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Biomedical subjects

D W Williams

Publications and source records attributed to D W Williams.

At least 73 records · Page 4Linked to original sources
PubMed1996

High transgene activity in the yolk syncytial layer affects quantitative transient expression assays in zebrafish Danio rerio) embryos.

For the purpose of studying the factors that cause wide variation in transient transgene expression in individual fish, a lacZ reporter gene linked to a carp beta-actin regulatory sequence was introduced into zebrafish embryos. As a general trend, a correlation between the number of transgene copies injected and the level of transgene expression was found. However, a substantial variation in the level of expression still occurred that could not be attributed to technical factors such as the difference in injected volume of the transgene. Co-injection of 32P-dCTP and transgene into the same embryo followed by detection of beta-galactosidase activity, has shown that the volume used for transgene injection, which was determined in terms of radioactivity, is not closely related to the level and location of transgene expression. Injection into the animal pole at zygote stage and the yolk cytoplasmic layer (YCL) at the 64-cell stage followed by determination of transgene expression in terms of unit injection volume, revealed that there are marked differences among tissues with regard to their capacity for transgene expression, and that the yolk syncytial layer is higher in this capacity. This high activity is assumed to be due to the high transcriptional activity or enhanced transgene replication in the syncytial layer, which is known to contain giant polyploid nuclei. The high levels of expression in the YSL may influence transient expression studies using quantitative comparative analyses and should be taken into consideration when expression data are derived from homogenates of yolk sac embryos.

Actins↗
PubMed1996

Identification of Candida species in formalin fixed, paraffin wax embedded oral mucosa by sequencing of ribosomal DNA.

Aim-To identify Candida species in formalin fixed, paraffin wax embedded tissue by sequencing candidal rDNA.Methods-Target rDNA sequences were amplified by polymerase chain reaction (PCR) from fresh isolates of Candida and from 18 preserved oral mucosal tissue samples (16 cases of chronic hyperplastic candidiasis and two fibroepithelial polyps), shown histologically to contain Candida. Identification of Candida species within tissue was based on a comparison of the rDNA sequences obtained with those from the fresh isolates of Candida and those present in the GenBank database.Results-The PCR products obtained from 12 of the 18 tissue specimens studied were characteristic of Candida albicans. In two of these cases a second, larger PCR product was obtained and these sequences were characteristic of Candida glabrata.Conclusions-Candidal DNA was amplified successfully from formalin fixed, paraffin wax embedded tissue. Sequencing of the PCR product enabled identification of the Candida species present.

Journal Article↗
PubMed1996

The effect of castration on steady state levels of luteinizing hormone-releasing hormone (LHRH) mRNA and proLHRH processing: time course study utilizing semi-quantitative reverse transcription/polymerase chain reaction.

Many studies have consistently shown that castration induces a prompt increase in serum levels and pituitary content of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as a concomitant rise in steady state levels of the messenger RNAs directing their synthesis. The reports of effects of castration on the overall physiology of hypothalamic luteinizing hormone-releasing hormone (LHRH)--steady state levels of LHRH mRNA, post-translational processing and secretion--have, however, not been consistent. The goal of the studies reported here was to provide the first analysis of the effect of castration, at multiple postoperative time points, on steady state levels of LHRH mRNA and on the levels of hypothalamic proLHRH. All these data are correlated with hypothalamic levels of the mature LHRH decapeptide and with serum and pituitary levels of immunoreactive LH and FSH. Adult male rats were either castrated or sham-castrated (controls) and then sacrificed at 1, 3, 5, 7, 14, 21 or 28 days postoperatively. As expected, there was a prompt and sustained rise in serum immunoreactive LH and FSH in castrates compared with sham-operated animals. Intra-pituitary LH levels rose above levels in the sham-operated animals by 14 days post castration. Intra-pituitary FSH showed a biphasic response, first falling significantly below control levels, then rising above control levels at 21 days. Steady state levels of LHRH mRNA in castrates, measured by reverse transcription/polymerase chain reaction, were increased about 2-fold above control levels by 1 day postoperatively, but were virtually identical to control levels at each of the other time points despite marked changes in the gonadotropins. ProLHRH content in castrates was 1.8-times that seen in controls at 1 day post castration (P<0.05), concomitant with the rise in steady state levels of LHRH mRNA at that time point. However, proLHRH content in castrates was no different from that seen in controls at each of the later time points examined. LHRH content was unchanged through 7 days after castration, but then fell significantly to 57% of control levels in hypothalami from animals gonadectomized 14 to 21 days previously (P<0.001 vs control), and to 54% of sham-operated levels at 28 days postoperatively (P<0.001). We conclude that: (1) changes in steady state levels of LHRH mRNA after castration are small and transient and (2) increased proLHRH coupled with unchanged LHRH levels at 1 day post castration, and castrate animal proLHRH at control levels coupled with falling LHRH at later post-castration time points indicate that the effect of gonadectomy on post-translational processing of proLHRH to LHRH is, likewise, small and transient. In aggregate our data suggest that most of the increase in serum LH and FSH seen in male rats after castration is not mediated at the hypothalamic level.

Analysis of Variance↗
PubMed1995

Identification of Candida species by PCR and restriction fragment length polymorphism analysis of intergenic spacer regions of ribosomal DNA.

The PCR was used to amplify a targeted region of the ribosomal DNA from 84 Candida isolates. Unique product sizes were obtained for Candida guilliermondii, Candida (Torulopsis) glabrata, and Candida pseudotropicalis. Isolates of Candida albicans, Candida tropicalis, Candida stellatoidea, Candida parapsilosis, and Candida krusei could be identified following restriction digestion of the PCR products.

Base Sequence↗
PubMed1995

Positron emission tomography in the evaluation of laryngeal carcinoma.

Positron emission tomography (PET) is a relatively new radiologic imaging technique based on glucose analog uptake and metabolism in tumor tissue. In this study, PET was used in evaluating 38 patients with laryngeal cancer. Twenty-five patients were examined with PET prior to treatment to study the reliability of PET in identifying the primary tumor and assessing regional nodal status; 13 patients who had previously received irradiation with curative intent and who represented differential diagnostic problems were imaged to differentiate between irradiation effects and recurrent or residual cancer. Findings for both groups were compared to results of clinical evaluation and those of computed tomography (CT) and magnetic resonance imaging (MRI). The PET results were essentially identical to those of CT, MRI, and clinical evaluation in identifying metastatic lesions (82% correct), and were as reliable as CT and MRI for correctly identifying primary tumors (88%). Positron emission tomography was most helpful in differentiating recurrent tumor from postirradiation tissue sequelae. However, its lack of anatomic detail made PET less valuable for primary staging and therapeutic planning. It may enhance the diagnostic accuracy of CT and MRI where anatomic distortions occur or where diagnostic criteria for CT and MRI are ambiguous.

Carcinoma↗
PubMed1995

A comparative diagnostic study of head and neck nodal metastases using positron emission tomography.

A prospective study was conducted to compare the accuracy of clinical examination, computed tomography (CT), and positron emission tomography (PET) in identifying head and neck squamous cell carcinoma metastatic to cervical lymph nodes. The findings in the necks of 49 patients evaluated by clinical examination and CT were compared to the findings in the same necks by PET, a newly available metabolic imaging modality. Pathology specimens were available for 45 of the necks. The findings of PET and CT correlated in 84% of cases. In the cases that did not correlate, CT proved correct in four of five cases. PET (82%) and CT (84%) were comparable and were both better than clinical examination (71%) in correctly identifying the presence or absence of metastatic disease.

Carcinoma, Squamous Cell↗
PubMed1995

Preoperative identification of benign versus malignant parotid masses: a comparative study including positron emission tomography.

Various diagnostic tools were used in 26 patients with parotid masses to determine their value in preoperative malignant or benign categorization. These tools were positron emission tomography (PET), clinical examination, fine-needle aspiration biopsy (FNAB), computed tomography (CT), and magnetic resonance imaging (MRI). PET identified all 26 lesions and all 12 malignant lesions, but made the correct categorization in only 69% of cases. Thus, it was not as good as the more conventional diagnostic methods, their correct categorizations being 85% (clinical), 87% (CT/MRI), and 78% (FNAB) in the same patients.

Biopsy, Needle↗
PubMed1994

Importance of obesity, race and age to the cardiac structural and functional effects of hypertension. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

OBJECTIVES: The purpose of this study was to determine the effects of obesity and its interaction with age, race and the magnitude of blood pressure elevation in a large cohort of patients with mild to moderate hypertension and a high prevalence of left ventricular hypertrophy. BACKGROUND: Obesity, race and age each have important effects on the incidence and severity of hypertension and may contribute to the effects of blood pressure elevation on the cardiac manifestations of hypertension. METHODS: Left ventricular structure and function were assessed with two-dimensional targeted M-mode echocardiography in 692 men with mild to moderate hypertension (average blood pressure 153/100 mm Hg), and the data were compared in relation to obesity (determined from body mass index), age, race, blood pressure, physical activity, plasma renin activity, urinary sodium excretion, hematocrit, heart rate and serum lipids. RESULTS: Left ventricular hypertrophy was common (63% with increased left ventricular mass, 22% with left ventricular hypertrophy on the electrocardiogram [ECG]). On multivariable regression analysis, body mass index was the strongest predictor of left ventricular mass and magnified the slope relation of blood pressure to left ventricular mass. Despite a greater prevalence of ECG left ventricular hypertrophy in blacks (31%) than in whites (10%), left ventricular mass and echocardiographic prevalence of left ventricular hypertrophy did not differ by race. However, septal, posterior left ventricular and relative wall thickness were greater in black than in white men. CONCLUSIONS: Obesity is the strongest clinical predictor of left ventricular mass and left ventricular hypertrophy in men, even in those with mild to moderate hypertension of sufficient severity to be associated with a high prevalence of left ventricular hypertrophy. Moreover, independent effects of systolic blood pressure on left ventricular mass are amplified by obesity. Although race does not affect left ventricular mass or the prevalence of left ventricular hypertrophy, black race is associated with greater relative wall thickness, itself a predictor of unfavorable cardiovascular outcome.

Age Factors↗
PubMed1994

Positron emission tomography of patients with head and neck carcinoma before and after high dose irradiation.

BACKGROUND: Positron emission tomography (PET) with labeled fluorodeoxyglucose (FDG) demonstrates increased tracer uptake in many neoplasms. This study was undertaken to define the patterns of FDG uptake in head and neck neoplasms before and after high dose irradiation. METHODS: Twenty-five patients were evaluated prospectively with PET and standard clinical and radiographic techniques before and after irradiation. RESULTS: Twenty-seven primary sites were confirmed pathologically in 23 patients and included the nasopharynx (four lesions), oropharynx (14 lesions), larynx (five lesions), oral cavity (two lesions), and paranasal sinuses (two lesions). Two patients had unknown primary sites. Twenty-four of 27 primary sites correlated with areas of increased tracer uptake on PET scans. Five patients had increased uptake in cervical lymph nodes that were uninvolved by radiographic or clinical criteria. Positron emission tomography seemed to be able to differentiate tumor activity from fluid-filled sinuses in two patients with paranasal sinus tumors. In two patients with unknown primary sites, increased uptake in the base of tongue after PET suggested occult primary sites. Positron emission tomography scans obtained 1 month after high dose irradiation (RT) indicated decreased levels of FDG uptake in all patients' tumors. However, these scans did not accurately reflect the status of disease in these patients. Scans obtained 4 months after RT were believed to assess more accurately the presence of malignancy. CONCLUSIONS: Positron emission tomography is a new modality that may be useful in defining tumor activity in clinically negative areas. Appropriately timed posttreatment PET may be useful in predicting outcome after definitive RT and in distinguishing viable tumors from normal tissue changes after RT in patients with head and neck carcinomas.

Carcinoma↗
PubMed1994

Distinguishing tumor recurrence from irradiation sequelae with positron emission tomography in patients treated for larynx cancer.

PURPOSE: Distinguishing persistent or recurrent tumor from postradiation edema, or soft tissue/cartilage necrosis in patients treated for carcinoma of the larynx can be difficult. Because recurrent tumor is often submucosal, multiple deep biopsies may be necessary before a diagnosis can be established. Positron emission tomography with 18F-2fluoro-2deoxyglucose (FDG) was studied for its ability to aid in this problem. METHODS AND MATERIALS: Positron emission tomography (18FDG) scans were performed on 11 patients who were suspected of having persistent or recurrent tumor after radiation treatment for carcinoma of the larynx. Patients underwent thorough history and physical examinations, scans with computerized tomography, and pathologic evaluation when indicated. Standard uptake values were used to quantitate the FDG uptake in the larynx. RESULTS: The time between completion of radiation treatment and positron emission tomography examination ranged from 2 to 26 months with a median of 6 months. Ten patients underwent computed tomography (CT) of the larynx, which revealed edema of the larynx (six patients), glottic mass (four patients), and cervical nodes (one patient). Positron emission tomography scans revealed increased FDG uptake in the larynx in five patients and laryngectomy confirmed the presence of carcinoma in these patients. Five patients had positron emission tomography results consistent with normal tissue changes in the larynx, and one patient had increased FDG uptake in neck nodes. This patient underwent laryngectomy, and no cancer was found in the primary site, but nodes were pathologically positive. One patient had slightly elevated FDG uptake and negative biopsy results. The remaining patients have been followed for 11 to 14 months since their positron emission studies and their examinations have remained stable. In patients without tumor, average standard uptake values of the larynx ranged from 2.4 to 4.7, and in patients with tumor, the range was 4.9 to 10.7. CONCLUSION: Positron emission tomography with labeled FDG appears to be useful in distinguishing benign from malignant changes in the larynx after radiation treatment. This noninvasive technique may be preferable to biopsy, which could traumatize radiation-damaged tissues and precipitate necrosis.

Deoxyglucose↗
PubMed1994

Intrasacral myxopapillary ependymoma.

Intrasacral ependymomas are rare, accounting for only a small fraction of primary sacral tumors. They are typically large at diagnosis, which is preceded by a long history of pain. We present a case discovered during investigation of infertility. MRI features of the myxopapillary subgroup are described.

Adult↗
PubMed1994

Salivary gland tumors: pretherapy evaluation with PET.

PURPOSE: To determine whether positron emission tomography (PET) can help differentiate benign from malignant lesions of the salivary glands before surgery. MATERIALS AND METHODS: Masses of the salivary glands were examined in 26 patients by means of computed tomography, magnetic resonance imaging, PET, biopsy (n = 18), and surgery. Contiguous PET scans were obtained from the midcranium to the lower chest 45 minutes after administration of 370 MBq (10 mCi) of fluorine-18 fluorodeoxyglucose (FDG). Standard uptake values (SUVs) were determined for all suspect lesions and for normal parotid glands and cerebellum. RESULTS: All lesions were visualized, and all but two showed some increase in FDG uptake. PET findings helped correctly differentiate benign from malignant masses in 18 (69%) but were false-positive for malignancy in eight (31%). SUV analysis, lesion-to-normal SUV ratios, and lesion-to-cerebellar SUV ratios also failed to differentiate the lesions. CONCLUSION: FDG PET is not useful in classifying salivary gland tumors as benign or malignant.

Adult↗
PubMed1990

SIMUL: an accurate method for the determination of receptor subtype proportions using a personal computer.

Many tissues possess two classes of binding sites for a drug. To estimate the proportions of each it is necessary either to use selective ligands or to perform competition experiments in which the binding of a radioligand is inhibited by a selective unlabeled ligand. However, this method will only be accurate provided the radioligand is non-selective. A selectivity of 2- to 3-fold for one receptor may produce errors of 50% or more in the estimates, depending on the concentration of radioligand chosen. Since most ligands are selective to some extent simple estimates will often provide inaccurate information. The computer program described here (SIMUL) determines the proportions of receptor subtypes by considering the relative affinities of the competing agent for the receptor subtypes, the selectivity of the radioligand and their associated concentrations.

Animals↗
PubMed1990

Effects of prolonged infusion of dopexamine on beta 1- and beta 2-adrenoceptors in guinea-pig myocardium.

1. The effects of 7-day infusion of dopexamine (50 and 200 micrograms kg-1h-1) were examined on beta 1- and beta 2-adrenoceptors in guinea-pig left ventricular membranes. 2. Receptor binding performed using the high affinity radioligand (-)-[125I]-cyanopindolol (CYP) and the beta 1-adrenoceptor antagonist CGP 20712A showed that treatment with dopexamine 200 micrograms kg-1h-1 caused a 45% reduction in beta 2-adrenoceptors and a small but not significant increase in beta 1-adrenoceptors. 3. Functional effects of dopexamine were examined in the guinea-pig isolated electrically driven left atria and K(+)-depolarized uterus. Dopexamine was an antagonist at beta 1-adrenoceptors in left atria (pKB = 4.49), and a partial agonist at beta 2-adrenoceptors in the uterus (alpha = 0.78, pD2 = 6.59). 4. The effects of dopexamine on beta 1- and beta 2-adrenoceptor density in guinea-pig ventricular myocardial membranes may be related to agonist activity at beta 2-adrenoceptors and antagonist activity at beta 1-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1990

Pituitary gland: MR imaging of physiologic hypertrophy in adolescence.

The size and shape of pituitary glands in 169 children, adolescents, and young adults were analyzed with T1-weighted sagittal magnetic resonance (MR) images. In patients younger than 12 years old, no pituitary gland was found to be more than 6 mm in height. In adolescents, definite evidence for physiologic (pubertal) pituitary hypertrophy was seen in both sexes, although it was much more prominent in girls. The pituitary glands of four of 32 teenage girls measured 8-10 mm, but no teenage boy had a gland taller than 7 mm. Young adults aged 21-30 years had significantly (P less than .05) smaller glands than teenagers of the same sex. Significant (P = .0001) variations in the shape of the pituitary glands according to patient age and sex were also noted. Convex upper margins were seen in 56% of teenage girls, while this shape was noted in only 18% of the remaining patients of either sex. In eight of 32 teenage girls (25%) the pituitary glands were nearly spherical on sagittal images; this shape was not recorded in any other group. The normal maturation sequence of the pituitary gland apparently involves a period of physiologic hypertrophy in teenagers. This is manifest in girls by a significant change in both pituitary size and shape, while the glands of boys undergo a transformation in size only.

Adolescent↗