Biomedical subjects

O Kessler

Publications and source records attributed to O Kessler.

11 recordsLinked to original sources

PubMed2001

The contribution of proangiogenic factors to the progression of malignant disease: role of vascular endothelial growth factor and its receptors.

Vascular endothelial growth factor is a major inducer of angiogenesis and a vascular permeability inducing factor. Its expression is upregulated in many types of tumors and it is thought to be a major inducer of tumor angiogenesis. This article focuses on the role of vascular endothelial growth factor in tumor progression and on current efforts aimed at the inhibition of tumor progression through the inhibition of vascular endothelial growth factor activity.

Cell Hypoxia↗

PubMed1999

Long-term incidence of acute myocardial infarction after open and transurethral resection of the prostate for benign prostatic hyperplasia.

PURPOSE: Acute myocardial infarction was found to be the main cause of increased long-term mortality in patients after transurethral compared to open prostatectomy in various retrospective studies. We performed a randomized prospective study to compare morbidity and incidence of acute myocardial infarction in patients after transurethral compared to open prostatectomy for benign prostatic hyperplasia. MATERIALS AND METHODS: We studied 365 patients who were assigned to transurethral (236) or open (129) prostatectomy only according to the size of the prostate and who were followed for 7 to 8 years. The clinical status of the patients in both groups before and after the operation was compared, and the rate of myocardial infarction and long-term mortality was studied. RESULTS: More patients with a history of cerebrovascular accident (5.4 versus 0.8%) and indwelling catheters (16.3 versus 7.6%) before the operation were in the open prostatectomy group. Among the 236 patients operated on transurethrally 31 were reoperated on (6 more than once) during followup compared to 4 of the 129 patients who underwent open prostatectomy. In 15 patients from the transurethral prostatectomy group myocardial infarction developed compared to 9 patients in the open prostatectomy group. This difference was not statistically significant. The rate of acute myocardial infarction after prostatectomy, no matter which approach was used, was greater than 6% and it appeared to be higher when compared to the rate of infarction in the general population of the same age group, which is approximately 2.5% in our county. There was no statistically significant difference in the overall mortality rate between the transurethral and open prostatectomy groups, which was 14.4 and 8.5% respectively. CONCLUSIONS: Open prostatectomy is more effective in overcoming urinary obstruction than the transurethral approach. No significant differences in myocardial infarction or overall mortality rates were found between the 2 groups.

Aged↗

PubMed1998

Posterior cloaca: a unique defect.

The authors present nine cases of a unique defect in which urethra and vagina are fused together forming a urogenital sinus that deviates posteriorly and opens in the anterior rectal wall at the anus or immediately anterior to it. The rectum is essentially normal or may be minimally anteriorly mislocated. The authors call this defect posterior cloaca. The diagnosis requires a suspicious observer and a meticulous examination of the female genitalia. A complete urologic evaluation is mandatory because 88% of these patients have important associated urologic defects. Our patients were operated on via a posterior sagittal transanorectal approach, which allowed a full dissection and mobilization of urethra and vagina together to be placed in a normal location. Rectal dissection and mobilization was avoided to preserve bowel control. Seven patients enjoy bowel and urinary control. One patient was lost to follow-up, and one patient with a severely dysplastic sacrum suffers from fecal and urinary incontinence.

Child↗

PubMed1996

Is contralateral exploration of the kidney necessary in patients with Wilms tumor?

PURPOSE: Surgical exploration of the contralateral kidney in patients with Wilms tumor is standard practice. The introduction of modern imaging techniques (ultrasound, computerized tomography and magnetic resonance imaging) in place of excretory urography has led to a more accurate definition of intrarenal pathology. Is contralateral kidney exploration still necessary in patients with Wilms tumor? MATERIALS AND METHODS: We reviewed the records of 75 patients from 3 medical centers who were evaluated and treated for Wilms tumor in the last 14 years. All children underwent preoperative excretory urography, computerized tomography, ultrasound and/or magnetic resonance imaging. RESULTS: Seven bilateral Wilms tumors were diagnosed preoperatively and confirmed surgically, whereas extensive operative exploration of the contralateral kidney in the other 69 patients revealed no additional pathological condition. This concurred with preoperative radiological findings with 100% sensitivity and specificity. Furthermore, 1 month to 12 years of followup (mean 4.3 years) revealed no tumor in the contralateral kidney. The major postoperative complication was small bowel obstruction in 5 patients 15 to 180 days (mean 77.2) after explorative laparotomy. CONCLUSIONS: In all patients preoperative radiological investigation was accurate in excluding bilaterality. With modern imaging techniques and effective chemotherapy extensive contralateral renal exploration may no longer be mandatory for managing Wilms tumor.

Adolescent↗

PubMed1996

Effects of nonsense mutations on nuclear and cytoplasmic adenine phosphoribosyltransferase RNA.

We have analyzed Chinese hamster ovary (CHO) cell mutants bearing nonsense codons in four of the five exons of the adenine phosphoribosyltransferase (aprt) gene and have found a pattern of mRNA reduction similar to that seen in systems studied previously: a decrease in steady-state mRNA levels of 5- to 10-fold for mutations in exons 1, 2, and 4 but little effect for mutations in the 3'-most exon (exon 5). Nuclear aprt mRNA levels showed a similar decrease. Nonsense-containing aprt mRNA decayed at the same rate as wild-type mRNA in these cell lines after inhibition of transcription with actinomycin D. Nonsense-containing aprt mRNA is associated with polysomes, ruling out a model in which stable residual mRNA escapes degradation by avoiding translation initiation. A tetracycline-responsive form of the aprt gene was used to compare the stability of nonsense-containing and wild-type aprt mRNAs without globally inhibiting transcription. In contrast to measurements made in the presence of actinomycin D, after inhibition of aprt transcription with tetracycline, a nonsense-mediated destabilization of aprt mRNA was indeed demonstrable. The increased rate of decay of cytoplasmic aprt mRNA seen here could account for the nonsense-mediated reduction in steady-state levels of aprt mRNA. However, the low levels of nonsense-bearing aprt mRNA in the nucleus suggest a sensibility of mRNA to translation or translatability before it exits that compartment. Quantitation of the steady-state levels of transcripts containing introns revealed no accumulation of partially spliced aprt RNA and hence no indication of nonsense-mediated aberrancies in splicing. Our results are consistent with a model in which translation facilitates the export of mRNA through a nuclear pore. However, the mechanism of this intriguing nucleocytoplasmic communication remains to be determined.

Adenine Phosphoribosyltransferase↗

PubMed1996

[Surgery for women with urethral diverticulum].

Urethral diverticulum in the female is an acquired lesion following infection of the para-urethral glands. Its symptoms are often nonspecific and only by increased awareness of this condition can delay in diagnosis be avoided. Radiologic imaging of the urethra allows diagnosis of this lesion and determination of its location, extent and the number of lesions. Complete surgical excision is the optimal therapy. In recent years 8 women with this condition were admitted aged 21-52 years. It had been an average of 11 months before their lesions were diagnosed. All had complete surgical excision without perioperative complications. In 5 a Martius labial fat pad was used to facilitate prompt healing of the urethral defect. 6 have been followed for over a year and are completely symptom-free. Judicious choice of surgical technique is required to reduce the rate of complications in the management of these lesions.

Adult↗

PubMed1994

Effect of improved diagnosis of renal cell carcinoma on the course of the disease.

The impact of the improved diagnosis of renal cell carcinoma (RCC) on the course of the disease was evaluated in 188 patients who were diagnosed and treated at a single medical center. Sixty-seven patients (group A) who had undergone nephrectomy between 1979 and 1983 for RCC initially diagnosed by intravenous pyelography (IVP) were compared with 121 patients (group B) who had undergone nephrectomy between 1983 and 1989, diagnosed by ultrasound and/or computed tomography (CT) scan. Incidental asymptomatic tumors were found in 18 of 67 (26.9%) group A patients and in 57 of 121 (47.1%) group B patients (P < 0.001). The incidence of small tumors of < 5 cm in diameter was significantly lower in group A compared to group B (25.4% vs. 47.9%, respectively, P < 0.01). The disease-free 5-year survival rate for group A was 40% compared to 80% for group B. It is concluded that the introduction of modern imaging techniques has improved the survival of patients with RCC and decreased the progression rate of the disease.

Carcinoma, Renal Cell↗

PubMed1993

Order of intron removal during splicing of endogenous adenine phosphoribosyltransferase and dihydrofolate reductase pre-mRNA.

Using a strategy based on reverse transcription and the polymerase chain reaction, we have determined the order of splicing of the four introns of the endogenous adenine phosphoribosyltransferase (aprt) gene in Chinese hamster ovary cells. The method involves a pairwise comparison of molecules that retain one intron and have either retained or spliced another intron(s). A highly preferred order of removal was found: intron 3 > 2 > 4 = 1. This order did not represent a linear progression from one end of the transcript to the other, nor did it correlate with the conformity of the splice site sequences to the consensus sequences or to the calculated energy of duplex formation with U1 small nuclear RNA. By using actinomycin D to inhibit RNA synthesis, the in vivo rate of the first step in splicing was estimated for all four introns; a half-life of 6 min was found for introns 2, 3, and 4. Intron 1 was spliced more slowly, with a 12-min half-life. A substantial amount of RNA that retained intron 1 as the sole intron was exported to the cytoplasm. In the course of these experiments, we also determined that intron 3, but not intron 4, is spliced before 3'-end formation is complete, probably on nascent transcripts. This result is consistent with the idea that polyadenylation is required for splicing of the 3'-most intron. We applied a similar strategy to determine the last intron to be spliced in a very large transcript, that of the endogenous dihydrofolate reductase (dhfr) gene in Chinese hamster ovary cells (25 kb). Here again, intron 1 was the last intron to be spliced.

Adenine Phosphoribosyltransferase↗

PubMed1993

Seminal vesicle congestion as a cause of postprostatectomy dysuria.

A series of benign prostatic hypertrophy patients were routinely evaluated, including transrectal echography, before and at regular intervals following surgery. Five patients had persistent symptoms of dysuria at 14-30 months after surgery. There was no infection, residual urine or malignancy to explain their symptoms. The seminal vesicles (SVs) were severely dilated on transrectal echography, a finding which was definitely not present on initial examination. The patients were treated by transrectal echo-guided aspiration of the SVs by the perineal approach. The fluid aspirated was examined, and antibiotics were directly injected into the SVs. In 4 of the patients, there was a dramatic relief of symptoms with prolonged improvement. In only 1 case, following transurethral resection, there was but slight improvement. Dilated, obstructed SVs after prostatectomy, clearly diagnosed on transrectal echography, may be the cause of persistent irritative urinary symptoms. Treatment can be instituted by echo-guided aspiration of the fluid with simultaneous injection of a potent antibiotic, resulting in probable immediate relief.

Aged↗

PubMed1992

Construction and molecular dynamics simulation of calmodulin in the extended and in a bent conformation.

Analysis of sequence similarity and comparison of the three-dimensional (3D) structures of troponin C and calmodulin have revealed a sequence in the central helix of calmodulin with a high probability for bending. The three amino acids known to form a bend in the N-terminal portion of troponin C are also found in the central helix of calmodulin. The modelling of a bent calmodulin structure, using the dihedral angles of the three residues in the bend of troponin C as a 3D template, results in a conformation of calmodulin where the N- and C-terminal domains are able to form contacts. Dynamics simulations starting from the X-ray structure of calmodulin and from the modelled bent calmodulin were carried out to compare flexibility and correlated movements of Ca2+ in the binding loops. Both conformations of calmodulin remained stable during the period of simulation. In the simulation of calmodulin in the extended form, the motions of the Ca2+ atoms in the two domains (Ca2+1 and Ca2+2 in one domain, and Ca2+3 and Ca2+4 in the other) are correlated. In the simulation of the bent form, an additional correlation between the Ca atoms in the two different domains is observed. The results are compatible with the occurrence of a bent conformation of calmodulin in the presence of targets, and with increased Ca2+ affinity and cooperativity of the Ca(2+)-binding loops in the calmodulin-peptide complexes.

Calcium↗

PubMed1992

[Immunotherapy for metastatic renal cell carcinoma: treatment with PLAK cells and low-dose interleukin-2].

During the past 5 years publications from the NIH (Rosenberg et al.) and other centers have reported encouraging results in the treatment of metastatic renal cell carcinoma. Adoptive immunotherapy was applied, using lymphocytes activated by interleukin-2 (LAK cells) plus high doses of interleukin (IL-2) systemically. The mean clinical response rate was 20-35%. Severe lifethreatening adverse reactions to high doses of IL-2 were noted, although they were all of short duration. Laboratory findings of Novogrodsky et al. from Beilinson Medical Center, Israel showed that oxidizing mitogens can induce lymphocyte activation (PLAK cells). Further studies suggested that a combination of such activated cells with low doses of IL-2 could produce effective toxicity to tumor cells without the need for high doses of IL-2 which could be very toxic for the patient. In the past year we treated 7 patients with PLAK cells and IL-2. 4 completed the treatment, of whom 1 responded partially (regression of more than 50% of lung metastases), 1 is stable and in 1 liver metastases regressed but metastases in lumbar vertebrae and in the pelvis progressed. 1 patient died a month after discharge from hospital, probably due to rapid progression of the disease. Our protocol follows that of the Phase II clinical study of 40 patients treated at the Rogosin Institute, New York Hospital--Cornell Medical Center. The mean clinical response rate was 23.6%. Toxicity of IL-2 is dose-dependent. In this protocol, the low doses of IL-2 gave significantly fewer adverse reactions.

Adult↗