Search PubMed⌕ Search

Biomedical subjects

A L Manson

Publications and source records attributed to A L Manson.

At least 19 recordsLinked to original sources
PubMed1999

In vivo analysis of DNase I hypersensitive sites in the human CFTR gene.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator gene (CFTR) shows a complex pattern of expression. The regulatory elements conferring tissue-specific and temporal regulation are thought to lie mainly outside the promoter region. Previously, we identified DNase I hypersensitive sites (DHS) that may contain regulatory elements associated with the CFTR gene at -79.5 and at -20.5 kb with respect to the ATG and at 10 kb into the first intron. MATERIALS AND METHODS: In order to evaluate these regulatory elements in vivo we examined these DHS in a human CFTR gene that was introduced on a yeast artificial chromosome (YAC) into transgenic mice. The 310 kb human CFTR YAC was shown to restore the pheno-type of CF-null mice and so is likely to contain most of the regulatory elements required for tissue-specific expression of CFTR. RESULTS: We found that the YAC does not include the -79.5 kb region. The DHS at -20.5 kb is present in the chromatin of most tissues of the transgenic mice, supporting its non-tissue-specific nature. The DHS in the first intron is present in a more restricted set of tissues in the mice, although its presence does not show complete concordance with CFTR expression. The intron I DHS may be important for the higher levels of expression found in human pancreatic ducts and in lung submucosal glands. CONCLUSION: These data support the in vivo importance of these regulatory elements.

Animals↗
PubMed1997

Complementation of null CF mice with a human CFTR YAC transgene.

We have made transgenic mice carrying a 320 kb YAC with the intact human cystic fibrosis transmembrane regulator (CFTR) gene. Mice that only express the human transgene were obtained by breeding with Cambridge null CF mice. One line has approximately two copies of the intact YAC. Mice carrying this transgene and expressing no mouse cftr appear normal and breed well, in marked contrast to the null mice, where 50% die by approximately 5 days after birth. The chloride secretory responses in these mice are as large or larger than in wild-type tissues. Expression of the transgene is highly cell type specific and matches that of the endogenous mouse gene in the crypt epithelia throughout the gut and in salivary gland tissue. However, there is no transgene expression in some tissues, such as the Brunner's glands, where it would be expected. Where there are differences between the mouse and human pattern of expression, the transgene follows the mouse pattern. We have thus defined a cloned fragment of DNA which directs physiological levels of expression in many of the specific cells where CFTR is normally expressed.

Animals↗
PubMed1997

Copy number-dependent expression of a YAC-cloned human CFTR gene in a human epithelial cell line.

Initial studies for gene therapy of cystic fibrosis have used heterologous promoters to drive expression of the cystic fibrosis transmembrane regulator (CFTR) cDNA. An alternative approach would be to have constructs based on the endogenous promoter which could give tissue-specific and normal, regulated levels of expression. The DNA elements necessary for this remain unidentified so we have investigated CFTR expression from a 310 kb yeast artificial chromosome (YAC) clone which contains the intact human CFTR gene consisting of 27 exons spread over 230 kb of genomic DNA and also about 50 kb of 5' DNA. In order to distinguish the gene on the YAC, a restriction site change was introduced into the 3' untranslated region of the gene in the YAC. The YAC was then transferred into the human colonic adenocarcinoma cell line Caco-2 which expresses endogenous CFTR. The CFTR gene on the YAC was found to be well expressed in the Caco-2 cells and, in the two cell lines analysed, the ratio of YAC-derived mRNA to endogenous mRNA was the same as the ratio of YAC DNA to endogenous DNA. This indicates that each copy of the CFTR gene on a YAC integrated in the Caco-2 cells is being expressed at approximately the same level as each of the endogenous genes. Thus, the YAC clone contains all the long-range elements necessary to confer full levels of expression, independent of position of integration, in human Caco-2 cells. Deletion of this YAC clone should allow the elucidation of the DNA elements controlling human CFTR expression and the development of constructs for gene therapy.

Caco-2 Cells↗
PubMed1995

Relationship of the third heart sound to transmitral flow velocity deceleration.

BACKGROUND: The third heart sound (S3) occurs shortly after the early (E-wave) peak of the transmitral diastolic Doppler velocity profile (DVP). It is thought to be due to cardiohemic vibrations powered by rapid deceleration of transmitral blood flow. Although the presence, timing, and clinical correlates of the S3 have been extensively characterized, derivation and validation of a causal, mathematical relation between transmitral flow velocity and the S3 are lacking. METHODS AND RESULTS: To characterize the kinematics and physiological mechanisms of S3 production, we modeled the cardiohemic system as a forced, damped, nonlinear harmonic oscillator. The forcing term used a closed-form mathematical expression for the deceleration portion of the DVP. We tested the hypothesis that our model's predictions for amplitude, timing, and frequency of S3 accurately predict the transthoracic phonocardiogram, using the simultaneously recorded transmitral Doppler E wave as input, in three subject groups: those with audible pathological S3, those with audible physiological S3, and those with inaudible S3. CONCLUSIONS: We found excellent agreement between model prediction and the observed data for all three subject groups. We conclude that, in the presence of a normal mitral valve, the kinematics of filling requires that all hearts have oscillations of the cardiohemic system during E-wave deceleration. However, the oscillations may not have high enough amplitude or frequency to be heard as an S3 unless there is sufficiently rapid fluid deceleration (of the Doppler E-wave contour) with sufficient cardiohemic coupling.

Blood Flow Velocity↗
PubMed1995

Comparison of diastolic filling models and their fit to transmitral Doppler contours.

Anatomic/physiologic and kinematic mathematical models of diastolic filling which employ (lumped) parameters of diastolic function have been used to predict or characterize transmitral flow. The ability to determine model parameters from clinical transmitral flow, the Doppler velocity profile (DVP), is equivalent to solving the "inverse problem" of diastole. Systematic model-to-model and model-to-data comparison has never been carried out, in part due to the requirement that DVPs be digitized by hand. We developed, tested and verified a computerized method of DVP acquisition and reproduction, and carried out numerical determination of model-to-model and model-to-data goodness-of-fit. The transmitral flow velocity of two anatomic/physiologic models and one kinematic model were compared. Each model's ability to fit computer-acquired and reproduced transmitral DVPs was assessed. Results indicate that transmitral flow velocities generated by the three models are 'graphically indistinguishable and are able to fit the E-wave of clinical DVPs with comparable mean-square errors. Nonunique invertibility of the anatomic/physiologic models was verified, i.e., multiple sets of model parameters could be found that fit a single DVP with comparable mean-square error. The kinematic formulation permitted automated, unique, model-parameter determination, solving the "inverse problem" for the Doppler E-wave. We conclude that automated, quantitative characterization of clinical Doppler E-wave contours using this method is feasible. The relation of kinematic parameters to physiologic variables is a subject of current investigation.

Algorithms↗
PubMed1992

Rhabdomyoma of prostate.

An asymptomatic nineteen-year-old white man presented with a markedly enlarged and indurated prostate. Urologic evaluation including cystoscopy, prostatic ultrasound, pelvic computerized tomography (CT) scan, and pelvic nuclear magnetic resonance imaging revealed a prostatic mass impinging on the bladder. Transrectal biopsies returned the pathologic diagnosis of rhabdomyomatous hamartoma. We report the first case in the English literature of extracardiac rhabdomyoma found in the male genitourinary tract.

Adult↗
PubMed1990

Anatomic explanation for bulbar urethral pseudostricture.

Interpretation of retrograde urethrography can be complicated by the appearance of an apparent well-defined proximal bulbous urethral stricture which later is not identified on urethroscopy. Two illustrative cases of this confusing finding are presented, and the anatomic explanation is reviewed.

Adult↗
PubMed1990

Mumps orchitis.

Explore the source record for details and available documents.

Adolescent↗
PubMed1989

Choice of antibiotic for lower urinary tract infections in men.

When lower urinary tract infection is present in a male patient, prostatic involvement must be considered. A 30-day course of treatment with one of the antibiotics shown to be superior in treating prostatitis is recommended. It is hoped that this program will eliminate needless progression or relapse of infection and reduce the subsequent risk for development of chronic prostatitis.

Adult↗
PubMed1989

Small cell carcinoma of prostate.

Small cell anaplastic carcinoma (SCC) involving the prostate is extremely unusual, either as a primary or as a secondary metastatic focus. A case of SCC presenting as prostatic obstruction and diagnosed with prostate biopsy is presented and the literature reviewed.

Aged↗
PubMed1989

Simple aid for upright voiding after partial penectomy.

Inadequate penile length after partial penectomy may result in the socially unacceptable inability to project the urinary stream over the scrotum. A simple adaptation of a 60 cc syringe is described as an aid to contain and direct the urinary stream.

Humans↗
PubMed1989

Traumatic testicular torsion: case report.

Trauma has been reported as an infrequent cause of testicular torsion. A case of trauma-induced testicular torsion is reported and literature reviewed. The inclusion of torsion in the differential diagnosis of post-traumatic acute scrotal pain is important to ensure early appropriate management.

Adolescent↗
PubMed1988

Is antibiotic administration indicated after outpatient cystoscopy.

The incidence of urinary tract infection was examined in 138 patients who underwent diagnostic cystoscopy in an outpatient clinical setting with preoperatively sterile urine. A prospective randomized trial was conducted to compare the incidence of infection in patients who received no antibiotic (controls, group 1) and those who received a postoperative course of oral antibiotics (group 2). The incidence of bacteriuria after cystoscopy was 2.8 per cent in group 1 (control) and 1.5 per cent in group 2, with an over-all incidence of 2.2 per cent. Only 1 patient presented with a symptomatic infection (0.7 per cent). This study has confirmed the safety of outpatient cystoscopy and has demonstrated that routine administration of postoperative antibiotics is not indicated.

Ambulatory Surgical Procedures↗
PubMed1988

Pure primary testicular carcinoid: a case report and discussion.

We report a case of pure primary testicular carcinoid tumor and review the literature. Distinctions are emphasized among the 3 subgroups of testicular carcinoids and their clinical significance. Criteria to establish the diagnosis of pure primary testicular carcinoid are offered.

Adult↗
PubMed1988

Trial of ibuprofen to prevent post-vasectomy complications.

Sperm granuloma and epididymitis remain 2 of the most common and incapacitating complications of vasectomy. A study was designed to evaluate the possibility of reducing these inflammatory complications with a prophylactic course of a nonsteroidal anti-inflammatory drug. Patients undergoing outpatient vasectomy were randomized into 2 groups. Group 1 received a prophylactic course of ibuprofen and group 2 received no medication. The ibuprofen was tolerated well and no adverse reactions were noted. There was no increase in postoperative bleeding or hematoma formation. There was no clinical benefit or decrease in complication rate in the ibuprofen-treated group.

Adult↗
PubMed1987

"Turban" scrotal dressing.

Edema and hematoma are common complications of scrotal surgery. We describe a new technique of scrotal wrap dressing that diminishes markedly the incidence of these postoperative complications.

Bandages↗