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J Fleischmann

Publications and source records attributed to J Fleischmann.

At least 19 recordsLinked to original sources
PubMed2001

Polyadenylation of ribosomal RNA by Candida albicans.

Candida albicans is the leading fungal pathogen in immunocompromised patients such as those with AIDS and malignancies. It is a polymorphic organism existing as a unicellular yeast or as filamentous forms that include pseudohyphae and true hyphae. While studying the early period of hyphal transformation, comparing cDNAs from yeast to those in early transition, we were surprised to find 25S rRNA represented frequently in our differential display assays, suggesting that our reverse transcription with poly-T primers was copying rRNA with extended poly-A 3' ends. We now report that both the yeast forms and germinating organisms polyadenylate some of their 25S rRNA transcripts. We also found a rapid and transient enhancement of this process upon stimulation with serum. These data indicate that 25S rRNA polyadenylation is part of the biological repertoire of C. albicans and its transient upregulation just prior to hyphal development raises the possibility of a regulatory role in this transition.

Animals↗
PubMed1999

Expression of deoxyuridine triphosphatase (dUTPase) in colorectal tumours.

We report the generation of 2 monoclonal antibodies (MAbs), 2B12 and 3E6, suitable for the detection of human dUTPase in routinely processed paraffin sections by immunohistochemistry. Using these MAbs, we observed nuclear expression of dUTPase in the proliferation zones of normal colorectal mucosa as well as in hyperplastic polyps. Colorectal adenomas and adenocarcinomas revealed a wide spectrum of dUTPase expression, ranging from 5 to 63% (median 42%) and from 5 to 71% of tumour cells (median 42%) respectively. Non-parametric correlation of dUTPase expression with proliferation as determined by a Ki-67 antigen-specific MAb revealed a significant and moderately strong correlation between proliferation rate and dUTPase expression in adenomas, but not in adenocarcinomas. This finding was confirmed by double-labelling immunofluorescence. Unexpectedly, we found significantly lower levels of dUTPase expression in primary colorectal carcinomas without lymph-node metastases at the time of surgery (Dukes A and B stages) than in Dukes C carcinomas. While this observation requires confirmation in larger studies, it suggests that dUTPase expression may be a negative prognostic marker in colorectal carcinomas. Moreover, these reagents should prove useful in the context of attempts to develop dUTPase inhibitors for cancer chemotherapy. Since it has been demonstrated that dUTPase expression can mediate resistance to 5-fluorouracil, it is also possible that these MAbs may be helpful in identifying patients with colorectal carcinomas resistant to adjuvant chemotherapy using this and related compounds. Int. J. Cancer (Pred. Oncol.) 84:614-617, 1999.

Adenocarcinoma↗
PubMed1999

Intraoperative electrical stimulation of cavernosal nerves with monitoring of intracorporeal pressure in patients undergoing nerve sparing radical prostatectomy.

OBJECTIVE: To explore the utility of intraoperative cavernosal nerve stimulation in facilitating atraumatic nerve dissection during radical prostatectomy, and thus help predict postoperative erectile function. PATIENTS AND METHODS: Fourteen patients (aged 51-72 years) underwent nerve-sparing radical retropubic prostatectomy (NSRRP); 10 were potent before surgery (group 1), and four had erectile dysfunction (group 2). A multi-acquisition system (MacLab/8e) with a Macintosh computer was used for real-time display and recording of intracavernosal pressure (ICP) during surgery. Nerves were stimulated with a bipolar probe (monophasic rectangular pulses, 10 mA, 20 Hz, 0.22 s) before and after removal of the gland. The follow-up consisted of interviews with patients and their partners' 12-18 months after treatment. RESULTS: The mean (sem) basal ICP of 8. 0 (2.0) cmH2O remained unchanged during nerve dissection. The mean increase in ICP during electrical stimulation was >50 cmH2O in seven potent patients (group 1) and was sustained as long as the nerve was stimulated. Postoperatively, these seven patients reported erections sufficient for sexual intercourse. However, the three remaining patients in group 1 had pressure rises of <30 cmH2O, of whom two reported partial erections and one reported total impotence postoperatively. The recovery time for erectile function was 6-12 months after surgery. Two patients from group 2 had transient increases in ICP to <40 cmH2O; one had an increase to 20 cmH2O and one had no response at all. All four patients remained totally impotent postoperatively. There were no complications. CONCLUSIONS: Intraoperative electrical stimulation of the cavernosal nerves with ICP monitoring before and after NSRRP is a safe and reliable method for documenting nerve continuity and its functional status. Patients who have normal preoperative erectile function and show an adequate rise in ICP upon electrical nerve stimulation during NSRRP will almost certainly be potent after surgery. This tool may be used to facilitate atraumatic nerve dissection during NSRRP.

Aged↗
PubMed1998

Efficient trans-splicing of mutated spliced leader exons in Leishmania tarentolae.

Every kinetoplastid mRNA receives a common, conserved leader sequence via the process of trans-splicing. In Leishmania tarentolae the precursor spliced leader RNA is 96 nucleotides, with a 39-nucleotide exon that is 7meG-capped and methylated on the first 4 nucleotides. trans-Splicing was inferred from the presence of tagged leader in the high molecular weight RNA population and confirmed for accuracy by cDNA cloning. Linker scan substitutions within the exon between positions 10 and 39 did not affect trans-splicing. The trans-splicing efficiency for three of the scan exons was proportional to the tagged:wild type ratio in the spliced leader precursor population. Two scan leader RNAs that were efficiently spliced showed reduced methylation. Longer exons showed reduced splicing, whereas 10- or 20-base pair deletions abolished splicing. These results indicate that size, but not content, of the exon is a constraint on the splicing process. These results, in combination with previous data eliminating a role in transcription initiation, suggest that translation may be the selective pressure on the leader content.

Alternative Splicing↗
PubMed1998

Intracavernous pressure responses to physical and electrical stimulation of the cavernous nerve in rats.

OBJECTIVES: To better define the techniques of nerve-sparing prostate dissection that would result in preservation of erectile function, we characterize the effects of physical pressure on the prostate and cavernous nerve, electrical stimulation of the cavernous nerve, and pharmacologic manipulations on intracavernous pressure (ICP) in normal and diabetic rats. METHODS: Fischer-34 rats, both normal and diabetic, underwent dissections that isolated the cavernous bodies and cavernous nerves. Cavernous body pressures were characterized during surgical manipulation, during electrical stimulation of the cavernous nerves, and following papaverine hydrochloride injection. RESULTS: In normal rats, baseline cavernous pressures ranged from 5 to 15 cm H2O (mean 12.29). In diabetic rats, the baseline pressure was significantly lower (3 to 7.5 cm H2O). Lateral nerve displacement caused ICP to rise to approximately 35 cm H2O in normal rats, but only to 20 cm H2O in diabetic rats. Electrostimulation resulted in cavernous pressure increases of 10-fold from baseline in normal rats and sevenfold from baseline in diabetic rats. ICPs were not disturbed appreciably with nerve-sparing dissection techniques. Neurotomy resulted in declines in baseline cavernous pressures in all rats. Electrostimulation of the distal end of a severed nerve resulted in pressure rises to 50% of those observed in rats with intact cavernous nerves. Intracavernous papaverine injection before or after nerve stimulation masked subsequent (expected) pressure changes. CONCLUSIONS: A change in cavernous pressure is a sensitive indicator of cavernous nerve manipulation. Both cavernous pressure measurements and electrostimulation of cavernous nerves may aid surgeons during radical prostatectomy.

Animals↗
PubMed1997

Biologic response modifiers in the management of superficial bladder cancer.

For the treatment of existing transitional-cell carcinoma or for prophylaxis of recurrent disease, intravesical therapy should be chosen according to stage. Papillary disease (stages Ta, Tl) may be treated effectively either with an alkylating agent or with bacillus Calmette-Guérin (BCG). BCG is the agent of choice for the treatment of Hat carcinoma in situ (Tis), with the recommended treatment course comprising 12 weekly and 12 monthly instillations. Intravesical interferon and many of the other biologic response modifiers mentioned herein may be effective for patients with Ta disease who have failed BCG therapy.

Administration, Intravesical↗
PubMed1996

Intravesical bacille Calmette-Guérin therapy for muscle invasive bladder cancer.

OBJECTIVES: This investigation attempted to determine whether the degree of fibronectin expression in the bladders of patients with invasive transitional cell carcinoma correlated with their clinical response to intravesical bacille Calmette-Guerin (BCG) therapy. METHODS: Following transurethral resection of all invasive disease, 13 patients with Stages T2-T4 bladder cancer were administered intravesical BCG (fo 6 weeks followed by monthly instillations). Fibronectin expression in the patients' resected tumors and normal mucosa was determined by immunohistochemical staining techniques. Minimum disease-free follow-up was 60 months. RESULTS: Only 1 of 13 patients had neither local nor systemic disease recurrence; 10 of 13 patients developed systemic disease and 7 patients died from metastases. Fibronectin expression was not correlated with the clinical response to BCG. CONCLUSIONS: Intravesical BCG therapy for the treatment of muscle invasive transitional cell carcinoma of the bladder is ineffective. Fibronectin expression in the bladder of patients with invasive disease is variable and does not correlate significantly with the clinical response to BCG therapy.

Administration, Intravesical↗
PubMed1995

Renal cell carcinoma: considerations for nephron-sparing surgery.

OBJECTIVES: The performance of nephron-sparing surgery in patients with a normally functioning contralateral kidney is controversial. To explore the risk factors that may contribute to the success or failure of nephron-sparing surgery, we examined the radiology and pathology reports of 278 patients who underwent radical nephrectomy for the treatment of clinically localized renal cell carcinoma. METHODS: We collated patient data from the records of 278 patients with Stage III renal cell carcinoma entered into the Eastern Cooperative Oncology Group protocol EST 2886 and compared preoperative clinical staging with postoperative pathologic results. Patients were considered potential candidates for nephron-sparing surgery if their preoperative radiographic studies indicated that the carcinoma was a single polar lesion 5 cm or less in diameter. RESULTS: Of 278 radical nephrectomy specimens, 36 had primary lesions 5 cm or less in diameter. Preoperative radiographic studies showed 14 of 36 would not have been considered eligible for nephron-sparing surgery. Of the remaining 22 potential candidates, pathologic studies showed multifocal lesions in 11, renal vein disease in 4, and nodal disease in 2. Only 5 of 22 patients might have had specimen-confined disease (T3a lesion). CONCLUSIONS: Capsular-penetrating (T3a) renal cell carcinoma is not often appreciated preoperatively and is associated frequently with multifocal lesions, renal vein or nodal disease. Frozen section studies to rule out T3a disease at the time of nephron-sparing surgery may help determine which patients need radical surgery.

Carcinoma, Renal Cell↗
PubMed1995

Cytoreductive surgery for stage IV renal cell carcinoma.

To facilitate the regression of extra renal disease in response to systemic therapy, cytoreductive surgery has been advocated as step 1 in the treatment of stage IV renal cell carcinoma. To determine the effect of surgery on subsequent clinical course, we reviewed the treatment records of 30 patients with known stage IV carcinoma of the kidney who underwent nephrectomy or additional procedures in preparation for systemic therapy. Of 30 patients only 7 (23%) underwent systemic therapy postoperatively. Progression of the disease, surgical morbidity and mortality were the factors preventing 77% of our patients from continuing with treatment. Since regression of extra renal lesions is the goal of systemic therapy, our data suggest that nephrectomy and most other cytoreductive operations in preparation for systemic therapy are not efficient treatment strategies.

Adult↗
PubMed1995

Dental treatment considerations for the pre- and post-organ transplant patient.

Organ transplantation is a viable treatment for individuals whose quality of life is significantly impaired. There has been a dramatic increase in the number of whole organ transplants being performed over the past few years; and although somewhat limited by donor availability, these numbers have continued to increase as success rates improve and more medical centers perform them. The number of solid organ transplants performed throughout the world has grown from 35,628 (1980-1990) to 285,561 (1989-1991). The number of patients on the waiting list for organs has increased by 59.4 percent from 1988 to 1993. As this patient population grows, the community-based dental practitioner will be faced with a special set of concerns. Understanding the diverse precautions for treatment of pre- and post-organ transplant patients will help the practitioner adequately treat the dental needs of this patients population.

Dental Care for Chronically Ill↗
PubMed1994

Expression of the Leishmania tarentolae ubiquitin-encoding and mini-exon genes.

To develop models for transcription and trans-splicing in kinetoplastid protozoa, we have characterized ubiquitin (Ubi) gene organization and mRNA processing in Leishmania tarentolae (Lt). Three ubi loci were characterized: two discrete Ubi-extension protein 52 (EP52)-encoding genes (ubiA and ubiB) and a polymorphic polyubiquitin-encoding gene (ubiC). The three loci resided on chromosomes of 2.05 Mb, 630 kb and 2.9 Mb, respectively. On the basis of upstream flanking gene identity, ubiB appears to be the homologue of the tandemly repeated ubi-EP52/1 and 2 in Trypanosoma brucei (Tb). Similar to Trypanosoma cruzi, Lt did not contain a homologue of the ubi-EP76 that has been found in Saccharomyces cerevisiae and multicellular organisms. All three Lt ubi loci were transcribed. The primary transcripts from the ubi loci were processed at the 5'-end by trans-splicing with the mini-exon. A Lt mini-exon gene (min) that gave rise to a 95-nt primary transcript, which is the second template in the trans-splicing reaction, was also characterized.

Amino Acid Sequence↗
PubMed1994

Combined laparoscopic pelvic lymph node dissection and modified belt radical perineal prostatectomy for localized prostatic adenocarcinoma.

OBJECTIVE: Despite many known advantages, the radical perineal prostatectomy (RPP) had fallen out of favor because of the need for a second incision for the regional lymph node dissection. Laparoscopic lymphadenectomy, however, provides an accurate and minimally invasive alternative to open lymph node dissection. Herein are reported the practical advantages of combining laparoscopic lymph node dissection (LPLND) with RPP. METHODS: Forty-nine patients with clinically localized carcinoma of the prostate were considered candidates for RPP using a modified Belt technique. Thirty-five patients underwent attempted LPLND and 31 of these patients subsequently underwent RPP; 14 patients underwent RPP alone. Variables examined included total operative time, transfusion requirement, length of hospital stay, continence, and potency. RESULTS: The mean operative time for LPLND combined with RPP in 31 patients, including time for repositioning, was 4.5 hours (range 3.0 to 7.0 hours). Only 26 percent of the patients who underwent the combined approach required blood transfusions of which 75 percent received autologous units. Mean length of stay was six days, and laparoscopy did not contribute significantly to postoperative morbidity. Eighty-four percent of the patients are completely continent. Of 27 potent patients who underwent nerve-sparing surgery, 22 percent are potent and an additional 30 percent are sexually active with intracavernous pharmacotherapy. There were no perioperative deaths, 2 major complications, and 5 minor complications. CONCLUSIONS: Laparoscopic techniques now permit the urologist to utilize the perineal approach, and its many advantages, to radical prostatic extirpation without the need for a formal abdominal incision. The minimal blood loss and low morbidity associated with laparoscopic pelvic lymphadenectomy combined with the radical perineal prostatectomy make this procedure an attractive alternative to the open retropubic approach for clinically localized prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1994

The effects of human immunodeficiency virus infection on macrophage phagocytosis of Candida.

The effects of infection by human immunodeficiency virus (HIV) on phagocytic function towards Candida pseudotropicalis were tested using monocytotropic and nonmonocytotropic HIV strains on peripheral blood monocytes. There were no differences in either quantitative phagocytic activity or efficacy between the two infected and control mock-infected monocytes. Immunofluorescence for cytoplasmic p24 antigen and in situ hybridization for detection of HIV-specific RNA sequences revealed that very few cells (10(-4)) exhibit productive infection. Occasional cells with active infection as defined by microscopically detectable fluorescence labelling contained phagocytized yeasts.

AIDS-Related Opportunistic Infections↗
PubMed1994

Management of recurrent penile cancer following partial or total penectomy.

The initial management of localized penile carcinoma determines the probability of recurrence. Although potentially disfiguring, the management of recurrent carcinoma of the penis requires aggressive surgical resection of both the primary lesion and nodal sites to effect the best chance for long-term survival.

Adult↗
PubMed1994

Calcium channel antagonists in the treatment of interstitial cystitis.

The calcium channel antagonist nifedipine has shown efficacy in the treatment of interstitial cystitis and the urethral syndrome. The optimal daily dose of nifedipine can be determined with the use of a nifedipine titration test. To complete the repair of damaged bladder and/or urethral mucosa, nifedipine therapy should be used for a minimum of 3 months. Patients who do not respond well to nifedipine are those with the pelvic floor muscle spasm syndrome variant of interstitial cystitis.

Cystitis↗
PubMed1993

Management of superficial transitional cell carcinoma of the bladder.

Intravesical therapy for the treatment of existing bladder cancer or for prophylaxis of recurrent disease should be chosen according to the stage of transitional-cell cancer. Papillary disease (stages Ta, T1) may be treated effectively with either an alkylating agent or with BCG. BCG is the agent of choice for the treatment of Tis, provided that the treatment course includes 12 weekly and 12 monthly instillations.

Administration, Intravesical↗