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PubMed2001

MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer.

The predictive value of MLH1 or MSH2 protein expression for the presence of truncating germline mutations was examined in benign and (pre)malignant endometrial samples from 3 patient groups: (I) 10 endometrial cancer patients from hereditary non-polyposis colorectal cancer (HNPCC) families with (n = 6) or without (n = 4) a known germline mutation; (II) 15 women from HNPCC families with (n = 7) or without (n = 8) a known germline mutation, who underwent endometrial sampling for non-malignant reasons; (III) 38 endometrial cancer patients <50 years of age, without HNPCC family history. Immunostaining for MLH1 and MSH2 was performed on paraffin-embedded sections. In group III, tumor DNA was examined for microsatellite instability (MSI) and MLH1, MSH2 and MSH6 mutation analysis was carried out. In 6/6 MLH1/MSH2 mutation carriers with endometrial cancer (group I), concordance was found between protein loss in the tumor and the corresponding mutation. In 3 MLH1 mutation carriers, MLH1 protein loss was also observed in concurrent endometrial hyperplasia. In group II, no protein loss was detected in normal endometrial tissue samples; in 3/4 patients with endometrial hyperplasia, MLH1/MSH2 protein loss was observed. In group III, protein loss was detected in 12/38 patients (9 MLH1, 3 MSH2), while in 3/11 patients with concurrent endometrial hyperplasia protein loss was also observed in the hyperplasia. MSI analysis in group III revealed 26 MSI-low and 12 MSI-high tumors. Mutation analysis in 28/38 patients showed only 1 missense MSH6 and no MLH1 or MSH2 germline mutations. In group III, loss of MLH1/MSH2 protein expression was not related to the presence of MSI or MLH1/MSH2 germline mutations. In conclusion, MLH1 or MSH2 protein loss in HNPCC-related endometrial neoplasia is strongly related to corresponding germline mutations. This relation was not clearly present in young sporadic endometrial cancer patients. Immunohistochemical pre-screening of the MLH1 and MSH2 proteins in endometrial hyperplasia or cancer can thus be helpful in HNPCC families. Frequent loss of MLH1 or MSH2 protein in endometrial hyperplasia indicates that this loss is an early event in endometrial carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed1990

Hyperplasia of mouse duodenal crypts and its control by NK cells during the initial phase of DMH carcinogenesis.

The possible regulatory role of NK cells on early events in chemical carcinogenesis remains undefined. The present study examined whether NK cells control 1,2-dimethylhydrazine (DMH)-induced hyperplasia of the duodenal crypt in CD1 mice. Mice receiving chronic DMH treatment showed a dose-dependent hyperplasia confined to the proliferative zone, with a parallel increase in mitotic and 3H-TdR-labelled cells and significant suppression of splenic NK activity. Complete ablation of splenic NK activity with anti-asialo GM-I antibody (alpha AGM-I) treatment slightly enhanced hyperplasia. Halving of the DMH dose for 2 weeks led to regression of hyperplasia, which was totally prevented by alpha AGM-I treatment. The alpha AGM-I treatment alone did not influence crypt size in normal mice. Finally, a stimulation of NK activity with Poly I:C treatment in DMH-treated mice caused regression of the DMH-induced hyperplasia. Our results suggest that hyperplastic cells with possible genetic alterations induced by the carcinogen express target structures for NK cells, but that simultaneous carcinogen-induced suppression of NK activity hampers their containment, allowing progression of hyperplasia to neoplasia, possibly owing to additional genetic changes.

1,2-Dimethylhydrazine↗
PubMed1993

Novel microsurgical model of experimental vascular neointimal hyperplasia.

Neointimal hyperplasia is a common finding after trauma to blood vessels and also as a primary change in atherosclerosis. In this study we have developed a simple model, using microsurgical techniques, for the initiation of neointimal hyperplasia in the rat. In 24 Wistar rats, a 2 mm-diameter arteriotomy in the aorta was repaired with a "patch" of iliolumbar vein, using eight evenly spaced 10-0 Ethilon sutures. The patch overlapped the edges of the arteriotomy, and the sutures fastened the patch to the subjacent aorta. At 2, 6 and 12 weeks after surgery, the venous patch grafts and segments of the adjacent aortae of eight rats were removed. One-half of the specimens were analyzed by scanning electron microscopy and the other one-half by light microscopy. All patch grafts were surgically successful. Endothelial cells regenerated to cover the patch within 2 weeks of insertion. By 6 weeks after surgery, neointimal hyperplasia, consisting predominantly of smooth muscle, had developed in all patches to a thickness that was not significantly different from that of the adjacent aorta. These findings are consistent with data from other more complex experimental models of neointimal hyperplasia in the rat. We consider that this venous patch technique is a simple but effective model for the initiation of neointimal hyperplasia in the rat and may easily be used to study the experimental effects of various injurious or therapeutic agents on neointimal hyperplasia.

Animals↗
PubMed2003

Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice.

BACKGROUND: The norepinephrine (NE) analog phenylephrine has previously been shown to induce atypical prostate hyperplasia in rats. The objective of the present study was to provide further insight into the mechanism of phenylephrine-induced prostate growth. METHODS: Adult male C57/BL6 mice were given daily subcutaneous injection of phenylephrine, isoproterenol, or phenylephrine in combination with BMY7378, cyclazosin, RS100329, or yohimbine, and the effects on ventral prostate histology, and proliferative and apoptotic indices determined. Phenylephrine was also administered in combination with testosterone in castrated mice. RESULTS: Atypical prostatic hyperplasia characterized by piling up and/or papillary infolding of epithelial cells with concomitant stromal smooth muscle hyperplasia was seen in adult mice given subcutaneous injection of phenylephrine daily for 26 days. Phenylephrine induced hyperplasia was more severe proximally and was associated with significantly reduced rates of apoptosis (but no change in cell proliferation) in both stromal and epithelial compartments. Only the alpha(1A)-adrenoceptor selective subtype antagonist RS100329 abrogated the phenylephrine-induced hyperplasia. Using selective antibodies, the alpha(1A-1)-adrenoceptor subtype was predominantly localized to the stromal compartments of the mouse and rat ventral prostates. The effects of phenylephrine were mediated independent of testicular androgens. CONCLUSIONS: Prostatic hyperplasia in mice occurs as a consequence of subchronic administration of the sympathomimetic phenylephrine. Response to phenylephrine is mediated by the alpha(1A)-adrenoceptor, which predominates in the stroma of the rodent ventral prostate. Conceivably, therefore, phenylephrine could directly modulate prostate stromal growth, and indirectly modulate epithelial growth in a paracrine fashion. We cannot, however, rule out the contribution of other indirect effects such as hypoxia/reperfusion or effects on intermediary metabolism.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

Does hysteroscopy improve upon the sensitivity of dilatation and curettage in the diagnosis of endometrial hyperplasia or carcinoma?

OBJECTIVE: The objective of this study was to determine whether hysteroscopy improved upon the diagnostic sensitivity of dilatation and curettage (D+C) in the detection of endometrial hyperplasia and carcinoma. METHODS: A retrospective chart review was conducted of all patients undergoing hysteroscopy/D+C for abnormal uterine bleeding between 1991 and 1995. Hysteroscopic impressions and D+C diagnoses were compared. RESULTS: Three hundred seventy-three patients were included in the study. Of the 61 patients with D+C demonstrating hyperplasia, the hysteroscopic impression was hyperplasia in 32 (52%). Of the 10 patients with D+C demonstrating carcinoma, the hysteroscopic impression was hyperplasia in 8 (80%) and carcinoma in 2 (20%). Two additional cases of carcinoma were diagnosed within 6 months of hysteroscopy/D+C, and both had been missed on both hysteroscopy and D+C. Of 204 patients with a normal hysteroscopic impression, 23 (11%) had hyperplasia on D+C. CONCLUSIONS: Hysteroscopy did not improve upon the sensitivity of D+C in the detection of endometrial hyperplasia or carcinoma.

Adult↗
PubMed1999

Adipose tissue distribution in postmenopausal women with adenomatous hyperplasia of the endometrium.

OBJECTIVE: To investigate body fat distribution in postmenopausal women with adenomatous and atypical hyperplasia of the endometrium. METHODS: A prospective population-based case control study was performed in a health care county in Sweden. General obesity, as reflected by body mass index (BMI), and adipose tissue distribution, expressed as waist to hip circumference ratio (WHR), were evaluated in a cohort of 367 postmenopausal women who underwent dilatation and curettage because of uterine bleeding. The study group consisted of 29 women with adenomatous or atypical hyperplasia of the endometrium. The controls consisted of 49 age-matched postmenopausal women randomly selected from the computerized population register of the same region. RESULTS: The frequency of endometrial adenomatous and atypical hyperplasia in postmenopausal women with bleeding was 7.2%. In the total population of postmenopausal women the incidence of these endometrial lesions was 44 per 100,000 per year. Body weight (P = 0.039), BMI (P = 0.007), and WHR (P = 0.022) were higher in postmenopausal women with endometrial adenomatous and atypical hyperplasia than in controls. In multivariate analysis only BMI remained statistically associated with adenomatous hyperplasia (P = 0.012). CONCLUSIONS: General obesity, but neither upper nor lower body fat distribution, was characteristic of postmenopausal women with adenomatous and atypical hyperplasia of the endometrium. Overall obesity is a risk factor for these endometrial precancerous lesions, as it is also claimed to be for endometrial cancer.

Adipose Tissue↗
PubMed1998

Local inhibition of tyrosine kinase activity markedly attenuates the development of intimal hyperplasia in experimental vein grafts.

BACKGROUND: Intimal hyperplasia is due to the migration and proliferation of vascular smooth muscle cells after bypass surgery. Tyrosine kinases are involved in many signal transduction pathways including cell proliferation. This study examines the effects of local treatment with the tyrosine kinase inhibitor, tyrphostin AG-51, on the formation of intimal hyperplasia in vein grafts. MATERIALS AND METHODS: Thirty-nine New Zealand White rabbits underwent interposition bypass grafting of the carotid artery using the jugular vein. In the first group (TKI), tyrphostin AG-51 (5 mg), dissolved in 600 microliter of dimethyl sulfoxide and Ringer's lactate (2:1, v:v), was used to incubate the veins ex vivo prior to grafting and delivered locally in 2.5 ml of 30% pluronic gel after grafting. The second group (DMSO) received the same treatment but without tyrphostin. In the third group (control), tyrphostin and DMSO were omitted from the incubation and gel delivery solutions. Postoperatively, vein grafts were harvested on Day 3 for Western analysis using an antiphosphotyrosine antibody (PY-20) to assess for tyrosine kinase activity, and on Day 28 for either morphologic or contractile function studies. RESULTS: Local application of the TKI to vein grafts resulted in a 49% reduction in intimal hyperplasia compared to DMSO-treated vein grafts (31 +/- 4 micrometer vs. 61 +/- 5 micrometer, P < 0.01). Treatment with DMSO alone reduced intimal hyperplasia by 28% compared to control (85 +/- 4 micrometer, P < 0.05). The contractile responses in the DMSO and TKI-treated vein grafts were equivalent. Western analysis showed a 39-fold decrease in tyrosine phosphorylation with TKI treatment compared to control. CONCLUSION: This study demonstrates that local short-term treatment with TKI produces a 49% reduction in intimal hyperplasia and suggests that phosphorylation of tyrosine residues is involved in the signaling pathways leading to the development of intimal hyperplasia in vein grafts.

Administration, Topical↗
PubMed1994

Hyperplasia of epithelium adjacent to transitional cell carcinoma can be induced by growth factors through paracrine pathways.

Hyperplasia of transitional cell epithelium adjacent to human transitional cell carcinomas (TCC) is a common finding in pathology. This hyperplasia may be a precancerous aberration. Alternatively, it has been suggested that the hyperplasia is due to paracrine action of tumour-derived growth factors. In this study we tested the latter hypothesis using the mouse tumorigenic TCC cell line NUC-1. Transplantation of NUC-1 tumour cells into the urinary bladder submucosa of syngeneic mice in vivo induced hyperplasia of normal adjacent urothelium in all tested mice. Implantation of normal mouse bladder mucosa did not induce urothelial hyperplasia. In vitro, conditioned medium of NUC-1 cells induced the proliferation of the mouse urothelial cell line g/G, which closely resembles normal urothelial cells. This induction was inhibited by transforming growth factor beta 1 (TGF beta 1). Similarly, TGF beta 1 inhibited the fibroblast growth factor-1 (FGF-1) and FGF-2 induced proliferation of g/G cells. Chemico-physical examination, bioassays with conditioned media, and RNA analysis of NUC-1 cells revealed that these cells secreted a growth factor with FGF-like properties. These results indicate that epithelial hyperplasia surrounding carcinomas is not necessarily a precancerous aberration, but may result from direct paracrine action of tumour-derived growth factors.

Animals↗
PubMed1977

[The hyperplasia forms of the endometrium and their correlations to the endometrium carcinoma (author's transl)].

In cases of endometrial carcinoma where hysterectomy was performed, we examined histologically the marginal endometrium. For comparison we formed a control group of women of the same age. In the age between 45 and 65 adenomatous hyperplasia in the cancer group is found significantly more often. The glandular-cystic hyperplasia is found more frequently in the age group beyond 55, especially in women beyond 65. The simultaneous incidence of adenomatous hyperplasia and endometrial carcinoma suggests this form of hyperplasia being precancerous. Before the menopause the glandular-cystic hyperplasia does not seem essential for the origin of the endometrial cancer. It is not yet known why the glandular-cystic hyperplasia is found more frequently in postmenopausal women with endometrial carcinoma. The role of the estrogenic hormones as agents possibly forming a good terrain for the endometrial cancer is discussed.

Aged↗
PubMed1987

Human cystic kidney diseases: epithelial hyperplasia in the pathogenesis of cysts and tumors.

Several examples of human renal cystic disease are associated with tubular epithelial hyperplasia. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease; neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease; a histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In all of these conditions the epithelial hyperplasia appears to be responsible for cyst formation by causing tubular or ductal luminal obstruction, and in all of these conditions, save localized cystic disease (a rare condition with very few reported cases), epithelial hyperplasia imposes an increased risk of malignancy. The risk seems to be highest in patients under treatment with long-term hemodialysis for end-stage kidney disease. Some of these diseases may share common features, but it appears likely that the histopathological differences reflect different features converging on a common result.

Epithelium↗
PubMed1992

Histopathology of myoepithelial (basocellular) hyperplasias in adenosis and epitheliosis of the breast demonstrated by the reactivity of cytokeratins and S100 protein. An analysis of heterogenic cell proliferations in 90 cases of benign and malignant breast diseases.

This study on the different types of epithelial hyperplasia in fibrocystic disease was inspired by the observation of myoepithelial (basocellular) hyperplasia identified by strong expression of S100 protein and a weak reaction with antibodies against cytokeratin (KL1) in cells forming solid and acinar buds. The cells do not contain immunohistochemically detectable actin or desmin. Glandular transformation and proliferation give rise to basocellular circumductal adenosis. Normal breast tissue, 51 cases of fibrocystic disease with mild, florid and atypical hyperplasias, 7 fibroadenomas and 20 cases of carcinoma in situ were studied and a semiquantitative analysis revealed basal buds and adenosis in less than 40% of cases of mild hyperplasia and up to 73% in florid hyperplasia. Epitheliosis is characterized by a heterogeneous cell pattern with cells positive for S100 protein in 30-60%, but in small ducts up to 100% with an immediate connection to the basal cell layer were positive. Carcinoma in situ contained very rare tumour cells positive for S100 protein. The cells expressing S100 protein in terminal ducts, in adenosis and epitheliosis showed only some of the characteristics of myoepithelial cells, since they lack immunoreactivity with antibodies against actin. These basal clear cells are interpreted as transitional or indeterminate cells with features of myoepithelial precursor cells, but with the ability to develop basocellular nodular and glandular hyperplasia in the ductulo-lobular units in cases of adenosis and juvenile fibroadenoma.

Adenofibroma↗
PubMed1994

Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide.

Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 +/- 2.3%; group II (enalaprilat), 9.5 +/- 0.7%; and group III (DMSO), 17.6 +/- 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p < 0.01, ANOVA, Student's t test), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1996

Foveolar hyperplasia following partial gastrectomy results from expansion of surface mucous cell compartment.

Antrectomy with gastroenterostomy reconstruction is often associated with the development of foveolar hyperplasia and oxyntic atrophy. While a role for bile reflux in the etiology of foveolar hyperplasia is well established, the identity of the mucous cell lineages responsible for this condition have not been well characterized. We have studied three patients who demonstrated foveolar hyperplasia in their gastric remnant following antrectomy and gastroenterostomy. Mucosal samples were stained with antibodies against the trefoil peptides pS2 and hSP, to identify surface mucous and mucous neck cell lineages, respectively. Postoperative biopsies from all three patients showed oxyntic atrophy as documented by staining of parietal cells with antibodies against H/K-ATPase. All three patients demonstrated an exclusive expansion of pS2 immunoreactive mucous cells. The hSP staining cells were located deep in the expanded foveolar region. The results suggest that foveolar hyperplasia following antrectomy with gastroenterostomy results from a reactive hyperplasia of surface mucous cells. This pattern of surface cell hyperplasia is more consistent with a reactive expansion of mucous cells than with a response to chronic injury.

Adult↗
PubMed1999

Refractory proctosigmoiditis caused by myointimal hyperplasia of mesenteric veins: report of a case.

PURPOSE: Proctosigmoiditis occurring in young adults is usually idiopathic and usually responds to medical management. If the process progresses to pancolitis and is refractory to medical management, proctocolectomy may be required. Myointimal hyperplasia of mesenteric veins, though rare, may also cause proctosigmoiditis, but this entity, in contrast to the idiopathic variety, does not respond to medical management; surgical excision limited to the involved colonic segment is curative. Because the treatment of the two entities differs significantly, it is important to distinguish them diagnostically. The purpose of this case report is to increase awareness of myointimal hyperplasia of mesenteric veins and to emphasize the clinical features that distinguish it from idiopathic proctosigmoiditis. METHODS: We report the case of a twenty-two-year-old male with an inflammatory process involving the distal colon and rectum, initially thought to be idiopathic proctosigmoiditis. The inflammation did not respond to an extensive course of medical management, and the patient developed complications associated with both the disease process and his medical therapy. Surgical resection of the rectosigmoid was performed. RESULTS: Histologic examination of the resected colon revealed the underlying process to be colonic ischemia caused by myointimal hyperplasia of mesenteric veins not associated with idiopathic inflammatory bowel disease or systemic vasculitis. CONCLUSION: Proctosigmoiditis caused by myointimal hyperplasia of mesenteric veins and idiopathic proctosigmoiditis may present in a similar fashion. Although patients with myointimal hyperplasia of mesenteric veins do not respond to medical management, segmental resection is usually curative, and long-term drug therapy or even proctocolectomy can be avoided. Physicians should consider the possibility of myointimal hyperplasia of mesenteric veins when patients with apparent idiopathic proctosigmoiditis do not respond to medical therapy.

Adult↗
PubMed1996

Surgical biopsy findings in patients with atypical hyperplasia diagnosed by stereotaxic core needle biopsy.

PURPOSE: To correlate the stereotaxic core needle biopsy results with those of surgical biopsy in patients with atypical lobular or ductal hyperplasia (atypical hyperplasia) diagnosed at stereotaxic core needle biopsy (SCNB). METHODS: We retrospectively reviewed the mammograms and pathology reports of 358 consecutive SCNBs performed in 323 patients. The results of SCNBs of 22 lesions reported as atypical hyperplasia were correlated with histologic findings at surgical biopsy. RESULTS: A histologic diagnosis of atypical hyperplasia at SCNB was found to be a poor predictor of the final surgical results. In the 19 patients with 22 lesions, surgical biopsy and SCNB results were in disagreement in 16, partial agreement in two, and complete agreement in only four lesions. Furthermore, five cases of atypical hyperplasia were shown to have invasive carcinoma on open biopsy, and five had ductal carcinoma in situ in the surgical biopsy, none of which was present on SCNB. CONCLUSION: Given the frequent occurrence of malignancy in patients diagnosed with atypical hyperplasia by SCNB, it is recommended that all such patients undergo excisional biopsy.

Biopsy, Needle↗
PubMed2002

Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia.

The development of human benign prostatic hyperplasia (BPH) clearly requires a combination of testicular androgens and the ageing process. Although the role of androgens as the causative factor for human benign prostatic hyperplasia is debated, they undoubtedly play, at least, a permissive role. The principal prostatic androgen is dihydrotestosterone. Although not elevated in human benign prostatic hyperplasia, dihydrotestosterone levels in the prostate remain at a normal level with ageing, despite a decrease in the plasma testosterone. Dihydrotestosterone (DHT) is generated by a reduction in testosterone. Two isoenzymes of 5alpha-reductase have been discovered. Type 1 is present in most tissues in the body where 5alpha-reductase is expressed, and is the dominant form in sebaceous glands. Type 2 5alpha-reductase is the dominant isoenzyme in genital tissues, including the prostate. Finasteride is a 5alpha-reductase inhibitor that has been used to treat BPH and male-pattern baldness. At doses used clinically, its major effect is to suppress type 2 5alpha-reductase, because it has a much lower affinity for the type 1 isoenzyme. Finasteride suppresses DHT by about 70% in serum and by as much as 85%-90% in the prostate. The remaining DHT in the prostate is likely to be the result of type 1 5alpha-reductase. The suppression of both 5alpha-reductase isoenzymes with GI198745 results in greater and more consistent containment of serum dihydrotestosterone than that observed with a selective inhibitor of type 2 5alpha-reductase. Physiological and clinical studies comparing dual 5alpha-reductase inhibitors, such as GI198745, with selective type 2, such as finasteride, will be needed to determine the clinical relevance of type 1 5alpha-reductase within the prostate. There have been two large, international multicentre, phase III trials published documenting the safety and efficacy of finasteride in treating human benign prostatic hyperplasia. Combining these two studies, randomised, controlled data are available for 12 months. Non-controlled extension of these data from a subset of patients, who elected to continue on the drug for 3, 4 and 5 years, are also available. Long-term medical therapy with finasteride can reduce clinically significant endpoints, such as acute urinary retention or surgery. According to the meta-analysis of six randomised, clinical trials with finasteride, finasteride is most effective in men with large prostates. A more effective dual inhibitor of type 1 and 2 human 5alpha-reductase may lower circulating dihydrotestosterone to a greater extent than finasteride and show advantages in treating human benign prostatic hyperplasia and other disease states that depend on dihydrotestosterone. A clinical evaluation of potent dual 5alpha-reductase inhibitors may help to define the relative roles of human type 1 and 2 5alpha-reductase in the pathophysiology of benign prostatic hyperplasia and other androgen-dependent diseases.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Atypical ductal hyperplasia of the pancreas associated with a stricture of the main pancreatic duct.

Atypical ductal hyperplasia of the pancreas is thought to be a precancerous lesion. We report a case of atypical ductal hyperplasia associated with a stricture of the main pancreatic duct. A 70-year-old man was admitted to our hospital because of abdominal pain with an elevated serum pancreatic isoamylase level. Endoscopic retrograde cholangiopancreatography disclosed a stricture of the main pancreatic duct in the body of the pancreas. Cytological evaluation of endoscopic brushings suggested adenocarcinoma. Distal pancreatectomy was performed. Microscopic examination of the stenotic pancreatic duct showed a hyperplastic epithelium without atypia. Atypical hyperplasia, however, was found in the distal portion of the main pancreatic duct in close proximity to the stricture. Atypical hyperplasia extended along the main pancreatic duct into the ductal branches of the pancreatic tail. In contrast to the vast majority of patients with atypical hyperplasia, the atypical hyperplasia seen in the present patient had no histological features suggestive of intraductal extension of the invasive carcinoma or intraductal papillary-mucinous tumor, thus representing a sporadic precancerous lesion, and it may have been equivalent to carcinoma in situ. Pancreatic duct stricture and the resultant stasis of the pancreatic juice may have promoted the atypical changes in the ductal cells upstream of the stricture.

Adenocarcinoma↗
PubMed2004

Evidence of oxidative stress in the brains of fetuses with CNS anomalies and islet cell hyperplasia.

Infants of diabetic mothers have an increased frequency of congenital anomalies, including CNS malformations. Fetal hyperglycemia may promote such damage via oxidative stress. Postmortem studies have shown that fetal hyperglycemia associated with maternal diabetes results in islet cell hyperplasia. Islet cell hyperplasia may correlate with the presence of oxidative stress injury in the CNS because of hyperglycemia and related metabolic derangement. This study examines 3-nitrotyrosine immunoreactivity as a marker of oxidative stress in the brains of fetuses stratified by the presence or absence of islet cell hyperplasia and CNS developmental anomalies. Fetuses with both islet cell hyperplasia and CNS developmental anomalies showed a 1.8-fold increase in semiquantitatively scored 3-nitrotyrosine immunostaining compared to negative controls. Fetuses with islet cell hyperplasia but no CNS anomalies demonstrated a 1.6-fold increase. Comparison between fetuses with islet cell hyperplasia which were stratified by presence or absence of CNS anomalies were not statistically different but did show more intense staining in those with CNS malformations. These results support the contention that hyperglycemia may contribute to CNS malformation via oxidative stress.

Adolescent↗