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Biomedical subjects

A Carter

Publications and source records attributed to A Carter.

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

Antinociceptive activity of pentamorphone, a 14-beta-aminomorphinone derivative, compared to fentanyl and morphine.

The analgesic potency of pentamorphone, a 14-beta-aminomorphinone derivative, was compared to that of fentanyl and morphine by examining quantal dose-effect curves generated from data obtained in the mouse hot plate, rabbit tooth-pulp, and dog tail clamp tests. Onset and duration of antinociceptive effects were also compared. The ED50 values (mg/kg) were determined in mice for pentamorphone (0.0039), fentanyl (0.016), and morphine (7.3). In the rabbit tooth pulp test the ED50 values were 0.0009 mg/kg for pentamorphone, 0.0074 mg/kg for fentanyl, and 1.1 mg/kg for morphine; in the dog tail clamp test these values were 0.012 mg/kg for pentamorphone and 0.018 mg/kg for fentanyl. Duration of action (defined as the time until response to tooth pulp stimulation declined to 50% of maximum possible effect [MPE]) was 10 min with twice the IV ED50 for pentamorphone in mice. This duration was similar to that of the equipotent dose of fentanyl but much shorter than the duration of an equipotent potent dose of morphine (60 min). The duration in rabbits of the ED98 (IV) dose of pentamorphone was 65 min compared to 35 min for an equipotent dose of fentanyl and 200 min for morphine. Intramuscular doses of pentamorphone had significantly faster onset and shorter duration times than equipotent doses of morphine in both mice and rabbits. Pretreatment with naloxone in mice and rabbits attenuated the development of the antinociceptive effects of pentamorphone. This study shows that pentamorphone is a potent analgesic with a duration of action similar to that of fentanyl.

Analgesics↗
PubMed1989

Antigen stimulated IgM secretion by circulating B lymphocytes in patients with benign and malignant IgG gammopathy. Relationship to stage of disease.

In the present investigation antigen-driven (sheep red blood cells, SRBC) IgM antibody secretion by B lymphocytes of 22 MM (IgG kappa) patients and 15 patients with IgG kappa monoclonal gammopathy of undetermined significance (MGUS) was studied and compared to that of 20 age-matched healthy controls and five patients with Waldenstrum (IgM) macroglobulinemia (WM). Antibody production by cultured lymphocytes of MM and WM patients was significantly decreased, whereas in MGUS patients it fell within normal limits. We could divide MM patients into three subsets: those who secrete normal amounts of IgM in vitro (patients with the stable type); a second subset of patients whose B lymphocytes secreted low amounts of IgM (MM patients in remission); and a third subset of patients who manifested an intrinsic block of B cell differentiation into IgM-secreting cells (patients with the progressive stage). Sephadex G-10 adherent suppressor cells had no effect on antibody production in the stable and progressive types of disease, whereas in the remission stage they markedly inhibited IgM secretion. Measurement of antigen-driven IgM antibody secretion might help in the differentiation of MGUS and stable (smouldering) MM from frank (progressive) MM at diagnosis. It may also provide a tool for monitoring progression of disease and response to therapy.

Aged↗
PubMed1988

Purification of heterotrimeric GTP-binding proteins from brain: identification of a novel form of Go.

Using high-resolution Mono-Q anion-exchange chromatography, we purified four distinct GTP-binding proteins from bovine brain. Each consists of alpha and associated beta/gamma subunits, and each is a substrate for pertussis toxin catalyzed ADP-ribosylation. We defined the relationship between the alpha subunits of the purified proteins and cloned cDNAs encoding putative alpha subunits (1) by performing immunoblots with peptide antisera with defined specificity and (2) by comparing the migration on two-dimensional gel electrophoresis of the purified proteins, and of the in vitro translated products of cDNAs encoding alpha subunits. Purified G proteins with alpha subunits of 39, 41, and 40 kDa (G39, G41, and G40 in order of abundance) correspond to the products of Go, Gi1, and Gi2 cDNAs. We purified a novel G protein with an alpha subunit slightly above 39 kDa (G39*). G39* is less abundant than G39, elutes earlier than G39 on Mono-Q chromatography, and has a more basic pI (6.0 vs 5.6) than G39. G39 and G39*, however, are indistinguishable on immunoblots with a large number of specific antisera. The data suggest that G39* may represent a novel form of Go, differing in posttranslational modification rather than primary sequence.

Animals↗
PubMed1988

Identification of the GTP-binding protein encoded by Gi3 complementary DNA.

Three closely related, but distinct, GTP-binding proteins (G-proteins) are encoded by cDNAs arbitrarily designated Gi1, Gi2, and Gi3. The in vitro translated products of mRNAs prepared from Gi1, Gi2, and Gi3 cDNAs migrate as 41-, 40-, and 41-kDa proteins, respectively, on sodium dodecyl sulfate-polyacrylamide gels. Antisera were raised against synthetic decapeptides corresponding to a divergent sequence (residues 159-168 for Gi1 and Gi3; 160-169 for Gi2) of the three cDNAs and tested on immunoblots for reactivity with three purified G-proteins, G41 and G40 from brain and G41 from HL-60 cells. LD antisera (Gi1 peptide) react only with brain G41. LE antisera (Gi2 peptide) react only with brain G40, and SQ antisera (Gi3 peptide) react exclusively with HL-60 G41. The results indicate that the 41-kDa G-protein purified from HL-60 cells differs from the purified brain 41-kDa protein and suggest that the HL-60 cell protein corresponds to that encoded by Gi3 cDNA.

Amino Acid Sequence↗
PubMed1988

Hepatocellular carcinoma imaging.

Radionuclide scintigraphy can give a specific diagnosis when a hypervascular "cold" defect on colloid scans "fills in" with gallium scanning. The majority of hepatocellular carcinomas will also accumulate hepatobiliary agents especially in delayed images. Magnetic resonance imaging is superior to other modalities in providing anatomic detail, such as location and relation to vessels, needed by the surgeon in operative planning.

Carcinoma, Hepatocellular↗
PubMed1988

Chemiluminescence response of polymorphonuclear leucocytes to serum-opsonized zymosan--a predictive parameter for infections and prognosis in multiple myeloma patients.

Serum opsonization capability and phagocytosis by polymorphonuclear leucocytes (PMNL) were investigated in 37 patients with multiple myeloma (MM), 32 patients with chronic lymphocytic leukaemia (CLL), and 30 healthy controls. Opsonophagocytosis was assessed by measuring the chemiluminescence (CL) response of controls' and patients' PMNL to control- and patient-serum-opsonized zymosan particles. Control PMNL CL responses were significantly reduced both by MM and CLL sera. Normal sera restored the CL responses in MM patients, but only partially corrected the CL responses in CLL patients. Significant correlations were found between the CL responses in MM patients and four clinical parameters: clinical stage, presence of disease-related symptoms, incidence of bacterial infections, and outcome. The findings suggest a defect in MM and CLL sera opsonization ability which, at least in part, could account for the increased susceptibility to infections observed in these patients. Furthermore, the assessment of the CL response in MM patients is recommended as a simple and useful clinical tool for prediction of susceptibility to infection, and prognosis.

Acridines↗
PubMed1988

Immunochemical studies of the 36-kDa common beta subunit of guanine nucleotide-binding proteins: identification of a major epitope.

Twenty-four of 24 rabbits immunized with the beta subunit common to guanine nucleotide binding proteins developed antibodies reactive on immunoblots with the 15-kDa (amino-terminal) tryptic fragment of beta. Only 2 of 24 developed antibodies reactive with the 26-kDa (carboxy-terminal) tryptic fragment. The 15-kDa fragment-reactive antibodies were also detected in several nonimmune sera. Antibodies reactive with the 15-kDa fragment could be affinity-purified from all beta-immune sera by adsorption to a fusion protein encoded by a cDNA clone identified by expression vector screening. The 15-kDa fragment antibodies in nonimmune sera did not bind to the fusion protein. Limited amino acid sequence homology between the 36-kDa beta subunit and the protein encoded by the cDNA clone suggested that the amino-terminal decapeptide of beta contains a major epitope. A synthetic decapeptide, corresponding to the amino terminus of the 36-kDa beta subunit, effectively and specifically blocked binding of antibodies in beta-immune sera (but not in beta-reactive nonimmune sera) to nitrocellulose-bound 15-kDa fragment. The 15-kDa fragment-reactive antibodies could be affinity-purified from beta-immune sera on a matrix containing bound decapeptide; affinity-purified antibodies reacted equally well with the 36- and 35-kDa forms of the beta subunit. Native transducin beta/gamma complexes readily blocked binding of 15-kDa fragment-reactive antibodies in immune but not nonimmune sera from binding to the nitrocellulose-bound fragment. The results show that nonimmune sera may contain antibodies directed against an epitope of the 15-kDa fragment that is buried in the native beta/gamma complex. In contrast, the amino terminal decapeptide of the beta subunit is exposed on the surface of the native protein and contains a major antigenic site in both the 35- and 36-kDa forms.

Amino Acid Sequence↗
PubMed1987

Prognostic significance of plasma cell morphology in multiple myeloma.

The effect of bone marrow plasma cell morphology at diagnosis on survival time was evaluated in 139 patients with multiple myeloma. According to the morphological classification scheme the patients were categorized as mature (30 patients), immature (76 patients) or plasmablastic (33 patients). The plasmablastic group had an estimated median survival (Kaplan-Meier method) of 10.9 months, compared with 32.2 months for immature and 60 months for mature types (P = 0.0000). The prognostic value of a morphologic classification in multiple myeloma was further demonstrated by means of a multivariate linear regression analysis of survival data. Expected survival was calculated using clinical features and morphologic subtypes. The estimated survival time for plasmablastic myeloma was shorter by 51.4 months and for immature myeloma patients by 35 months, compared with mature myeloma patients with similar clinical characteristics. Plasma cell morphology at diagnosis is an important predictor of survival duration in patients with multiple myeloma.

Bone Marrow↗
PubMed1987

Immunoglobulin synthesis in myelodysplastic syndromes: normal B-cell and immunoregulatory T-cell functions.

Peripheral blood cells from patients with myelodysplastic syndromes were assayed for B-cell and immunoregulatory T-cell functions. The B/T cell ratio in myelodysplastic patients (n = 11) was significantly higher than in controls (n = 12). These patients had a reduction in total T-cell (OKT3+) frequency and in T-cell subset (OKT4+/OKT8+) ratios. The response of patients' cells to both pokeweed mitogen (PWM) and phytohemagglutinin (PHA) was reduced, but patients' B cells responded normally to stimulation with Staphylococcus aureus Cowan (SAC). The levels of IgG and IgM detected in 7-day culture supernatants of PWM-stimulated patient and control cells were similar. Normal B-cell and immunoregulatory T-cell functions were subsequently demonstrated in allogeneic co-culture combinations of enriched T and B cells from patients and controls. The data presented indicate that the frequent infections of myelodysplastic patients are not causally related to impaired humoral mechanisms. The data also favor the possibility that the stem cell disorder in these syndromes is functionally expressed at a subsequent stage to the lymphoid differentiation pathway.

Antibody Formation↗
PubMed1987

Human cDNA clones for an alpha subunit of Gi signal-transduction protein.

Two cDNA clones were obtained from a lambda gt11 cDNA human brain library that correspond to alpha i subunits of G signal-transduction proteins (where alpha i subunits refer to the alpha subunits of G proteins that inhibit adenylate cyclase). The nucleotide sequence of human brain alpha i is highly homologous to that of bovine brain alpha i [Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H. & Numa, S. (1986) FEBS Lett. 197, 305-310] and the predicted amino acid sequences are identical. However, human and bovine brain alpha i cDNAs differ significantly from alpha i cDNAs from human monocytes, rat glioma, and mouse macrophages in amino acid (88% homology) and nucleotide (71-75% homology) sequences. In addition, the nucleotide sequences of the 3' untranslated regions of human and bovine brain alpha i cDNAs differ markedly from the sequences of human monocyte, rat glioma, and mouse macrophage alpha i cDNAs. These results suggest there are at least two classes of alpha i mRNA.

Amino Acid Sequence↗
PubMed1987

Reduced expression of multiple forms of the alpha subunit of the stimulatory GTP-binding protein in pseudohypoparathyroidism type Ia.

We examined the expression of the alpha subunit of the stimulatory GTP-binding protein (Gs) in fibroblasts of subjects with pseudohypoparathyroidism (PHP) type Ia by transfer blot hybridization and S1 nuclease analyses. Six subjects with PHP type Ia showed decreased steady-state content of Gs alpha mRNA. S1 nuclease analysis indicates that both long and short forms of Gs alpha mRNA are decreased, with no apparent change in the ratio of long to short forms in PHP compared with normal individuals. It appears likely that in some cases of PHP type Ia the genetic lesion affects the maintenance of mRNA levels for all forms of the Gs alpha subunit.

DNA↗
PubMed1987

Scintigraphic evaluation of brain death: significance of sagittal sinus visualization.

Radiotracer scintigraphy has been commonly used in this country to confirm and document the clinical diagnosis of brain death. Whether the presence of radiotracer activity in the region of sagittal venous sinus (SVS) represents actual blood flow to the brain in the absence of demonstrable cerebral arterial flow remains a controversial issue. Our retrospective study was performed to review the significance of such sagittal tracer activity. Of the 53 patients showing no cerebral arterial flow, 26 showed tracer activity in the region of SVS. The clinical status, EEG findings, and outcome of all 53 patients were the same irrespective of the presence or absence of SVS tracer activity. We conclude that the mere presence of SVS in the absence of demonstrable cerebral arterial flow activity is not clinically significant and does not contradict the diagnosis of brain death.

Brain Death↗