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Biomedical subjects

T Miller

Publications and source records attributed to T Miller.

At least 253 records · Page 14Linked to original sources
PubMed1986

Cholecystokinin receptors: relationships among phosphoinositide breakdown, amylase release and receptor affinity in pancreas.

The gut hormone cholecystokinin (CCK) octapeptide stimulates the release of amylase from exocrine pancreas, a process believed to be the result of the breakdown of phosphatidylinositol lipids. To examine further the relationship between phosphoinositide (PI) breakdown and amylase release, we have investigated the effect of N-terminally protected CCK C-terminal fragments in these systems using guinea-pig pancreatic lobules. There was a good correlation between the ability of these fragments to elicit amylase release and their potency in enhancing PI breakdown. In general, the EC50 for amylase release is 10-fold lower than the EC50 for PI breakdown. In addition, a good correlation existed between amylase release and the affinity of CCK fragments for [125I]Bolton Hunter-CCK octapeptide binding sites in pancreatic membranes. We also discovered that N-carbobenzyloxy-CCK tetrapeptide was relatively inefficient in causing PI breakdown, but it caused a near maximal stimulation in amylase release. These findings might reflect an amplification mechanism between PI breakdown and amylase release or that N-carbobenzyloxy-CCK tetrapeptide-induced amylase release is independent of PI breakdown.

Amylases↗
PubMed1986

Immunologic complexity of lymphoblastic lymphoma.

Twelve patients with a histologic diagnosis of lymphoblastic lymphoma (LBL) were studied immunologically using the methodologic refinement of comparative serial section immunochemistry. By this means, we demonstrate complex LBL phenotypic profiles, revealing 3 major immunologic subtypes: immature T cell, 7 cases; intermediate or mature T cell, 3 cases; immature B cell (pre-pre-B), 2 cases. This phenotypic diversity challenges the basic belief that all LBL are the same. Our immature T-cell cases with frequent simultaneous Leu 2/3/6/9/CALLA/Tdt expression correspond to cortical thymic phenotypes; our mature T-cell phenotypes with Leu 9/la expression and absent L6/Tdt correspond either to medullary thymocytes or post-thymic T cells; our pre-pre-B phenotypes with simultaneous Tdt/CALLA/B4 expression correspond to common acute lymphocytic leukemia (ALL) phenotypes. Mature T-LBL phenotypes are similar to "novel" peripheral T-cell lymphoma phenotypes. Scant or absent Tdt expression in mature LBL is not an isolated antigenic change but a complete phenotypic profile difference from immature T-LBL. The major T- and B-cell phenotypes of LBL might have therapeutic significance. Treatment among LBL phenotypes may need to vary as with acute lymphocytic leukemia phenotypes. Further study is needed; in the meantime, comparative serial section immunotyping promises substantial utility in revealing the immunologic complexity of the lymphomas.

Adolescent↗
PubMed1985

Translation and functional expression of cell-cell channel mRNA in Xenopus oocytes.

mRNA from estrogen-stimulated rat myometrium, a tissue known to upregulate cell-cell channels in response to this hormone, was microinjected into Xenopus laevis oocytes. The oocytes had been freed from covering layers of follicle cells and vitelline to allow direct cell membrane interactions when paired. About 4 hours after the mRNA injection, paired oocytes become electrically coupled. This coupling was due to the presence of typical cell-cell channels characterized by size-limited intercellular tracer flux, the presence of gap junctions at the oocyte-oocyte interface, and the reversible uncoupling that occurred in the presence of carbon dioxide. The induction of new cell-cell channels in the oocyte membrane was observed against a zero background or a low level of endogenous coupling, depending on the maturation stage of the oocytes. The time course of development of cell-cell coupling after the microinjection of mRNA was determined. The mRNA capable of inducing cell-cell coupling was confined to an intermediate size class when fractionated on a sucrose gradient.

Animals↗
PubMed1985

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow.

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.

Antibodies, Monoclonal↗
PubMed1985

Expanding horizons: innovations in community health nursing education.

Application of this learning process (problem assessment, program planning, intervention, and evaluation) at the aggregate level, was a creative, enjoyable, growth producing experience for the senior nursing students. It is a process that is not only useful in the local community, but also prepares nurses for working at county, state, and national levels. They learn to make valid observations and firm decisions, to carry out actions, to overcome obstacles, to alter behavior, and to evaluate results. It does not replace other practices and former services of community health nursing, but complements them. There exists a tremendous potential for nurses in planning health care, already being realized in many settings. Certainly grass roots communities, rural populations and urban neighborhoods are in the highest need of creative, effective health programs that take into account the total population. Given such creativity, it is possible by the year 2000, that the Community Health Nurse may become a combination medical advisor, health instructor, community leader, playwright, photographer, author and television director; certainly a captivating career for people of the New World.

Adolescent↗
PubMed1985

Characterization of cholecystokinin receptor sites in guinea-pig cortical membranes using [125I]Bolton Hunter-cholecystokinin octapeptide.

[125I]Bolton Hunter-cholecystokinin octapeptide (BH-CCK8) has been prepared using a modified method and was used to study putative cholecystokinin (CCK) receptor sites in the guinea-pig cerebral cortex. Specific binding of [125I]BH-CCK8, defined as the difference in binding in the absence and presence of 10(-6) M CCK8, was 70% of total binding. In saturation experiments, the apparent dissociation constant (Kd) was 1 nM and total binding capacity was 28 fmol/mg of protein. In association experiments, conducted at 30 degrees C, binding of [125I]BH-CCIK8 reached equilibrium in approximately 150 min. Binding was stable for 4 hr and was reversed by the addition of unlabeled CCK8-sulfated. Dissociation of bound ligand was biphasic and the apparent T1/2 was 45 min. Analyses of kinetic experiments yielded an association rate constant of 0.58 X 10(8) min-1 M-1 and a dissociation rate constant for the slower component of 0.012 min-1. Dithiothreitol increased and N-ethylmaleimide decreased specific binding of [125I]BH-CCK8, indicating that CCK receptor sites involve sulfhydryl groups. In competition experiments, the potency of CCK4 was enhanced 50-fold with addition of protease inhibitors. The rank order of CCK-related peptides was CCK8-sulfated greater than or equal to Gastrin 17 greater than or equal to CCK33 greater than CCK4 greater than or equal to CCK8-desulfated. Proglumide, a proposed CCK antagonist in the periphery and brain, was inactive at 10(-3) M. The specificity of [125I]BH-CCK8 binding sites are similar to that reported for [125I]BH-CCK33.

Animals↗
PubMed1984

The hypothermic effect of 4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl (CGP 6085 A) in Wistar Kyoto rats.

CGP 6085 A [4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl], a reported serotonin uptake and MAO (16) inhibitor, is a potent hypothermic agent. The hypothermic action of CGP 6085 A is dose dependent with a maximal reduction in rectal core temperature of greater than 1 degree C within one hour after drug administration. Fluoxetine and citalopram elicit a similar response at equal doses. These results suggest that inhibition of serotonin uptake may produce the hypothermic effect. To assess the in vivo action of CGP 6085 A in inhibiting hypothalamic serotonin uptake, CGP 6085 A (10 mg/kg) was injected one hour prior to injection of 3-hydroxy-4-methyl-alpha-ethyl-phenylethylamine (H75/12), a serotonin depletor. The ability of CGP 6085 A to block the uptake of H75/12 by the 5HT uptake system was indicative of its ability to block serotonin uptake. Pretreatment with p-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, resulted in the loss of the hypothermic response to CGP 6085 A. Thus, these data are consistent with the idea that CGP 6085 A may produce its hypothermic response by inhibiting serotonin uptake.

Amphetamines↗
PubMed1984

In vivo evidence for prostaglandin inhibitory activity in New Zealand green-lipped mussel extract.

Prostaglandin synthetase inhibitors (eg, aspirin, indomethacin and naproxen) interfere with ovulation and prolong the gestation period in the rat. These properties could provide a novel test bed for the assessment of agents with prostaglandin biosynthesis inhibitory activity. Rats were fed green-lipped mussel extract and the effects on conception and the subsequent gestation period were determined. Parturition was delayed and fetal development was retarded in the Seatone-fed animals. The observations were consistent with the known effects of nonsteroidal anti-inflammatory drugs, suggesting that Seatone does contain pharmacologically active material inhibiting prostaglandin biosynthesis.

Animals↗
PubMed1984

Storage of chemotherapy drugs for use in the human tumor stem cell assay.

Tumor chemosensitivity assays require the frequent in vitro use of antineoplastic drugs. Economy and convenience are greatly enhanced if these drugs are stored in aliquots for use as needed. This study investigated the stability of eight common antineoplastic agents at -60 degrees C. Activity was measured as inhibition of colony formation in a commonly used soft agar culture system using an experimentally induced murine sarcoma. Our results indicate no loss of activity with these drugs under the specified storage conditions.

Animals↗
PubMed1984

Quantitative and qualitative effects of m-AMSA (amsacrine) on cellular immune components.

The recently developed acridine derivative 4'-[(9-acridinyl)amino] methanesulphon-m-anisidine (m-AMSA) has become one of the preferred agents in the management of acute leukaemia but little is known of its effects on cellular immune components. We evaluated the qualitative and quantitative effects of m-AMSA on immune cell numbers and function, during both the leucopenic and myelorestorative phases, following intermittent high-dose therapy. Cell-mediated and inflammatory responses were depressed in the treated animals during the leucopenic phase but restoration of immune capability paralleled the recovery of circulating leucocyte numbers. Additionally, m-AMSA displayed unexpected immunomodulatory features: thymus-dependent antibody and delayed-type hypersensitivity responses were actually increased, suggesting the potential of m-AMSA as an immunoregulator in clinical and experimental studies.

Aminoacridines↗
PubMed1984

Pyelonephritis: the role of cell-mediated immunity defined in a congenitally athymic rat.

Thymus-derived lymphocytes (T-cells) have been shown to be present in the inflammatory infiltrate in renal infection but their role in host defense mechanisms has not been defined. Indirect evidence suggested that T-cells contributed to host protection but selective depletion of T-cells did not influence the course of pyelonephritis. In the present report, the characteristics of the athymic New Zealand nude rat (rnunz), which lacks T-lymphocytes, are detailed. This mutant was then used to assess the effect of an absence of T-cells on the bacteriological and histopathological features of pyelonephritis. No significant differences in the bacteriological course of the disease were found. Apart from fewer lymphocytes in the kidney lesions of nude rats and a slight, lag in the resolution of these lesions, no differences were observed in the histopathological course either. These observations, which have analyzed the quantitative relationship between cell-mediated immunity (CMI) and host resistance to renal infection, have shown that a gross reduction in CMI does not affect host resistance once bacteria have gained access to the kidney.

Animals↗
PubMed1983

Nuclear magnetic resonance imaging of mammary adenocarcinomas in the rat.

A study of 24 rats implanted in the hind leg with mammary adenocarcinomas and five sham-implanted rats, followed from the second to the eight week postimplantation, showed nuclear magnetic resonance imaging capable of detecting all the tumors without yielding any false-positives in the control rats. The T1 relaxation time of tumors overlapped that of muscle, and the T2 times overlapped fat, but the combination was unique when comparing tumors to muscle and fat. Necrotic regions of the tumor and the bladder contents tended to have very long T1 and T2 relaxation times. The difference in relaxation time between tumors and muscle could be accounted for in terms of water content, which was approximately 8% higher for the tumors. The study corroborates data from previous studies indicating that NMR imaging is a highly sensitive modality, although T1 and T2 times are not exclusive indicators of malignancy.

Adenocarcinoma↗