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Biomedical subjects

K L de Mesy Jensen

Publications and source records attributed to K L de Mesy Jensen.

12 recordsLinked to original sources
PubMed2001

The cyclin-dependent kinase inhibitor p21 protects the lung from oxidative stress.

The lung is a major target tissue for oxidative stress, including hyperoxia used to relieve tissue hypoxia. Unfortunately, severe hyperoxia damages DNA, inhibits proliferation, and kills cells, resulting in morbidity and mortality. Although hyperoxia induces the tumor suppressor p53 and its downstream target, the cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1) (p21), their role in pulmonary injury remains unknown. Using p53- and p21-deficient mice we demonstrate that hyperoxia induces p21 in the absence of p53, suggesting that previous conclusions that p53 does not modify hyperoxic lung injury cannot be extrapolated to p21. In fact, mean survival of p21-deficient mice decreased by 40% and was associated with terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining of alveolar debris, indicative of DNA fragmentation and cell death. Ultrastructural analyses revealed that alveolar endothelial and type I epithelial cells died rapidly by necrosis. Although hyperoxia decreased DNA replication in p21-wild-type lungs, it had no effect on replication in p21-deficient lungs. Our findings suggest that p21 protects the lung from oxidative stress, in part, by inhibiting DNA replication and thereby allowing additional time to repair damaged DNA. Our findings have implications for patients suffering from the toxic effects of supplemental oxygen therapies.

Animals↗
PubMed1993

Propagation of human papillomavirus type 11 in human xenografts using the severe combined immunodeficiency (SCID) mouse and comparison to the nude mouse model.

We report propagation of human papillomavirus (HPV) type 11 in human xenografts in the severe combined immunodeficiency (SCID) mouse and compare this new animal model for HPV infection to the previously established athymic nude mouse model. HPV-11-infected foreskin fragments grafted under the renal capsule of SCID mice formed large epithelial cysts that had the histologic and immunocytochemical features of HPV infection. This infection was successfully passaged to nude mice. Viral particles that reacted to an antibody directed to HPV-11 virions were identified from samples recovered from the SCID and nude mice. Viral DNA sequence analysis confirmed that the passaged virus was HPV-11. In a comparative experiment of the nude mouse and SCID mouse models, the latter produced HPV-11-infected xenografts that were larger and more often positive for HPV by immunocytochemistry and presence of viral mRNA than those propagated in the former model. Finally, we observed that growth of HPV-11-infected foreskin fragments in the SCID mouse model is not restricted to the kidney as in the nude mouse, but also can occur in the subcutis and the peritoneum.

Animals↗
PubMed1989

Calcitonin, katacalcin, and calcitonin gene-related peptide in the human prostate. An immunocytochemical and immunoelectron microscopic study.

We recently described for the first time the presence of calcitonin immunoreactivity (CTIR) in a subpopulation of prostatic and urethral endocrine-paracrine (EP) cells. We now further evaluate the distribution of the CTIR cell, characterize the coexistence of serotonin and calcitonin, and for the first time describe the coexpression of calcitonin and other calcitonin gene family peptides (calcitonin gene-related peptide and katacalcin) in the CTIR cell. Finally, the morphological ultrastructure of the secretory granule of the CTIR cell is analyzed. The finding of multiple calcitonin gene family peptides in prostatic and urethral EP cells and the specific localization of calcitonin to secretory granules strongly suggest that the calcitonin gene is expressed in this region and the products stored in the EP cells. The relatively high levels of calcitonin reported in the semen and the dendritic and nondendritic morphological features of the CTIR cell, respectively, suggest a lumencrine (exocrine), paracrine, and possibly endocrine role for calcitonin. The production of calcitonin and related peptides by the prostate may have implications in various pathologic processes of the prostate.

Calcitonin↗
PubMed1987

Endocrine-paracrine (APUD) cells of the human female urethra and paraurethral ducts.

The distribution, immunostaining profile and ultrastructural morphology of human female urethral and paraurethral endocrine-paracrine (APUD) cells was studied. Five urethras obtained from radical cystectomy specimens were stained with antisera to serotonin, neuron-specific enolase, chromogranin, bombesin, calcitonin, somatostatin, prostatic acid phosphatase, prostatic specific antigen and with the Churukian-Schenk argyrophil method. Numerous endocrine-paracrine cells were observed along the entire length of resected urethra, with these cells most numerous in the paraurethral ducts. The endocrine-paracrine cells were positive for serotonin, neuron-specific enolase, chromogranin and the argyrophil reaction. Scattered bombesin and very rare calcitonin immunoreactive cells were noted. The endocrine-paracrine cells were of the open (luminal extensions) and closed cell types and often had multiple long dendritic processes suggesting a primarily paracrine function. By electron microscopy the secretory granule morphology was highly variable. Autonomic innervation of endocrine-paracrine cells was noted. The relationship of female urethral and paraurethral endocrine-paracrine cells to those of the male prostate and urethra is discussed with speculation as to the functional role these cells may play.

APUD Cells↗
PubMed1987

Neuroendocrine differentiation in prostatic carcinoma.

Specimens from 53 cases of prostatic carcinoma obtained during total prostatectomy or transurethral resection of prostate were analyzed for neuroendocrine differentiation with immunocytochemical tests for serotonin, neuron-specific enolase, and chromogranin as well as with the Churukian-Schenk argyrophil reaction. Forty-seven per cent (25 of 53) of the prostatic carcinomas were positive for neuroendocrine differentiation, usually with an overlapping combination of these techniques. Nine per cent (five cases) contained areas with numerous neuroendocrine cells, 11 per cent (six cases) had focal scattered neuroendocrine cells, and 26 per cent (14 cases) had rare neuroendocrine cells. The positive cases spanned the histologic spectrum of prostatic adenocarcinoma; histologically none resembled a carcinoid tumor or a small cell carcinoma. Positive cases were further studied with a battery of antisera to 12 polypeptide hormones. Immunoreactivity to only bombesin (one case) and calcitonin (two cases) was detected. In five cases, neuroendocrine differentiation was studied by electron microscopy and verified at the ultrastructural level.

Carcinoma↗
PubMed1987

Age-related changes in the neuroendocrine (endocrine-paracrine) cell population and the serotonin content of the guinea pig prostate.

Neuroendocrine (endocrine-paracrine, APUD) cells of the guinea pig prostatic complex (prostate and coagulating gland) were studied at three age points (9-day-old weanlings, 11 to 12 week mature pre-breeders, and retired breeders) using serotonin immunocytochemistry for detection and subsequent morphometric analysis. Prostatic complex serotonin levels were determined for the same age groups using high performance liquid chromatography with electrochemical detection. The numbers of neuroendocrine (NE) cells in the prostatic complex of retired breeders was 1.42 +/- 0.29 NE cells/mm gland length (mean +/- SEM) and was increased nearly 24-fold when compared with mature pre-breeders with 0.06 +/- 0.03 NE cells/mm gland length and nearly 16-fold when compared with the weanlings with 0.09 +/- 0.04 NE cells/mm gland length. The increase in cell number in the retired breeders versus each of the other age groups was highly significant (p less than 0.001). The increase in NE cells appeared to take place exclusively in the prostate, whereas the number of NE cells in the coagulating gland were few and not significantly different in the three age groups. The number of urethral NE cells also appeared similar in all three age groups. The number of prostatic epithelial cells/gland length increased with age. The number of NE cells/100 prostatic epithelial cells was examined in the three age groups and the increase in retired breeders over the other two groups was still highly significant (p less than 0.001). Serotonin levels, which were measured for the whole prostatic complex, indicated a nearly 6-fold increase with age: retired breeders had 97.72 +/- 21.26 ng/g of wet tissue (mean +/- SEM) whereas mature pre-breeders had 17.1 +/- 2.88 ng/g of wet tissue (p less than 0.01). Weanling serotonin levels were not detectable. This dramatic age-related increase in prostatic NE cells and serotonin content could reflect a compensation for a decreased effectiveness of NE cell hormones, a nonfunctional primary hyperplasia, a hyperplasia secondary to endogenous hormonal or involutional changes or exogenous factors. Whatever the mechanism, this increase in prostatic NE cells with age is of great interest since human prostatic carcinoma and benign nodular hyperplasia are both strongly correlated with advanced age. Prostatic NE cells may, therefore, directly or indirectly be in the pathogenesis and/or evolution of these important pathologic processes.

Aging↗
PubMed1985

Human prostatic endocrine-paracrine (APUD) cells. Distributional analysis with a comparison of serotonin and neuron-specific enolase immunoreactivity and silver stains.

Prostatic endocrine-paracrine (PEP) cells from the prostates of 25 radical cystectomy specimens were studied using serotonin and neuron-specific enolase immunocytochemistry and argyrophil and argentaffin silver stains. Three populations of PEP cells were identified as follows: (1) serotonin-positive only, (2) serotonin-positive and argyrophil-positive (the largest population), and (3) serotonin-positive, argyrophil-positive, and argentaffin-positive. Neuron-specific enolase immunoreactivity correlated closely with serotonin immunoreactivity. The entire PEP cell cytoplasm was serotonin and neuron-specific enolase immunoreactive, while the silver stains only stained the granulated cytoplasm. The PEP cells were present in all areas of all prostates with a surprisingly large number in the large periurethral ducts with somewhat fewer PEP cells in the prostatic urethra and smaller ducts and ductules. The peripheral acini generally contained the smallest number of PEP cells. Prostatic endocrine-paracrine cells were of the open (luminal extension), closed, and dendritic types.

APUD Cells↗
PubMed1984

Somatostatin and/or somatostatin-like immunoreactive endocrine-paracrine cells in the human prostate gland.

We demonstrated the presence of somatostatin and/or somatostatin-like immunoreactive (SSLI) endocrine-paracrine (EP) cells for the first time in the human prostate gland. Specimens from 26 prostates removed at radical cystectomies were studied using the unlabeled-antibody peroxidase-antiperoxidase technique. The SSLI cells were located predominantly in the prostatic ducts in widely scattered clusters and were mostly of the closed type. Some SSLI cells had processes that were prominent, suggesting a paracrine role. The SSLI cells were always associated with aggregates of numerous argyrophil cells. The finding of SSLI cells in the prostate gland (particularly in association with other EP cells) is circumstantial evidence that other polypeptide hormones are present. The SSLI and other prostatic EP cells may play major roles in the pathophysiology of the prostate gland and have an effect on such diverse conditions as infertility, nodular prostatic hyperplasia, and prostatic carcinoma.

APUD Cells↗
PubMedDate not supplied

Large block embedding and "pop-off" technique for immunoelectron microscopy.

A technique for immunoelectron microscopy is described whereby tissue is embedded in large (6 x 12 mm) plastic blocks and reembedded ("popped off") directly from semithin (3-microns) sections for thin sectioning. This technique is particularly useful in locating relatively sparse cells or tissue structures. Three acrylic plastics were evaluated: Lowicryl K4M, LR Gold, and LR White. Results indicated excellent ultrastructural morphologic preservation and retention of antigenicity with the first two plastics both comparable to conventional methods of processing. Lowicryl and LR Gold were successfully adapted to the large block pop-off technique. Technical problems were encountered with LR White.

Acrylic Resins↗
PubMedDate not supplied

Plastic-embedded semi-thin sections of fine needle aspiration biopsies with dibasic staining. Diagnostic and didactic applications.

The diagnostic and didactic utility of plastic-embedded semi-thin sections of fine needle aspiration biopsies is presented using a case-study approach. The Spurr epoxy semi-thin sections were stained with a newly developed sequential basic fuchsin-methylene blue stain, which gives hematoxylin-and-eosin-like staining and simultaneously substitutes for a wide variety of special stains. The informational content of the sections can approach that of electron microscopy. The use of a direct off-the-slide "pop-off" technique in preparing the plastic-embedded sections allows for a direct comparison between similar groups of cells embedded in plastic and present on the routine aspiration slides; retrospective analysis can discern subtle, previously unrecognized morphologic features in the alcohol-fixed, Papanicolaou-stained slides. The limitations of this comparative approach, however, become manifest when the effects of alcohol fixation on cells are directly compared in plastic and at the ultrastructural level to aldehyde fixation.

Adenoma↗
PubMedDate not supplied

Chlamydia trachomatis in routine cervical smears. A microscopic and ultrastructural analysis.

This study examined cervical smears for cytologic evidence of Chlamydia trachomatis in 380 women seen for routine gynecologic examination or follow-up for an abnormal cervical smear. Cervical smears and Chlamydiazyme samples were obtained. Fifteen patients tested Chlamydiazyme positive and were considered to be Chlamydia positive. Cellular samples meeting the screening criteria were examined carefully for evidence of Chlamydia, including type II (central target inclusions) and type III (granular inclusions or nebular inclusions). Electron microscopy was performed on representative inclusions from both Chlamydia-positive and -negative patients. Inclusions were identified in 6 of the Chlamydia-positive and 31 of the -negative patients. Electron microscopy of type II and III inclusions, from both positive and negative patients, revealed chlamydial organisms to be present only in nebular inclusions. Intracytoplasmic inclusions, other than nebular inclusions, result from inflammatory changes and, as such, may be induced by a chlamydial infection but are not specific to Chlamydia.

Adult↗