Biomedical subjects

R V Lloyd

Publications and source records attributed to R V Lloyd.

At least 55 records · Page 3Linked to original sources

PubMed2000

Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patients.

BACKGROUND: Neuroglycopenia from endogenous hyperinsulinism usually is caused by insulinomas in adults. We recently reported a novel hypoglycemic disorder in 5 patients (patients 1 to 5) with postprandial neuroglycopenia, negative 72-hour fasts, negative perioperative imaging studies, but positive calcium stimulation tests and islet hypertrophy and nesidioblastosis in the gradient-guided resected pancreata. METHODS: In this report we compare our experience with 5 additional patients (patients 6 to 10) with this syndrome to that in the original report. RESULTS: The clinical features of patients 6 to 10 were similar to those of patients 1 to 5. Each had positive calcium stimulation testing that guided the extent of the distal pancreatectomy and histologic evidence of islet cell hypertrophy or nesidioblastosis. All 10 patients are alive from 9 to 50 months after operation, 1 of whom had no amelioration of neuroglycopenia. Minor perioperative complications occurred in 3 patients. One patient has experienced repeated bouts of acute pancreatitis, pseudocyst formation, and exocrine insufficiency. CONCLUSIONS: We have identified adult patients with severe, postprandial hyperinsulinemic hypoglycemia from diffuse islet cell disease, 80% of whom have been well palliated with surgery. The results in 7 men have been better than those in the 3 women for reasons that are not obvious.

Adolescent↗

PubMed2000

The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors.

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.

Animals↗

PubMed2000

Differentiation of primary and metastatic clear cell tumors in the liver by in situ hybridization for albumin messenger RNA.

Clear cell neoplasms presenting as metastatic hepatic masses may be difficult to differentiate histologically and immunohistochemically from hepatocellular carcinoma (HCC) with prominent clear cell features, especially in small biopsy specimens. In situ hybridization (ISH) for albumin messenger RNA (mRNA) has been previously shown to be sensitive and specific for the detection of hepatocellular differentiation, but its use for the identification of clear cell HCC has not been previously evaluated. Among 309 cases of hepatocellular carcinoma diagnosed at Mayo Clinic between 1985 and 1998, 30 cases (9.7%) with at least 30% (range, 30%-90%; median 60%) clear cells were studied by ISH for albumin mRNA. In addition, immunohistochemical expression of AFP and polyclonal CEA, serum determination of AFP, and histopathologic analyses of the tumor were done. Forty-two clear cell tumors were used as a control group: 21 metastatic clear cell tumors to the liver (14 renal cell carcinomas and 7 adrenal cortical carcinomas) and 21 primary clear cell tumors of the retroperitoneum (10 renal cell carcinomas, 5 adrenal cortical adenomas, 4 adrenal cortical carcinomas, and 2 ovarian carcinomas). ISH for albumin mRNA was reactive in 28 of 30 cases of clear cell HCC (93%). Clear cell HCC expressed AFP (15 cases; 50%) and polyclonal CEA (19 cases; 63%). Tumors expressed either AFP or polyclonal CEA in 23 cases (77%). Elevated serum AFP was present in 24 of 26 cases (92%). These results indicate that ISH for albumin mRNA is a useful method to distinguish clear cell HCC from other clear cell carcinomas metastatic to the liver and clear cell neoplasms in the retroperitoneum.

Adenocarcinoma, Clear Cell↗

PubMed2000

Myxoid neoplasms of the adrenal cortex: a rare histologic variant.

The myxoid variant of adrenocortical carcinoma is a rare neoplasm described previously in only two case reports. Because of the rarity of these lesions, the presence of myxoid changes in adrenal cortical neoplasms usually raises the possibility of malignancy. We studied the histopathologic features of 14 cases of myxoid adrenocortical neoplasms, including six adenomas and eight carcinomas. All patients with adenomas with sufficient follow-up (n = 5) were alive with no recurrence of their tumors or evidence of metastatic disease. Four patients with carcinomas died of their disease, two were alive with metastatic disease, and one was alive with no evidence of recurrence or metastatic disease. Histologically, the 14 tumors varied in their myxoid composition, ranging from 10% to 95%. The myxoid foci stained positively with Alcian blue and were usually negative with periodic acid-Schiff and mucicarmine stains. As a group, the immunophenotype of the lesions was typical of other adrenal cortical neoplasms, with positive immunostaining for vimentin, synaptophysin, and alpha-inhibin. One tumor was focally positive for keratin. Myxoid adrenal cortical neoplasms should be included in the differential diagnosis of myxoid retroperitoneal neoplasms. Myxoid changes in adrenal cortical neoplasms may be present in both adenomas and carcinomas, and the usual clinical and histopathologic features for adrenocortical neoplasms should be used to diagnose these neoplasms.

Adolescent↗

PubMed2000

Clinically silent corticotroph tumors of the pituitary gland.

OBJECTIVE: To determine the clinical presentation, imaging characteristics, microscopic and ultrastructural characteristics, and treatment outcomes of patients with clinically silent pituitary corticotroph adenomas. METHODS: All silent corticotroph adenomas diagnosed at the Mayo Clinic during the years 1975 through 1997 were selected from the files of the Mayo Tissue Registry. RESULTS: We studied 23 cases, occurring in 16 male and 7 female patients (age range, 11-79 yr; mean age, 48 yr), who presented with headaches (50%), visual field defects (61%), extraocular muscle paresis (13%), hypopituitarism (26%), and galactorrhea/amenorrhea (43%/29% of the female patients). No patients exhibited clinical hypercortisolism. All tumors were macroadenomas (2.4+/-0.8 cm; range, 1.5-4.0 cm) and exhibited suprasellar extension in 87% of the cases and hemorrhage, necrosis, and/or cystic changes in 61%. All tumors stained were variably periodic acid-Schiff-, adrenocorticotropic hormone-, and beta-endorphin-positive, particularly Subtype I lesions. Ultrastructural classification was performed in 19 cases. In a comparison of Subtype I and II tumors, differences were observed with respect to sex (male/female, 1.4:1 versus 6:1), preoperative hyperprolactinemia (5 of 16 versus 0 of 6 cases), preoperative hypopituitarism (9 of 16 versus 5 of 7 cases), radiographic or gross invasion (7 of 16 versus 5 of 7 cases), and partial or total postoperative pituitary failure (6 of 16 versus 6 of 6 cases). The overall median postoperative follow-up period was 4.9 years (range, 0.3-16.6 yr); 54% of the patients had persistent or recurrent tumors. CONCLUSION: Clinically silent corticotroph adenomas behave in an aggressive manner and are characterized by the following: lack of clinical signs or symptoms of Cushing's syndrome and normal cortisol levels; no or only minor elevations of serum adrenocorticotropic hormone levels; macroadenomas with hemorrhagic infarction; and presentation dominated by mass effect symptoms. The high persistence/recurrence rate underscores the need for long-term follow-up.

Adenoma↗

PubMed2000

The long form of the leptin receptor (OB-Rb) is widely expressed in the human brain.

Leptin exerts important effects on the regulation of food intake and energy expenditure by acting in the brain. Leptin action is mediated by the interaction with a receptor that is alternatively spliced, resulting in at least five different isoforms. The long form (OB-Rb) has a long intracellular domain that is essential for intracellular signal transduction. The specific aim of this study was to further investigate the role that the brain may play in the pathogenesis of obesity in humans. We studied the expression of OB-R mRNA (both short or common and long isoforms) in the brains of obese, lean and diabetic subjects, by in situ hybridization, semiquantitative RT-PCR and Northern blots analysis. We used two alternative probes: one that recognizes all known splice variants (OB-Ra) and a second that recognizes only the long form, OB-Rb. Several brain regions, including hypothalamus, cerebellum, neocortex, entorrhinal cortex, amygdala, and rostral medulla, were evaluated. In situ hybridization studies revealed that both OB-Ra and OB-Rb mRNAs are widely distributed in the human brain. The specific hybridization signal with both probes was detected exclusively in the cytoplasm of the cell body, dendrites and proximal axons of neurons. Hypothalamic nuclei, Purkinje cells and dentate nuclei of the cerebellum, inferior olivary and cranial nerves nuclei in the medulla, amygdala and neurons from both neocortex and entorrhinal cortex demonstrated positive signals. The hybridization signal obtained in ependyma was lower than that in neurons and no specific hybridization was detected in glial cells. No significant differences were identified among the regions or among the three groups studied. These results match those previously obtained by us [Couce et al.: Neuroendocrinology 1997;66:145] in which the distribution of the OB-R protein in the human brain was first described. RT-PCR indicated that the OB-Rb was highly expressed in the hypothalamus and cerebellum. No significant differences of OB-Ra or OB-Rb mRNA expression were identified in lean or obese individuals in these two cerebral regions. The levels of OB-Rb were significantly higher in cerebellum compared to hypothalamus in lean and obese individuals. The original hypothesis that OB-Rb is present only in the hypothalamus needs to be reconsidered. This OB-Rb isoform seems to be widely expressed in the human brain with highest levels in the cerebellum. Obesity and hyperleptinemia appears not to be associated with down-regulation of the OB-Rb in the human brain.

Adult↗

PubMed2000

Subcellular localization of leptin in non-tumorous and adenomatous human pituitaries: an immuno-ultrastructural study.

Leptin is a key mediator in the maintenance of neuroendocrine homeostasis. Recently, leptin and leptin receptor expression were demonstrated in non-tumorous and adenomatous human pituitaries. This study was performed to determine the subcellular localization of leptin in human adenohypophyses (n = 3) and in various types of pituitary adenoma (n = 16). Immunoelectron microscopy showed leptin immunolabeling in most hormone-producing cells of the human non-tumorous adenohypophysis, but not in stellate cells. Labeling was noted over secretory granules. Immunocytochemistry using double labeling revealed leptin expression in GH-, ACTH-, TSH-, and FSH/LH-containing cells but not in PRL cells. The percentage of immunopositive cells and the intensity of immunostaining varied considerably among the various cell types. Immunoelectron microscopy with double gold labeling showed co-localization of leptin and adenohypophysial hormones in the same secretory granules. Among pituitary tumors, leptin immunolabeling was evident only in corticotroph adenomas. Compared to non-tumorous corticotrophs, leptin immunoexpression was less abundant in corticotroph adenomas. The presence of leptin and adenohypophysial hormones in the same secretory granules suggests that leptin is secreted concomitantly with various adenohypophysial hormones and that its release is under the control of hypothalamic stimulating and inhibiting hormones.

Adenoma↗

PubMed2000

p27(kip1) protein expression correlates with survival in myxoid and round-cell liposarcoma.

PURPOSE: The p27(kip1) protein (p27) is a cyclin-dependent kinase inhibitor that has been shown to be an independent prognostic factor in a variety of human neoplasms. Low expression of p27 tends to occur in more aggressive neoplasms. The role of p27 as an independent prognostic factor in the spectrum of myxoid and round-cell liposarcomas has not been examined. MATERIALS AND METHODS: Forty-seven cases of myxoid and round-cell liposarcomas were examined. Clinicopathologic features and immunohistochemical expression of p27 and Ki-67 antigen were studied in all cases. Survival analysis was performed using the log-rank test and the Cox multivariate regression model. RESULTS: The male:female ratio was 1. 4:1, and the mean age at diagnosis was 45 years. The tumors were located in the lower extremities (94%) and retroperitoneum (6%). The median tumor size was 13.5 cm. The median follow-up was 6.3 years, and the overall 5- and 10-year survival rates were 76% and 67%, respectively. Low expression of p27 was identified in 34 cases (72%) and correlated with decreased metastasis-free (P =.026) and overall survival (P =.008). In a multivariate analysis, only round-cell differentiation and low expression of p27 independently predicted decreased metastasis-free and overall survival. CONCLUSION: p27 expression predicts the clinical behavior of myxoid and round-cell liposarcomas, even in neoplasms with few or no round-cell differentiation.

Adult↗

PubMed2000

Leptin and leptin receptor expression in rat and mouse pituitary cells.

Leptin is a circulating hormone secreted mainly by adipose tissue. Recent studies have shown leptin production by other tissues, including the placenta, stomach, and mammary tissues. Various reports have suggested that the anterior pituitary may have a role in the regulatory effects of leptin. We recently localized leptin in the human anterior pituitary, but analysis of leptin in rodent pituitary has not been previously reported. In this study we examined rat and mouse pituitary tissues and various cell lines for leptin by RT-PCR, immunohistochemistry, and Western blotting. Leptin receptor messenger RNA was also examined in these tissues by RT-PCR. Leptin was present in a small percentage of rat (4.8 +/- 0.7%) and mouse (7 +/- 2%) pituitary cells. Colocalization studies with leptin and pituitary hormones showed leptin expression mainly in TSH cells (24 +/- 2% of TSH cells in the rat pituitary and 31 +/- 1% of TSH cells in the mouse pituitary). A folliculo-stellate (FS) cell line, TtT/GF, also expressed leptin. The long isoform of leptin receptor (OB-Rb) was present in normal pituitary and in various pituitary cell lines, including FS, GH3, and alphaT3-1 cells. Treatment of GH3 and FS cells with leptin (1 x 10(-8) M) inhibited cell proliferation assessed by [3H]thymidine incorporation in GH3, but not in FS, cells. These findings show for the first time that leptin is expressed in rat and mouse anterior pituitaries mainly by TSH cells and by a mouse FS cell line. The finding of leptin and of the long isoform of leptin receptor in normal rat and mouse pituitaries and in various cell lines implicates an autocrine/paracrine loop in the production and regulation of leptin and leptin receptor in the rodent pituitary.

Animals↗

PubMed2000

Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate.

Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients. Although latent EBV commonly is detected in lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate, p53 protein expression has not been reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients with connective tissue disease treated and not treated with methotrexate. Increased p53 staining was detected in 10 of 11 lymphomas arising in patients after methotrexate therapy vs 5 of 11 in patients not treated with methotrexate. Latent EBV was detected in 7 of 13 lymphomas arising in patients after methotrexate therapy vs 2 of 11 in patients not treated with methotrexate. Concordant p53 expression and latent EBV were detected in 5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed after methotrexate therapy was withdrawn. These findings suggest that cell cycle dysregulation and EBV-related transformation are important in the pathogenesis of lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate.

Adolescent↗

PubMed2000

Aberrant DNA methylation of cyclin D2 and p27 genes in rodent pituitary tumor cell lines correlates with specific gene expression.

We previously reported that increased DNA methylation was an important mechanism of silencing the p27 gene in some pituitary tumor cell lines [1]. DNA methylation correlated inversely with p27 gene expression. The p27 and cyclin D2 genes are located in the same region of mouse chromosome 6, rat chromosome 4, and human chromosome 12p13. Because both genes are located in the same gene cluster, we investigated whether methylation was a principal mechanism regulating cyclin D2 as well as p27 expression in rodent pituitary cell lines. Bisulfite genomic sequencing showed that the normally unmethylated cytosines of the p27 gene in normal pituitary (NP) were extensively methylated in GH3 and GHRH-CL1 cells, but not in AtT 20, alphaT3-1 and LbetaT2 cells; but cyclin D2 was extensively inactivated in various pituitary tumor cell lines by increased DNA methylation. These abnormalities of methylation in p27 and cyclin D2 genes occurred with different frequencies in five pituitary tumor cell lines with 100% (5/5) methylation of the cyclin D2 gene and 40% (2/5) methylation of the p27 gene. Treatment with the methyl transferase inhibitor 5'-aza-2'-deoxycytidine (AZAdC) increased expression of cyclin D2 and p27 in GH3 and GHRH-CL1 pituitary tumor cells. There was a correlation between hypermethylation and gene expression. GH3 tumors implanted into Wistar-Furth rats in vivo did not change the methylation status of the p27 and cyclin D2 genes. These data indicate a coordinately reduced expression of these two linked genes in most rodent pituitary tumor cell lines and suggest that methylation of cyclin D2 and p27 might occur in a "hot spot" in this gene-rich cluster.

Journal Article↗

PubMed2000

Ethical guidelines for publication of clinical and basic research in Endocrine Pathology.

The Endocrine Pathology Society wishes to remind all members and other individuals submitting manuscripts for publication about the rules of good conduct as they apply to the publication of research. The fundamentals include honesty, fairness, and the promulgation of common interest for the profession and society. The rules of good conduct for authors, reviewers, and editors are summarized below (modified in part from ref. 1). These ethical guidelines have been reviewed and approved by the members of the Endocrine Pathology Society.

Journal Article↗

PubMed2000

Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats.

Leptin exerts important effects on the regulation of food intake and energy expenditure by acting in the brain. Leptin is secreted by adipocytes into the bloodstream and must gain access to specific regions in the brain involved in regulating energy balance. Its action is mediated by interaction with a receptor that is mainly expressed in the hypothalamus but is also present in other cerebral areas. To reach these target areas, leptin most likely needs to cross the blood-brain barrier (BBB). In this study, we compared the permeability of leptin at the BBB in homozygous lean (FA/FA), high-fat diet-induced (HFD) obese rats (FA/FA rats on a highfat diet), and genetically obese fa/fa Zucker rats by quantifying the permeability coefficient surface area (PS) product after correction for the residual plasma volume (Vp) occupied by leptin in the vessel bed of different brain regions. The intravenous bolus injection technique was used in the cannulated brachial vein and artery using leptin radioiodinated with 2 isotopes of iodine (125I and 131I) to separately determine the PS and Vp values. The PS for leptin at the BBB in lean FA/FA rats ranged from 11.0 +/- 1.6 at the cortex to 14.8 +/- 1.4 x 10(-6) ml x g(-1) x ml(-1) at the posterior hypothalamus. The PS for leptin in HFD obese FA/FA and obese fa/fa rats ranged from 3.0- to 4.0-fold lower than in lean FA/FA rats. The Vp values were not significantly different among the 3 groups studied. SDS-PAGE analysis of the radioiodinated leptin after 60 min of uptake revealed intact protein in the 8 different brain regions. Plasma leptin levels were significantly higher in both obese rat groups compared with those in lean FA/FA rats. Leptin levels in cerebrospinal fluid were not significantly different among the 3 groups of rats. These findings strongly suggest that the leptin receptor (OB-R) in the BBB can be easily saturated. Saturation of the BBB OB-R in obese individuals would explain the defect in leptin transport into the brain described in this study.

Animals↗

PubMed2000

The cell cycle inhibitors p21WAF1 and p27KIP1 are associated with survival in patients treated by salvage prostatectomy after radiation therapy.

We evaluated p27KIP1 and p21WAF1 expression in 52 patients treated by salvage radical prostatectomy and bilateral pelvic lymphadenectomy for biopsy-proven locally persistent or recurrent prostate cancer after external beam radiation therapy. We defined low and high expression based on the median value observed in our sample. Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p21 (< or =5%), compared with 94 and 100%, respectively, for those with high expression of p21 (>5%; P = 0.02 and 0.01, respectively). Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p27 (<50%), compared with 88 and 96%, respectively, for those with high expression of p27 (> or =50%; P = 0.06 and 0.01, respectively). These findings indicate that p21 and p27 expression levels are significant predictors of survival for patients selected for salvage prostatectomy for recurrent prostate cancer.

Aged↗

PubMed2000

Bone marrow histochemical studies of fibrogenic cytokines and their receptors in myelodysplastic syndrome with myelofibrosis and related disorders.

Cellular and extracellular alterations of various fibrogenic cytokines have been described in a number of different chronic myeloid disorders that are associated with myelofibrosis. However, the available information related to both myelodysplastic syndrome with myelofibrosis (MDS-f) and bone marrow histochemical analysis is limited. In the current study, bone marrow immunohistochemical staining for platelet-derived growth factor, transforming growth factor (TGF)-beta, basic fibroblast growth factor (bFGF), and their receptors was performed in 9 patients with MDS-f, 9 patients with essential thrombocythemia (ET), 8 patients with 5q- syndrome, and 5 healthy control subjects. In addition, TGF-beta1 messenger RNA (mRNA) analysis was performed in 5 patients, each with MDS-f, myelofibrosis with myeloid metaplasia (MMM), polycythemia vera (PV), ET, and immune thrombocytopenic purpura, and in healthy control subjects. In general, protein and transcript expression patterns were similar to normal patterns and not significantly different among the various disease groups. The only exception was a reduced concentration of bFGF-expressing stromal cells in patients with PV, ET, and MMM.

Adult↗

PubMed1999

Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2.

Mutations in myosin XV are responsible for congenital profound deafness DFNB3 in humans and deafness and vestibular defects in shaker 2 mice. By combining direct cDNA analyses with a comparison of 95.2 kb of genomic DNA sequence from human chromosome 17p11.2 and 88.4 kb from the homologous region on mouse chromosome 11, we have determined the genomic and mRNA structures of the human (MYO15) and mouse (Myo15) myosin XV genes. Our results indicate that full-length myosin XV transcripts contain 66 exons, are >12 kb in length, and encode 365-kDa proteins that are unique among myosins in possessing very long approximately 1200-aa N-terminal extensions preceding their conserved motor domains. The tail regions of the myosin XV proteins contain two MyTH4 domains, two regions with similarity to the membrane attachment FERM domain, and a putative SH3 domain. Northern and dot blot analyses revealed that myosin XV is expressed in the pituitary gland in both humans and mice. Myosin XV transcripts were also observed by in situ hybridization within areas corresponding to the sensory epithelia of the cochlea and vestibular systems in the developing mouse inner ear. Immunostaining of adult mouse organ of Corti revealed that myosin XV protein is concentrated within the cuticular plate and stereocilia of cochlear sensory hair cells. These results indicate a likely role for myosin XV in the formation or maintenance of the unique actin-rich structures of inner ear sensory hair cells.

Alternative Splicing↗

PubMed1999

Epstein-Barr virus infection in Richter's transformation.

Chronic lymphocytic leukemia (CLL) may convert to a diffuse large cell lymphoma (Richter's syndrome) over time. In occasional cases of Richter's transformation, Epstein-Barr virus (EBV) has been identified in the lymphoma cells. To evaluate the association of EBV infection with Richter's syndrome, the biopsy specimens and clinical records of 25 patients who were seen at the Mayo Clinic between 1984-1996 were retrospectively evaluated for the presence of EBV by immunoperoxidase staining for expression of EBV latent membrane protein (LMP), as well as the expression of EBV RNA and DNA in the cells by in situ hybridization. Four of the 25 patients showed evidence of EBV in the diffuse large cell lymphoma cells-three patients with a B-cell phenotype were positive for LMP, EBV DNA, and RNA; and one patient with a T-cell phenotype had positive EBV RNA in the large cell lymphoma cells. The Richter's syndrome was treated with combination chemotherapy in 15 patients, three received radiotherapy, three were followed without further therapy after a splenectomy, two died before treatment could be started, and one patient had insufficient follow-up. One patient with evidence of EBV in large cell lymphoma cells was treated with acyclovir as initial therapy. The median survival of EBV-positive patients was three months compared with nine months for EBV-negative patients, but this difference was not statistically significant (P = 0.385). Evidence for EBV infection related to Richter's transformation was present in 16% of the patients in this study and may be associated with a poorer outcome. Primary therapy with acyclovir in one patient did not seem to be beneficial and other therapeutic modalities in patients with EBV-positive Richter's transformation need to be explored.

Adult↗

PubMed1999

p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers.

p27kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family. p27 expression is regulated by cell contact inhibition and by specific growth factors, such as transforming growth factor (TGF)-beta. Since the cloning of the p27 gene in 1994, a host of other functions have been associated with this cell cycle protein. In addition to its role as a CDKI, p27 is a putative tumor suppressor gene, regulator of drug resistance in solid tumors, and promoter of apoptosis; acts as a safeguard against inflammatory injury; and has a role in cell differentiation. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid, and endocrine tissues. This decrease occurs mainly at the post-translational level with protein degradation by the ubiquitin-proteasome pathway. A large number of studies have characterized p27 as an independent prognostic factor in various human cancers, including breast, colon, and prostate adenocarcinomas. Here we review the role of p27 in the regulation of the cell cycle and other cell functions and as a diagnostic and prognostic marker in human neoplasms. We also review studies indicating the increasingly important roles of p27, other CDKIs, and cyclins in endocrine cell hyperplasia and tumor development.

Cell Cycle↗