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C J Harrison

Publications and source records attributed to C J Harrison.

At least 91 records · Page 5Linked to original sources
PubMed1995

Penicillin-resistant Streptococcus pneumoniae in acute otitis media: risk factors, susceptibility patterns and antimicrobial management.

From January, 1992, to January, 1994, penicillin-resistant (minimal inhibition concentration (MIC) > 0.06 microgram/ml) Streptococcus pneumoniae (PRSP) isolates accounted for 48 (17%) of 283 isolates from acute otitis media (AOM) or recurrent AOM in 246 ambulatory patients in rural Kentucky. By broth microdilution, relatively penicillin-resistant (MIC > 0.06 to 1.0 microgram/ml) and highly penicillin-resistant (MIC > or = 2.0 micrograms/ml) strains were detected in 25 (16%) and 23 (15%), respectively, of 157 pneumococcal middle ear isolates. Using 1994 National Committee for Clinical Laboratory Standards breakpoints for pneumococci (unavailable for oral cephalosporins except cefuroxime), highly PRSP strains were almost uniformly susceptible to clindamycin and vancomycin. In contrast highly PRSP strains were resistant to most oral antimicrobials customarily used for AOM with one-third of strains highly resistant (MIC > or = 2.0 micrograms/ml) to ceftriaxone. Serotypes 6B, 19F and 23F accounted for 95% of highly PRSP strains and serotype 9V for 48% of relatively PRSP strains. By multivariate analysis, otitis-prone condition (P = 0.0008) and number of antibiotic courses before day of culture (P < 0.0001) were independently predictive of PRSP. Highly PRSP isolates were more commonly isolated from patients recently treated within 3 days (30%) vs. those who completed therapy more than 3 days earlier (2%) (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Colonization with penicillin-resistant Streptococcus pneumoniae in a child-care center.

We obtained nasopharyngeal cultures for Streptococcus pneumoniae from 54 children ages 2 to 24 months attending an Omaha child-care center (CCC) in April 1994. Thirty-two (59%) of the 54 children were colonized with S. pneumoniae belonging to serotypes 23, 19, 6 and 11. Seventeen (53%) of the pneumococcal isolates were highly resistant to penicillin (minimal inhibitory concentration > or = 2.0 micrograms/ml; HR-SP) and 7 (22%) were intermediately resistant to penicillin (0.12 < or = minimal inhibitory concentration < or = 1.0 microgram/ml; IR-SP). Within each pneumococcal capsular serotype, there were 1 to 3 DNA subtypes based on pulsed field gel electrophoresis analysis. A single pulsed field gel electrophoresis strain predominated in most CCC rooms, suggesting horizontal transmission among cohorted children. Nasopharyngeal cultures obtained 4 months later revealed similar S. pneumoniae colonization rates (28 of 52, 54%); however, only 2 (7%) of 28 isolates were HR-SP and 11 (39%) were IR-SP. Colonization with resistant pneumococci persisted after 4 months in 4 (12%) of 34 children cultured on both occasions. Antibiotic use by attendees had decreased notably between the two sampling periods, suggesting that selective pressure within the CCC might contribute to seasonal variation in colonization rates with HR-SP and IR-SP. We conclude that multiple genetic clones of penicillin-resistant pneumococci can occur simultaneously in a single CCC, especially during periods of heavy antibiotic selection pressure. However, individual clones of penicillin-resistant S. pneumoniae may be spread from child to child, suggesting that colonization with penicillin-resistant S. pneumoniae should now be considered a CCC-associated phenomenon.

Anti-Bacterial Agents↗
PubMed1995

Detection of CBFB/MYH11 transcripts in patients with inversion and other abnormalities of chromosome 16 at presentation and remission.

The pericentric inversion of chromosome 16 [inv(16)(p13q22)] and t(16;16)(p13;q22) are chromosomal rearrangements frequently associated with AML FAB type M4Eo resulting in the production of a fusion gene CBFB/MYH11. We studied 17 patients with a chromosome 16 abnormality (eight M4Eo, two M1, one M2, three M4 without abnormal eosinophils, three MDS) for the presence of CBFB/MYH11 transcripts using an RT-PCR technique. 10 AML patients with inv(16) tested RT-PCR positive (eight at presentation, one in remission, one in remission and relapse). Three of these patients were originally reported by cytogenetic analysis to have del(16q22) but the positive RT-PCR results prompted a cytogenetic re-examination, resulting in the correction of the reports to inv(16). We show that although inv(16) is closely associated with AML M4Eo, it can also be detected in cases of AML M4 without abnormal eosinophils. Three cases of MDS with inv(16) were also RT-PCR positive. Four patients with other chromosome 16 abnormalities were RT-PCR negative. Four AML patients with inv(16) were studied in remission. All were RT-PCR positive, including one patient in remission for 108 months and one 22 months post allogeneic bone marrow transplant. In the latter two remission patients, RT-PCR evaluation was positive in bone marrow (BM) but not in peripheral blood, suggesting that BM may be the more informative. We conclude that this technique is valuable in the accurate molecular classification of AML, particularly as treatment options may be influenced by such information. Though RT-PCR is highly sensitive in detecting CBFB/MYH11 fusion transcripts during remission, monitoring of minimal residual disease in patients with inv(16) remains to be established.

Acute Disease↗
PubMed1995

Dicentric (9;12) in acute lymphocytic leukemia and other hematological malignancies: report from a dic(9;12) study group.

Fourteen cases of dic(9;12)(p11-13;p11-12) in early B-lineage acute lymphoblastic leukemia (ALL) and other hematological malignancies are reported with a review of the literature. Altogether 36 cases were collected for analysis: ALL at diagnosis (31 cases) or in relapse (one case), chronic myeloid leukemia in lymphoid blast crisis (two cases), T-cell lymphoblastic lymphoma (one case) and T-cell non-Hodgkin's lymphoma (one case). We report the first cases of dic(9;12) with a T-cell phenotype. Dic(9;12) occurs predominantly in B-progenitor ALL of childhood and young adults (age range, 1-47 years, median 12 years) but not of infancy. One or more adverse clinical features, age > 10 years, WBC > 100 x 10(9)/l, pre-B immunophenotype, platelets < 100 x 10(9)/l, were found in over 90% of cases. Additional structural chromosomal changes or trisomy 8 were frequently present. Nevertheless with a median follow-up of 5 years, 29/31 cases (94%) remain in first remission conferring an excellent prognosis to this leukemia. Additional cases are being sought to confirm the prognostic value of this cytogenetic aberration in various hematological malignancies.

Adolescent↗
PubMed1995

Neonatal herpes simplex virus (HSV) infections.

Prevention remains the best form of "treatment" of neonatal HSV infection. Prompt work-up and initiation of antiviral therapy provide the best outcome once infection has occurred. It is critical that practitioners be aware of the urgency of initiation of therapy as well as the signs/symptoms of maternal and neonatal HSV infection.

Acyclovir↗
PubMed1994

Yeast heat shock transcription factor contains a flexible linker between the DNA-binding and trimerization domains. Implications for DNA binding by trimeric proteins.

All heat shock transcription factors (HSFs) share two regions of homology, identified as the DNA binding and trimerization regions. The DNA binding region consists of two parts, an 89-amino-acid minimal DNA-binding domain and an additional 21 amino acids which are not necessary for specific DNA binding of a monomeric DNA-binding domain. These 21 amino acids may act as a flexible linker between the DNA-binding and trimerization domains. Saccharomyces cerevisiae HSF has an additional 52 amino acids between the proposed flexible linker and the trimerization domain. Deletion of this unique region has no effect on the structural integrity or essential in vivo functions of HSF. To investigate the role of the 21-amino-acid proposed linker, a series of internal deletions was created in fragments containing the DNA-binding and trimerization domains. The deletions have no effect on the structural integrity of the protein as assayed by circular dichroism spectroscopy. However, alterations of the linker do affect affinity of trimeric HSF binding to its target DNA. In addition, deletion of part or all of the proposed linker from full-length yeast HSF, an essential protein, disrupts growth of yeast.

Amino Acid Sequence↗
PubMed1994

Crystal structure of the DNA binding domain of the heat shock transcription factor.

The structure of the DNA binding domain, determined at 1.8 angstrom resolution, contains a three-helix bundle that is capped by a four-stranded antiparallel beta sheet. This structure is a variant of the helix-turn-helix motif, typified by catabolite activator protein. In the heat shock transcription factor, the first helix of the motif (alpha 2) has an alpha-helical bulge and a proline-induced kink. The angle between the two helices of the motif (alpha 2 and alpha 3) is about 20 degrees smaller than the average for canonical helix-turn-helix proteins. Nevertheless, the relative positions of the first and third helices of the bundle (alpha 1 and alpha 3) are conserved. It is proposed here that the first helix of the three-helix bundle be considered a component of the helix-turn-helix motif.

Amino Acid Sequence↗
PubMed1994

Deletion of a common region on the long arm of chromosome 6 in acute lymphoblastic leukaemia.

We have characterised a region of deletion on the long arm of chromosome 6 (6q) in six cases of acute lymphoblastic leukaemia, by fluorescence in situ hybridisation, using a series of YAC clones which map to 6q. Conventional cytogenetic analysis of four of these cases had been interpreted as showing terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions were interstitial. D6S246 (6q16.3) was the only marker which was missing in all six cases, indicating a common region of deletion between the markers M6P1 at 6q14-15 and FYN at 6q21. Our results suggest the presence of a tumour suppressor gene within this interval.

Adolescent↗
PubMed1994

Common region of deletion on the long arm of chromosome 6 in non-Hodgkin's lymphoma and acute lymphoblastic leukaemia.

We have used fluorescence in situ hybridisation (FISH) with a series of yeast artificial chromosome (YAC) clones that map to the long arm of chromosome 6 (6q) to define the region(s) of deletion in seven cases of non-Hodgkin's lymphoma (NHL), in which a deletion of 6q had been detected by conventional cytogenetics. The FISH analysis detected two regions of deletion: (i) A proximal region flanked by M6P1 (6q14-15) and FYN (6q21), containing D6S246, which was missing in all seven cases. This locus was also found to be deleted in all six cases of acute lymphoblastic leukaemia (ALL) studied previously. (ii) A second region of 6q, which was distal to 6q23.1 (D6S238) and included ESR (6q25.1) and D6S281 (6q27), which was shown to be present in all our cases of ALL, was found to be deleted in 4 of the 7 cases of NHL. Our results support the suggestion that tumour suppressor genes, involved in the pathogenesis of lymphoid malignancies, may be present within these regions.

Adult↗
PubMed1994

Solution structure of the DNA-binding domain of the heat shock transcription factor determined by multidimensional heteronuclear magnetic resonance spectroscopy.

The solution structure of the 92-residue DNA-binding domain of the heat shock transcription factor from Kluyveromyces lactis has been determined using multidimensional NMR methods. Three-dimensional (3D) triple resonance, 1H-13C-13C-1H total correlation spectroscopy, and 15N-separated total correlation spectroscopy-heteronuclear multiple quantum correlation experiments were used along with various 2D spectra to make nearly complete assignments for the backbone and side-chain 1H, 15N, and 13C resonances. Five-hundred eighty-three NOE constraints identified in 3D 13C- and 15N-separated NOE spectroscopy (NOESY)-heteronuclear multiple quantum correlation spectra and a 4-dimensional 13C/13C-edited NOESY spectrum, along with 35 phi, 9 chi 1, and 30 hydrogen bond constraints, were used to calculate 30 structures by hybrid distance geometry/stimulated annealing protocol, of which 24 were used for structural comparison. The calculations revealed that a 3-helix bundle packs against a small 4-stranded antiparallel beta-sheet. The backbone RMS deviation (RMSD) for the family of structures was 1.03 +/- 0.19 A with respect to the average structure. The topology is analogous to that of the C-terminal domain of the catabolite gene activator protein and appears to be in the helix-turn-helix family of DNA-binding proteins. The overall fold determined by the NMR data is consistent with recent crystallographic work on this domain (Harrison CJ, Bohm AA, Nelson HCM, 1994, Science 263:224) as evidenced by RMSD between backbone atoms in the NMR and X-ray structures of 1.77 +/- 0.20 A. Several differences were identified some of which may be due to protein-protein interactions in the crystal.

Amino Acid Sequence↗
PubMed1994

The karyotype of Alligator mississippiensis, and chromosomal mapping of the ZFY/X homologue, Zfc.

Comparative mapping studies of X-linked genes in mammals have provided insights into the evolution of the X chromosome. Many reptiles including the American alligator, Alligator mississippiensis, do not appear to possess heteromorphic sex chromosomes, and sex is determined by the incubation temperature of the egg during embryonic development. Mapping of homologues of mammalian X-linked genes in reptiles could lead to a greater understanding of the evolution of vertebrate sex chromosomes. One of the genes used in the mammalian mapping studies was ZFX, an X-linked copy of the human ZFY gene which was originally isolated as a candidate for the mammalian testis-determining factor (TDF). ZFX is X-linked in eutherians, but maps to two autosomal locations in marsupials and monotremes, close to other genes associated with the eutherian X. The alligator homologue of the ZFY/ZFX genes, Zfc, has been isolated and described previously. A detailed karyotype of A. mississippiensis is presented, together with chromosomal in situ hybridisation data localising the Zfc gene to chromosome 3. Further chromosomal mapping studies using eutherian X-linked genes may reveal conserved chromosomal regions in the alligator that have become part of the eutherian X chromosome during evolution.

Alligators and Crocodiles↗
PubMed1994

Acute lymphoblastic leukaemia following Hodgkin's disease is associated with a good prognosis.

Acute leukaemia, both myeloid and lymphoblastic, in patients treated for Hodgkin's disease (HD) is thought to have a poor prognosis. We report four adults who developed secondary acute lymphoblastic leukaemia (ALL) following chemoradiotherapy for HD. The chromosomal translocation t(4;11) (q21;q23) was found in two patients who received a chemotherapeutic regimen containing the DNA topoisomerase II inhibitor etoposide. Three of the four patients are alive and in unmaintained first remission at 3, 5 and 9 years from diagnosis of ALL, two following autologous bone marrow transplantation. These results suggest that ALL following HD may have a good prognosis when treated aggressively.

Adult↗
PubMed1994

Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs.

Imiquimod, an immunomodulator with no direct in vitro antiviral activity, has in vivo anti-herpesvirus activity by inducing interferon and enhancing other only partially defined immune responses. Imiquimod treatment of primary genital herpes simplex virus (HSV) infection in guinea pigs reduces the level of genital disease by 90%. We further investigated its utility as suppressive therapy of recurrent disease in animals that had recently recovered from primary genital HSV-2 disease. Imiquimod administered intravaginally once per day for 5 days reduced the number of recurrences only during treatment, while a 21-day regimen reduced the number of recurrences for 8 weeks. For the entire 10 weeks of observation, overall numbers of recurrences were reduced 67% by the 21-day imiquimod treatment (P < 0.0001). Latent HSV in ganglia was not affected by either regimen. Increased circulating alpha interferon activity was observed during therapy with both regimens. Interferon levels rapidly returned to baseline with cessation of treatment. Posttreatment, 5-day imiquimod treatment did not provide clinical benefit or enhancement of cell-mediated or cytokine responses. Twenty-one-day imiquimod treatment reduced both the number of clinical recurrences and levels of HSV antibody for 5 to 6 weeks posttreatment compared with the placebo. Additionally, 21-day imiquimod treatment enhanced HSV antigen-specific interleukin 2 production and proliferative responses by mononuclear cells (P < 0.001) for 4 weeks after treatment. Twenty-one-day imiquimod therapy suppressed recurrent HSV genital disease during and for weeks after therapy, enhanced memory-dependent cytokine and T-cell responses, and reduced the level of antibody responses.

Adjuvants, Immunologic↗
PubMed1993

Residual Ph- cells in chronic myeloid leukemia: detection and usefulness.

Bone marrow cells from patients with chronic myeloid leukemia (CML) in in vitro long-term bone marrow culture (LTBMC) show an impaired survival of Philadelphia (Ph) positive cells and, in a proportion of patients, the emergence of Philadelphia negative hemopoiesis. The standard conditions of in vitro cultures provide optimal purging effect. Selected patients can now have autologous bone marrow transplants (ABMT) with in vitro purged cells.

Bone Marrow Transplantation↗
PubMed1993

Description of a nurse practitioner inpatient service in a public teaching hospital.

A new nurse practitioner service at a public teaching hospital received patients from internal medicine teaching services. To determine the characteristics of the patients, the ratings by the residents, and the professional team costs, the authors performed a case-series study of the first 248 patients. Transferred patients had conditions that necessitated long hospitalizations, most frequently cerebrovascular accident, dementia, and pneumonia. Housestaff rated the service positively. Estimated professional costs were similar to teaching service costs after 15 months. The nurse practitioner inpatient service effectively cared for internal medicine patients with long lengths of stay and received favorable housestaff ratings.

Hospital Bed Capacity, 300 to 499↗
PubMed1993

Effects of therapy with an immunomodulator (imiquimod, R-837) alone and with acyclovir on genital HSV-2 infection in guinea-pigs when begun after lesion development.

We evaluated the effects of the immunomodulator, imiquimod (R-837) applied topically, alone and in combination with i.p. acyclovir (ACV) on acute, recurrent and neural HSV-2 genital infection in guinea-pigs when 10 days of therapy was begun after HSV lesions developed. The combined therapy was most effective, significantly reducing the severity of the acute disease, as early as 2 days (P < 0.05), and vaginal viral shedding (P < 0.05) as early as 1 day after therapy was begun. The total lesion score for the acute disease was also significantly less in the group receiving imiquimod and ACV (5.4 +/- 0.5) compared to controls (13.1 +/- 1.2, P < 0.001) or imiquimod alone (9.8 +/- 1.2, P < 0.05). Therapy, however, had no significant effect on the number of days with recurrent lesions. Imiquimod increased the lymphoproliferative response to HSV (P < 0.01), while combined therapy reduced HSV antibody titers (P < 0.01) on day 28 compared to placebo and also reduced the effect of imiquimod alone on the lymphoproliferative response. The combination of this effective immunomodulator, imiquimod, and acyclovir appears to provide effective therapy for acute genital HSV-2 infection even when begun after lesion development.

Acute Disease↗