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Biomedical subjects

M Clayton

Publications and source records attributed to M Clayton.

At least 37 records · Page 2Linked to original sources
PubMed1993

Characteristics of woodchuck hepatitis X-antigen in the livers and sera from infected animals.

This study tests the hypothesis that woodchuck hepatitis virus encoded X-antigen expression correlates with viral replication, with hepatitis, or with both. Paired liver and serum samples from each of 55 infected woodchucks were used. Seven of 8 carriers with high levels of viral DNA in serum also had X-antigen in serum. In contrast, the frequency of X-antigen in serum was low among infected woodchucks that did not have viral surface antigen in the serum. Statistical analysis showed a significant relationship between X-antigen in serum and markers of viral replication. Woodchuck hepatitis X-antigen (WHxAg) expression in liver but not serum of carriers closely correlated with the presence of hepatitis. The finding of X-antigen in the liver of infected animals with hepatitis that cleared the virus surface antigen from serum also suggests that X-antigen is associated with ongoing hepatitis. Hence, the persistence of WHxAg in serum may signal continuing viral replication and, in liver, may contribute to the pathogenesis of chronic infection.

Animals↗
PubMed1992

Urethral diverticular carcinoma.

BACKGROUND: Urethral diverticular carcinoma is an unusual finding in a urologic lesion commonly found in female patients. METHODS: This report presents 6 new cases and reviews the other 53 cases in the English literature. RESULTS: Adenocarcinoma occurs more frequently than transitional and squamous cell cancers combined. CONCLUSION: The prognosis of the former is more favorable. In general, radical therapy is recommended. However, in some instances of localized disease, and with careful follow-up, a more conservative approach might be attempted.

Adult↗
PubMed1991

Phase I-II evaluation of intravesical novantrone (mitoxantrone) in superficial bladder cancer.

The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse after the use of at least one other standard anti-cancer agent. The patient was to have received no prior radiotherapy or intravesical therapy for at least 4 weeks prior to entry. Patients also did not suffer significant cardiac dysfunction, such as angina, congestive heart failure, or uncompensated cardiomyopathy. All patients were given 4-6 doses of intravesical novantrone at the same dose level at weekly dosing interval. Patients were required to retain the drugs in the bladder for 2 h. Baseline study included history/physical, hematology, blood chemistry, cystoscopy, bladder barbotage, urine cytology, cystometrogram to assess the bladder capacity, and finally, chest X-ray, EKG, and MUGA scan, if indicated. Weekly assessment involved toxicity notation, blood chemistry, hematology and urinalysis. Monthly assessment included physical examination, toxicity notation, hematology, urinalysis and blood chemistry. Within 4 weeks of completion of the last dose, patients underwent repeat cystoscopy to assess disease status. Patients who responded to the 4-6 week induction phase were entered in a monthly dose regimen for up to 5 months. A total of 23 patients were enrolled: 22 males and 1 female. One patient dropped out before receiving medication because of a protocol violation for entry criteria. Twenty-two patients were eligible for assessment of safety and 20 were eligible for assessment of efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Preferential denervation of the adductor muscles of the equine larynx. II: Nerve pathology.

The terminal branches of the recurrent laryngeal nerve (RLN) of three normal ponies and six horses with sub-clinical laryngeal disease were examined qualitatively and quantitatively in an attempt to explain the preferential denervation of the laryngeal adductor muscles in the neuropathy of idiopathic laryngeal hemiplegia (ILH). The myelinated fibre spectra of all the motor nerve fibres in the left and right abductor and adductor branches of the RLN in three normal ponies were measured. The density of myelinated fibres was also calculated. There was no significant difference between the larger group of myelinated fibres in the adductor or abductor branches. In the six horses with laryngeal hemiparesis, however, there was a marked preferential loss of the medium/large size myelinated fibres in the left adductor branch, although nerve fibre densities were not significantly different. While no simple morphometrical feature was found to explain the selective muscle denervation, the greater loss of large diameter myelinated fibres in the adductor branches confirms the earlier observation of adductor muscle susceptibility in the neuropathy of ILH.

Animals↗
PubMed1990

Picolinic acid, a catabolite of tryptophan, as the second signal in the activation of IFN-gamma-primed macrophages.

We have studied the effects of picolinic acid, a product of tryptophan degradation, on the activation of mouse peritoneal macrophages (M phi). Picolinic acid acts synergistically with IFN-gamma in activating M phi from C57BL/6 mice. Moreover, M phi from C3H/HeJ mice and C3H/HeN that do not become cytotoxic in response to IFN-gamma alone could be fully activated by exposure to picolinate plus IFN-gamma. These results indicate that picolinic acid is a potent costimulator of M phi activation that functions as a second signal. Inasmuch as we have previously demonstrated that the activation of cytotoxic M phi correlates with specific changes in ribosomal RNA (rRNA), we investigated whether picolinic acid could modify M phi RNA metabolism. Picolinic acid inhibited the synthesis of total M phi RNA, the accumulation of newly synthesized 28S rRNA, and augmented the steady state levels of rRNA precursors (pre-rRNA). These changes in RNA metabolism were similar to those previously described in murine M phi activated in vitro or in vivo to express tumoricidal activity. These results demonstrate that picolinic acid is a potent, biologic M phi second signal, suggest that the changes in rRNA are causally connected with the expression of tumoricidal activity, and suggest the existance of an autocrine effect mediated by picolinic acid.

Animals↗
PubMed1990

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate.

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.

Clinical Trials as Topic↗
PubMed1989

Familial XX chromosomal maleness does not arise from a Y chromosomal translocation.

To determine the mechanism for the coexistence of XX chromosomal maleness and true hermaphroditism in the same family, we performed cytogenetic and molecular genetic analyses, using DNA probes from the short arm of the Y chromosome. These studies excluded the following possible mechanisms: (1) an inherited, mitotically unstable Y chromosome that results in chromosomal mosaicism, (2) an inherited Y-to-X or Y-autosomal translocation, (3) recurrent Y-to-X translocation, and (4) incomplete inactivation of the X chromosomal homolog for the testicular determining factor. We conclude that the disorder of sexual differentiation observed in this family can be best explained by a dominant autosomal gene with variable expressivity.

Blotting, Southern↗
PubMed1988

Liver organelle changes on exposure to hypoxia.

Exposure of mice to hypoxia reduces the length of each element of endoplasmic reticulum. This may shorten the path length of oxygen within the cell and have an adaptive advantage. There were no significant changes in the other organelles.

Animals↗
PubMed1987

Localized urethral cancer in women.

The results of treatments for localized carcinoma of the urethra were assessed in 21 consecutive women treated at our institutions over a twenty year period. Only one of the tumors was confined to the distal urethra. Eighty-six percent invaded the periurethral tissues and 24% were known to be associated with regional lymph node metastases. Fifty-seven percent were adenocarcinomas. Five patients refused active therapeutic intervention and expired within one to 30 months following diagnosis. Sixteen patients were treated with extirpative surgery, radiation therapy, or combinations of the two. Four are free of disease at one, four, eleven, and 15 years after treatment. Nine developed pelvic recurrences, two developed pelvic recurrences and distant metastases and one developed distant metastases only from six to 72 months (mean, 19 months) after initial treatment. Eight of these 12 patients died at two to 13 months (mean, 8 months) after secondary treatment, two are alive with residual pelvic tumor, and two are clinically free of disease at 7 and 48 months. Only six patients were known to have distant metastases at the time of death and five of these six had adenocarcinomas. Advanced localized urethral cancer in women is difficult to eradicate and usually fatal.

Adenocarcinoma↗
PubMed1987

Erythroid differentiation and modulation of c-myc expression induced by antineoplastic drugs in the human leukemic cell line K562.

The human leukemia cell line K562 expresses constitutively high levels of c-myc mRNA and can be induced to differentiate along the erythroid lineage. Treatment of K562 cells with the antineoplastic drugs 1-beta-D-arabinofuranosylcytosine and daunomycin causes differentiation into hemoglobin-producing cells. The differentiation process is associated with an early block of cellular proliferation occurring during the first 24 h of treatment. RNA synthesis is progressively reduced to 20 to 30% of the control levels after 3 days of exposure to the drugs. Dot and Northern blot analyses were performed to evaluate the levels of c-myc or globin mRNA during the differentiation of K562. Daunomycin and 1-beta-D-arabinofuranosylcytosine, despite their distinct chemical nature, induced similar modulation of mRNA levels. Globin mRNA did not change during the first 24 h of culture and began to increase after 48 h of treatment with drugs, reflecting the kinetic of appearance of hemoglobin-producing cells. In contrast, a transient decrease of c-myc mRNA was observed after the first 24 h of drug treatment, followed by a return to normal levels of c-myc mRNA after 48 h of treatment. Thus, the expression of c-myc mRNA in K562 did not reflect their proliferative activity nor their stage of differentiation. We speculate that the transient down-regulation of c-myc mRNA may be an initial event in the erythroid differentiation of K562.

Cell Differentiation↗
PubMed1987

Interferon-alpha, -beta, and -gamma augment the levels of rRNA precursors in peritoneal macrophages but not in macrophage cell lines and fibroblasts.

We have studied the ribosomal RNA content in murine peritoneal macrophages activated to cytotoxicity with interferon-alpha (IFN-alpha), interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma). Total RNA was purified from IFN-alpha, -beta, or -gamma activated macrophages, and Northern blot analysis was performed by using subcloned fragments specific for precursor rRNA (pre-rRNA) as probes. All types of interferon (alpha, beta, gamma) at the doses normalized for induction of cytotoxic activity caused accumulation of 45S, 41S, and 36S pre-rRNA. In contrast, the levels of 32S pre-RNA and 28S, 5.8S, and 18S mature rRNA were not affected by IFN treatment. Therefore, the accumulation of pre-rRNA in macrophages activated to cytotoxicity by IFN was not paralleled by changes in total content of mature rRNA. No accumulation of pre-rRNA upon IFN treatment was found in a murine fibroblast cell line (L929 cells) or in a macrophage cell line (GG2EE) immortalized from bone marrow of C3H/HeJ mice. Neither of those cell lines become cytotoxic in response to IFN. Overall, our data support the concept that IFN acts selectively on the mechanism controlling the levels of some pre-rRNA and that the mechanism of IFN action involves the post-transcriptional control of ribosomal gene expression.

Animals↗
PubMed1987

Selective inhibition of 28S ribosomal RNA in macrophages activated by interferon-gamma or -beta.

We have investigated the metabolism of RNA in mouse peritoneal exudate macrophages activated by interferon (IFN)-gamma or -beta. Both species of IFN induce cytotoxic activity in macrophages. We observed a decrease in the incorporation of [3H]-uridine into total RNA in macrophages treated with doses of IFN that induce cytotoxic activity. IFN-gamma was 100-fold to 1000-fold more potent that IFN-beta in inhibiting RNA synthesis. [3H]Uridine-labeled RNA was purified from IFN-activated and control macrophages and was size fractionated on agarose gels. Macrophages activated by either IFN-gamma or IFN-beta had an imbalanced accumulation of 28S ribosomal RNA compared with their accumulation of 18S ribosomal RNA. Pulse-chase experiments suggested that IFN induced a selective inhibition of the processing of 28S ribosomal RNA. These results provide the first evidence that IFN can modulate ribosomal gene expression at the post-transcriptional level. Moreover, they indicate that inhibition of 28S ribosomal RNA accumulation in macrophages is a molecular event triggered by IFN-gamma, as well as IFN-beta.

Animals↗
PubMed1987

Early experience with Walsh technique of radical retropubic prostatectomy.

We analyzed the operative experience and postoperative and late complications of pelvic lymphadenectomy and radical retropubic prostatectomy in 27 consecutive cases in which the modifications of prostatectomy described by Walsh were employed, and compared the results with those of 29 cases performed in the preceding three years when the Campbell technique of prostatectomy was employed. The mean operative time, mean blood loss, and incidences of early postoperative complications and incontinence were less for patients treated with the Walsh technique than with the Campbell technique. After surgery 85 per cent of evaluable patients remained potent with the Walsh technique compared with 16 per cent of patients treated with the Campbell technique. Although other factors besides operative approach may have biased our results, we are persuaded that the innovations of radical retropubic prostatectomy detailed by Walsh constitute important advances in surgical technique, and we now use this procedure in all suitable patients electing treatment by radical prostatectomy for localized prostatic cancer.

Erectile Dysfunction↗
PubMed1987

Effect of liquid diphenoxylate hydrochloride and atropine sulfate (Lomotil) instillations on dynamics and function of continent cecal urinary reservoirs.

We assessed the impact of twice daily instillations of 10 ml. liquid diphenoxylate hydrochloride and atropine sulfate (Lomotil) on the dynamics and function of continent urinary reservoirs constructed from intact cecum and ascending colon. Six patients were treated for 1 to 3 weeks at 3 to 8 months postoperatively. The treatments reduced the frequency of spontaneous reservoir contractions, as well as the basal and contraction pressures of the reservoirs. The reservoir capacities were increased modestly. These alterations in reservoir dynamics were accompanied by a decrease in the cramping characteristically associated with reservoir distension and increased intervals between reservoir catheterization. Two patients who had incontinence after initially successful operations regained continence during treatment. No systemic side effects were observed, although dilution of the drug may be required to prevent reservoir irritability. Diphenoxylate hydrochloride and atropine sulfate instillations may prevent acute and possibly long-term pressure-related complications of continent urinary reservoirs constructed from intact cecum and ascending colon.

Atropine↗