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Biomedical subjects

K Reynolds

Publications and source records attributed to K Reynolds.

At least 91 records · Page 5Linked to original sources
PubMed1989

Reactivity of anti-human milk fat globule antibodies with synthetic peptides.

The nucleotide sequence of partial cDNA clones coding for the core protein of a human polymorphic epithelial mucin has recently been obtained, this mucin consists of a highly conserved 60 bp tandem repeat and the amino acids commonly found are PDTRPAPGSTAPPAHGVTSA. We synthesized three peptides, 1) P1.24 containing the 20 amino acids and four amino acids (PDTR) of the adjoining repeat; 2) P1.15 consisting of the first fifteen (PDTRPAPGSTAPPAH) and P1.09 the second nine amino acids (GVTSAPDTR) of peptide P1.24. The reactivities of the synthetic peptides with mAb known to react with breast cancer (BC1, BC2, BC3, HMFG-1, 3E1.2, and RCC-1) were studied. The synthetic peptide, P1.24, corresponding to the antigenic sequence predicted from the tandem repeat reacted with antibodies BC1, BC2, and BC3 (known to react with human milk mucin and mucin expressed in breast cancer) and the antibody HMFG-1 which was used to select the cDNA clones. In addition, the epitopes recognized by BC1, BC2, and BC3 appear to be in the same region of the molecule represented by their reactions with the nine amino acids in peptide P1.09 (GVTSAPDTR). By contrast, other antibodies such as 3E1.2 which reacts only weakly with components of human milk, and RCC-1 that detects a low Mr component (95 kDa) in breast cancer, had no specific reaction with the synthetic peptides, indicating that their epitopes are distinct from those of BC1, BC2, BC3, and HMFG-1. Inasmuch as the antibodies HMFG-1, BC1, BC2, and BC3 react with the fully processed milk mucin, it is likely that some of the peptide is exposed, even in the fully glycosylated molecule. Identification of the different epitopes could lead to the development of "second generation" mAb with enhanced specificity for breast carcinoma using the appropriate synthetic peptides as immunogens.

Amino Acid Sequence↗
PubMed1989

Prolongation of heterotopic heart allograft survival by local delivery of continuous low-dose cyclosporine therapy.

The effectiveness of local versus systemic low-dose CsA (2 mg/kg/day) therapy delivered by osmotic pump for a 14-day continuous infusion was examined in the rat model. Systemic subtherapeutic CsA treatment of WFu recipients either by oral gavage or intravenously using an osmotic pump resulted in quick rejection of BUF heart allografts within a median survival time (MST) of 8 days in comparison with untreated controls (MST = 7 days). In contrast, direct local subtherapeutic CsA delivery to BUF heart allografts produced significantly (P less than 0.01) prolonged heart allograft survivals up to MST of 40 days. Splenic T cells, isolated on days 10 to 12 from locally immunosuppressed WFu recipients, revealed a nonspecifically reduced proliferative response toward alloantigens. Coculture experiments demonstrate that these T cells have the capacity to inhibit normal T cell proliferative responses in a nonspecific fashion either by their suppressor function or more likely by carrying CsA to the culture plate. In contrast, T cells isolated from WFu recipients three weeks after transplantation and tested in vitro demonstrated the presence in alloantigen specific T suppressor cells that coincided with a decreased frequency of alloantigen-specific T cytotoxic cells and may explain the extended heart allograft survival beyond the time of CsA delivery. CsA therapy delivered directly to the graft resulted in high CsA levels within the heart graft (1108 ng/0.1 g) but subtherapeutic levels in other tissues. These results demonstrate that local drug delivery is effective in inhibiting the rejection process within the graft itself, as manifested by prolonged heart allograft survival. Further, subtherapeutic CsA therapy facilitates development of Ts cells that may be responsible for the survival of heart allografts beyond the CsA delivery time.

Animals↗
PubMed1987

The effect of dexamethasone on tissue water distribution and proton relaxation in Panc02 tumors.

The present experiments were conducted to determine the effects of dexamethasone mediated changes in tumor water distribution on proton relaxation times (T1, T2) in a murine pancreatic adenocarcinoma (Panc02). Spin lattice (T1) and spin-spin(T2) relaxation times were determined by ex vivo methods (10 MHz) and by in vivo imaging techniques (6.25 MHz) at various intervals after single or multiple dexamethasone treatments. In complementary studies, dexamethasone mediated changes in tumor capillary permeability, tumor water distribution, relative tumor blood flow and tumor cell proliferation were also determined. Proton spin lattice (T1) and spin-spin (T2 relaxation times for Panc02 tumors shortened within two hours of a single dexamethasone treatment. The time course and magnitude of this response was dexamethasone dose dependent. The time dependent changes in T1 and T2 after dexamethasone were similar at 10 MHz (ex vivo) and 6.25 MHz (in vivo imaging). Although dexamethasone produced little or no change in total tumor water content and tumor cell proliferation, transient changes in the physiologic distribution of tumor water were clearly demonstrated. The data supports the idea that dexamethasone induced changes in the distribution of tumor water were mediated by changes in capillary permeability and tumor blood flow. These physiologic responses produced serial changes in tumor extracellular extravascular water content that were consistent with the observed changes in tumor T1 and T2. The results from these experiments might imply that therapy associated changes in tumor proton relaxation times may not only reflect changes in tissue water content, but may also reflect physiologic responses which alter the distribution of tissue water and solute.

Adenocarcinoma↗
PubMed1986

Biological implications of androgen dependent changes in proton-NMR relaxation times in rat ventral prostate.

The present studies were conducted in rat ventral prostate to determine if proton nuclear magnetic resonance (1H-NMR) might be a useful tool to monitor physiologic changes in an androgen-dependent target tissue after ablation and reconstitution. Ventral prostate mass and blood flow (86RbCl distribution) decreased markedly after castration. Although prostate water content was not affected by androgen ablation, 1H-NMR spin-lattice (T1) and spin-spin (T2) relaxation times determined on excised prostate tissue were reduced by 10% and 50%, respectively. Testosterone propionate (Tp) reconstitution resulted in a prompt but transient increase in total water content, marked increases in prostate blood flow, and regrowth of the gland. 1H-NMR studies indicated that although T1 lengthening after Tp was temporally related to changes in prostate water content, T1's remained prolonged after total prostate water content returned to control levels. Increased Gd-DTPA-dimeg modification of prostate T1 by Gadolinium-DTPA-dimethyl glucamine in androgen reconstituted rats implied that prostate extracellular water volumes were markedly increased during intervals of increased T1. Recovery of prostate T2 relaxation times after Tp was delayed with respect to changes in T1, water content, and prostate blood flow, but was temporally correlated with increase in prostate dry mass. Studies to assess Gd-DTPA-dimeg T2 modification showed that prostate T2 changes after androgen depletion and replacement reflected spin-spin relaxation of water protons outside the in vivo Gd-DTPA-dimeg distribution volume. The results from these studies indicate that 1H-NMR and paramagnetic probes may be useful to noninvasively monitor biologically relevant changes in cellular and extracellular water in androgen-dependent target tissues during hormonal manipulations.

Androgens↗
PubMed1982

Colobus type C virus: molecular cloning of unintegrated viral DNA and characterization of the endogenous viral genomes of Colobus.

The unintegrated viral DNA intermediates of colobus type C virus (CPC-1) were isolated from infected human cells that were permissive for viral growth. There were two major species of DNA, linear molecules with two copies of the long terminal repeat and relaxed circles containing only a single long terminal repeat. In addition, there was a minor species (approximately 10%) composed of relaxed circles with two copies of the long terminal repeat. A restriction endonuclease map of the unintegrated DNA was constructed. The three EcoRI fragments of circular CPC-1 DNA were cloned in the EcoRI site of lambda gtWES . lambda B and then subcloned in the EcoRI site of pBR322. Using these subgenomic fragments as probes, we have characterized the endogenous viral sequences found in colobus cellular DNA. They are not organized in tandem arrays, as is the case in some other gene families. The majority of sequences detected in cellular DNA have the same map as the CPC-1 unintegrated DNA at 17 of 18 restriction endonuclease sites. There are, however, other sequences that are present in multiple copies and do not correspond to the CPC-1 map. They do not contain CPC-1 sequences either in an altered form or fused to common nonviral sequences. Instead, they appear to be derived from a distinct family of sequences that is substantially diverged from the CPC-1 family. This second family of sequences, CPC-2, is also different from the sequences related to baboon endogenous type C virus that forms a third family of virus-related sequences in the colobus genome.

Animals↗
PubMed1979

Dacron bypass grafting in the relief of obstructive jaundice.

A new technique using a 'Dacron' tube bypass graft for relief of obstructive jaundice due to malignant disease is described. This method is applicable when a conventional bypass operation is technically impossible. Good palliation was achieved in all seven patients who survived the immediate postoperative period.

Carcinoma↗
PubMed1977

Effect of lysolecithin on gastric mucosal structure and potential difference.

The effect of lysolecithin (100 mg%) on the guinea-pig gastric mucosa was studied by instilling a solution for 30 minutes, preceded and followed by 100 MN HCl into 10 total gastric pouches. Ten control animals had HCl throughout. Lysolecithin produced a significant change in transmucosal potential difference, macroscopic erosions, and mucosal damage on histology and electron scanning microscopy. None of these changes was seen in the control animals. This is further evidence that the reflux of lysolecithin from the duodenum is an important factor in causing active gastritis and gastric erosions.

Animals↗