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Biomedical subjects

D Stark

Publications and source records attributed to D Stark.

50 records · Page 3Linked to original sources
PubMed1985

Genetic restriction of immune responsiveness to synthetic peptides corresponding to sequences in the pre-S region of the hepatitis B virus (HBV) envelope gene.

Proteins of the HBV envelope (env) are coded for by two adjacent regions of the HBV env gene: the pre-S and S regions. Antigenic determinants corresponding to amino acid sequences of both regions are recognized by human antibodies and are important in virus-neutralizing responses. Protective immune responses to HBV appear to be linked to the major HLA histocompatibility complex. Inbred and congenic strains of mice represent a model system relevant for studies on the genetic control of immune responsiveness of humans to HBV envelope proteins. Such mouse strains were ranked according to their antibody response to the S protein and divided into high [d,q], intermediate [a,k,b], and low [s] responders (letters in brackets indicate H-2 haplotype.) Selected pre-S antigenic determinants can be mimicked with high fidelity by synthetic peptide analogues that are immunogenic without any carriers. Thus it is possible to study directly the genetic control of immune responsiveness to pre-S epitopes mimicked by these peptides without having to consider the influence of carriers or of S protein. The results presented here show that inbred mouse strains can be ranked according to their antibody responses to the synthetic peptide pre-S(120-145) as follows: A/J[a] approximately equal to SWR/J[q] greater than C57BL/6J[b] approximately equal to AKR/J[k] approximately equal to SJL/J[s] much greater than DBA/2J[d] greater than BALB/cJ[d]. Only SJL/J[s] mice responded well to another synthetic peptide pre-S (12-32). Thus, H-2-linked genes regulating the immune response to S protein and to epitopes on pre-S-coded sequences are distinct. Anti-pre-S(120-145) responses in S protein-nonresponders circumvent this nonresponsiveness. This should be considered in the design of hepatitis B vaccines.

Amino Acid Sequence↗
PubMed1985

Assessment of cardiac anatomy using nuclear magnetic resonance imaging.

Nuclear magnetic resonance imaging has emerged in the past few years as a completely noninvasive method for medical imaging of internal organs. Because of the loss of signal intensity by motional nuclei (hydrogen) using most proton imaging techniques, flowing blood within the cardiovascular system generates little or no signal and consequently there is high natural contrast between blood and the walls of blood vessels or cardiac chambers. However, motion during imaging also complicates cardiac imaging because signal is lost from the nuclei in the moving cardiac structures. Consequently electrocardiographic gating of data acquisition is required for nuclear magnetic resonance imaging of the heart. Distinct advantages of nuclear magnetic resonance imaging in relation to other imaging modalities are good contrast between soft tissues and the capability for characterization of specific tissues by estimation of magnetic relaxation times. Early in vitro studies measuring relaxation times of myocardial tissue samples of excised hearts indicate that nuclear magnetic resonance imaging will be capable of discriminating infarcted from normal myocardium. Recent studies using electrocardiographically gated nuclear magnetic resonance imaging of dogs with acute infarction showed the infarct as a region of high intensity on spin-echo images. Initial clinical experience with electrocardiographically gated nuclear magnetic resonance imaging (0.35 tesla) in patients has clearly defined internal cardiac anatomy without the use of contrast media. This technique has demonstrated the consequence of previous myocardial infarction such as regional wall thinning, aneurysm, thrombus and contractile dysfunction, a number of pericardial abnormalities and the morphology of hypertrophic and congestive cardiomyopathies.

Coronary Circulation↗
PubMed1985

Localization studies in patients with persistent or recurrent hyperparathyroidism.

Preoperative localization studies are essential for patients who have undergone previous parathyroid operations. This is because the remaining parathyroid glands are more difficult to identify at operation because of increased scarring with loss of normal tissue planes and because the remaining abnormal parathyroid tissue is more likely to be situated in an ectopic position. This investigation concerns the accuracy of preoperative localization studies in 36 consecutive patients. All patients had symptoms and clinical and laboratory data diagnostic of primary (31 patients) or secondary (five patients) hyperparathyroidism. Ultrasonography was performed in all 36 patients; 18 (50%) were positive, 14 (39%) were negative, and four (11%) were false positive examinations. Eight of the negative study results occurred in patients with abnormal parathyroid glands situated in the mediastinum. Computerized tomography (CT) was performed in 25 patients. There was an equal number of positive (11; 44%) and negative (11; 44%) studies with three (12%) false positive test results. CT was helpful in identifying substernal lesions and other abnormal parathyroid glands situated in ectopic positions. Thallium chloride 201-technetium 99m pertechnetate scans were used in 22 patients. There was an equal number of positive (eight; 36%) and negative (eight; 36%) studies. Six patients (27%) had false positive scans. One or more of these noninvasive tests was positive in 27 of the 36 patients (75%). Highly selective venous catheterization for the measurement of immunoreactive parathyroid hormone concentrations localized the elusive parathyroid tumor in 12 of the 16 patients (75%) overall and in six of the nine patients (66%) whose tumors were not identified by other studies. One patient had both a false positive ultrasound and thallium chloride 201-technetium 99m pertechnetate scan. Preoperative localization studies were therefore very helpful for locating hyperfunctioning parathyroid glands in patients with recurrent or persistent hyperparathyroidism, and 75% of the tumors were identified by noninvasive studies. Seventy-five percent of the tumors not identified by noninvasive studies were localized by selective venous catheterization. Most tumors not identified by noninvasive studies were mediastinal or ectopic in position.

Adult↗
PubMed1984

Imaging by nuclear magnetic resonance in patients with chronic ischemic heart disease.

Cardiac anatomy was defined by gated nuclear magnetic resonance (NMR) imaging at a magnetic field strength of 3.5 kGauss in eight normal subjects and 10 patients with chronic myocardial infarctions. Multisectional imaging was performed with the spin-echo technique and encompassed most of the left ventricle in an imaging time of 5 to 12 min. In all subjects internal cardiac structure was well delineated without the use of any type of contrast medium. The myocardial wall-blood interface was sharply defined, resulting in visualization of trabeculations, papillary muscle, and chordal structures in both ventricles. In patients with ischemic heart disease, the extent of postinfarctional wall thinning, aneurysms, and mural thrombi were depicted on NMR images. Images obtained with the second spin-echo (delay time = 56 msec) demonstrated high signal intensity in regions of the left ventricular chamber adjacent to the site of aneurysms or infarctions; this finding suggested stasis of blood in a region of akinesis or dyskinesis. The results of this study show that gated NMR is feasible as a technique for imaging the human heart and is capable of demonstrating a variety of left ventricular abnormalities associated with chronic myocardial infarction. NMR is a completely noninvasive technique for clinical imaging of the cardiovascular system.

Adult↗
PubMed1984

Multiplane magnetic resonance imaging of the heart and major vessels: studies in normal volunteers.

The feasibility of magnetic resonance imaging for defining anatomy of internal cardiac structures and major blood vessels was assessed in 14 normal subjects. Both electrocardiogram-gated and standard spin-echo images were obtained. The R-R interval determined the pulse repetition times in gated sequences. Gated images provided better visualization of internal cardiac morphology and of upper mediastinal vessels than did nongated images. Trabecular detail and components of the mitral valve could be resolved. All segments of the left ventricular wall could be evaluated by combining axial, coronal, and sagittal images. Gated acquisition of magnetic resonance images did not increase imaging time; five transverse slices of the left ventricle were obtained in 6.0-8.5 min. The good image quality, ease of gated acquisition, large field of view, capability of direct imaging in multiple planes, and noninvasiveness of the technique suggest that it will be an important imaging method in cardiovascular disease.

Adult↗
PubMed1983

H-2 linked genetic control of immune responsiveness to hepatitis B surface antigen (HBsAg) in mice.

Recent data suggest that genes involved in the control of (1) immune responses of humans to HBsAg and (2) the susceptibility to the development of chronic hepatitis B are linked to the major HLA histocompatibility complex. Studies on the genetic regulation of anti-HBs responses and on the possible abrogation of nonresponsiveness to HBsAg in humans are difficult. In an attempt to develop a relevant animal model system, the anti-HBs response of inbred and congenic strains of mice was investigated. A great variation in anti-HBs responses among individual mice belonging to the same strains was observed. Nevertheless, it was possible to rank the inbred mouse strains studied according to their decreasing anti-HBs responses as follows: BALB/c[d] congruent to SWR/J[q] greater than C57BL/6J[b] congruent to DBA/2J[a] greater than AKR/J[k] greater than A/J[a] greater than CBA/CaJ[k] greater than SJL/J[s]. (Letters in brackets indicate H-2 haplotype). Only a small proportion of SJL mice had an anti-HBs response. Therefore, this strain may serve as a model for human nonresponders. Studies with the congenic strains B10.D2[d] and B10.S[s] indicated that genes conferring responsiveness to HBsAg are linked to the H-2 histocompatibility complex. However, genes not linked to H-2 also probably play a role in regulating anti-Hbs responses.

Animals↗
PubMed1983

Clinical nuclear magnetic resonance imaging of the body.

NMR promises great advances in diagnosis and has delivered so much already that it is expected that in the future it will replace many applications of the currently used imaging modalities. Although x-ray computed tomography is continuing to advance in speed of scanning and resolving power, NMR will most likely soon eliminate its use in many studies of the central nervous system and also in many other areas of the body. The promise of combining topical spectroscopy with imaging is also exciting and should provide further information about metabolic processes of various organs. Progress in NMR is so rapid and the future is so bright that one of the great problems will be to develop a new breed of radiologists who are versatile in biochemistry, mathematics, and computers, as well as competent in morphologic anatomy and pathologic physiology. As time goes on, advances in NMR will be achieved only by teams of clinical and basic scientists encompassing multiple disciplines.

Aortic Aneurysm↗
PubMed1983

Resection of gastrinomas.

Exploratory laparotomy and a search for gastrinomas was performed in 52 patients with the Zollinger-Ellison syndrome (ZES). Gastrinoma tissue was resected in 11 patients (21%), 6 (12%) of whom appear to have been cured. After surgery, serum gastrin levels in these six patients have remained normal from 10 months to 10 years. In the 46 other patients, tumor was unresectable because of metastases or multiple primary tumors (21 patients; 40%) or inability to find the tumor at laparotomy (21 patients; 40%). Multiple pancreatic islet cell adenomata were found in six of seven patients with multiple endocrine neoplasia (MEN), indicating that patients with this condition usually have diffuse involvement of the pancreas. The results of CT scans correlated with findings at laparotomy in 13 of 16 patients. The smallest tumor detected by CT scans was 1 cm in diameter. CT technology is more accurate in finding gastrinomas now than in the past and has a useful role in preoperative evaluation. The possibility of resection should be seriously considered in every patient with Zollinger-Ellison syndrome. Abdominal CT scans, transhepatic portal venous sampling, and laparotomy should be used to find the tumor and to determine whether it is resectable. Using presently available methods, it should be possible to cure about 25% of patients with gastrinomas who do not have MEN and over 70% of those without MEN who appear to have a solitary tumor. Total pancreatectomy may be necessary to cure some patients with MEN, but that operation is rarely justified. The morbidity and mortality of surgical attempts at curing this disease have become minimal; we have had no deaths or serious complications following such operations in over 10 yrs. Total gastrectomy and indefinite use of H2-receptor blocking agents are the therapeutic options for patients with unresectable gastrinomas. Because H2-receptor blocking agents fail to control acid secretion in many patients after several yrs of therapy, total gastrectomy is indicated in a large proportion of patients whose tumors cannot be resected. Total gastrectomy in patients with ZES is also safe using current techniques; our last death following this operation for ZES occurred 15 yrs ago.

Adenoma, Islet Cell↗
PubMed1982

Localization of parathyroid adenoma by computed tomography.

Sixteen consecutive patients with the clinical diagnosis of hyperparathyroidism, nine with and seven without previous surgery, had computed tomography (CT) examinations preoperatively to evaluate the use of CT in localizing parathyroid adenomas. The patients were scanned at 5 mm intervals from the level of the hyoid bone to the lung apex. Scanning of the mediastinum was performed at 10 mm intervals from apex to lung base. Computed tomography correctly identified prospectively the site of the adenoma in 10 of 13 patients (77%), with surgically proven adenomas. In retrospect, all 13 adenomas could be identified. One false positive diagnosis of adenoma was made. Our study suggests that CT may be beneficial in the preoperative localization of parathyroid tumors, particularly in ectopic locations.

Adenoma↗
PubMedDate not supplied

A multicenter clinical trial of Gadolite Oral Suspension as a contrast agent for MRI.

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49-1.18 for reader 1: .46-1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.

Administration, Oral↗
PubMedDate not supplied

Extractive bioconversion of 2-phenylethanol from L-phenylalanine by Saccharomyces cerevisiae.

The bioconversion of L-phenylalanine (L-Phe) to 2-phenylethanol (PEA) by the yeast Saccharomyces cerevisiae is limited by the toxicity of the product. PEA extraction by a separate organic phase in the fermenter is the ideal in situ product recovery (ISPR) technique to enhance productivity. Oleic acid was chosen as organic phase for two-phase fed-batch cultures, although it interfered to some extent with yeast viability. There was a synergistic inhibitory impact toward S. cerevisiae in the presence of PEA, and therefore a maximal PEA concentration in the aqueous phase of only 2.1 g/L was achieved, compared to 3.8 g/L for a normal fed-batch culture. However, the overall PEA concentration in the fermenter was increased to 12.6 g/L, because the PEA concentration in the oleic phase attained a value of 24 g/L. Thus, an average volumetric PEA production rate of 0.26 g L(-1) h(-1) and a maximal volumetric PEA production rate of 0.47 g L(-1) h(-1) were achieved in the two-phase fed-batch culture. As ethanol inhibition had to be avoided, the production rates were limited by the intrinsic oxidative capacity of S. cerevisiae. In addition, the high viscosity of the two-phase system lowered the k(l)a, and therefore also the productivity. Thus, if a specific ISPR technique is planned, it consequently has to be remembered that the productivity of this bioconversion process is also quickly limited by the k(l)a of the fermenter at high cell densities.

Fermentation↗