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H K Wolf

Publications and source records attributed to H K Wolf.

At least 19 recordsLinked to original sources

Hepatocyte regeneration in acute fulminant and nonfulminant hepatitis: a study of proliferating cell nuclear antigen expression.

It has been suggested that in fulminant hepatitis it is the lack of hepatocyte regeneration that in the presence of an ongoing loss of hepatocytes leads to hepatic failure and ultimately determines the grim prognosis of this disease. However, little data are available concerning hepatocyte regeneration in human acute hepatitis. We compared the nuclear expression of proliferating cell nuclear antigen with the incorporation of bromodeoxyuridine in formalin-fixed, paraffin-embedded liver tissues of rats at different stages of regeneration after two-thirds partial hepatectomy. Immunohistochemical staining for proliferating cell nuclear antigen was performed using the monoclonal antibody 19F4. A good correlation was seen between nuclear labeling for bromodeoxyuridine and proliferating cell nuclear antigen, which indicates that the immunoreactivity for proliferating cell nuclear antigen accurately reflects hepatocyte proliferation. Subsequently, we determined the nuclear expression of proliferating cell nuclear antigen on archival paraffin-embedded samples of the normal human liver (8 cases), acute nonfulminant hepatitis (10 cases) and fulminant hepatitis (4 cases). The mean proliferating cell nuclear antigen labeling indices were the following: normal liver = 0.4%; acute nonfulminant hepatitis = 43.0%; and fulminant hepatitis = 45.9%. The indices for proliferating cell nuclear antigen were significantly greater in acute hepatitis than in the normal liver, reflecting the high cell turnover in hepatitis. However, no significant difference was seen between the expression of proliferating cell nuclear antigen in nonfulminant and fulminant acute hepatitis. These data suggest that the net loss of hepatocytes in fulminant hepatitis may not be caused by a lack of hepatocyte regeneration but rather results from overwhelming hepatocyte injury with subsequent cell death.

Acute Disease

Detection of proliferating cell nuclear antigen in diagnostic histopathology.

We describe the effects of tissue preservation, fixation time, and hydrolytic treatment on the detection of proliferating cell nuclear antigen (PCNA) by immunoperoxidase staining with three commercial anti-PCNA antibodies (19A2, 19F4, PC10). Our goal was to provide guidelines for PCNA immunohistochemistry in formalin-fixed, paraffin-embedded specimens. In proliferative cell compartments, nuclear staining was achieved with all three antibodies. In some cases PCNA was also expressed in non-proliferative, histologically normal tissues associated with tumors or other lesions elsewhere. In most autopsy specimens PNCA immunoreactivity was markedly diminished as compared with similar surgical specimens. Incubation overnight with primary antibody at 4 degrees C enhanced PCNA immunoreactivity over incubation at 42 degrees C for 45 min. Pre-treatment with 2 N HCl did not increase staining. Staining with the PC10 antibody was much better preserved than staining with the antibodies 19A2 and 19F4 after prolonged formalin fixation of surgical specimens and in tissues obtained at autopsy. With all three antibodies, however, PCNA immunoreactivity was well preserved during formalin fixation for 8-24 hr and during fixation delays for 8 hr at room temperature. This indicates that PCNA is stable under conditions routinely encountered in diagnostic surgical pathology and facilitates its potential use as a diagnostic proliferation marker.

Autoantigens

The presence of hepatocyte growth factor in the developing rat.

Hepatocyte growth factor (HGF), a heparin-binding polypeptide mitogen, stimulates DNA synthesis in adult rat and human hepatocytes and in several other cells of epithelial origin. Recently, it was determined that scatter factor (SF), a protein that has been shown to cause the dispersion and migration of epithelial cells in culture, is identical to HGF. Moreover, the receptor for HGF was identified as the product of the proto-oncogene, c-MET, a tyrosine kinase-containing transmembrane protein. c-MET expression has been reported in a variety of adult and embryonic mouse tissues. Similarly, we and others have demonstrated that HGF is expressed in various adult rat and human tissues. In the present study, the tissue distribution of HGF during rat development was determined by immunohistochemistry using an HGF-specific polyclonal antiserum. Between day 12 and day 19, immunoreactivity for HGF was present in various locations such as hematopoietic cells, somites, squamous epithelium of the esophagus and skin, periventricular germinal matrix of the brain, bronchial epithelium, renal collecting tubules and chondrocytes. After day 19, HGF immunoreactivity was also present in the pancreas, submaxillary glands and neural tissues. In addition to immunolocalizing HGF in tissue sections, bioreactive and immunoreactive HGF was extracted and purified from rat fetuses. Other studies demonstrated the presence of HGF and c-MET mRNA in total fetal rat, and in fetal and neonatal rat liver. Addition of purified HGF to fetal and neonatal rat liver cultures enriched for hepatocytes stimulated DNA synthesis up to six-fold over controls. These findings strongly suggest a pivotal role for this potent regulator of growth and development.

Animals

Oncocytic differentiation in intrahepatic biliary cystadenocarcinoma.

An intrahepatic biliary cystadenocarcinoma in a 56-yr-old white man was characterized by pronounced oncocytic differentiation. Grossly the tumor was a well-demarcated cyst filled with numerous branching papillary fronds. Most tumor cells had abundant granular, intensely eosinophilic cytoplasm on light microscopic examination and large numbers of densely packed mitochondria by electron microscopy. Mucin-secreting cells were also present. The patient returned 20 mo after resection of the primary tumor with recurrent tumor in the liver and widely disseminated disease throughout the abdominal cavity, and he died 5 mo later. Although less differentiated, the recurrent tumor again contained greatly increased numbers of mitochondria. The partial loss of oncocytic differentiation in the evolution of the present case and the benign nature of purely oncocytic tumors suggest that in the presence of mixed histologic features the potential for tumor progression is primarily determined by the lesser differentiated or nononcocytic component. To the best of our knowledge, oncocytic differentiation has not been previously described in biliary neoplasia.

Bile Duct Neoplasms

Prediction of left ventricular mass from the electrocardiogram.

Multiple stepwise regression methods were used to derive electrocardiographic (ECG) models for prediction of the echocardiographic left ventricular (LV) mass index from standard 12-lead ECG measurements using data files of 203 men and 252 women. The correlation between echocardiographic and ECG estimates of LV mass index was R2 = 0.58 for men and R2 = 0.42 for women. A separate logistic regression model was derived for classification of LV hypertrophy as a dichotomized dependent variable. This classifier chose R (aVL), T (V6), and S (V1) for men and R (aVL), T (V6), and S (I) for women and produced a moderate sensitivity (53.7% for men and 63.4% for women) and specificity (94.9% for men and 92.9% for women). We conclude that the initial performance of these and other recently developed multivariate estimators of LV mass and LV hypertrophy classifiers is promising enough to subject them to further studies to evaluate their utility as risk predictors.

Adolescent

Lipomas of the internal auditory canal.

Intracranial lipomas are rare tumors which may occur in the cerebellopontine angle (CPA) or internal auditory canal (IAC). Although seemingly innocuous in other parts of the body, lipomas within the CPA and IAC often involve the surrounding cranial nerves, making attempts at hearing conservation largely unsuccessful. In an attempt to differentiate the IAC lipoma from the more commonly found acoustic schwannoma, the preoperative imaging studies (magnetic resonance and computerized tomography) on five previously unreported cases of IAC lipomas were evaluated. Based on these studies, features were determined that may allow the surgeon to diagnose IAC lipomas preoperatively. These features will be discussed, as well as the surgical and pathological findings.

Adult

Localization of hepatocyte growth factor in human and rat tissues: an immunohistochemical study.

Hepatocyte growth factor is a protein growth factor with a strong mitogenic effect on hepatocytes. Recently, hepatocyte growth factor and hepatocyte growth factor messenger RNA have been extracted from several organs of humans, rats and rabbits. This study was undertaken to comprehensively define and compare the cellular localization of hepatocyte growth factor in human and rat tissues in detail. Paraffin-embedded sections and frozen sections were examined by immunohistochemistry using a polyclonal antiserum to hepatocyte growth factor. The distribution of hepatocyte growth factor was almost identical in humans and rats. Strong or moderate cytoplasmic immunoreactivity for hepatocyte growth factor was present in most surface epithelia, distal tubules and collecting ducts of the kidneys, large neurons, megakaryocytes, granulocytes, exocrine pancreas, salivary glands, prostate, epididymis and trophoblast. Varying degrees of immunoreactivity were observed in endothelial cells, chondrocytes and macrophages. We conclude that hepatocyte growth factor is widely distributed in numerous tissues and cell types independent of their regenerative activity. This suggests that hepatocyte growth factor may have mitogenic and/or trophic effects on multiple cell types in addition to hepatocytes.

Animals

Hepatocyte growth factor in human placenta and trophoblastic disease.

The hepatocyte growth factor (HGF) is an acidic protein with a strong mitogenic effect on hepatocytes. Hepatocyte growth factor mRNA recently was cloned from a placental cDNA library. Here we demonstrate the purification of HGF from human placenta with heparin-agarose chromatography and TSK-heparin high-pressure liquid chromatography and describe the distribution of placental HGF by immunohistochemistry using a polyclonal antibody to HGF. The yield of HGF from the placenta was approximately 100 to 200 times greater than that previously obtained from human plasma. Placental HGF was expressed strongly in the villous syncytium, extravillous trophoblast, and amnionic epithelium, and, to a lesser degree in endothelial cells and villous mesenchyme. Hepatocyte growth factor also was identified in the trophoblast of complete hydatidiform moles, choriocarcinomas, and a case of blighted ovum. The presence of HGF in an organ characterized by rapid cell proliferation during gestation and in trophoblastic tumors strongly suggests that the growth-regulating effect of HGF is not limited to hepatocytes.

Abortion, Spontaneous

Barotrauma and air embolism in hyperbaric oxygen therapy.

A 69-year-old woman underwent hyperbaric oxygen therapy because of a nonhealing ulcer of her foot. During decompression, she developed a left-sided hemiplegia and confusion. Recompression resulted in transient neurologic improvement, but she eventually became comatose. Ventricular dysrhythmias developed and she died without regaining consciousness 17 h after onset of symptoms. An autopsy revealed diffuse interstitial pulmonary fibrosis with severe paracicatricial emphysema, chronic interstitial inflammation, and chronic bronchitis with abundant intrabronchial mucus. There was extensive multifocal ischemic injury of the cerebral cortex. The hippocampi, basal ganglia, and cerebellum were spared. Scattered acute myofiber necrosis was present in the heart. Clinical presentation and autopsy findings strongly support the diagnosis of air embolism and illustrate a potential risk of hyperbaric oxygen therapy in patients with preexisting pulmonary disease.

Aged

Multicentric malignant fibrous histiocytoma of soft tissue.

We present an unusual case of multicentric malignant fibrous histiocytoma of soft tissue. Over the past 24 years, a 67-year-old woman developed malignant fibrous histiocytoma in four different soft-tissue sites. There were two local recurrences of one of the tumors. Currently, there is no evidence of visceral involvement. The evidence suggests that this patient has a predisposition of the connective tissue to develop malignant tumors of fibrohistiocytic differentiation.

Aged

Exocrine pancreatic tissue in human liver: a metaplastic process?

Numerous microscopic foci of exocrine pancreatic tissue consisting of acini and small ductules were distributed throughout the liver of a 41-year-old patient with severe posthepatitic cirrhosis. The acinar cells were characterized by abundant zymogen granules on electron microscopic examination and a strong reaction with antibodies to alpha-amylase on immunoperoxidase staining. The pancreatic tissue was associated with proliferations of bile ductules within areas of fibrosis. No relationship with hepatocytes was observed. A metaplastic origin of the pancreatic tissue from the intrahepatic biliary epithelium is suggested.

Adult

Methodology of ECG interpretation in the Dalhousie program; NOVACODE ECG classification procedures for clinical trials and population health surveys.

The Dalhousie ECG Program was designed specifically for the needs of epidemiologic studies, health surveys, and clinical trials. The program logic is dynamic in that it can accommodate any combination of ECG leads, record length and sampling rate. The NOVACODE module of the program classifies ECGs according to the Minnesota Code, supplemented with new sets of logic criteria for conduction defects, acute myocardial infarction, and serial ECG changes. Improved statistical models are incorporated for enhanced detection of myocardial infarction using the Cardiac Infarction Injury Score, and for quantification of left ventricular mass estimation. It is anticipated that these program improvements will enhance its utility particularly in monitoring progression and regression of cardiac involvement in hypertensive and ischemic heart disease, and in the assessment of the effectiveness of intervention on cardiovascular disease risk factors.

Adolescent

Electrocardiographic estimate of left ventricular mass versus radiographic cardiac size and the risk of cardiovascular disease mortality in the epidemiologic follow-up study of the First National Health and Nutrition Examination Survey.

The prognostic value of a left ventricular (LV) mass index (g/m2) estimated from an electrocardiographic model and radiographic estimates of the relative heart volume (ml/m2) and cardiothoracic ratio for predicting the risk of cardiovascular disease mortality were investigated using Cox regression analysis to adjust for age, systolic blood pressure and history of heart attack in 1,807 men (1,609 white, 198 black) and 2,143 women (1,884 white, 259 black). The study population (ages 35 to 74 years at baseline) was followed from 5 to 12 years (average 9.5 years) for cardiovascular disease mortality. LV mass index and relative heart volume were independent predictors of cardiovascular disease mortality among white men. All 3 cardiac size estimates were independent predictors for cardiovascular disease mortality among white and black women. When LV mass index was used as a dichotomized variable to indicate the presence or absence of LV hypertrophy, the age-adjusted relative risk of cardiovascular disease mortality was 2.48 (95% confidence interval 1.77 to 3.46) for white men, 3.03 (1.49 to 6.16) for black men, 1.86 (1.21 to 2.87) for white women and 2.05 (0.83 to 5.05) for black women. The corresponding prevalence of LV hypertrophy was 15.4% for white men, 36.6% for black men, 20.1% for white women and 17.4% for black women. It is concluded that the electrocardiographic estimate of LV mass index can identify a substantially larger fraction of persons at increased risk for cardiovascular mortality than conventional electrocardiographic criteria for LV hypertrophy and that LV mass index estimated by electrocardiogram is a valuable supplement to radiographic cardiac size estimates in epidemiologic applications.

Adult

The emerging prominence of computer electrocardiography in large population-based surveys.

The year 1987 marks the centennial of electrocardiography. As Beamish reminds us, it was the first and foremost technical aid to the cardiologist. During the history of cardiovascular epidemiology, which dates back roughly forty years, electrocardiography has played a central role as a relatively specific marker for coronary and hypertensive heart disease. The lack of sensitivity of electrocardiography and the advent of new technologies such as ultrasonography for assessment of such heart disease in cardiology and cardiovascular epidemiology has raised questions as to whether electrocardiography might be replaced in the next century. Recent developments in computer electrocardiography have rendered suggestions of the decreased importance of electrocardiography premature. Use of computer analysis of electrocardiograms in epidemiologic studies, which dates back less than three decades, has renewed interest in and expanded the role of electrocardiography in cardiology in general and cardiovascular epidemiology in particular. The computer analysis of electrocardiograms has allowed the processing and analysis of large numbers of electrocardiograms in a rapid, efficient, systematic and consistent manner. This has led to new, more sensitive criteria for detection of left ventricular hypertrophy as a discrete variable. In addition, the numerous waveform amplitude and duration measurements by computer have allowed the development of mathematical models to express the likelihood of coronary heart disease (myocardial infarction) and degree of left ventricular hypertrophy (estimates of left ventricular mass) on continuous scales. These developments have contributed substantially to the potential of electrocardiography (and particularly computer electrocardiography) in future studies and clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly