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Biomedical subjects

J Hannon

Publications and source records attributed to J Hannon.

11 recordsLinked to original sources
PubMed2004

SRA880, in vitro characterization of the first non-peptide somatostatin sst(1) receptor antagonist.

This report describes the in vitro features of the first somatostatin sst(1) receptor selective non-peptide antagonist, SRA880 ([3R,4aR,10aR]-1,2,3,4,4a,5,10,10a-Octahydro-6-methoxy-1-methyl-benz[g] quinoline-3-carboxylic-acid-4-(4-nitro-phenyl)-piperazine-amide, hydrogen malonate). SRA was evaluated in a number of in vitro systems of various species, both at native and recombinant receptors, using radioligand binding and second messenger/transduction studies. SRA880 has high affinity for native rat, mouse, monkey and human cerebral cortex somatostatin sst(1) receptors (pK(d) = 7.8-8.6) and for human recombinant sst(1) receptors (pK(d) = 8.0-8.1). SRA880 displayed significantly lower affinity for the other human recombinant somatostatin receptors ( pK(d) < or = 6.0) or a wide range of neurotransmitter receptors, except for the human dopamine D4 receptors. SRA880 was characterized in various transduction assays: somatotropin release inhibiting factor (SRIF) induced inhibition of forskolin-stimulated cAMP accumulation, SRIF stimulated-GTPgammaS binding, and SRIF stimulated luciferase gene expression; in all tests, SRA880 was devoid of intrinsic activity and acted as an apparently surmountable antagonist with pK(B) values of 7.5-7.7. Combined with the data from binding studies, these results suggest that SRA880 acts as a competitive antagonist. Thus, SRA880 is the first non-peptide somatostatin sst(1) receptor antagonist to be reported; SRA880 will be a useful tool for the characterization of somatostatin sst(1) receptor-mediated effects both in vitro and in vivo.

Animals↗
PubMed2004

Evaluation of red blood cells stored at -80 degrees C in excess of 10 years.

BACKGROUND: RBCs frozen in 40 percent (wt/vol) glycerol are currently approved by the FDA and the AABB for storage at -80 degrees C for up to 10 years. STUDY DESIGN AND METHODS: This study examined 20 RBC units that had been cryopreserved in 40 percent (wt/vol) glycerol and stored at -80 degrees C for up to 22 years. Measures of the freeze-thaw-wash (FTW) recovery, ATP, 2,3-DPG, methemoglobin, RBC indices, morphology, and osmotic fragility were made immediately after deglycerolization and after 24 hours of storage at 4 degrees C. RESULTS: RBCs frozen for longer than 10 years had acceptable mean FTW recovery, normal oxygen transport function, RBC morphology, RBC indices, methemoglobin, and osmotic fragility. Statistical analysis indicated that the in-vitro viability and function of cryopreserved RBCs was not dependent on the length of frozen storage or postthaw storage at 4 degrees C but did correlate with the storage length at 4 degrees C before cryopreservation. CONCLUSION: The data reported in this study demonstrate that RBCs can be stored at -80 degrees C beyond 10 years with acceptable in-vitro quality and suggest that more defined criteria for the cryopreservation process be adopted.

2,3-Diphosphoglycerate↗
PubMed2001

Damage and protection of UC blood cells during cryopreservation.

BACKGROUND: Current procedures for the cryopreservation of umbilical cord blood (UCB) progenitor cells, which are based on techniques used for BM, have had varying degrees of success (survival 9-118%). Improving the effectiveness of UCB cell therapies demands a more comprehensive understanding of freezing injury during cryopreservation. METHODS: Leukocyte concentrates from UCB, with or without 10% DMSO were cooled at 1 degrees C/min to different subzero temperatures (-5 to -50 degrees C), then either thawed directly (thaw) or plunged into liquid nitrogen before thawing (plunge). Single-platform flow cytometry with 7-amino-actinomycin D was used to directly quantify survival of CD34(+) cells. Fluorescent microscopy was used to examine plasma membrane integrity of nucleated cells. RESULTS: Without DMSO, recovery of nucleated cells was approximately 80% for both thaw and plunge. Survival was 9%, indicating damage to the plasma membrane. With 10% DMSO, nucleated cell recovery was also approximately 80%, indicating that DMSO does not improve recovery of nucleated cells. Survival, however, was much higher with DMSO, > 60% for nucleated cells thawed directly, and 30-55% for cells thawed from plunge, demonstrating cryoprotection conferred by DMSO. With DMSO, survival of CD34(+) cells was higher than that of nucleated cells, indicating that CD34(+) cells with 10% DMSO are more tolerant to cryopreservation than the total nucleated cell population. DISCUSSION: This study provides the necessary data on the low temperature response of UCB progenitor cells that are critical for the development of standards for the cryopreservation of UCB.

Antigens, CD34↗
PubMed2000

New genotypes in Fy(a-b-) individuals: nonsense mutations (Trp to stop) in the coding sequence of either FY A or FY B.

Duffy blood group antigens are carried on a glycoprotein that is predicted to pass through the erythrocyte membrane seven times and is a promiscuous chemokine receptor. The Fy(a- b-) phenotype is present in two-thirds of African-American Blacks but is rare in Caucasians. In Blacks, the phenotype is due to a non-functional GATA-1 motif in the FY B, which silences the gene in erythrocytes but not in other tissues, and these patients do not generally make anti-Fyb or anti-Fy3. We describe here the molecular analysis of FY in three unrelated Caucasians who were studied because they had strong anti-Fy3 in their serum. Each was found to have a point mutation that was predicted to change a tryptophan to a premature stop codon in the coding sequence. In one patient (patient 1), the nonsense mutation was at nucleotide 287 of the major transcript in FY A; in another (patient 2), it was at nucleotide 407 in the major transcript of FY B; and in a third (patient 3), it was at nucleotide 408 of the major transcript of FY A.

Aged↗
PubMed1997

Notifying patients exposed to blood products associated with Creutzfeldt-Jakob disease: integrating science, legal duties and ethical mandates.

The issue of notifying people who have been exposed to blood products that have been associated with Creutzfeldt-Jakob disease (CJD) has arisen at a time when the Canadian blood system is under intense scrutiny. As a result, the Canadian Red Cross Society issued a recommendation to health care institutions that recipients of CJD-associated blood products be identified, notified and counselled. Although Canadian jurisprudence in the realm of informed consent may support a policy of individual notification, a review of the scientific evidence and the applicable ethical principles arguably favours a policy of a more general public notification. Indeed, situations such as this require a unique approach to the formation of legal and ethical duties, one that effectively integrates all relevant factors. As such, the authors argue that individual notification is currently not justified. Nevertheless, if a system of general notification is implemented (e.g., through a series of public health announcements), it should provide, for people who wish to know, the opportunity to find out whether they were given CJD-associated products.

Beneficence↗
PubMed1997

Transfusion- and community-acquired cytomegalovirus infection in children with malignant disease: a prospective study.

BACKGROUND: The use of cytomegalovirus (CMV)-"safe" blood has been recommended for CMV seronegative patients with newly diagnosed malignant disease for whom bone marrow transplantation is a future option. STUDY DESIGN AND METHODS: To evaluate this policy, 76 CMV-seronegative children with lymphoreticular malignancies or solid tumors were randomly assigned to receive either blood components that were not screened for CMV antibody or CMV-seronegative red cell (RBC) and platelet units. Subjects were followed for evidence of CMV infection by the use of enzyme-linked immunosorbent assays and virus isolation. Follow-up continued long after the blood transfusions to determine the risk of community-acquired CMV infection. RESULTS: No cases of transfusion-acquired CMV infection were documented. The prevalence of CMV IgG and IgM antibody in blood donors was 40.5 and 0.9 percent, respectively. Patients assigned to receive standard blood components and CMV-negative components were given a median (range) of 7 (1-30) and 9 (1-38) RBC units and 11 (0-123) and 14 (0-71) platelet units, respectively. The risk of transfusion-acquired CMV infection is estimated to be less than 1 in 698 donor exposures. Two patients developed asymptomatic community-acquired CMV infection, for an incidence of 1.7 percent per patient-year of follow-up. CONCLUSION: The risk of transfusion-acquired CMV infection in this population is low, largely because of the patients' low level of exposure to seropositive blood and the use of relatively white cell-reduced components for purposes other than CMV prevention. Such children at this center therefore continue to receive standard blood components. Strategies to prevent CMV seroconversion in these children should include parental education to minimize the risk of community-acquired infection.

Adolescent↗
PubMed1994

Benign retrorectal tumors in adults: the choice of operative approach.

Six adult patients were treated for tumors of the retrorectal space from 1975 to 1990 at the University of Mississippi Medical Center. All were female; ages ranged from 19 to 64 (mean, 37.8) years. Two asymptomatic tumors were discovered in the peripartum period, and two patients had symptoms of local fullness or pain. One patient presented with a pelvic abscess, and one patient had had recurrent pilonidal cyst abscesses drained. All lesions were completely excised (one by a transsacral route, two by a transanal route, and three by a combined abdominosacral approach). All were histologically benign (four tailgut cysts and two epidermoid cysts). One tailgut cyst recurred after transanal excision and was removed by a transsacral route without further recurrence. Adequate excision may be achieved by any of several approaches. Transanal excision, although convenient for small low-lying dermoid tumors, resulted in the only recurrence in our series.

Adult↗
PubMed1975

Benzopyranopyridine derivatives. 1. Aminoalkyl derivatives of the azaxanthenes as bronchodilating agents.

The preparation of the four isomeric azaxanthones 3 and a number of their aromatic ring substituted derivatives is described. These ketones were converted into the title compounds which were examined for their biological properties. The most interesting compound in this series, the 1-methyl-4-piperidylidene derivative of 1-azaxanthene, shows the profile of an orally effective potent bronchodilating agent as well as a moderate antihistamine. Biological properties of this compound were compared to a number of antihistamines as well as known bronchodilating agents. Structure-activity relationships are also discussed.

Airway Resistance↗