-lighted.

Adult↗

Diagnosis of HIV infection with instrument-free assays as an alternative to the ELISA and western blot testing strategy: an evaluation in Central Africa.

The efficiency of an alternative instrument-free testing strategy was evaluated using a membrane-based rapid screening assay (HIVCHEK and its new version HIVCHEK1 + 2) in serial combination with a particle agglutination assay (SERODIA-HIV). Among 1,054 Zairian individuals at high risk of HIV infection, 573 were Western blot-positive for HIV-1 (54.4%) and none were Western blot-positive for HIV-2. In this group, the sensitivities of the serial combination HIVCHEK plus SERODIA-HIV and HIVCHEK1 + 2 plus SERODIA-HIV were 98.1 and 98.2%, respectively, and the specificities were 99.6 and 99.5% compared with HIV-1 Western blot. The positive predictive values were 99.6% for HIVCHEK plus SERODIA-HIV and 99.5% for HIVCHEK1 + 2 plus SERODIA-HIV; the negative predictive values were 97.8 and 97.9%, respectively. Among 1,495 pregnant women, 90 were Western blot-positive for HIV-1 (6.0%), and 54 of 1,510 blood donors were HIV-1 Western blot-positive (3.6%). None were positive for HIV-2. The sensitivities of HIVCHEK plus SERODIA-HIV and HIVCHEK1 + 2 plus SERODIA-HIV in these groups were 98.6 and 99.3%, respectively, and the specificities were 99.8 and 99.7%. The positive and negative predictive values of HIVCHEK plus SERODIA-HIV were 96.6 and 99.9%, respectively, and they were 94.1 and 99.9%, respectively, for HIVCHEK1 + 2 plus SERODIA-HIV. These instrument-free testing strategies are efficient alternatives for serodiagnosis of HIV-1 infection, although their cost should be further reduced.

AIDS Serodiagnosis↗

Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells.

To determine whether mononuclear cell secretory products contribute to the changes in bone turnover that characterize the development of postmenopausal osteoporosis, we evaluated the effects of oophorectomy and subsequent estrogen replacement on the spontaneous secretion of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and on the phytohemagglutinin A-induced secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) from peripheral blood mononuclear cells. In 15 healthy premenopausal women who underwent oophorectomy, increases in GM-CSF activity were observed as early as 1 week after surgery, whereas elevations in IL-1 and TNF-alpha and in hydroxyproline/creatinine and calcium/creatinine ratios, two urinary indices of bone resorption, were detectable 2 weeks after the surgical procedure. Six of the oophorectomized women received no estrogen therapy after surgery and in these subjects hydroxyproline/creatinine and calcium/creatinine ratios plateaued 6 weeks postoperatively, and all three cytokines reached the highest levels 8 weeks after oophorectomy, when the study ended. In the remaining 9 women, who were started on estrogen replacement therapy 4 weeks after oophorectomy, decreases in the indices of bone resorption paralleled decreases in the secretion of the cytokines, with lower levels detected after 2 weeks of therapy. In the women who did not receive estrogen therapy, circulating osteocalcin, a marker of bone formation, increased beyond preoperative levels 8 weeks after oophorectomy, whereas in the estrogen-treated subjects osteocalcin remained unchanged in the entire study period. In 9 female controls who underwent simple hysterectomy, cytokine release and biochemical indices of bone turnover did not change after surgery. These data indicate that changes in estrogen status in vivo are associated with the secretion of mononuclear cell immune factors in vitro and suggest that alterations in the local production of bone-acting cytokines may underlie changes in bone turnover caused by surgically induced menopause and estrogen replacement.

Adult↗