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Biomedical subjects

A E Katz

Publications and source records attributed to A E Katz.

At least 19 recordsLinked to original sources
PubMed1997

Human prostatic carcinoma oncogene PTI-1 is expressed in human tumor cell lines and prostate carcinoma patient blood samples.

Rapid expression cloning and differential RNA display identifies a gene, named prostate tumor inducing gene-1 (PTI-1), that is differentially expressed in prostate cancer versus normal prostate and benign prostatic hypertrophy. PTI-1 encodes a truncated and mutated human elongation factor 1 alpha, and its 5' untranslated region (UTR) shares significant homology with the 23S rRNA gene of Mycoplasma hyopneumoniae. PCR with human genomic DNAs, using PTI-1 5' UTR-specific primers, suggests that this sequence is part of the human genome. Furthermore, reverse transcription (RT)-PCR, with one primer specific to the 5' UTR region and the other to the elongation factor 1 alpha coding region, amplifies PTI-1 transcripts from total RNA of various human tumor cell lines and blood samples from prostate carcinoma patients. RT-PCR products with the predicted size and sequence of PTI-1 are detected in RNAs from cell lines of human prostate, breast, and colon carcinomas. This RT-PCR product is shown by Southern blotting and sequence analyses to contain the junction sequence between the 5' UTR and the coding region of the PTI-1 gene. Furthermore, RT-PCR analysis indicates that the PTI-1 gene is also expressed in prostate carcinoma patient-derived blood samples. On the basis of serial dilution experiments, PTI-1 can detect 1 prostate carcinoma cell in 10(8) cells not expressing PTI-1. In this context, PTI-1 represents a sensitive marker for detecting human prostate cancer in the bloodstream. This study confirms the authenticity of the PTI-1 gene and documents its potential clinical utility as a sensitive and specific indicator of prostate cancer progression.

Base Sequence↗
PubMed1996

The role of the reverse-transcriptase polymerase chain reaction assay for prostate-specific antigen in the selection of patients for radical prostatectomy.

Prostate cells present in the peripheral circulation can be detected using an enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) assay. In one study, preoperative enhanced RT-PCR for PSA status was a significant predictor of surgical pathology and postoperative biomechanical recurrence. The use of RT-PCR may enhance the urologist's ability to stage potential candidates for radical prostatectomy, as the assay is a more sensitive and specific predictor of microscopic extracapsular extension than conventional staging modalities. This highly adaptable assay also may have roles in screening for recurrence and in staging other solid tumors.

Adenocarcinoma↗
PubMed1996

The use of RT-PCR for prostate-specific antigen assay to predict potential surgical failures before radical prostatectomy: molecular staging of prostate cancer.

OBJECTIVE: To assess the potential role of a recently developed reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen (PSA), that detects circulating prostate cells in patients with prostate cancer, in the management of clinically localized cancer. PATIENTS AND METHODS: A total of 138 men (mean age 62.5 years, range 49-70) scheduled for radical retropubic prostatectomy had an RT-PCR assay before surgery. The results were compared with the final pathological stage of disease, the results from local imaging techniques, serum PSA levels, digital rectal examination (DRE) and Gleason score. RESULTS: Enhanced RT-PCR for PSA was the best predictor of potential surgical failures; 70% of patients with positive surgical margins or invasion into the seminal vesicle were identified pre-operatively by a positive RT-PCR assay (odds ratio = 12.0, positive predictive value = 64%, negative predictive value = 87%). RT-PCR was able to identify pre-operatively patients with adverse pathology, despite low serum PSA values (< 4.0 ng/mL). In patients with high PSA level (> 10 ng/mL), RT-PCR discriminated between potentially curable candidates and those with established extraprostatic disease. CONCLUSIONS: RT-PCR for PSA adds unique prognostic information when considering patients for radical surgery. The final role for the RT-PCR assay is as yet undefined; however, the ability to detect potential surgical failures pre-operatively using a molecular approach should have a significant impact on the management of patients with prostate cancer.

Aged↗
PubMed1996

Preoperative reverse transcriptase polymerase chain reaction for prostate specific antigen predicts treatment failure following radical prostatectomy.

PURPOSE: We previously demonstrated than an enhanced reverse transcriptase-polymerase chain reaction assay for prostate specific antigen (PSA) can predict final pathological stage in radical prostatectomy patients. The potential role of the assay in predicting serum PSA recurrence after radical prostatectomy was explored. MATERIALS AND METHODS: We evaluated 100 radical prostatectomy candidates by reverse transcriptase polymerase chain reaction preoperatively, and status was compared to serum PSA, Gleason score and final pathological results. Potential surgical failure was defined as tumor at the surgical margin or extending into the seminal vesicle. Patients were monitored postoperatively by serum PSA every 4 months. Kaplan-Meier analysis was used to evaluate the correlation between reverse transcriptase polymerase chain reaction and disease recurrence, defined as a PSA of 0.2 ng/ml. or greater. RESULTS: Enhanced reverse transcriptase polymerase chain reaction for PSA had a stronger correlation with potential surgical failure than preoperative serum PSA or Gleason score (relative risks 15.2, 5.9 and 3.2, respectively). The correlation between these modalities and PSA recurrence was evaluated during a mean followup of 13.6 months (range 5 to 26). Of 36 patients with positive reverse transcriptase polymerase chain reactions 9 had failure by PSA compared to 3 of 64 (4.7%) with negative polymerase chain reactions (p<0.0286). The relative risk for failure by reverse transcriptase polymerase chain reaction was 3.6. Gleason score and serum PSA had higher correlations with postoperative PSA elevations (relative risk 13.2 and 7.6, respectively). A Cox regression analysis model demonstrated that reverse transcriptase polymerase chain reaction for PSA can be used in conjunction with Gleason score and provides statistically significant risk information. CONCLUSIONS: Enhanced reverse transcriptase polymerase chain reaction for PSA is a statistically significant predictor of potential failure by pathological analysis and of disease recurrence by PSA. Longer followup data are required to define further the role of the assay in the management of patients with prostate cancer.

Aged↗
PubMed1995

Enhanced reverse transcriptase-polymerase chain reaction for prostate specific antigen as an indicator of true pathologic stage in patients with prostate cancer.

BACKGROUND: As up to 50% of all patients with prostate cancer who have undergone radical prostatectomy are found to be understaged subsequent to surgery, a more sensitive early staging modality currently is needed. A molecular assay that detects prostate specific antigen (PSA)-synthesizing cells in the peripheral circulation of patients with prostate cancer is described. METHODS: An enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) assay specific for PSA mRNA was performed on RNA extracted from blood drawn from 94 patients before radical prostatectomy. Surgical specimens were examined to determine the extent of tumor spread. The assay was compared with imaging modalities, digital rectal examination, and serum PSA level as predictors of pathology. Additionally, patients were monitored postoperatively by serum PSA level to determine any potential correlation between patient RT-PCR scores and subsequent tumor recurrence. RESULTS: Postoperative pathology revealed that 36 of the 94 patients had extraprostatic disease at the time of surgery. Enhanced RT-PCR identified 26 of these patients from preoperative blood specimens (72% sensitivity). The test was negative for 51 of the 58 patients with organ-confined disease (88% specificity). An odds ratio analysis showed that no other preoperative staging modality was related more strongly to extraprostatic or organ-confined disease. Follow-up PSA determinations revealed that RT-PCR positive patients were at higher risk for a recurrence. At 6 months after surgery, the rates for an increased PSA were 19 and 2% for RT-PCR-positive and -negative patients, respectively. CONCLUSIONS: The data from this follow-up study continue to support the utility of enhanced RT-PCR as an early staging modality for radical prostatectomy candidates.

Androgen Antagonists↗
PubMed1995

Molecular staging of prostate cancer. II. A comparison of the application of an enhanced reverse transcriptase polymerase chain reaction assay for prostate specific antigen versus prostate specific membrane antigen.

Current imaging modalities used to stage prostate cancer clinically fail to detect extracapsular disease in a significant subset of patients. A molecular based peripheral blood assay using the reverse transcriptase polymerase chain reaction has recently been shown to be a highly sensitive staging modality for detecting extraprostatic disease preoperatively. The assay uses primers that are specific for prostate specific antigen (PSA). We compare the application of the reverse transcriptase polymerase chain reaction assay using primers specific for the human prostate specific membrane antigen with results obtained from the same specimens by reverse transcriptase polymerase chain reaction for PSA. Prostate specific membrane antigen, a recently cloned prostatic antigen, is a transmembrane glycoprotein that has been described as prostate specific. These assays were applied to ribonucleic acids extracted from the peripheral blood lymphocyte fraction of 80 patients with clinically localized prostate cancer. In addition, blood specimens from 20 female patients, 20 young male patients, 25 age-matched control men under treatment for benign prostatic hypertrophy and 20 men with established, untreated metastatic prostate cancer were tested. All 3 groups of noncancer patients had negative polymerase chain reactions for PSA as well as prostate specific membrane antigen. Of 20 metastatic prostate cancer patients 16 (80%) had positive polymerase chain reactions for PSA, while only 10 (50%) had positive results for prostate specific membrane antigen. Among the 80 patients with clinically localized disease (stages T1 to T2cN0M0), 27 and 19 had positive polymerase chain reaction for PSA and prostate specific membrane antigen, respectively, from blood specimens obtained preoperatively. Analyzing the final pathology in each patient with the reverse transcriptase polymerase chain reaction assay identified a significantly stronger correlation with tumor invasion using the results of the PSA test rather than the results of the prostate specific membrane antigen reverse transcriptase polymerase chain reaction test (67% versus 34% sensitivity for detecting capsular penetration, 87% versus 46% sensitivity for detecting disease to the surgical margin and 83% versus 16% sensitivity for detecting seminal vesicle invasion). In contrast to the reverse transcriptase polymerase chain reaction assay for PSA, a similar assay done for prostate specific membrane antigen did not correlate with pathological stage of prostate cancer.

Adenocarcinoma↗
PubMed1994

Molecular staging of prostate cancer with the use of an enhanced reverse transcriptase-PCR assay.

OBJECTIVE: Because up to 40 percent of surgically treated patients with prostate cancer are subsequently found to be clinically understaged, a more sensitive staging modality to identify extraprostatic disease prior to surgery is required. METHODS: We describe an enhanced reverse transcriptase [RT] polymerase chain reaction (PCR) assay utilizing oligonucleotide primers specific for the human prostate-specific antigen (PSA). This assay identifies PSA-synthesizing cells from reverse transcribed mRNA. This assay was applied to RNAs extracted from the peripheral blood lymphocytes of 65 patients with clinically localized prostate cancer. In addition, blood from 20 women, 20 young men, 25 age-matched control men under treatment for benign prostatic hyperplasia (BPH), and 18 men with established, untreated metastatic prostate cancer was tested. RESULTS: An RT-PCR assay for PSA can recognize one PSA-expressing cell diluted into one hundred thousand lymphocytes. The sensitivity of this assay can be enhanced by the addition of digoxigenin-modified nucleotides to the PCR reaction and this assay was applied to RNAs extracted from the peripheral lymphocyte fraction of 148 prostate cancer patients and controls at this institution. Although no specimen from women or men without cancer was positive in this assay, 14 of 18 metastatic prostate cancer patients were positive (77.8%). Additionally, 25 of 65 (38.5%) patients with clinically localized disease (T1-2b) were positive from blood specimens obtained prior to surgery. Final pathologic results from this group of patients identified a correlation between positivity on this assay and the presence of capsular tumor penetration (sensitivity, 68%; specificity, 84%) as well as strong correlation with the finding of carcinoma at the surgical margin (sensitivity, 87%; specificity, 76%). Logarithmic regression analysis of the results of the RT-PCR assay indicates its remarkable superiority to digital rectal examination, computed tomography scan, endorectal coil magnetic resonance imaging, PSA, prostate-specific antigen density, or Gleason score for predicting the true pathologic stage of prostate cancer in these surgically treated patients. CONCLUSIONS: An RT-PCR assay using PSA primers to detect prostate cells in the peripheral circulation of surgical-candidate patients is significantly correlated with capsular penetration and tumor-positive surgical margins. This molecular assay provides a sensitive and specific means to stage correctly apparent localized prostate cancer prior to radical prostatectomy.

Adult↗
PubMed1994

Massive cystic heterotopic brain tissue.

The differential diagnosis of large cystic masses in the newborn should include heterotopic brain tissue. This lesion is attributed to early displacement of pluripotential cells and cyst formation may result from cerebrospinal fluid production by choroid plexus-like structures. Treatment consists of surgical excision.

Brain Diseases↗
PubMed1993

Update on immunology of head and neck cancer.

The history of immunotherapy in head and neck cancer is filled with disappointing results and clinical trials of nonspecific immunotherapeutic protocols. Most of these protocols did not concern themselves with some of the possible underlying etiologies of immunosuppression, such as alcoholism, malnutrition, aging, and the oncologic therapies that the patients were undergoing. These factors must be appreciated, and attempts must be made to deal with their devastating effects. It is also becoming increasingly apparent that the humoral immune system does have a major impact on the effectiveness of the cellular immune system, and that the various components of this system need to be more fully understood. The complexity of these interactions will probably not allow for an effective immunotherapeutic protocol to be attained in the near future. It is, however, more likely that the establishment of immunoprognosis and immunodiagnosis may be achieved as these complex interactions are more fully identified and understood.

Antibody Formation↗
PubMed1992

The purse-string suture in facial reconstruction.

Mohs surgical defects in 26 patients were reconstructed utilizing a purse-string suture and a full-thickness graft. The placement of the purse-string suture decreased the surface area of the wound an average of 53%. A full-thickness graft was then placed in the remaining defect. This technique enabled us to repair large wounds of the facial region with a relatively small full-thickness graft. There were no complications in our series. The resultant areas were cosmetically acceptable and resistant to trauma.

Adult↗
PubMed1990

Characterization of the products of a gene expressed during androgen-programmed cell death and their potential use as a marker of urogenital injury.

Regression of the rat ventral prostate gland following castration is accompanied by the induced expression of messenger RNA encoding Testosterone Repressed Prostate Message-2 (TRPM-2). Subsequent studies have shown that this gene is also induced during renal injury. In each of these tissues, the TRPM-2 RNA products are expressed by cells undergoing programmed death as a result of the hormonal stimuli or the traumatic insult. In an attempt to characterize this gene and its products, we partially sequenced complementary DNAs for TRPM-2 isolated from a recombinant library constructed using RNA of a hydronephrotic kidney. The sequence of these clones showed close homology with the sulfated glycoprotein-2 (SGP-2/clusterin) gene, expressed constitutively by mammalian Sertoli cells. Antibody recognition studies confirm this homology. Antiserum made against rat clusterin recognized TRPM-2 encoded polypeptides in extracts of regressing rat ventral prostate glands. Western blot analysis allowed us to demonstrate large increases in the concentration of these proteins in extracts of regressing ventral prostate gland and in rat serum and urine during the acute period of prostatic regression. These results indicate that proteins are synthesized from the large amount of TRPM-2 RNA produced by dying prostate cells and imply that these proteins are shed into the serum and urine. Based on the intense synthesis of TRPM-2 gene products by dying cells in the urogenital tract and the ability to assay for these products in serum and urine, we suggest that an assay for TRPM-2 products might allow us to monitor the extent of cellular damage associated with specific urogenital disease states.

Animals↗
PubMed1989

Gene activity during the early phase of androgen-stimulated rat prostate regrowth.

Androgenic steroids regulate the proliferation rate of normal and malignant prostate cells. In order to investigate the molecular basis of this control, we utilized Northern and Western blot techniques to measure changes in the expression of individual genes during the early phase of prostate regrowth. Vestigial ventral prostate glands of 7-day castrated rats showed increased numbers of replicating cells within 12 h of continuous pharmacological testosterone replacement as demonstrated by flow cytometric procedures. The period prior to the onset of proliferative enhancement was accompanied by the sequential induction of a variety of transcripts encoding gene products often associated with cell growth. Within 1 h of treatment, mature mRNA transcripts for c-fos were induced 6-fold, returning to control levels by 2 h. Other genes showed transiently elevated transcript levels after 2 h (c-Ha-ras, c-Ki-ras) or after 8 h (c-myc,c-myb, beta-actin, and Mr 70,000 heat shock protein) of testosterone replacement. Expression of the polypeptide encoded by c-Ha-ras was coordinately enhanced (2-fold) during this period, but not to the levels of the transcript (20-fold induction). Transcripts encoding basic fibroblast growth factor were increased 16 h and later, subsequent to the earlier enhancement in the proliferation rate. By placing these genes in a defined temporal order with regard to their expression in response to testosterone, we have constructed a map of gene activity during early prostate regrowth. This map shows a number of genes, the products of which might participate in the mechanism by which androgens induce mitogenesis of prostate cells.

Animals↗
PubMed1987

Tumor regression and temporary restoration of immune response after plasmapheresis in a patient with recurrent oral cancer.

A major response to plasmapheresis is reported in a patient with advanced, recurrent squamous cell cancer of the oral cavity, similar to that previously reported in three of six comparable patients. Tumor regression followed temporary reduction of inhibition of normal lymphocyte response to phytohemagglutinin (PHA) by the patient's serum (from 99% to zero) and partial restoration of the patient's lymphocyte response (from 2% to 38% of control). The IgE level rose both overall and during some exchanges; this correlate of tumor response had been noted earlier. The tumor showed extensive necrosis, but the clinical effects were relatively short-lived and the patient died 11 weeks later. Biopsy specimens taken early in apheresis showed intense new infiltration of tumor by lymphocytes and monocytes; later biopsy specimens showed predominantly plasma cells with trapping and lysis of tumor cells. No other anti-cancer therapies had been used for 16 months before this trial, and no replacements were given other than saline and albumin.

Antigens, Surface↗
PubMed1986

Cheek-neck advancement-rotation flaps following Mohs excision of skin malignancies.

The cheek-neck advancement-rotation flap has proved extremely useful for delayed reconstruction of the face following the microscopically controlled surgical excision (MCSE) of skin malignancies. We have recently used these flaps successfully to repair combined defects of the cheek and nose in eight patients, isolated cheek defects in six patients, combined defects of the cheek and lips in two patients, and isolated defects of the nose, temple, and an antral cutaneous fistula in each of three patients. Defects as large as 6.0 X 10.0 cm have been closed in one stage with this flap. This flap is extremely hearty and its scars can be well concealed. It is especially valuable in the elderly patient and should always be considered as one of the options for reconstruction of the face following MCSE of skin malignancies.

Aged↗
PubMed1986

Surgical treatment of rhinophyma with the Shaw scalpel.

We present our experience with the Shaw scalpel in the treatment of a patient with extensive rhinophyma. The heated blade of the scalpel provides rapid maintenance of hemostasis with minimal tissue damage and thus allows for rapid and accurate removal of tissue. After removing the bulk of tissue with the Shaw scalpel, the carbon dioxide laser and dermabrader are used to refine nasal contours.

Aged↗