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Biomedical subjects

E Cook

Publications and source records attributed to E Cook.

At least 19 recordsLinked to original sources
PubMed2006

Phagocytic efficacy of macrophage-like cells as a function of cell cycle and Fcgamma receptors (FcgammaR) and complement receptor (CR)3 expression.

Previous studies have shown that the efficiency of phagocytosis is a function of cell cycle and that phagocytosis promotes cell cycle progression. Because phagocytosis is dependent on cellular receptors we hypothesized that Fcgamma receptors (FcgammaR) and complement receptors (CR) expression varied with cell cycle. Consequently, we used centrifugal elutriation of macrophage-like cells, fluorescence activated cell sorting analysis and receptor staining to investigate expression of FcgammaR and CR as a function of cell cycle. We confirmed that FcgammaR expression on macrophage-like cells increased as the cells progressed from G1 to G2 phases. Moreover, CR3 expression varied as a function of cell cycle in a manner similar to FcgammaR. Correlation of receptor expression with cell size showed that FcgammaR and CR3 expression on macrophages was determined largely by cell size enlargement during the cell cycle. The efficacy of both Fc- and complement-mediated phagocytosis of live Cryptococcus neoformans (Cn) showed a biphasic pattern with the efficacy of phagocytosis decreasing when the cells approached the G1-S interface, which paralleled the changes in receptor surface expression when cells exited G1 phase. Live Cn cells were significantly more resistant to phagocytosis than dead cells at all stages of macrophage-like cell cycle. In contrast to live cells, the efficacy of phagocytosis of dead Cn decreased as surface receptor expression increased. Hence, the efficacy of phagocytosis in this system as function of cell cycle is not related to phagocytic receptor expression.

Animals↗
PubMed2006

Phenotypic switching in a Cryptococcus neoformans variety gattii strain is associated with changes in virulence and promotes dissemination to the central nervous system.

This is the first report of a Cryptococcus neoformans var. gattii strain (serotype B) that switches reversibly between its parent mucoid (NP1-MC) colony morphology and a smooth (NP1-SM) colony morphology. Similar to C. neoformans var. grubii and C. neoformans var. neoformans strains, the switch is associated with changes in the polysaccharide capsule and virulence in animal models. In murine infection models, NP1-MC is significantly more virulent than NP1-SM (P < 0.021). In contrast to the serotype A and D strains, the serotype B strain switches in vivo reversibly between both colony morphologies. The polysaccharide of NP1-MC exhibits a thicker capsule, and thus NP1-MC exhibits enhanced intracellular survival in macrophages. Consistent with this finding, switching to the mucoid variant is observed in pulmonary infection with NP1-SM. In contrast, the thin polysaccharide capsule of NP1-SM permits better crossing of the blood-brain barrier. In this regard, only smooth colonies were grown from brain homogenates of NP1-MC-infected mice. Our findings have important implications for the pathogenesis of cryptococcosis and suggest that phenotypic switching affects host-pathogen interactions in the local microenvironment. This altered interaction then selects for specific colony variants to arise in a pathogen population.

Animals↗
PubMed2001

An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans.

alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype.

Black People↗
PubMed2000

[Hereditary hearing impairment. Mutation analysis of connexin 26 and POU3F4 genes in Icelanders with nonsyndromic hearing impairment.].

AIMS: Mutations in the connexin 26 (Cx26) gene have recently been shown to be a major cause of hereditary nonsyndromic sensorineural hearing impairment in Caucasians. Studies indicate that approximately 10-30% of all childhood deafness are due to Cx26 mutations and the most frequently observed mutation is Cx26 35delG. Mutations in the POU3F4 are the most common cause of X-linked nonsyndromic hereditary hearing impairment. The aim of our study was to determine presence and type of Cx26 and POU3F4 mutations in an Icelandic cohort with nonsyndromic hearing impairment. MATERIAL AND METHODS: All 15 individuals participating in the study, fulfilled the criteria of severe congenital nonsyndromic hearing impairment of unknown cause and the hearing loss was documented by audiologic testing in a clinical facility. Eleven had a family history and four were sporadic cases. All exons of the Cx26 and POU3F4 genes were amplified using PCR and six pairs of primers. The amplified DNA fragments were screened for sequence variations using enzymatic mutation detection and the nucleotide sequence of fragments showing signs of variation was determined. RESULTS AND CONCLUSIONS: Using the methods described above four distinct sequence variations were detected in the Cx26 gene. The 35delG allele causing hereditary recessive hearing impairment was identified in one homozygous and one heterozygous individual. The heterozygous 35delG individual was also shown to carry the recessive allele 358-360delGAG (E). A missense mutation, 101Teth C (M34T), supposed to cause autosomal dominant form of hearing impairment with variable penetrance, was detected in one heterozygous individual. A novel sequence variation without known clinical significance, -63Teth G, was found in the 5'-noncoding sequence in one control sample. No mutations were detected in the POU3F4 gene.

English Abstract↗
PubMed1999

Long-term (4 year) efficacy and tolerability of doxazosin for the treatment of concurrent benign prostatic hyperplasia and hypertension.

BACKGROUND: The alpha1-adrenoceptor antagonist doxazosin has proved successful in treating patients with concurrent benign prostatic hyperplasia (BPH) and hypertension in short-term studies. However, both conditions are chronic and may worsen over time. The aim of this study was, therefore, to examine the tolerability and efficacy of doxazosin in the long-term treatment of concurrent BPH and hypertension. METHODS: This study was a longitudinal extension of earlier double-blind trials. Patients were enrolled into the study on a rolling basis. From a total of 178 BPH patients with hypertension enrolled into the study, 28 had reached 48 months of open-label treatment with doxazosin at the time of the final data cutoff. RESULTS: Treatment with doxazosin resulted in sustained benefits for BPH patients over the whole study period, with significant improvements in the severity (12.2%, P < 0.001) and bothersomeness (13.2%, P < 0.001) of BPH symptoms, and in the maximum urinary flow rate (26.6%, P < 0.05) from baseline to the end of the 4-year period. There was also a significant and sustained reduction in diastolic blood pressure. The efficacy of doxazosin treatment for both BPH and hypertension was maintained over the 4-year period, despite the tendency of these conditions to worsen with time. Comparison of adverse events in patients with long- and short-term hypertension and BPH demonstrates that the safety of doxazosin is not altered during long-term therapy. CONCLUSIONS: This study demonstrates that doxazosin appears to be well tolerated and efficacious in the long-term management of concurrent BPH and hypertension.

Adrenergic alpha-Antagonists↗
PubMed1999

Summary of the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults with Autism and other Pervasive Developmental Disorders. American Academy of Child and Adolescent Psychiatry.

This summary provides an overview of the assessment and treatment recommendations contained in the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults With Autism and Other Pervasive Developmental Disorders. The parameters were written to aid clinicians in the assessment and treatment of children and adolescents with autism and other pervasive developmental disorders. Autism and the related pervasive developmental disorders are characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills, which arise in the first years of life. Although frequently associated with mental retardation, these conditions are distinctive in terms of their course and treatment. These conditions have a wide range of syndrome expression, and their management presents particular challenges for clinicians. Individuals with these conditions can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with these conditions often require the care of multiple providers; coordination of services and advocacy for individuals and their families is important. Early, sustained intervention is indicated, as is the use of various treatment modalities (e.g., pharmacotherapy, special education, speech/communication therapy, and behavior modification.

Adolescent↗
PubMed1999

Hip and ankle range of motion and hip muscle strength in young female ballet dancers and controls.

OBJECTIVES: To compare the hip and ankle range of motion and hip muscle strength in 8-11 year old novice female ballet dancers and controls. METHODS: Subjects were 77 dancers and 49 controls (mean (SD) age 9.6 (0.8) and 9.6 (0.7) years respectively). Supine right active hip external rotation (ER) and internal rotation (IR) were measured using an inclinometer. A turnout protractor was used to assess standing active turnout range. The measure of ER achieved from below the hip during turnout (non-hip ER) was calculated by subtracting hip ER range from turnout range, and hip ER:IR was derived by dividing ER range by IR range. Range of right weight bearing ankle dorsiflexion was measured in a standing lunge using two methods: the distance from the foot to the wall (in centimetres) and the angle of the shank to the vertical via an inclinometer (in degrees). Right calf muscle range was measured in weight bearing using an inclinometer. A manual muscle tester was used to assess right isometric hip flexor, internal rotator, external rotator, abductor, and adductor strength. RESULTS: Dancers had less ER (p<0.05) and IR (p<0.01) range than controls but greater ER:IR (p<0.01). Although there was no difference in turnout between groups, the dancers had greater non-hip ER. Dancers had greater range of ankle dorsiflexion than controls, measured in both centimetres (p<0.01) and degrees (p<0.05), but similar calf muscle range. After controlling for body weight, controls had stronger hip muscles than dancers except for hip abductor strength which was similar. Regression analyses disclosed a moderate relation between turnout and hip ER (r = 0.40). There were no significant correlations between range of motion and training years and weekly training hours. CONCLUSIONS: Longitudinal follow up will assist in determining whether or not hip and ankle range in young dancers is genetically fixed and unable to be improved with further balletic training.

Ankle Joint↗
PubMed1998

Variants in the alpha2A AR adrenergic receptor gene in psychiatric patients.

In various studies of psychiatric patients, alterations in adrenergic receptor (AR) expression or function have been suggested. Herein, the alpha2A AR gene was screened in 206 patients with schizophrenia, attention deficit hyperactivity disorder (ADHD), autism, alcohol dependence, or cocaine dependence. The entire coding region was examined for single base pair changes, using restriction endonuclease fingerprinting (REF), a screening method that can detect virtually 100% of mutations in 2-kb DNA segments. In the approximately 600 kb of screened sequence, six novel nucleotide changes were identified. The changes resulted in four missense changes (A25G, N251K, R368L, and K370N), and a sequence in the 3' untranslated region. In addition, a silent change (G363G) was found at high frequency in Asians and Native Americans. Of the four missense changes, two found in patients with alcohol/drug dependence occur in highly conserved amino acids, suggesting that these are of likely functional significance. As the alpha2A ARs are widely distributed both pre- and postsynaptically, and as many pharmacological agents with multiple effects target these receptors, the novel missense changes described herein may be candidates for involvement in alcohol/drug dependence, in other clinical disorders or traits, or in differential response to pharmacotherapy.

Animals↗
PubMed1998

Interclass drug effects and changes in regional brain glucose metabolism.

We have developed an innovative use of positron emission tomography that has broad applications in drug development. Based on the FDG method (Phelps et al. 1979) for assessing glucose metabolism, the method requires rigorous experimental control of subjects and standardized data acquisition and analyses. In localizing net metabolic drug effects, measured in quantifiable terms, we have derived a new conceptual basis for examining pharmacologically induced changes in brain function and a new model for predicting drug effectiveness. We applied this method to studies of drugs in three different classes and noted marked differences in distribution and magnitude of metabolic effects. This approach presents an opportunity to selectively examine measurements of the glucose metabolic changes induced by specific pharmacological probes on intermediary metabolic pathways, including regulation of gene expression and the metabolic consequences of neurotransmitter alteration in pharmacologically targeted neuronal systems. Development of these methods provides new approaches for studying neurobiological mechanisms, and can contribute significantly to the process of new drug development.

Brain↗
PubMed1998

A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix.

OBJECTIVE: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). METHODS: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using chi2 statistics, logistic regression analysis, and the Cox proportional hazards model. RESULTS: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6-37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). CONCLUSION: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.

Adolescent↗
PubMed1997

What the licensed practical/vocational nurse should know about pharmacological therapy for AIDS sufferers.

Illnesses can rob persons of their dignity and pride. Nowhere has this been more apparent than with people who suffer from Acquired Immunodeficiency Syndrome (AIDS). Because AIDS is a progressive and debilitating disease whose fatal outcome seems hopeless, it is often hard for the sufferer to maintain a sense of human worth. Add to that a prevailing public prejudice that keeps the individual at an arm's length from the support of the community, and a grim picture is given. However, unknown to lay persons and professionals alike, this bleak picture is no longer so grim. With the advent of drug combination therapy treatments (taking several commonly prescribed anti-HIV drugs at the same time), new hope has been given. The purpose of this paper is to describe for the licensed practical/vocational nurse the different and various drugs used for therapy and their effects on the AIDS population. Particular emphasis is placed on the modern combination therapy programs that are being utilized. Current knowledge of AIDS treatment can enable the licensed practical/vocational nurse to increase a client's feelings of hope, self worth, and dignity.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Isolation and purification of functional bovine lung mast cells (BLMCs).

Purified pulmonary mast cells were obtained from bovine lung using a combination of enzymatic digestion of tissue, density gradient centrifugation using Percoll, and centrifugal elutriation. In the initial procedure, lung tissue was enzymatically digested with collagenase, hyaluronidase, protease and elastase in three 30 min incubations at 37 degrees C. Monodispersed cell suspensions contained between 2 and 6% mast cells. Further purification of these mast cells by Percoll gradients and elutriation consistently yielded mast cells of > 90% purity. These cells were morphologically intact, viable and functional, as determined by histamine release evoked by secretagogue challenge. Incubation of BLMCs with Pasteurella haemolytica A1 culture supernate containing leucotoxin (LCT) alone, resulted in increased histamine release compared to controls. LCT also potentiated calcium ionophore (CaI)-induced histamine release from BLMCs.

Animals↗
PubMed1996

Asperger syndrome associated with Steinert's myotonic dystrophy.

Steinert's myotonic dystrophy was diagnosed in a 10-year-old girl with Asperger syndrome. This form of myotonic dystrophy is one of a growing list of genetic diseases that can be diagnosed by analysis of a gene with trinucleotide repeats that may expand. The patient has the largest such expansion known within her pedigree. She has many of the psychological deficits that have been reported in adult-onset myotonic dystrophy. This is the first known report of an association of this disorder with Asperger syndrome. Recently Moebius syndrome has been found in association with disorders of the autistic spectrum; physicians practicing developmental medicine should now also consider Steinert's myotonic dystrophy when evaluating children with facial diplegia.

Child↗
PubMed1996

Vulvar intraepithelial neoplasia and vulvar cancer.

Vulvar carcinoma is a rare cancer. It is more frequent among older women, but the incidence is increasing among younger women. The incidence of VIN may be rising in younger women as well. Different factors have been associated with an increased risk for vulvar cancer (HPV, age, smoking, education, diet, genital infections, infrequent pelvic examinations, socioeconomic status, immunosuppressive diseases); however, conclusive epidemiologic evidence is lacking. More studies with larger sample sizes are needed to understand more fully the role of these and other as yet unknown factors in the etiology of vulvar cancer. At present, studies of the molecular risk assessment for VIN and vulvar cancer focus mostly on HPV. The treatments for VIN are painful, and the disease has a high risk of recurrence. The treatments for vulvar cancers are morbid, even though radical vulvectomy is being replaced by the less morbid wide local excision and unilateral groin lymph node dissection. Therefore, VIN and vulvar cancer benefit from early detection, and their morbidity is decreased by early treatment. Screening should be performed by the primary care practitioner and should focus on women with HPV; women who smoke; and women who have other preinvasive disease of the cervix, vagina, or perianal area. Chemoprevention and an HPV vaccine may eventually be promising, but no studies have yet been performed. Patients should be educated about performing vulvar self-examination stopping smoking, being persistent about insisting on a biopsy if symptoms persist, and avoiding exposure to HPV.

Biomarkers, Tumor↗