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Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 37 records · Page 2Linked to original sources
PubMed1994

Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow.

Polymerase chain reaction (PCR) amplification of the t(14;18) has been shown to be a highly sensitive method to detect minimal residual disease in patients with non-Hodgkin's lymphoma (NHL) whose tumors bear this translocation. The ideal tissue source to detect residual lymphoma would be from a previously involved lymph node. However, lymphoid tissue is rarely available once patients achieve complete remission. Although PCR amplification has been used to detect residual lymphoma cells in both bone marrow (BM) and peripheral blood (PB) of patients in complete remission, it is presently unknown whether BM and PB are equivalent tissue sources to detect residual disease. In the present study, we compared the clinical utility of the detection of residual lymphoma in both the BM and the PB of patients with advanced-stage non-Hodgkin's lymphoma before, at the time of, and after high-dose therapy and autologous BM transplantation (ABMT). The detection of residual lymphoma in either the BM or PB was associated with decreased disease-free survival. However, in the present study, 44% of patients who relapsed had no evidence of circulating lymphoma cells in their PB. At the time of BM harvest, PCR-detectable residual lymphoma cells were detected in 211 of 212 patients; although, in a subset of these patients analyzed, lymphoma cells were detected in the peripheral blood of only 49% of patients. When residual lymphoma cells within the autologous BM are infused into the patient these cells are rapidly detectable circulating in the PB in the patient. These cells continue to circulate during the immediate posttransplant period and be detectable in the PB in the majority of patients who are infused with marrow containing residual lymphoma. We conclude that BM is a more informative tissue source than PB in detecting minimal residual disease at the time of and after ABMT, and that contamination of PB early after ABMT appears to be the consequence of reinfusion of lymphoma cells within autologous marrow.

Base Sequence↗
PubMed1994

A fungal metabolite which inhibits the interaction of CD4 with major histocompatibility complex-encoded class II molecules.

CD4, a cell-surface glycoprotein expressed on a subpopulation of T cells, is the receptor for class II molecules of the major histocompatibility complex (MHC II) and a receptor for the envelope glycoprotein (gp 120) of human immunodeficiency virus-1 (HIV-1). Screening of microbial metabolites for CD4-binding activity using an enzyme-linked immunosorbent assay based on the binding of the CD4-specific monoclonal antibody (mAb), anti-Leu3a, identified a family of compounds comprising several novel polyketides. The parent compound (411F, Vinaxanthone) is a C28 molecule probably arising from a dimerization of two C14 polyketide units. It strongly inhibited the interaction of anti-Leu 3a and that of several other D1/D2 epitope-specific mAb with CD4, but only weakly inhibited the binding of HIV-1 gp120. Binding of a representative MHC class II molecule, HLA-DRB*0401, was also inhibited by 411F with a comparable inhibitory concentration (IC50 = 1 microM). In functional assays 411F inhibited antigen-induced CD4-dependent T cell proliferative responses of peripheral blood mononuclear cells. At the clonal level 411F exhibited selectivity in that the compound inhibited peptide-induced CD4+ T cell proliferative responses but not alloantigen-induced CD8+ T cell proliferation. It is hypothesized that 411F, a polyanionic compound in aqueous solution at neutral pH, inhibits CD4-dependent functions by binding over a broad area of the positively charged amino-terminal D1 and D2 domains implicated in the interaction with MHC II molecules. 411F has the potential for development as an immunosuppressive agent with a novel mechanism of action.

Animals↗
PubMed1994

Detrusor-myoplasty, innervated rectus muscle transposition study, and functional effect on the spinal cord injury rat model.

The purpose of this investigation was to determine the feasibility of striated muscular augmentation of the urinary bladder (detrusor-myoplasty, DMP). Initial studies, transposition, and bladder wrap using several distinct muscle groups was attempted in laboratory rats, goats, and fresh human cadavers. The rectus abdominus muscle was found to be best suited to completely encompass the bladder with an intact neural and vascular supply. The technique was then applied in a rat model of spinal cord injury (SCI). Modified Tarlov ratings were employed to assess neurologic function 30 days after SCI. The median final neurological score of SCI rats with and without DMP was 4 and 5, respectively. Sham-operated SCI (control) rats, with and without DMP, both had normal final Tarlov scores of 12 (P < 0.05). Muscle blood flow values for the flap and the contralateral undissected rectus muscles were not significantly different (97 +/- 34 and 105 +/- 40 ml/100 g tissue/min, respectively, P = 0.47). Postoperatively, no bowel or abdominal wall functional deficits were apparent. The rotated muscular flap remained innervated and vascularized. Analysis of 24 hr micturition patterns demonstrated no differences in oral fluid intake/24hr, voided volume/24hr, and ratio of number of micturitions during the night vs. day among the four groups: (1) control (neither SCI nor DMP), (2) DMP only, (3) SCI only, and (4) SCI with DMP. Spinal cord injured rats with and without detrusor-myoplasty demonstrated a significant decrease in the number of micturitions/24hr, an increased volume per micturition, and greater largest and smallest micturition volumes (P < 0.05) when compared to controls. The micturition patterns among SCI rats with and without DMP were similar, as were non-SCI animals with and without DMP. This is the first report of the principle and technique of detrusor-myoplasty. Dissection of rats, goats, and human cadavers revealed that a vascularized and innervated rectus muscle flap can be rotated into the pelvis and wrapped around the bladder without tension. Significant loss of bladder capacity did not occur with skeletal muscle adaptation. Detrusor-myoplasty may be applicable for patients with an areflexic detrusor and non-intact sacral motor roots who are not candidates for sacral anterior root neurostimulation.

Abdominal Muscles↗
PubMed1994

In vitro assessment of compounds for anti-HIV activity.

Human immunodeficiency virus types 1 and 2 (HIV-1, -2), the etiological agents of AIDS, are retroviruses that replicate in CD4+ T lymphocytes, monocytes, and macrophages. Early anti-HIV therapies were directed at the step in the virus life cycle that was considered the most readily blocked: the transcription of viral RNA into its DNA copy by the viral enzyme reverse transcriptase (RT). Unfortunately, to date, patient therapies have been relatively unsuccessful and hampered by toxicological problems. This has promoted further research into inhibitors of HIV replication, which may act at alternative stages in the viral replicative cycle as well as more effective RT inhibitors. In order to facilitate such research, simple and accurate in vitro assays are highly desirable. Here we describe such assays that measure components of the HIV replicative cycle and are suitable for use within antiviral experiments.

Amino Acid Sequence↗
PubMed1994

Endocrine changes with the aromatase inhibitor fadrozole hydrochloride in breast cancer.

Fadrozole hydrochloride is a potent aromatase inhibitor with proven clinical effectiveness. However, its optimal dose and its effects on serum aldosterone levels/electrolyte balance have been disputed. To resolve these issues, a double-blind randomised endocrine study of three doses of fadrozole hydrochloride [0.5 mg twice daily (bd); 1.0 mg bd; 2.0 mg bd] was conducted in 80 (68 evaluable) postmenopausal patients with advanced breast cancer over a period of 3 months. There were substantial falls in the serum levels of oestradiol, oestrone and oestrone sulphate. For oestrone only, there was a significant effect of dose (on-treatment means: 0.5 mg, 38.0 pmol/l; 1.0 mg, 25.0 pmol/l; 2.0 mg, 23.9 pmol/l). All oestrogens showed a similar pattern in relation to time, with the 3-month mean being higher than those at 1 and 2 months, and this was significant for oestradiol (P = 0.012). There was an indication that complete suppression of oestradiol and oestrone was not maintained throughout the 12-h dosing period, but the data and its interpretation are complicated by a minor diurnal rhythm in these parameters. There were significant increases in 17-hydroxyprogesterone and androstenedione which may be due to a block of 11 beta-hydroxylase. There was a statistically non-significant fall in aldosterone levels (P = 0.06) during treatment (median pretreatment, 446 pmol/l; median decrease, 125 pmol/l). However, the concurrent significant fall in the plasma sodium: potassium ratio indicated that changes in aldosterone secretion did occur. None of these effects on adrenal pathways was of a degree which is likely to have clinically relevant consequences. It is concluded that fadrozole hydrochloride achieves near maximal suppression of oestrogens at 1 mg bd, and that its effects on aldosterone synthesis are unlikely to be of clinical significance.

Adult↗
PubMed1994

The use of cisplatin plus 5-fluorouracil chemotherapy in an unselected group of patients with recurrent squamous cell carcinoma of the head and neck.

Cisplatin and infusional 5-fluorouracil (5-FU) has become regarded as the standard chemotherapy for squamous cell carcinoma (SCC) of the head and neck. Results of phase II studies vary widely and do not always reflect the activity of regimen in general clinical practice. We have treated 20 consecutive patients with cisplatin 100 mg/m2 and 5-FU given as a 4-day infusion at 1 g/m2 for 24 h. In order to reflect more accurately the activity of this regimen in everyday practice we have followed as many patients as possible to relapse and death and measured the duration of remissions from the end of treatment. 6 patients responded (30%, 95% CI: 10-48%) with 1 patient achieving a complete remission. Partial remission lasted for 3-18 months and the complete remission lasted for 7 months. Median survival of patients from the date of first treatment was 7 months (range 1 week-20.5 months). The regimen was well tolerated but required hospitalisation. We conclude that this regimen is well tolerated, active and a good choice for treating recurrent SCC of the head and neck in an unselected population of patients with recurrent disease in the context of everyday oncological practice.

Adult↗
PubMed1994

The role of Chlamydia pneumoniae in severe acute tonsillitis.

Chlamydia pneumoniae has been implicated as a cause of tonsillitis and pharyngitis, but the incidence has varied from one to 19 per cent in various studies. We investigated 51 patients admitted to University College Hospital, Galway, with severe tonsillitis. Throat swabs were examined for evidence of Chlamydia pneumoniae using a direct monoclonal antibody test. Blood was taken for serology from 45 patients. A further specimen was taken at six weeks. A control group of 32 blood bank sera was used. Mean hospital stay was three days (one to eight). Five patients (10 per cent) were monospot positive. Chlamydia pneumoniae was identified by direct immunofluorescence on a tonsillar swab from one patient who did not seroconvert. IgG antibody was identified in 13 cases (29 per cent) and in seven of the control group (22 per cent). No serological evidence of recent infection was found. Chlamydia pneumoniae was not found to be a cause of severe acute tonsillitis in our study group.

Acute Disease↗
PubMed1994

Cystoscopic autogenous fat injection treatment of vesicoureteral reflux in spinal cord injury.

The purpose of this investigation was to determine the safety and efficacy of subtrigonal, periureteral injections of autogenous fat grafts for the treatment of vesicoureteral reflux. Seven patients (12 renal units) with vesicoureteral reflux were treated with subtrigonal autogenous fat injection. Fat harvesting was obtained from abdominal and thigh subcutaneous tissue. Approximately 2 ml of fat was injected beneath each ureteral orifice with a modified 10 Fr needle through a 23.5 Fr rigid cystoscope. Two of the seven patients experienced durable (six months) resolution of reflux. In three patients, reflux resolved but recurred within three months and another developed recurrent reflux within six months. In one patient with a periureteral diverticulum, proper positioning of the needle tip for effective fat injection was not possible, resulting in persistent reflux. Two of the five patients with persistent reflux demonstrated a diminished grade of reflux on follow-up cystography. Neither complications nor ureteral obstruction have been encountered. The subtrigonal injection technique can be used with autogenous adipose tissue to treat vesicoureteral reflux. Anatomic variation may determine those patients less likely to enjoy durable results. Clinical success and reabsorption of the fat cannot be predicted or controlled at the present time. The ideal periureteral bulking agent for the treatment of vesicoureteral reflux remains to be determined.

Adipose Tissue↗
PubMed1994

Influence of sex and carcinogen treatment protocol on tumor latency and frequency of K-ras mutations in N-methyl-N-nitrosourea-induced lymphomas.

N-methyl-N-nitrosourea (MNU) induces thymic lymphomas in AKR mice after a 2-3 month latency. This study shows that hormonal factors profoundly influence MNU-induced lymphomagenesis. Tumor development is accelerated in females compared to males, regardless of whether a single high dose or multiple low doses of MNU are administered. Testosterone is implicated in this phenomenon, since castrated mice develop MNU-induced lymphomas with the same latency as intact females, while ovariectomized females have the same pattern of tumor development as intact females. Furthermore, reconstitution experiments demonstrated that testosterone replacement suppresses MNU-induced lymphoma development in castrated males. Although tumor development is delayed in male compared to female mice, sex does not influence tumor immunophenotype, clonality or the frequency of ras mutations in animals given identical MNU treatment protocols. In contrast, the frequency of ras mutations is dramatically altered depending on whether the animals are treated with a single high dose or multiple low doses of MNU. Nevertheless, there is no correlation between the presence of an activated K-ras allele and tumor latency. These data demonstrate that sex has a more profound influence on the progression of MNU-induced lymphomas than does the presence of an activated K-ras allele.

Animals↗
PubMed1994

Immunological parameters in peripheral blood of patients with renal cell carcinoma before and after nephrectomy.

OBJECTIVE: To determine the effects of nephrectomy on the immune response of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Five patients with RCC were monitored before and over a period of up to 3 months after nephrectomy. The aspects measured were the phenotypic expression of markers on circulating lymphocytes, circulating concentrations of cytokines, markers of inflammatory and immune responses, and natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMC). The suppressive activity of patients' plasma on NK activity and ability to generate interleukin-2 (IL-2) induced LAK cells in PBMC of normal volunteers was also investigated. RESULTS: The results indicated that high CD4/8 ratios were present pre-nephrectomy with evidence of inflammatory responses and immune activation in some patients, particularly those with metastatic disease. CONCLUSION: The effect of nephrectomy was to decrease the inflammatory response and increase immune activation. Various defects in NK cell activity and LAK cell generation were demonstrated pre-surgery which slowly improved once the primary tumour had been removed and it is suggested that such defects could have contributed to tumour growth and development due to an ineffective immune response.

Adult↗
PubMed1994

A reappraisal of the role of insulin-like growth factor I in the regulation of human hematopoiesis.

IGF-I has been reported to increase hematopoietic progenitor cell cloning efficiency. To investigate this phenomenon, we studied the IGF-I responsiveness of human marrow cells expressing IGF-I receptor (IGF-IR), a direct strategy not used previously. IGF-IR+ and control CD34+ marrow cells were isolated using immunoaffinity methods. Then, the cells were cloned in methylcellulose containing variable amounts of serum- and lineage-appropriate growth factors supplemented with recombinant human IGF-I. In contrast to CD34+ cells, IGF-IR+ cells never gave rise to CFU-Blast, CFU-Mix, CFU-GM, BFU-E, or CFU-E. To substantiate the suggestion that CD34+ and IGF-IR+ cells were distinct populations, we used reverse transcription PCR to detect IGF-I, EpO, and KIT receptor mRNAs in these cells. The mRNA phenotype of CD34+ cells was EpO (+), KIT (+), and IGF-IR (-), while IGF-IR+ cells were IGF-IR (+), EpO (-), and KIT (-). These results suggested that IGF-IR is either not expressed or expressed at low levels on normal hematopoietic progenitor cells. Functional significance of the latter possibility was tested by exposing CD34+ cells to IGF-IR antisense oligodeoxynucleotides. Colony formation was unaffected by oligodeoxynucleotide disruption of IGF-IR, suggesting that, even if expressed at low level, the receptor's functional significance was doubtful. Nevertheless, when cultured in the presence of IGF-I, IGF-IR+ cells elaborated an activity with mild BFU-E stimulatory effects. Accordingly, if IGF-I plays a role in hematopoietic colony formation, it is probably and results from stimulation of IGF-IR-positive ancillary cells to secrete growth factors. Studies carried out with human leukemia cells yielded similar results.

Base Sequence↗
PubMed1994

The Chola life course: Chicana heroin users and the barrio Gang.

The theoretical argument of the paper is as follows: Traditional values may deter many Latinas from drug use, but they operate to ostracize adolescent girls from cholo (street) families. Those girls may be propelled into drug-using youth gangs or similar peer groups, where they are further channeled to the more deviant subcliques. This pivotal experience initiates a drug-oriented adult lifestyle. Gender norms mean that the typical male career path to and from the gang is different. Data bearing on this argument are presented, and research and intervention implications are explored.

Adolescent↗
PubMed1994

A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial.

A phase III clinical trial was developed to test whether the addition of etoposide to a high-dose cytosine arabinoside regimen would improve the remission rate, duration of remission, and survival in relapsed and refractory patients with acute myelogenous leukemia. One hundred and thirty-one patients stratified by age, performance status, percentage of marrow blasts, platelet count, bilirubin and presence or absence of clinical infection, refractory or relapsed (+/- 9 months) were randomized to receive high-dose cytosine arabinoside, 3 g/m2 every 12 h for 6 days with or without three doses of etoposide, 100 mg/m2 days 7-9. Of 67 patients randomized to cytosine arabinoside alone, 31% obtained a complete remission with a median remission duration of 11.9 months. Of 66 patients randomized to the combination regimen, 38% obtained a complete remission with a median duration of 25 months. None of these differences were statistically significant. Significantly (p = 0.036) longer survival was seen in patients on the combination regimen under the age of 50. There was no difference in overall survival. Six and 8%, respectively, of patients were free of disease at 5 years. The addition of etoposide to a high-dose cytosine arabinoside regimen had at best a marginal effect at the expense of some increase in toxicity.

Adult↗
PubMed1994

Altered behavior in two species of blattid cockroaches infected with Moniliformis moniliformis (Acanthocephala).

Moniliformis moniliformis-infected Periplaneta australasiae and Blatta orientalis were less active than uninfected controls in behavioral arena tests under both red and white light regimes. There was a strong interaction between light regime and parasitism for substrate use by P. australasiae. Under red light, parasitism decreased the use of black horizontal surfaces, whereas under white light, parasitism increased the use of black horizontal surfaces. In contrast, B. orientalis substrate use was unaffected by parasitism, although infected animals were less active than uninfected conspecifics under both light regimes. For both species, parasitism did not change the percentage of time spent in light, the freeze time, or the directional response to light.

Animals↗
PubMed1993

Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1.

The ETS oncogene family member PU.1 is a transcriptional activator that is dysregulated by Friend erythroleukemia virus insertion. Northern analysis found that PU.1 is highly expressed in cells of myeloid and B-lymphoid origin, but not expressed at all in a number of nonhematopoietic tissues. Interferon-gamma and retinoic acid downregulated PU.1 expression in marrow macrophages. In situ immunohistochemistry found that PU.1 is expressed only in early granulocytic and erythroid cells and megakaryocytes, but not in mature erythroid cells, mature granulocytes, endothelial cells, or osteocytes. Thus, its expression pattern makes PU.1 a candidate for a genetic determinant of lineage commitment and stage progression in blood cell development. It also lends insight into how PU.1 might play a role in Friend virus erythroleukemia.

Animals↗