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R H Knop

Publications and source records attributed to R H Knop.

15 recordsLinked to original sources
PubMed1992

UDP-N-acetylhexosamine modulation by glucosamine and uridine in NCI N-417 variant small cell lung cancer cells: 31P nuclear magnetic resonance results.

Small cell lung cancer (SCLC) occurs as two neuroendocrine subtypes, SCLC-C (classic) and SCLC-V (variant). One reported difference is elevated levels of diphosphodiesters (DPDE) in the more differentiated SCLC-C subtype. DPDE have been identified as primarily UDP-N-acetylhexosamines (UDP-NAH) in a variety of tumors, and changes in DPDE levels have been observed during experiments designed to induce cell differentiation. UDP-NAH synthesis is controlled by negative feedback regulation of glutamine:fructose-6-P amidotransferase (EC 2.6.1.16), which can be circumvented by glucosamine. Using 31P nuclear magnetic resonance analysis of extracts and perfused cells, we have identified UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine as the primary metabolites in the DPDE spectral region of SCLC-V N-417 cells. Glucosamine addition causes a rapid increase in UDP-NAH levels. At glucosamine: glucose ratios of 1:1 and 10:1 formation of the UDP-NAH intermediates N-acetylglucosamine 6-phosphate and UDP-N-acetylglucosamine 1-phosphate is also observed, indicating UTP limitation. Subsequent uridine addition results in depletion of the intermediates and increased UDP-NAH formation. Moreover, N-417 cells retain the capacity to rapidly convert uridine to UTP despite low ATP and phosphocreatine levels. This expansion of the uridine pool may represent an additional metabolic reserve not yet addressed in the design of therapy options.

Carcinoma, Small Cell↗
PubMed1987

Levels of high energy phosphates in human lung cancer cell lines by 31P nuclear magnetic resonance spectroscopy.

Human lung cancers are divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on established criteria. SCLC differs from NSCLC by the expression of biomarkers, including creatine kinase-BB isoenzyme (EC 2.7.3.2). Subtypes of SCLC are referred to as classic and variant, both of which have elevated levels of creatine kinase-BB isoenzyme. We, therefore, applied 31P nuclear magnetic resonance spectroscopy to cell lines of classic SCLC, variant SCLC, and NSCLC human tumors, using continuous perfusion to identify any differences in the detectable levels of intracellular high-energy phosphate compounds. The spectra indicate that only the variant SCLC cells maintain high levels of phosphocreatine. Additionally, the classic SCLC cells express elevated levels of a diphosphodiester. Neither phosphocreatine nor diphosphodiesters are found in the NSCLC cell spectra.

Adenosine Triphosphate↗
PubMed1987

Magnetic resonance imaging versus computed tomography in the evaluation of soft tissue tumors of the extremities.

Twenty patients with extremity soft tissue tumors were prospectively evaluated with magnetic resonance imaging (MRI) and computed tomography (CT) scans with subsequent anatomic correlation of surgical findings. MRI and CT had a similar percentage of accuracy in assessing tumor relationship with major neurovascular (80% and 70%, respectively) and skeletal (80% and 75%, respectively) structures. MRI was significantly better than CT in displaying contrast between tumor and muscle when using the T2 weighted spin echo (SE) (p2 less than 0.002) and inversion recovery (IR) (p2 less than 0.005) pulse sequences. MRI and CT were comparable in demonstrating contrast between tumor and fat. The contrast between tumor and vessel was better displayed by MRI compared with CT when using the T1 weighted SE (p2 less than 0.001) and T2 weighted SE (p2 less than 0.001) pulse sequences. T1 and T2 values were measured on fresh tumor and normal tissue samples and were used to predict relative contrast on different MRI pulse sequences using isosignal contour plots. MRI appears to offer several advantages over CT in the evaluation of extremity soft tissue tumors.

Arm↗
PubMed1987

A reproducible model of metastatic brain and ocular tumor by hematogenous inoculation of the VX2 tumor in rabbits.

A metastatic brain-tumor model has been developed in rabbits by infusing the VX2 carcinoma into the internal carotid artery to simulate hematogenous dissemination of tumor. In a series of 25 New Zealand White rabbits, multiple metastases arose in the hemisphere of 24 (96%) and in the eye of 22 (92%); in all instances ocular metastases were ipsilateral to the site of infusion. Ocular metastases were visible in the anterior chamber in 80% of animals 3 to 12 days after the infusion of VX2 tumor cell suspension. All rabbits deteriorated neurologically or died by Day 15 after the inoculation. Multiple metastases were demonstrated by magnetic resonance imaging as early as 5 to 7 days after infusion of the tumor cells and were confirmed at autopsy. This technique models hematogenous metastases to the brain and eye and is useful in evaluating the response of metastases to chemotherapy and radiation therapy directed to the brain and eye.

Animals↗
PubMed1986

Gd(DOTA): an alternative to Gd(DTPA) as a T1,2 relaxation agent for NMR imaging or spectroscopy.

Methods have been devised for obtaining gadolinium(III) complexes of the ligands NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid), DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), TETA (1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid), and DTPA (diethylenetriaminepentaacetic acid) as solids for use as pharmaceuticals. Their effectiveness as in vitro and in vivo contrast agents for NMR imaging or T1,2 relaxation agents for spectroscopy has been investigated. The Gd(DOTA) complex was shown to be a more stable alternative to Gd(DTPA) by serum stability studies and measurement of stability constants. Images of tumors grown in athymic mice were obtained by NMR after injection of Gd(DOTA) and Gd(DTPA).

Animals↗
PubMed1986

Adrenal masses differentiated by MR.

Magnetic resonance imaging was performed in 30 patients with adrenal masses. The abnormalities included adrenal adenomas (n = 10), carcinomas (n = 2), pheochromocytomas (n = 12), and adrenal metastases (n = 6). By the ratio of the signal intensity of the adrenal mass to that of the liver, adenomas could be distinguished from adrenal metastases, adrenal carcinomas, and pheochromocytomas. Metastases and pheochromocytomas could generally be differentiated.

Adenoma↗
PubMed1985

Adaptive cellular response to hyperthermia: 31P-NMR studies.

Dynamic intracellular ATP and Pi levels were measured non-invasively for Chinese hamster V79 cells by 31P-NMR under conditions of thermotolerance and heat-shock protein induction. High densities of cells were embedded in agarose strands, placed within a standard NMR sample tube, and perfused with medium maintained either at 37 or 43 degrees C at pH 7.35. Cell survival and heat-shock protein synthesis were assessed either from parallel monolayer cultures or cells dislodged from the agarose strands post-treatment. Thermotolerance (heat resistance) and heat-shock protein synthesis was induced by a 1 h exposure to 43 degrees C followed by incubation for 5 h at 37 degrees C. After the 5 h incubation at 37 degrees C, marked thermal resistance was observed in regard to survival with concomitant synthesis of two major heat-shock proteins at 70 and 103 kDa. Studies were also conducted where tolerance and heat-shock protein synthesis were partially inhibited by depletion of cellular glutathione (GSH) prior to and during heat treatment. Dynamic measurement of intracellular ATP of cells heated with or without GSH depletion revealed no change in steady-state levels immediately after heating or during the 5 h post-heating incubation at 37 degrees C where thermotolerance and heat-shock proteins develop. These data are consistent with other reported data for mammalian cells and indicate that the steady-state ATP levels in mammalian cells remain unchanged during and after the acquisition of the thermotolerant state.

Adenosine Triphosphate↗
PubMed1985

Tumors and arteriovenous malformations of the spinal cord: assessment using MR.

Thirty-three patients with either primary spinal cord tumors (n = 18), intradural tumors excavating into the cord (n = 9), or spinal arteriovenous malformations (AVM) (n = 6) were studied with magnetic resonance (MR) imaging. In 25 of 38 examinations (66%) (five patients were studied twice), MR provided more information than that provided by other neuroradiologic procedures. In several cases, MR affected patient management decisions. Advantages of MR, in addition to the absence of ionizing radiation and its noninvasive nature, include good spinal cord-CSF-theca contrast, lack of bone-derived artifacts, ease of multiplanar imaging, improved discrimination between intra- and extramedullary lesions, better definition of tumoral cavities and possible distinction from true syringes, ability to help one recognize thrombus formation within an AVM, and ease of follow-up of cord lesions for possible size changes. Apart from factors precluding the study in several patients (life support systems, pacemakers, claustrophobia, neurovascular clips), disadvantages of MR imaging include motion artifacts (prevalent in thoracolumbar area), poor capability of typing and grading of tumors, potential of false-positive results, poor detection of calcification, and poor delineation of feeders and drainers of AVM.

Adolescent↗
PubMed1985

MR cisternography and myelography with Gd-DTPA in monkeys.

To enhance the contrast between cerebrospinal fluid (CSF), brain, spinal cord, and surrounding meninges and bone on magnetic resonance (MR) images, as well as to study CSF flow, gadolinium-DTPA was injected in the subarachnoid space of eight monkeys. Six doses of progressively higher concentrations (from .125 mmol to 250 mmol) were injected every 30-40 minutes. Images of head and spine were obtained at .26 T or .5 T in sagittal and axial planes, using both spin-echo and inversion-recovery sequences in 13 imaging experiments. Marked, consistent changes of signal intensity in the CSF cavities were observed following the injections. These changes were dose related and occurred at different times in the areas close to the injection site versus those distant, a disparity that obviously was related to CSF flow. Gd-DTPA cisternography and myelography may be valuable in MR imaging of central nervous system disease, such as tumors adjacent to the CSF cavities, abnormal CSF collections (e.g., arachnoidal cysts), CSF rhinorrhea and otorrhea, syringohydromyelia, and studies of hydrocephalus and CSF flow dynamics.

Animals↗
PubMedDate not supplied

Frequency shift artifacts in MR imaging.

Chemical shifts may be expressed as distortions and displacements in magnetic resonance (MR) images. Specifically, in two-dimensional Fourier transform reconstructions such shifts produce visible displacements in the direction of frequency encoding. This is readily observable at 0.26 T with phantoms comprised of in vitro solutions with known chemical shifts and human tissues with disparate fat content. Moreover, frequency shift artifacts are visible in routine abdominal scanning at the interfaces of structures of differing fat content. Two common examples of this involve the vertebral body and intervertebral disk and the kidney and surrounding retroperitoneal fat. Without appropriate changes in gradients, such distortions may be expected to increase with increasing magnetic field strength.

Humans↗
PubMedDate not supplied

Distinction between adrenal adenomas and metastases using MR imaging.

Magnetic resonance imaging was performed on 12 patients with known neoplastic disease and adrenal masses shown by CT. Three patients with metastases had high signal intensity in the adrenals on T2 weighted spin echo scans (SE 2,500/80) and nine patients with nonfunctioning adenomas had low signal intensity on T2 weighted images. The ability to distinguish metastases from nonhyperfunctioning adrenal adenomas may be of use in the pre-operative evaluation in patients with known carcinoma and incidental adrenal masses.

Adenocarcinoma↗
PubMedDate not supplied

Opening of blood-ocular barrier demonstrated by contrast-enhanced MR imaging.

Opening of the blood-ocular barrier following infusion of hyperosmolar agents into the internal carotid artery has been demonstrated by gadolinium enhanced magnetic resonance (MR) imaging. In five rhesus monkeys the disruption of the barrier was shown as increased signal intensity within the aqueous and vitreous humors. These findings suggest a potential use of contrast-enhanced MR imaging for detecting and evaluating the ocular microangiopathy of diabetic and hypertensive retinopathy and other diseases.

Animals↗
PubMedDate not supplied

Gadolinium cryptelates as MR contrast agents.

Gadolinium cryptelates are complexes of a lanthanide metal ion with amino acids of macrocyclic polyamines. These compounds are water soluble and possess reduced relaxation properties similar to Gd diethylene triamine pentaacetic acid (DTPA). Three Gd cryptelates (Gd NOTA, DOTA, TETA) were evaluated. Gadolinium DOTA is the most stable Gd complex with a dissociation constant of 10(-28) and appears to have a greater serum stability than Gd DTPA. Gadolinium NOTA and Gd TETA have lower dissociation constants than Gd DTPA at 10(-17) and 10(-19). Gadolinium DOTA has tissue distribution properties similar to Gd DTPA, is rapidly excreted by the kidneys, and provides a high degree of contrast enhancement on magnetic resonance (MR) images, both systemically and within the CNS. Hence, Gd DOTA is an alternative water-soluble MR contrast agent to Gd DTPA.

Animals↗