Search PubMed⌕ Search

Biomedical subjects

J C Reynolds

Publications and source records attributed to J C Reynolds.

At least 127 records · Page 7Linked to original sources
PubMed1989

Local distribution and concentration of intravenously injected 131I-9.2.27 monoclonal antibody in human malignant melanoma.

Regional measurements of 131I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of 131I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.

Adult↗
PubMed1989

Caloric content of a meal affects duration but not contractile pattern of duodenal motility in man.

The variability of the fasted duodenal contractile pattern and the patterns of contraction during the fed phase was examined in normal volunteers. Prolonged recordings from the duodenum and proximal jejunum were achieved using a series of transducers mounted on a 2.3-mm catheter. A total of 58 interMMC intervals and the response to 18 meals was examined. There was marked inter- and intrasubject variability in the fasted state, even within one study. The phase II pattern was examined in detail and propagated single peaks, propagated clusters, and repeated propagated clusters are described. Single peaks could be propagated as rapidly as 16 cm/sec. Single peaks were propagated more rapidly than propagated multiple peaks. During phase III, duodenal contractions occurred at 11.3 +/- 0.09/min and jejunal contractions at 10.73 +/- 0.15/min. The rate of progression of the onset of phase III was 0.145 +/- 0.015 cm/sec. The effect of the caloric content of the meal was examined by determining the effect of 150-kcal, 300-kcal, and 600-kcal meals on the fed pattern. Increasing caloric content increased the duration of the fed pattern but had no effect on the total or normalized motility index or on the change in motility index over time during the fed pattern. The types of contractions seen during the fed pattern are described. Propagated clusters over at least 16 cm are common during the fed phase in normals, with 10% of all contractions seen during the fed phase being propagated over 28 cm. No difference in the patterns of contractions or their propagation was seen with the different caloric contents of the meals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Colonic slow-wave analysis. Limitations of usefulness of fast Fourier transform (FFT).

The fast Fourier transform (FFT) has been used to determine frequency components of colonic slow-wave activity. We studied the effect of (1) recorder filter characteristics, (2) number of data points and, (3) data window overlap technique and ingestion of a 1000-kcal meal on the resulting power spectrum. Human rectosigmoid slow-wave activity was recorded in nine normal subjects and stored on FM tape for computer analysis. The dynograph filter characteristics were tested using square wave signals, and derived compensation factors were applied to the FFT before viewing. The dynograph filter, when set to optimize visualization of slow waves, attenuates low frequencies nonlinearly. Failure to compensate for the dynograph filter results in inaccurate detection of slow-wave frequencies. FFT of 1-min data gives a different power spectrum than an FFT of 4 min data, indicating a rapidly changing waveform. FFT's of 1 min of data when examined over time fail to demonstrate a consistent frequency spectrum, confirming this conclusion. The lower frequencies in the normal human rectosigmoid are present at the greatest power. These studies indicate that the colon has slow waves of irregular frequencies, in contrast to the stomach or small intestine. No change in the dominant frequency was seen following the ingestion of a 1000-kcal meal.

Adult↗
PubMed1989

Calcitonin gene-related peptide: a sensory and motor neurotransmitter in the feline lower esophageal sphincter.

UNLABELLED: The effect of calcitonin gene-related peptide (CGRP) on the feline lower esophageal sphincter (LES) was determined and correlated with its anatomic distribution as determined by immunohistochemistry. Intraluminal pressures of the esophagus and LES were recorded in anesthetized cats. In separate cats, gastroesophageal junctions were removed after locating the LES manometrically and stained for CGRP-like immunoreactivity (LI) and substance P-LI (SP-LI) by indirect immunohistochemistry. CGRP-LI in the LES was most prominent in large nerve fascicles between the circular and longitudinal muscle layers and only rarely seen in nerve fibers within the circular muscle. The myenteric plexus contained numerous CGRP-LI nerve fibers but cell bodies were not seen. Many CGRP-LI nerve fibers in the myenteric plexus and occasional varicose nerves in the circular muscle demonstrated colocalization with SP-LI. Colocalization of CGRP-LI with SP-LI was also seen in the perivascular nerves of the submucosal and intramural blood vessels and in varicose fibers in the lamina propria of the gastric fundic mucosa. In the esophagus, CGRP-LI nerves extended through the muscularis mucosa and penetrated the squamous epithelium to the lumen. CGRP, given intra-arterially caused a dose-dependent fall in basal LES pressure, with a threshold dose of 10(-8) g/kg (2.63 pmol/kg). At the maximal effective dose, 5 x 10(-6) g/kg (1.31 x 10(3) pmol/kg), CGRP produced 61.0 +/- 6.0% decrease in basal LES pressure. At this dose, mean systemic blood pressure fell by 40.9 +/- 7.8%. The LES relaxation induced by a submaximal dose of CGRP (10(-6) g/kg, 262.7 pmol/kg), 50.3 +/- 3.2% relaxation was partially inhibited by tetrodotoxin (26.9 +/- 10.8% relaxation, P less than 0.025). The inhibitory effect of CGRP was not affected by cervical vagotomy, hexamethonium, atropine, propranolol, or naloxone. The LES contractile response to the D90 of SP (5 x 10(-8) g/kg, 37.1 pmol/kg) was not altered by CGRP 10(-8) or 10(-6) g/kg and the CGRP relaxation effect was not altered by the threshold dose of substance P (5 X 10(-9) g/kg, 3.71 pmol/kg). CONCLUSIONS: (1) CGRP-LI is present at the feline LES and is primarily seen in large nerve fascicles which pass from the intermuscular plane and through the circular muscle layer to the submucosa and in mucosal nerves. (2) CGRP colocalizes with SP-LI in some varicose nerve fibers of the circular muscle of the esophagus, LES and fundus, in perivascular nerves of the submucosal and intramucosal blood vessels, and in nerves of the lamina propria of the gastric fundus. (3) The luminal penetration of CGRP-LI nerves in the squamous mucosa of the esophagus suggests a sensory func

Animals↗
PubMed1989

Anti-murine antibody response to mouse monoclonal antibodies: clinical findings and implications.

Many patients given murine monoclonal antibody become immune to these proteins. Important factors in the development of immunity are (1) the patient's ability to become immune and (2) whether whole immunoglobulin or Fab fragment was used. Circulating anti-murine antibodies increase the murine antibody plasma clearance and the liver or spleen uptake while reducing tumor targeting. Clearance rates and radioassay measured levels of anti-murine antibodies are related to serum murine/anti-murine antibody complexes. Unlabeled murine antibody displaces radiolabeled antibody from these complexes.

Animals↗
PubMed1989

Comparison of bone marrow dosimetry and toxic effect of high dose 131I-labeled monoclonal antibodies administered to man.

131I-labeled monoclonal antibodies were used in therapeutic trials in two potentially useful clinical situations: disseminated melanoma (intravenously administered Fab fragments; 21 patients) and disseminated peritoneal adenocarcinomatosis (intraperitoneal injection of IgG; 5 patients). Acute toxicity observed is consistent with mild bone marrow suppression of acute radiation syndrome and the observed toxicity is dose related in a manner that conforms to the expected human response to total body irradiation. For single doses of both i.p. administered and intravenously administered 131I-labeled anti-tumor antibodies, 100 rad to red marrow, calculated by the absorbed dose fraction method (MIRD), appeared to be a threshold below which significant acute toxicity was unlikely.

Adenocarcinoma↗
PubMed1989

Neuropeptide Y augments adrenergic contractions at feline lower esophageal sphincter.

The purpose of this study was to determine the anatomic and physiological interactions between neuropeptide Y (NPY) and adrenergic transmitters at the feline lower esophageal sphincter (LES). Intraluminal pressures of the esophagus, LES, and gastric fundus were recorded in anesthetized cats. In a separate group of cats, gastroesophageal junctions were removed after locating the LES manometrically. Adjacent sections were stained with antibodies for NPY and tyrosine hydroxylase (TH). Indirect immunofluorescence revealed staining of TH- and NPY-like immunoreactive (LI) nerves in the circular muscle of the LES. Staining was also present for NPY-LI in longitudinal muscle, muscularis mucosa, periarterial nerves, and nerves and cell bodies of the myenteric plexus of the LES. In vivo, NPY produced a biphasic effect at the LES with an initial contraction (lasting approximately 30 s) followed by a relaxation (lasting approximately 3 min). NPY at the dose giving 50% of the maximum response (10(-6) g/kg) induced a contraction of 14.8 +/- 5.0 mmHg (P less than 0.05) followed by a decrease of basal LES pressure from 29.2 +/- 4.7 to 19.4 +/- 2.9 mmHg (P less than 0.01). Propranolol and phentolamine had no influence on either effect of NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Achalasia.

Achalasia is a chronic illness that can be treated effectively in 65 to 90 per cent of patients with either pneumatic dilatation or Heller esophagomyotomy. Prior to institution of therapy, clinicians must rule out secondary achalasia, especially malignancy-associated achalasia, with upper endoscopy, and if the clinical history is worrisome for malignancy, with a computerized tomography scan of the chest and abdomen. Medical therapy with isosorbide dinitrate or nifedipine is occasionally useful for temporary control of dysphagia prior to a more definitive treatment or for the elderly or medically complicated patient who has increased risks for surgery. Complications of pneumatic dilatation, though rare, can be recognized with the use of postprocedure contrast studies of the esophagus and monitoring the patient for 6 hours after the dilatation. The appropriate long-term management of the patient must include personal support and a clear understanding of the potential for developing complications.

Animals↗
PubMed1989

Prokinetic agents: a key in the future of gastroenterology.

Prokinetic drugs enhance the motility of the luminal organs of the gastrointestinal tract. Few drugs developed in this decade are likely to have a greater impact on the treatment of disorders of the gastrointestinal tract. Bethanechol and metaclopramide have proven the potential utility of this class of drugs, whereas newer agents promise to have both a greater margin of safety and tolerability and a broader scope of utility. The efficacy of these agents is reviewed for the treatment of impaired motility from gastroesophageal reflux to severe chronic constipation.

Biomechanical Phenomena↗
PubMed1989

Differences in biodistribution of indium-111-and iodine-131-labeled B72.3 monoclonal antibodies in patients with colorectal cancer.

We have compared the biodistributions of [131I]B72.3 and 111In-SCN-Bz-DTPA B72.3 monoclonal antibody (MoAb) in patients with metastatic colon cancers. B72.3 is an IgG1 that recognizes a mucin-like colon cancer associated antigen. Eight patients were infused with 3-5 mCi and 0.36-20 mg of 111In-labeled B72.3 prepared with a bifunctional chelate, isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA). The biodistribution was compared with that of 13 patients previously studied as part of a separate trial, with 1-10 mCi and 0.16-1.35 mg of [131I]B72.3. The Beta T1/2 in serum was 63 +/- 5 hr for 111In-SCN-Bz-DTPA B72.3 and 52 +/- 10 hr for [131I]B72.3. Whole-body retention of the 111In (T1/2 = 11.8 days) was significantly longer than for [131I]B72.3 (T1/2 = 3.3 days), p less than 0.000001. The 131I was excreted primarily through the urine. Urinary excretion of 111In was low and gamma camera images confirmed that some 111In was excreted in the bowel. Tumor localization was seen in one of seven evaluable patients receiving 111In-SCN-Bz-DTPA B72.3. Gamma camera images showed that the liver concentrates 111In but not 131I. We conclude that 111In-SCN-Bz-DTPA B72.3 is metabolized in a different manner from the iodinated B72.3. The high concentration and prolonged retention of 111In by the liver interferes with tumor imaging of metastases.

Antibodies, Monoclonal↗
PubMed1989

The effect of meal energy content on gastric emptying.

Gastric emptying (GE) has been reported to be influenced by meal weight (grams) and composition (% carbohydrate:protein:fat) but the effect of meal energy content (kcal) on gastric emptying, independent of composition, has not been thoroughly investigated by scintigraphic techniques. In order to determine the effect of caloric content on GE, 12 normal male volunteers, ranging in age from 19-28 yr (mean = 24 yr), had GE scans (n = 32) performed with a solid meal of fixed composition (carbohydrate 40%:protein 40%:fat 20%) but varying energy content [150 kcal (n = 9), 300 kcal (n = 14), and 600 kcal (n = 9)]. Increasing the energy content of the meal of fixed composition progressively delayed gastric emptying: T1/2 = 57', 70', and 95' for 150 kcal, 300 kcal and 600 kcal, respectively (p less than 0.05; Student's t-test). Reproducibility, evaluated by performing GE scans (n = 8) on different days in the same individual (n = 4) with the same meal (300 kcal), was good (r greater than or equal to 0.89). Variability varied inversely with meal energy content (CV:150 kcal greater than or equal to 300 kcal and 600 kcal). The 300 kcal mean seems to be the best compromise since it results in less intersubject variability than 150 kcal, has minimal intrasubject variability, but is not as prohibitively large as the 600 kcal meal.

Adult↗
PubMed1989

In vitro complex formation and biodistribution of mouse antitumor monoclonal antibody in cancer patients.

The serum clearance and biodistribution of a murine monoclonal antibody were compared to the in vitro complex formation of the antibody with patients' sera. Iodine-125-labeled 9.2.27, an anti-melanoma antibody, was incubated with sera from ten melanoma patients who had received 9.2.27 in an earlier study. Complexes were observed in all patients using size exclusion high performance liquid chromatography and complex formation was partially blocked by nonspecific murine antibody, suggesting the presence of human anti-murine antibody in serum. All patients subsequently underwent imaging studies with [131I] 9.2.27 given intravenously. The serum levels of the antibody obtained after the second administration were inversely correlated with the level of in vitro complex formation. Patients whose serum formed high levels of complex showed a rapid serum clearance, high hepatic uptake, and accelerated whole body clearance and urinary excretion of 131I. This suggests that in patients who receive repetitive administration of murine antibody the serum clearance rate and biodistribution of intravenously injected antibody are altered by antibody complex formation in the serum.

Adult↗
PubMed1989

Reduction of background activities by introduction of a diester linkage between antibody and a chelate in radioimmunodetection of tumor.

A diester linkage was added between monoclonal anti-melanoma antibody 96.5 and a diethylenetriaminepentaacetic acid derivative to test if a tumor-to-blood and -to-organ ratio of the injected antibody in nude mice with human melanoma FEM XII xenografts could be increased by the addition of the readily cleavable linkage. Compared to the 111In-labeled antibody DTPA with a peptide linkage, the diester conjugate cleared much faster from the blood and was retained much less in muscle and normal organs such as liver, spleen and kidney over a 48-hr period. On the other hand, the activity retained in the tumor was larger than or similar to that of the peptide conjugate for this time period. This resulted in a 2.5, 2.1, and 2.6 fold increase in a tumor to blood, to liver and to kidney ratio at 48 hr for the diester conjugate as compared to the peptide conjugate. The whole-body biologic half life of the antibody was 36 hr, three times shorter than the peptide conjugate. The external imaging demonstrated a clearly visible tumor at 4 hr and a lower pool activity at 72 hr for the diester conjugate. The peptide conjugate, however, showed a persistant blood-pool activity at 72 hr. The addition of the diester linkage, therefore may be beneficial for imaging tumors in patients at early time intervals after injection.

Animals↗
PubMed1988

Measurement of local Mr 97,000 and 250,000 protein antigen concentration in sections of human melanoma tumor using in vitro quantitative autoradiography.

An assay method that uses 125I-labeled monoclonal antibody (MoAb) and in vitro quantitative autoradiography was developed to determine the local concentration of tumor-associated antigens in tissue sections. Human melanoma biopsy specimens were evaluated for the expression of the Mr 97,000 and 250,000 protein antigens using MoAb-96.5 and MoAb-9.2.27, respectively. Tissue sections were incubated in solutions of increasing concentration of 125I-labeled MoAb with or without an excess of unlabeled antibody. Quantitative autoradiography was performed on the sections and compared with 125I standards to determine tumor-bound radioactivity and calculate bound pmol of MoAb per g of tumor. The total binding, nonsaturable binding, and specific binding of 125I-labeled MoAb to tumor were then computed. Specific binding of MoAbs to tumor tissue was saturable in all antigen-positive tumors. The maximal concentration of specific binding of antibody to tissue (Bmax) represented the tissue antigen concentration. Estimates of the Ka of antigen/antibody binding were also made. The reliability of the measurements was confirmed by testing sections from mixtures of antigen-positive and antigen-negative cells.

Antibodies, Monoclonal↗
PubMed1988

Brownian dynamics of cytochrome c and cytochrome c peroxidase association.

Brownian dynamics computer simulations of the diffusional association of electron transport proteins cytochrome c (cyt c) and cytochrome c peroxidase (cyt c per) were performed. A highly detailed and realistic model of the protein structures and their electrostatic interactions was used that was based on an atomic-level spatial description. Several structural features played a role in enhancing and optimizing the electron transfer efficiency of this reaction. Favorable electrostatic interactions facilitated long-lived nonspecific encounters between the proteins that allowed the severe orientational criteria for reaction to be overcome by rotational diffusion during encounters. Thus a "reduction-in-dimensionality" effect operated. The proteins achieved plausible electron transfer orientations in a multitude of electrostatically stable encounter complexes, rather than in a single dominant complex.

Chemical Phenomena↗