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Biomedical subjects

L R Begin

Publications and source records attributed to L R Begin.

12 recordsLinked to original sources
PubMed1996

Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma.

pp125FAK, a protein tyrosine kinase (PTK) co-localized with integrins in focal adhesion plaques, is known to transduce signals involved in the regulation of cell adhesion and motility as well as the anchorage-independent growth of transformed cells. We investigated whether pp125FAK could be part of a signalling pathway that contributes to the progression of human prostate carcinoma (PCa). Up-regulation of pp125FAK expression, its activation by phosphorylation on tyrosine and its association with paxillin and p50csk were preferentially observed in PCa tissues from patients with metastases, whereas normal and hyperplastic prostates and localized PCa tissues showed undetectable or low levels of both FAK mRNA and protein and an absence of pp125FAK signalling complexes. The increase in expression and activation of pp125FAK in metastatic PCa tissues was also corroborated by our findings in human PCa cell lines. Indeed, higher levels of pp125FAK and FAK mRNA were observed in highly tumorigenic PC-3 cells as was the presence of activated pp125FAK, as opposed to an inactive form in LNCaP cells, which have a lower tumorigenic ability. In addition, pp125FAK formed signalling complexes with both paxillin and p50csk in PC-3 cells as in metastatic PCa tissues. Together, our results show that an increase in FAK mRNA and protein, as well as pp125FAK activation and association with signalling proteins, correlates with progression and invasion in human PCa tissues and cells.

CSK Tyrosine-Protein Kinase↗
PubMed1996

Insular (poorly differentiated) carcinoma of the thyroid: an ultrastructural and immunocytochemical study of two cases.

Two cases of pure insular (poorly differentiated) carcinoma of the thyroid are reported, with emphasis on their ultrastructure. Notwithstanding their solid/primitive histologic character, a high degree of structural organization and differentiation was present at the submicroscopic level, namely a highly developed cytosecretory apparatus and numerous abortive/rudimentary follicles. A prominent inclusion/dot-like pattern (often paranuclear) of thyroglobulin immunoreactivity was observed, ultrastructurally corresponding to the following features: a) abortive/rudimentary follicular lumina with abundant periluminal dense bodies, and with varying amounts of colloid and microvilli, both at the intercellular and intracellular level; b) large inclusions of fibrillar/lamellar or finely granular material within dilated cisternae of endoplasmic reticulum and possibly of lysosomal nature as well, likely reflecting altered production and/or storage of thyroglobulin substrate. One tumor had many cytophenotypical attributes ascribed to differentiated papillary carcinoma (PC), whereas the other tumor was more analogous to differentiated follicular carcinoma (FC). The present study supports the concept that the insular pattern is a common pathway of dedifferentiation for follicular cell neoplasia of both PC and FC types, yet with maintenance of most of their respective cytophenotypical features, and with evidence of a high level of differentiation/maturation at the submicroscopic level.

Adenocarcinoma, Follicular↗
PubMed1995

Role of prostate-specific antigen density after applying age-specific prostate-specific antigen reference ranges.

OBJECTIVES: To determine the potential role of prostate-specific antigen (PSA) density (PSAD) in the early detection of prostate carcinoma if we apply age-specific PSA reference ranges (2.5 ng/mL or less for ages 40 to 49 years, 3.5 or less for ages 50 to 59, 4.5 or less for ages 60 to 69, and 6.5 or less for ages 70 to 79. METHODS: We retrospectively reviewed 3234 cases referred to us by urologists for transrectal ultrasound (TRUS) between January 1, 1991, and September 28, 1993. We included 2429 patients in the study, ages 40 to 79 years, with Hybritech or Abbott IMx serum PSA determinations and without previously diagnosed prostate cancer. We performed digital rectal examination (DRE) and TRUS in all cases, and TRUS-guided biopsies when indicated. We used stringent criteria to define 736 cases without clinical evidence of malignancy that were designated as a "benign group." RESULTS: In the benign group, we found serum PSA to increase with age in parallel with the increase in prostate volume with age (r = 0.25 and r = 0.26, respectively). The association between serum PSA and prostate volume was stronger (r = 0.46). Using multiple regression analysis, prostate volume accounted for 18% of the variation in serum PSA, whereas age accounted for only an additional 2%. PSAD, which directly relates serum PSA to prostate volume, showed a weak association with age (r = 0.1). In the entire study population of 2429 cases, 555 patients had negative DRE and TRUS results and a serum PSA level between the age-specific upper limit of normal and 10.0 ng/mL. According to the proposed age-specific algorithm, these patients would have required automatic biopsies. Of these, 315 cases (56.8%) still had a PSAD of less than 0.15. We performed biopsies in 108 of these 315 and detected only two cancers, for a positive biopsy rate (PBR) of 1.9%. The remaining 240 cases had a PSAD of 0.15 or higher, and we performed biopsies in 217 of these cases and detected 59 cancers, for a PBR of 27.2%. CONCLUSIONS: The use of age-specific PSA reference ranges does not totally account for the effect of prostate volume on serum PSA. Therefore PSAD can still be used to reduce safely the number of biopsies performed in patients with negative DRE and TRUS results and a serum PSA level 10.0 ng/mL or less and above the age-specific upper limit of normal.

Adult↗
PubMed1995

Nitric oxide mediated erectile activity is a testosterone dependent event: a rat erection model.

Classically, androgens were thought to be linked to sexual activity in man through their action on increased libido. Recently, the sex hormone dependent nature of nitric oxide synthase (NOS), the enzyme system producing the neurotransmitter of erection (nitric oxide) has been reported. Our study evaluated how changes in testosterone levels alter erectile function. In forty-seven rats the erectile response to cavernous nerve electrostimulation was recorded 1, 5, 10, 20 and 30 d post-bilateral orchiectomy, and compared to controls. Penile tissue was subsequently stained for the presence of NOS, using an NADPH diaphorase technique. Forty eight rats were used in part two. After orchiectomy exogenous testosterone was administered and the erectile function as well as density of NOS positive nerve fibers was assessed. All castrated animals showed a rapid decrease in serum free testosterone levels within 24 h. In contrast, a gradual decrease in intracavernous pressure was recorded with cavernous nerve stimulation, proportional to the time post orchiectomy. NADPH diaphorase staining showed a decreased density of nonadrenergic noncholinergic (NANC) nerve fibers innervating the cavernosal tissue proportional to the time post orchiectomy. With reconstitution of the androgen mileu the erectile response returned to near normal values and recovery of NADPH-positive nerve fibers was observed. Based on presented data we conclude that testosterone or a metabolite plays a direct role in erection acting through an effect on nitric oxide synthase within the corpora cavernosa.

Animals↗
PubMed1992

The value of nuclear morphometry in the management of patients with colorectal polyps that contain invasive adenocarcinoma.

Haggitt's classification is a useful guide in the management of patients with large bowel polyps which contain invasive adenocarcinoma in that patients with levels 1 to 3 require no operation. Nuclear morphometry has been shown to be a useful prognostic discriminant for patients with invasive carcinoma of the large bowel. The nuclear shape factor of 44 polyps with invasive carcinoma was studied to determine whether this parameter was of value to define those patients with Haggitt level 4 who should have a resection. The shape factor of 50 interphase nuclei was obtained through the use of image analysis by tracing the nuclear profiles as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. Our previous experience showed a nuclear shape factor greater than 0.84 was associated with a poor outcome. The overall mean shape factor was 0.71 (0.59-0.85). There was a tendency for the patients with residual disease to have values in the upper range. Our findings suggest that nuclear morphometry fails to add any predictive information in this clinical situation.

Adenocarcinoma↗
PubMed1992

Spinal cord tissue pressure during spinal cord distraction in dogs.

Spinal column distraction is a known cause of spinal cord injury. Laplace's law predicts that cord interstitial pressure will elevate during spinal cord distraction. To determine the significance of the Laplace predictions a series of in vitro and in vivo experiments examining spinal cord distraction were performed. In vitro experiments were carried out on 10 dog spinal cords in a specially designed distraction apparatus. These experiments verified the Laplace's law demonstrating a close correlation (R(avg) = 0.99) between the tension applied to the cord, and cord interstitial pressure. Cord interstitial pressure strain (elongation) curves show that initial elongation is accompanied by negligible elevations of cord interstitial pressure; the final 20% elongation being responsible for 80% of the elevation in cord interstitial pressure. In vivo experiments were carried out on five beta-blocked dogs. Significant elevations in cord interstitial pressure were obtained during stepwise spinal column distraction. Spinal cord blood flow and somatosensory evoked potentials were well maintained during distraction until cord interstitial pressure reached 47 mm Hg. At this point a simultaneous fall in spinal cord blood flow and somatosensory evoked potentials was noted. Release of the distracting force resulted in return of spinal cord blood flow, somatosensory evoked potentials, and cord interstitial pressure to baseline. The authors conclude that significant elevations in cord interstitial pressure occur with spinal cord distraction and that these cord interstitial pressure elevations are associated with a reversible ischemic response in the cord.

Animals↗
PubMed1991

Nuclear shape as a prognostic discriminant in colorectal carcinoma.

In search for a more reliable prognostic discriminant, a retrospective analysis of 100 cases of colorectal carcinoma having undergone curative resection and followed for at least 5 years were assessed by nuclear morphometry. Each case was staged according to the Dukes' classification as well as graded histologically. For all patients in this series, the perimeter, area, and nuclear shape factor of 50 interphase nuclei were determined for each carcinoma. The information was obtained through the use of an image analysis system by tracing the nuclear profiles (magnification 1000x) as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. A nuclear shape factor greater than 0.84 was associated with poor outcome. Multiple regression models showed that the single nuclear parameter of the shape factor was the most highly significant predictor of survival (P less than 0.0001). This variable remained highly significant even when corrected for sex, age, histologic grade, and Dukes' classification. These findings indicate that a nuclear shape factor greater than or equal to 0.84 as determined by nuclear morphometry is an independent morphometric nuclear variable of great importance in the prognosis of large bowel carcinoma.

Adult↗
PubMed1990

Extracranial primitive neuroectodermal tumor of the head and neck.

Malignant peripheral neuroectodermal tumors are rare neoplasms of the head and neck. We describe a case of a teenage girl presenting with this neoplasm in the head and neck. The clinical histological and ultrastructural features are reviewed and presented, along with guidelines for the management of this highly aggressive neoplasm.

Adolescent↗
PubMed1985

Soft-tissue chondromas.

Soft-tissue chondromas are benign, relatively rare lesions. The clinicopathologic and radiologic features in six cases are presented and the literature is reviewed. Five of six cases had calcifications. Peripheral curvilinear calcification was seen in two cases, multiple ringlike areas characteristic of cartilage in one, and discrete ossification in another. Histopathologically, they were diverse, ranging from an immature pattern with a preponderance of chondroblasts to a more mature form with chondrocytes. Although these lesions resemble a wide variety of other soft-tissue lesions, they can usually be differentiated by their small size, characteristic location in the extremities, the nature of their calcifications, and the histopathologic features. The importance of this lesion is that it is benign. It must be distinguished from more aggressive soft-tissue neoplasms such as soft-tissue chondrosarcoma so as to spare the patient unnecessary radical therapy.

Adolescent↗
PubMed1981

Fibrous histiocytoma of lung--a clinicopathological study of two cases.

Two cases of fibrohistiocytic tumours of the lung are presented and histogenesis of this group of this group of tumours is discussed. An essentially biphasic pattern of histiocytes and fibroblasts, and the presence of myofibroblasts and undifferentiated mesenchymal cells is similar to the fibro histiocytic neoplasms in other locations.

Aged↗