Biomedical subjects

P McCue

Publications and source records attributed to P McCue.

At least 37 records · Page 2Linked to original sources

PubMed1997

Comparative analysis of smooth muscle isoactin gene expression in normal and neoplastic tissues.

Monoclonal antibodies derived from the actin multigene family are routinely used as an adjunct to morphologic diagnoses of smooth muscle tumors. Northern blot analysis was performed on 60 surgical resections utilizing isoactin-specific cDNAs. A comparison of this analysis to immunohistochemical studies demonstrated that actin-specific monoclonal antibodies represent reliable markers of the smooth muscle lineage. Smooth muscle neoplasms showed a unique pattern of gamma-smooth muscle isoactin gene expression, providing a potentially valuable molecular adjunct to the morphologic diagnosis of uterine smooth muscle tumors.

Actins↗

PubMed1996

The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers.

A 200-300 kb region of chromosome 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines. Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme, diadenosine 5', 5''' P1, P4-tetraphosphate asymmetrical hydrolase. The FHIT locus is composed of ten exons distributed over at least 500 kb, with three 5' untranslated exons centromeric to the renal carcinoma-associated 3p14.2 breakpoint, the remaining exons telomeric to this translocation breakpoint, and exon 5 within the homozygously deleted fragile region. Aberrant transcripts of the FHIT locus were found in approximately 50% of esophageal, stomach, and colon carcinomas.

Acid Anhydride Hydrolases↗

PubMed1996

Interleukin 10 production by human melanoma.

Interleukin 10 (IL-10) has the physiological role of down-regulating cell-mediated immunity. We have recently reported that mRNA for IL-10 was present in most metastatic melanoma tissues. The purpose of this investigation was to determine whether melanoma metastases produce IL-10 protein. Single-cell suspensions were prepared by enzymatic dissociation of 28 lymph node metastases and 7 s.c. metastases and cryopreserved. Of these 35 samples, 30 produced IL-10 after a 24-h incubation (median, 125.1 pg/ml). IL-10 production was slightly diminished after 25 Gy irradiation but almost completely abrogated after modification with the hapten dinitrophenyl. After 7 or 14 days in tissue culture, melanoma cells continued to produce IL-10 but only at about 10% of the levels of freshly dissociated tissues. Moreover, of eight melanoma cell lines established from these cultures, only one produced IL-10 protein. To determine whether IL-10 was produced by melanoma cells or tumor-associated leukocytes, single-cell suspensions were fractionated with anti-CD45 antibody-conjugated magnetic beads. In four of five samples, IL-10 production was increased by depletion of leukocytes, suggesting that the primary source was the melanoma cells themselves. This was confirmed by immunohistochemical staining of cytospin preparations and frozen tissue sections. Finally, 10 of 55 patients with clinically evident metastases showed elevations of circulating IL-10; three patients who had been melanoma-free developed high serum IL-10 levels, concurrent with the appearance of distant metastases. These data indicate that production of IL-10 is characteristic of metastatic melanomas and raise the possibility that this cytokine allows tumors to avoid or to modulate immunological attack.

Cryopreservation↗

PubMed1995

Loss of heterozygosity at the familial RCC t(3;8) locus in most clear cell renal carcinomas.

Previously, we had observed that more than 80% of clear cell renal carcinomas (RCCs) exhibited loss of heterozygosity (LOH) between the microsatellite markers D3S1285 (in 3p14.1) and D3S1295 (in 3p21.1), a region which includes the protein tyrosine phosphatase gamma locus (PTPRG locus, PTP gamma gene) and the 3p14.2 break of the familial RCC-associated translocation, t(3;8)(p14.2;q24), which has been hypothesized to affect expression of an RCC suppressor gene or oncogene. Using seven microsatellite markers and four markers derived from a PTPRG YAC contig, we have further delineated the 3p14.2 region of LOH in RCCs. Eighty-nine % of clear cell RCCs (31 of 35) showed a common region of loss between the D3S1481 and D3S1312 loci which flank the 3p14.2 t(3;8) translocation breakpoint and the PTP gamma gene. The PTP gamma gene occupies approximately 780 kilobase pairs between markers D3S1480 and D3S1312, with its currently defined 5' end greater than 200 kilobase pairs centromeric to the 3p14.2 translocation break. Although most of the RCCs with LOH between D3S1481 and D3S1312 loci have lost at least a portion of one PTP gamma allele, we have tested all known exons of the remaining PTP gamma gene in a number of the kidney tumors and have not observed mutations. Thus, there may be another gene in the vicinity of the 3p14.2 break that is important not only in the familial RCCs in the t(3;8) family but in the majority of clear cell RCCs.

Adenocarcinoma, Clear Cell↗

PubMed1995

Isolated Castleman disease of the neck: MR findings.

Castleman disease in an 11-year-old girl appeared as a neck mass that grew despite antibiotic treatment. MR showed a well-defined solid mass, isointense with muscle on short-repetition-time/short-echo-time images, with a stellate area of central hypointensity on long-repetition-time/long-echo-time images, that did not enhance with gadolinium.

Castleman Disease↗

PubMed1994

Common regions of deletion in chromosome regions 3p12 and 3p14.2 in primary clear cell renal carcinomas.

Nearly all clear cell renal cell carcinomas (RCCs) exhibit loss of alleles on the short arm of chromosome 3. Loss and mutation at the von Hippel-Lindau (VHL) gene at 3p25 probably occurs in most RCCs and, since the VHL gene was recently cloned, data on VHL involvement in RCCs is accumulating. However, the region 3p14-p12, a region that contains the familial RCC-associated t(3;8)(p14.2;q24) chromosome translocation and the small cell lung carcinoma-associated homozygous deletion at 3p13-12, has also been reported to exhibit allele loss in a large fraction of RCCs. In order to focus future studies on potential suppressor genes in the 3p14-p12 region, we have studied allele loss in 30 RCCs with 9 polymorphic simple sequence repeat markers spanning 3p21.1-p12. Partial losses in the 3p21-p12 region were observed, allowing determination of common regions of loss of heterozygosity overlap in 15 RCCs. Results suggested that most RCCs exhibit loss in a region which brackets the t(3;8) familial chromosome translocation at 3p14.2, and some show additional deletions within the U2020 small cell lung carcinoma deletion at 3p12.

Adenocarcinoma, Clear Cell↗

PubMed1994

Urinary tract glycoprotein: distribution and antigenic specificity.

It has previously been demonstrated that the urinary tract contains a unique glycoprotein (GP1) that appears to serve a function in the clearance of pathogenic bacteria. We prepared a panel of monoclonal antibodies (mAbs) to human GP1 and examined its antigenic specificity and distribution in the human urinary tract. This was also observed in relation to another glycoprotein associated with infection, Tamm-Horsfall protein (THP), as well as to URO-5, a protein used in identifying the lower urinary tract. In enzyme-linked immunoadsorbent assays (ELISA), all of the GP1 mAbs reacted with GP1 prepared from both human urine and rabbit bladder mucosa. No immunoreactivity was observed with either THP mAbs or URO-5 mAbs. Western-blot analyses using GP1 mAbs with human urine GP1 preparations detected a single band of approximately 50-52 kDa. Human urinary tract tissues were also examined by immunohistochemical techniques using the GP1 mAbs, commercial THP, and URO-5 mAbs. In paraffin-embedded bladder sections, only GP1 mAbs reacted with the urothelium. Selective staining of distal collecting tubules, renal pelvis, and ureters was demonstrated for GP1 mAbs. Proximal convoluted tubules, loops of Henle, and Bowman's capsule failed to stain for GP1. In the same tissues, THP mAbs reacted with the thick and thin segments of medullary loops of nephrons (Henle's loops). URO-5 mAbs stained fresh frozen sections of bladder urothelium, distal collecting tubules, and portions of Henle's loops; however, they failed to stain paraffin-embedded tissue sections. These GP1 mAbs provide a new tool for biochemical and histochemical investigations of the mucin layer in both healthy and diseased urinary tract tissue.

Animals↗

PubMed1994

Laparoscopic interstitial contact laser ablation of renal lesions: an experimental model.

Tissue ablation with the interstitial Nd:YAG contact laser is a rapidly evolving technique. The urologic applications of interstitial lasers have not been fully investigated. We developed a model to test the feasibility of using interstitial laser energy, administered under laparoscopic guidance, to ablate porcine renal tissue. Utilizing a synthetic sapphire interstitial Nd:YAG contact probe, minimal tissue effects were observed using total energies between 120 and 240 J. At energies of 480 J (8 W/60 seconds), there was predominantly coagulation necrosis of the renal parenchyma. At 720 J (12 W/60 seconds), there was pronounced tissue vaporization surrounded by a zone of coagulation necrosis approximately 1.5 cm across. This preliminary investigation demonstrates that the interstitial Nd:YAG contact laser probe can be used for both controlled coagulation necrosis and vaporization of renal parenchymal tissue. This approach may be applicable to the laparoscopic ablation of small renal lesions in selected patients.

Animals↗

PubMed1994

Evaluation of the atypical cytologic smear. Validity of the 1991 Bethesda System.

The 1991 Bethesda System states that atypical squamous or glandular cells of undetermined significance should be further classified as reactive or premalignant/malignant. The validity of this qualification for identification of patients with cervical intraepithelial neoplasia (CIN) was tested. One hundred twenty-four cytologic smears with squamous atypia were reviewed retrospectively by two cytopathologists blind to the colposcopy results. The smears were classified as favoring either reactive or premalignant/malignant processes. Subjective criteria used in the classification were based on the pathologists' experience. All patients underwent colposcopy and selected biopsy under the direction of a gynecologic oncologist. Of the 124 atypical smears, 69 were classified as favoring reactive processes and 55 as favoring premalignant/malignant processes by cytopathologist 1. Cytopathologist 2 classified 68 as reactive and 56 as premalignant/malignant. Colposcopy and selected biopsy revealed the following lesions: 34 cases of human papillomavirus (27.4%), 17 of CIN 1 (13.7%), 4 of CIN 2 (3.2%), 2 of CIN 3 (1.6%) and 67 without pathology (54.0%). All six patients with squamous atypia and underlying CIN 2 and 3 lesions had their cytology classified as premalignant/malignant by the cytopathologists. In these patients this qualification had high sensitivity (100%) and negative predictive value (100%). The 1991 Bethesda System classification above, when applied to patients with squamous atypia, was effective in identifying patients with serious pathologic cervical lesions. If used as a triage method, colposcopy should be reserved for atypical lesions classified as premalignant/malignant, potentially decreasing the cost of health care without decreasing the quality of that care.

Adult↗

PubMed1993

Validation of flow cytometry analysis in the objective assessment of spermatogenesis: comparison to the quantitative testicular biopsy.

Objective determination of spermatogenesis has been accomplished by quantitative testicular biopsy, which, although laborious, has served as the standard for spermatogenic assessment. Aspiration deoxyribonucleic acid (DNA) flow cytometry of the testis, however, has simplified this determination, and has correlated with indirect hormonal parameters of spermatogenesis and qualitative observations of the seminiferous epithelium. Nevertheless, this important modality has yet to be validated against quantitative micrometry of the testis. To determine this correlation we submitted 29 incisional testicular biopsies for simultaneous quantitative analysis and DNA flow cytometry. Micrometric parameters included the mean tubular wall thickness, and the mean tubular concentration of late spermatids and Sertoli cells. The percentage of haploid, diploid and tetraploid cells was determined for each patient. For the entire patient population a statistically significant correlation was observed between the percentage of haploid cells and the tubular concentration of late spermatids (r = 0.784, p < 0.0005) as well as the mean tubular spermatid-to-Sertoli cell ratio (r = 0.824, p < 0.0005). A similar correlation was noted for various etiological subsets of patients: spinal cord injury (r = 0.809, p < 0.002), genital tract obstruction (r = 0.705, p < 0.02) and miscellaneous diagnoses (r = 0.828, p < 0.02). For the group with testicular failure quantitative micrometry and flow cytometry demonstrated severe impairment in all patients although a statistically significant correlation could not be shown because of the small range of values. DNA flow cytometry analysis correlates strongly with the current standard of quantitative spermatogenic assessment and, therefore, it may be validated as a simplified and highly objective method of determining spermatogenesis.

Biopsy↗

PubMed1993

Intravesical growth of murine bladder tumors assessed by transrectal ultrasound.

Experimental studies in the therapy of intravesically growing bladder tumors in mice have been hampered by an inability to monitor tumor growth before and during treatment. To establish a repeatable, noninvasive method to monitor the intravesical growth of bladder tumors, MB49 murine bladder tumor cells were instilled into the bladders of syngeneic C57BL/6 mice. Following 3 weeks of growth, the bladders of tumor-bearing and control mice were imaged using a 20 mHz, 6.2 F catheter-based ultrasound transducer inserted rectally. Bladders of tumor implanted and control mice were identified by high resolution endoluminal ultrasound after distension with 0.15 ml. of normal saline. When compared with the results of histologic analysis, transrectal ultrasound (TRUS) accurately identified tumor presence, size, and location.

Animals↗

PubMed1993

The value of quantitative testicular biopsy and deoxyribonucleic acid flow cytometry in predicting sperm recovery from electrostimulated ejaculates.

Spermatogenic abnormalities have been reported in the majority of men following spinal cord injury, and they contribute to the multifactorial etiology of reproductive dysfunction. Thus far, few have studied the seminiferous epithelium in this group of patients by objective criteria. While quantitative micrometry and flow cytometric analysis are accurate and reproducible methods of quantitating spermatogenesis, the latter is simpler and permits needle aspiration for tissue recovery. The objective of this study is to determine the value of quantitative micrometry and flow cytometric analysis as methods of predicting total sperm yield in electrostimulated ejaculates. Incisional testicular biopsy was performed in 12 anejaculatory men, and the tissue specimens were divided for analysis by quantitative micrometry and flow cytometric analysis. Quantitative micrometry consisted of determining the mean tubular wall thickness, mean tubular concentration of the Sertoli cells and mature spermatids in a minimum of 10 round seminiferous tubules per patient. Specimens were prepared for flow cytometric analysis and the deoxyribonucleic acid histogram was analyzed to determine the percentage of cells in each ploidy compartment. Of the quantitative micrometry parameters analyzed a significant correlation resulted between the total sperm yield per electroejaculate and the mean tubular concentration of late spermatids (p = 0.001) as well as with the mean tubular ratio of late spermatids to Sertoli cells (p = 0.003). The tubular concentration of spermatids resulted in a sensitivity and specificity of 100% and 75%, respectively, to predict adequate sperm yield in semen. Likewise, the mean tubular ratio of spermatids to Sertoli cells resulted in a sensitivity and specificity of 75% and 87.5%, respectively, in its ability to predict normal sperm yield in the recovered ejaculate. Deoxyribonucleic acid flow cytometry analysis showed a normal haploid compartment in all 6 specimens studied, and each was associated with high numbers of sperm in recovered semen. Quantitative histometric parameters correlate significantly with the total sperm yield obtained in electrostimulated ejaculates and may have a role in the selection of candidates for treatment in reproductive rehabilitation programs.

Biopsy↗

PubMed1993

Simplified and objective assessment of spermatogenesis in spinal cord injured men by flow cytometry analysis.

Deterioration of the germinal epithelium of the testis is a known sequela of spinal cord injury (SCI) that may influence the outcome of male reproductive rehabilitation efforts. Quantitative testicular biopsy, currently regarded as the standard of assessing the integrity of spermatogenesis, has not gained wide-spread clinical use because of its invasive nature and relative technical complexity. Alternatively, aspiration DNA flow cytometry analysis of the testis has offered a potential method of spermatogenic assessment that meets both the requirements of simplicity and objectivity. The objective of this study is to determine the capability of flow cytometry to assess spermatogenesis following SCI. Eleven SCI men underwent incisional testicular biopsy with the specimen simultaneously submitted for quantitative evaluation of the germinal epithelium by both quantitative histometry and DNA flow cytometry. The haploid percentage of cells showed highly significant levels of correlation with key micrometric parameters of the quantitative testicular biopsy: spermatid/tubule (p < 0.002) and the spermatid/Sertoli cell ratio (p < 0.0005). Since tissue procurement is accomplished less invasively for flow cytometry analysis, we recommend this method as the modality of assuring integrity of the germinal epithelium in candidates for reproductive rehabilitation.

Adult↗

PubMed1992

Multiple urothelial recurrences of renal cell carcinoma after initial diagnostic ureteroscopy.

Urothelial recurrence of renal cell carcinoma after radical surgery is exceedingly rare. We report on a 48-year-old man who underwent upper urinary tract flexible endoscopy to define a filling defect, which was found to be a perforating renal cell carcinoma. After radical nephrectomy the patient had multiple recurrences on the urinary surfaces, ureter and urethra. Urothelial lesions were treated endoscopically. He remains free of tumor 42 months after the last treatment.

Carcinoma, Renal Cell↗

PubMed1991

Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency.

Cryopreserved cell suspensions of freshly excised melanoma metastases from nine patients were injected s.c. into C.B-17 severe combined immunodeficiency (SCID) mice. All 9 tumors grew as s.c. masses and six of nine were successfully transplanted into other SCID mice. Transplant inocula as low as 5 x 10(5) cells resulted in 100% tumor incidence. Moreover, seven of nine tumors metastasized, five from the original s.c. implants and two from transplanted s.c. tumors. Metastases were detected mainly in the lungs but also were found in abdominal viscera (liver, spleen, and pancreas) and thoracic lymph nodes. Flow cytometric analysis showed that expression of a panel of melanoma antigens, melanoma-associated proteoglycan, ganglioside GD3, and ganglioside GD2, was maintained with SCID passage. The original tumor inocula contained a variable percentage of tumor-associated lymphocytes (1-76%). Flow cytometry analysis indicated that these were mainly CD3+ T-cells. However, there was no correlation between the percentage of tumor-associated lymphocytes and the time required for development of a palpable tumor after s.c. injection or the ability to metastasize. These results demonstrate the growth and spontaneous metastasis of fresh human melanoma in SCID mice and suggest that this model could be important for therapeutic and basic biological studies.

Animals↗

PubMed1991

ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin.

The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone.

ABO Blood-Group System↗

PubMed1991

Quantitative testicular biopsy in spinal cord injured men: comparison to fertile controls.

Spermatogenic abnormalities have been reported in the majority of spinal cord injured men on routine testicular biopsy. However, given the interim advances in their urological and rehabilitative care, a quantitative assessment of the germinal epithelium after spinal cord injury and comparison of these parameters to normal controls are warranted. Incisional testicular biopsy was performed in 14 spinal cord injured men. Quantitative micrometric techniques were applied to assess spermatogenesis and the results were compared to a normative data base of testicular biopsies previously obtained from a group of 15 fertile volunteers. From a minimum of 10 randomly selected round seminiferous tubules per subject the mean number of Sertoli cells, mature spermatids, tubular diameter and tubular wall thickness were determined in both groups and statistically analyzed. In the spinal cord injury group the mean number of spermatids per tubule was significantly lower and the mean number of Sertoli cells per tubule was significantly higher than in fertile controls (p less than 0.05). Moreover, the mean Sertoli cell-to-spermatid ratio per seminiferous tubule was significantly higher in the spinal cord injury group and discriminated between spinal cord injured men and controls, with a sensitivity of 93% and specificity of 100% (p less than 0.0001). Half of the spinal cord injury group showed a mean tubular spermatid density of less than 10. Compared to the fertile population, spinal cord injured men show significant differences in quantitative parameters of the germinal epithelium that may contribute to the reproductive dysfunction.

Adolescent↗

PubMed1990

Inverted papilloma of renal pelvis: flexible ureteroscopic diagnosis and treatment.

A case is reported of inverted papilloma of the renal pelvis in a patient with previous transitional cell carcinoma of the bladder. The renal pelvic lesion was diagnosed and treated with a flexible ureteropyeloscope. Although nephroureterectomy was avoided, the patient must be carefully followed endoscopically and radiographically for recurrence of lesions throughout the urinary tract. This case represents the first report of the endoscopic diagnosis and treatment of an inverted papilloma of the renal pelvis. It demonstrates the vast potential for endoscopic diagnosis, treatment, and surveillance throughout the urinary tract.

Endoscopy↗