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Biomedical subjects

P Stenzel

Publications and source records attributed to P Stenzel.

At least 19 recordsLinked to original sources
PubMed2000

Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2.

The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.

Adaptation, Physiological↗
PubMed1999

Fatal fulminant hepatitis associated with bromfenac use.

OBJECTIVE: To report a case of fulminant hepatic failure associated with the use of bromfenac, a new analog of the phenyl acetate class of nonsteroidal antiinflammatory drugs. CASE SUMMARY: A 60-year-old white woman with liver failure who had no known history of chronic liver disease was transferred to the liver transplant unit for evaluation. For three months preceding her illness, the patient was treated with bromfenac 25 mg po qid for arthritic pain. Prior to the initiation of bromfenac, her liver function test results were normal. Etiologic evaluation at presentation was unremarkable. The patient's condition continued to deteriorate, with the development of hepatic encephalopathy and worsening liver function test results while awaiting liver transplantation. Progressive hepatic and renal dysfunction along with respiratory decompensation ensued, and the patient died 48 days after initial presentation. CONCLUSIONS: Fulminant hepatic failure associated with the prolonged use of bromfenac appears to be an idiosyncratic response consistent with experience with other agents of its class. This case along with other cases of serious hepatotoxicity associated with the use of this agent ultimately resulted in bromfenac's removal from the market.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Novel arterial pathology in mice and humans hemizygous for elastin.

Obstructive vascular disease is an important health problem in the industrialized world. Through a series of molecular genetic studies, we demonstrated that loss-of-function mutations in one elastin allele cause an inherited obstructive arterial disease, supravalvular aortic stenosis (SVAS). To define the mechanism of elastin's effect, we generated mice hemizygous for the elastin gene (ELN +/-). Although ELN mRNA and protein were reduced by 50% in ELN +/- mice, arterial compliance at physiologic pressures was nearly normal. This discrepancy was explained by a paradoxical increase of 35% in the number of elastic lamellae and smooth muscle in ELN +/- arteries. Examination of humans with ELN hemizygosity revealed a 2. 5-fold increase in elastic lamellae and smooth muscle. Thus, ELN hemizygosity in mice and humans induces a compensatory increase in the number of rings of elastic lamellae and smooth muscle during arterial development. Humans are exquisitely sensitive to reduced ELN expression, developing profound arterial thickening and markedly increased risk of obstructive vascular disease.

Animals↗
PubMed1997

Endotoxin regulates corticotropin-releasing hormone receptor 2 in heart and skeletal muscle.

We tested the effect of endotoxin on the peripheral corticotropin-releasing hormone receptor (CRH-R2), which is highly expressed in the heart. Systemic injection of LPS markedly downregulated CRH-R2 mRNA levels in the heart in a dose and time dependent manner. In contrast, CRH-R2 levels in skeletal muscle increased following exposure to endotoxin. These results suggest that CRH-R2 may be differentially regulated in cardiac tissue and skeletal muscle. Finding that CRH-R2 expression in the heart is modulated by endotoxin, a potent inducer of cardiovascular dysregulation, suggests a possible link between CRH and the cardiovascular response to stress.

Animals↗
PubMed1995

Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart.

Corticotropin-releasing hormone (CRH) is the principal regulator of the stress response. CRH stimulates production of ACTH via specific CRH receptors located on pituitary corticotropes. In addition to pituitary and central nervous system effects, peripheral effects of CRH have been observed involving the immune and cardiovascular systems. Specific CRH binding studies in several peripheral organs, as well as functional studies, have implied the existence of peripheral CRH receptors. Although a pituitary/brain CRH receptor has recently been identified, it is expressed at very low levels in peripheral sites where CRH effects have been observed. We report here the identification of a novel murine CRH receptor that is highly expressed in the heart. The newly cloned CRH receptor cDNA (CRH-R2) was isolated from a mouse heart cDNA library and encodes a 430-amino acid protein containing seven putative transmembrane domains characteristic of G protein-coupled receptors. CRH-R2 is 69% identical with the previously identified murine pituitary CRH receptor and is encoded by a distinct gene. In addition to a high level of expression in the heart, weak expression was also observed in the brain and lungs. Functional studies using CRH-R2-transfected cells indicate that CRH and the CRH-related amphibian peptide, sauvagine, bind with high affinity to CRH-R2 and stimulate intracellular accumulation of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

The univin gene encodes a member of the transforming growth factor-beta superfamily with restricted expression in the sea urchin embryo.

We have identified a gene in the sea urchin Strongylocentrotus purpuratus that encodes a member of the transforming growth factor beta (TGF-beta) gene superfamily. We have named the gene univin, and it is the first member of this superfamily to be reported in echinoderms. The cDNA sequence predicts a 383-amino-acid residue protein with 7 cysteine residues characteristic of members of this superfamily and with a cluster of basic residues appropriately situated to signal proteolytic cleavage. Sequence comparisons place univin in the bone morphogenetic protein (BMP) group of the TGF-beta superfamily along with the vertebrate BMPs, decapentaplegic protein from Drosophila, and Vg-1 from Xenopus. Analyses of univin expression in early embryos by RNA blots and in situ hybridization revealed the highest levels of expression in the egg and prehatching blastula. During late cleavage stages, univin mRNA accumulation is progressively restricted to a circumequatorial band. Expression is further restricted during gastrulation when univin transcripts are detected primarily in the presumptive foregut and ciliated band. By pluteus stage, signals are detectable only in these cell types. The restricted temporal and spatial patterns of expression of univin during early blastula stages parallel those of SpAN, which encodes an astacin-like protease related to tolloid and BMP-1 (Reynolds et al., 1992). The fact that these proteases are thought to function in the proteolytic activation of TGF-beta-related proteins that, respectively, regulate Drosophila embryonic dorsal-ventral patterning and vertebrate bone development suggests that SpAN and univin could also have critical roles in early developmental decisions in the sea urchin embryo.

Amino Acid Sequence↗
PubMed1992

Characterization of the genomic corticotropin-releasing factor (CRF) gene from Xenopus laevis: two members of the CRF family exist in amphibians.

In mammals, the release of pituitary ACTH is stimulated by CRF. Two related peptides exist in nonmammalian vertebrates, sauvagine from frog skin and urotensin-I from the urophysis of teleost fish. Their related structures (approximately 50%) and capacity to stimulate the release of ACTH from mammalian and fish pituitaries has led to the proposal that sauvagine and urotensin-I are homologs of mammalian CRF. However, sauvagine does not appear to stimulate ACTH release in amphibians, although mammalian CRF (ovine) induces a potent response from amphibian pituitaries. This could indicate that the main function of sauvagine does not involve ACTH regulation and suggests that an additional CRF-like peptide exists in Amphibia. We report here the isolation of two highly homologous CRF-like genes from the frog, Xenopus laevis. Analysis of the expression pattern of these CRF-like genes revealed mRNA in splenic tissue and in the preoptic nucleus and paraventricular organ of the brain. The amino acid sequence of the mature peptide regions (1-41) of both X. laevis genes is strikingly conserved, sharing more than 93% homology with mammalian CRFs, yet only 50% homology with sauvagine. In view of the fact that these new amphibian CRF-like genes share far greater homology with mammalian CRF than that exhibited by sauvagine, we propose that the new Xenopus CRF-like genes are the amphibian counterparts to mammalian CRF. Thus, two members of the CRF family have now been identified in the Amphibia, namely CRF and sauvagine.

Amino Acid Sequence↗
PubMed1990

Gastrointestinal involvement in Langerhans cell histiocytosis (histiocytosis X): diagnosis by rectal biopsy.

We report two patients with biopsy-proven involvement of the gastrointestinal tract by Langerhans cell histiocytosis (LCH). The two patients were infants with congenital cutaneous lesions and bloody diarrhea beginning at 1 or 2 wk of age. Rectal biopsy specimens showed a mucosal infiltrate of typical Langerhans cells that focally invaded and destroyed the crypt epithelium. Gastrointestinal involvement by LCH is unusual and only rarely has represented a prominent clinical manifestation. In most cases, such involvement has been an indicator of widespread multisystemic disease. Its distinctive morphologic and immunohistochemical features allow LCH to be distinguished from other histiocytic infiltrations found in mucosal biopsy specimens.

Biopsy↗
PubMed1989

Bilateral ureteral stricture from polyarteritis nodosa.

A case of bilateral, asynchronous ureteral stricture from polyarteritis nodosa is described. Two cases of unilateral ureteral stricture from polyarteritis nodosa have been reported previously. Ureteral obstruction not associated with retroperitoneal fibrosis is rare with polyarteritis nodosa.

Adult↗
PubMed1989

Renal adenocarcinoma with solitary metastasis to the contralateral adrenal gland: report of 2 cases and review of the literature.

We report 2 rare cases of renal adenocarcinoma with solitary metastasis to the contralateral adrenal gland, 1 recognized synchronously with the primary neoplasm and 1 found 15 years after nephrectomy. The latter case represents the longest reported interval between nephrectomy and treatment of a solitary contralateral adrenal metastasis of renal adenocarcinoma. Distinction of these metastatic tumors from primary adrenocortical carcinoma was facilitated by immunohistochemical markers. Twelve other reported cases of renal adenocarcinoma with solitary contralateral adrenal metastasis support aggressive surgical management of this lesion.

Adrenal Gland Neoplasms↗
PubMed1989

Gastrointestinal multicentric infantile myofibromatosis: characteristic histology on rectal biopsy.

A 10-wk-old girl with growth failure and increasingly severe watery diarrhea underwent rectal biopsy which revealed diffuse mucosal fibrosis. Subsequent histologic study of mediastinal and subcutaneous masses established the diagnosis of multicentric infantile myofibromatosis. The patient died at 16 wk of age with tumor nodules in several visceral and parietal structures. The small and large intestines contained continuous, diffuse and nodular, mucosal and submucosal fibrosis. Twelve previously reported cases of multicentric infantile myofibromatosis involved the gastrointestinal tract; four had prominent gastrointestinal clinical manifestations. In two, diarrhea was prominent. The present case demonstrates the potential value of rectal biopsy in the diagnosis of infantile myofibromatosis with gastrointestinal manifestations.

Biopsy↗
PubMed1988

Small cell carcinoma of urinary bladder.

A fifty-seven-year-old woman with urinary bladder carcinoma with extensive areas resembling oat cell carcinoma of the lung in whom distant metastases developed, died seven months after diagnosis. Argyrophil cells could not be demonstrated, but electron microscopy demonstrated dense-core, membrane-bound intracytoplasmic granules. We reviewed 12 cases of epithelial neoplasms of the bladder from the literature in which there was ultrastructural evidence of neuroendocrine differentiation. Cases with malignant histologic features, like their pulmonary counterparts, have the potential for widespread dissemination and rapid growth. We support the previous suggestion that these neoplasms may be of considerable incidence and their recognition is important to determine prognosis and selection of therapy.

Carcinoma, Small Cell↗
PubMed1987

Intrapericardial yolk sac tumor in an infant girl.

This article is a report on the first known case of an intrapericardial yolk sac (endodermal sinus) tumor discovered in a 14-month-old girl. The patient presented with a systolic murmur, cardiomegaly, and manifestations of cardiac failure. At surgery a large, friable, intrapericardial mass with no evidence of extrapericardial spread was found. Histologic and immunohistochemical findings were diagnostic of yolk sac tumor. Following initial resection, chemotherapy, and a second resection 13 months after the first, the patient died 24 months after diagnosis. Tumor enlargement was associated with elevated serum alpha-fetoprotein levels.

Antineoplastic Agents↗
PubMed1987

Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting.

A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.

Blood Glucose↗
PubMed1987

Benign oncocytic endocrine tumor of the pancreas in a patient with polyarteritis nodosa.

An 8-cm mass in the tail of the pancreas was resected from a 40-year-old man with polyarteritis nodosa. The tumor cells contained abundant, finely granular, eosinophilic cytoplasm arranged in a gyriform pattern that suggested the tumor was an oncocytoma of the endocrine pancreas. Electron microscopy confirmed that the tumor was an oncocytoma by demonstrating tumor cell cytoplasm packed with mitochondria. Ultrastructural and immunocytochemical studies confirmed the neuroendocrine nature of the tumor by demonstrating dense-core, membrane-bound structures consistent with neurosecretory granules and neuron-specific enolase immunoreactivity. No immunoreactivity for insulin, glucagon, gastrin, somatostatin, or pancreatic polypeptide was found. No human chorionic gonadotropin alpha-chain immunoreactivity was detected. The patient is well without evidence of tumor five years after operation. The apparently benign behavior of the pancreatic endocrine oncocytoma reported here is in contrast to the malignant nature of another case reported recently.

Adult↗
PubMed1985

Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections.

Exoenzyme S is an extracellular ADP-ribosyltransferase enzyme produced by Pseudomonas aeruginosa. Mutants of Pseudomonas aeruginosa deficient in this enzyme have been shown to have reduced virulence in infections of burned mice. The contribution of exoenzyme S to the pathogenesis of chronic lung infections with this organism was evaluated by examining the incidence of exoenzyme S production by Pseudomonas aeruginosa strains isolated from cystic fibrosis patients and comparing an exoenzyme S deficient mutant and its exoenzyme S producing parent in a rat chronic lung infection model. Of 51 isolates examined, 43% produced detectable levels of exoenzyme S. While both the exoenzyme S deficient mutant and its parent strain were equally capable of colonizing and persisting in rat lungs, the exoenzyme S producing parent elicited a greater degree of lung damage. These data suggest that exoenzyme S contributes to the pathogenesis of chronic lung infections.

ADP Ribose Transferases↗