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Biomedical subjects

H Popper

Publications and source records attributed to H Popper.

At least 37 records · Page 2Linked to original sources

Aetiological association of a virus-like particle with enterically transmitted non-A, non-B hepatitis.

Virus-like particles, approximately 27 nm in diameter, were identified in faeces from an Indian patient with enterically transmitted non-A, non-B (ENANB) hepatitis. They were serologically distinct from hepatitis A virus (HAV). Nucleic acid extracted from the particles did not hybridize with cDNA probes representing the genomes of HAV, enteroviruses, and cardioviruses. Chimpanzees were experimentally inoculated with faecal suspensions containing this 27 nm particle or with faeces from another case of ENANB hepatitis. Mild histological and biochemical hepatitis developed in these animals and there was serological evidence of infection with the virus-like particle as shown by immunoelectronmicroscopy (IEM). Serological analysis by IEM suggested that this agent or an antigenically similar virus was the aetiological agent of two epidemics and a sporadic case of ENANB hepatitis in India and of an epidemic of the illness in the USSR. Antibody to the particle was found in sera from patients with ENANB hepatitis from various geographic areas over a 30-year period.

Animals

Viral versus chemical hepatocarcinogenesis.

Almost all experimental studies on hepatocarcinogenesis have been performed on models induced by chemicals. The human hepatocellular carcinoma (HCC), a highly malignant tumor, particularly frequent in the Far East and in Africa, is overwhelmingly associated with hepatitis B virus (HBV) infections and only very rarely is it caused by chemicals. This raises the question as to what degree observations on the preferentially studied chemical carcinogenesis apply to human HCC. This question is timely, since a woodchuck model has been developed in which laboratory infection with a hepadna virus, biologically and genomically similar to HBV, regularly produces HCC in prolonged surface antigen carrier woodchucks. Permanent surface antigen carriage by itself may also be a risk factor. A comparison, based on available observations of chemical and hepadna viral carcinogenesis, was attempted on four aspects: (1) histologic features, (2) growth patterns, (3) growth factors, and (4) molecular biological observations. At this time, only few conclusions can be drawn, mainly on a morphological and molecular biological basis. In the initial stage, chemicals cause mutations of very few bases, while in hepadna viral infections long sequences are inserted into both strands of chromosomal DNA. Additional studies appear to be indicated, to the greatest degree with existing methods and primarily on hepadna viral carcinogenesis. A key question is whether the active necroinflammation, preceding or observed at the time the HCC is recognized, in woodchuck and also in human chronic HBV infections is a promoting event or a secondary reaction. Additional therapeutic strategies, specific for hepadna viral carcinogenesis, can be considered, particularly elimination of hepatocytes carrying integrated viral sequences and prevention or suppression of the promoting necroinflammation. Success in HCC may be applicable to cancers related to papilloma virus in other organs, for instance, the female genital tract.

Aflatoxins

Solitary coin lesion in patients with malignant melanoma: an indication for thoracotomy?

In five patients solitary pulmonary lesions were detected radiographically during routine follow up after malignant melanoma. Surgical removal was done in each case under the tentative diagnosis of metastases. Histologically, two lesions turned out as benign chondroma, one as organized pulmonary infarction and one as bronchogenic carcinoma. Only in one patient was a melanoma metastasis present. The findings underline the usefulness also in malignant melanoma of a surgical approach in suspected solitary pulmonary metastases.

Adult

Studies of prototype live hepatitis A virus vaccines in primate models.

We have prepared two prototype live hepatitis A virus (HAV) vaccines by serial passage of the HM-175 strain of HAV in African green monkey kidney cells. Passage 21 (P-21) HM-175 virus shows evidence of attenuation for chimpanzees but not for marmosets; passage 32 (P-32) HM-175 virus shows evidence of attenuation for both species. Animals that received P-32 HAV had fewer elevations in levels of liver enzyme activity and evidence of less virus replication in the liver and excretion of virus in stool than did those that received wild-type virus. The P-21 and P-32 viruses were highly immunogenic in both species. The information provided by this study will aid in the development of a live HAV vaccine.

Alanine Transaminase

Chronic hepatitis D virus (HDV) infection in hepatitis B virus carrier chimpanzees experimentally superinfected with HDV.

Chimpanzees that were chronic hepatitis B virus carriers and that were superinfected with hepatitis D virus (HDV) apparently developed acute, self-limited type D hepatitis. Reevaluation with a sensitive hybridization-based assay using RNA probes specific for the HDV genome, however, demonstrated that greater than 50% of these animals still had detectable signs of ongoing HDV replication an average of 2.4 y (range, 1-6.4 y) after inoculation. The only positive marker for the presence of HDV was serum HDV RNA; HDV antigen was undetectable in both serum and the liver by an immunoblot assay and immunofluorescence, respectively. Because the detected amount of viral genome was very low, the previous failure to identify the chronic HDV carrier state in the chimpanzee can be attributed to the lower sensitivity of previously described assays.

Animals

The diagnostic significance of periportal hepatic necrosis and inflammation.

In this review the several types of cell damage and cell death which may be found in liver biopsy specimens are defined. We describe the different processes which occur at the portal/parenchymal or septal/parenchymal interface, viz. periportal spillover, periportal hepatitis, classic or lymphocytic piecemeal necrosis and biliary piecemeal necrosis. The diagnostic implications of these lesions in relation to the clinicopathological diagnosis and prognosis in various liver diseases are discussed.

Diagnosis, Differential

Pulmonary exchange of solutes during experimental lung lavage in pigs.

Unilateral continuous lung lavage in a nonregenerating system (3,000 ml isotonic cristalloid) was done in 12 pigs for 270 min. The concentration of substances in serum and fluid was measured. Half-time (t1/2) of exchange and permeability constants (P) were determined. In the fluid Na+ decreased significantly (t1/2 = 107 min, P = 7.8 x 10(-7]. Urea increased significantly, reaching serum level after 270 min (t1/2 = 109.1 min, P = 6.18 x 10(-6]. Ca2+ (t1/2 = 36.7 min, P = 4.1 x 10(-7] PO4 = (t1/2 = 173.3 min, P = 1.1 x 10(-7], and creatinine (t1/2 = 55.2 min, P = 6.2 x 10(-7] also increased markedly but did not reach serum level. The adjustment to serum concentration may be prevented by interaction between diffusion, active transport or Donnan's equilibria. K+ increased almost linearly, documented by the long half-time (t1/2 = 7,835.2 min, P = 7.7 x 10(-7] and did not reach serum level. The calculated limit value was higher than the serum level. Active transport systems or influx of K+ from cellular compartments rather than from the serum might be involved in its linear kinetics. Total protein (t1/2 = 61.5 min, P = 2.06 x 10(-9] and albumin (t1/2 = 58.8 min, P = 1.7 x 10(-9] increased initially but levelled far below the serum value. The low P indicates a lack of significant permeation. Initial increase may be due to washout of the epithelial lining fluid compartment. There was minimal transfer of lavage fluid into the organism (10-20 ml/30 min). Serum concentrations were not affected by the lavage.

Animals

Evolution of hepatocellular carcinoma associated with chronic hepatitis B virus infection in Alaskan Eskimos.

Hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection in Yupik Eskimos in southwestern Alaska, detected in early stages as a result of screening, appears to be more frequently associated with variants of chronic portal inflammation in the noninvolved liver than with fully developed cirrhosis, otherwise common in HBV-associated HCC from other geographic areas. Of 38 patients diagnosed with HCC since 1969, adequate tissue was available from both the tumor and nontumorous liver in 17. Of the 17 specimens, 14 had chronic portal inflammation and three had advanced cirrhosis; 12 of the 14 were from hepatitis B surface antigen carriers. These 12 cases were studied in detail to examine the features accompanying the development of HCC unobscured by cirrhotic transformation. In the noninvolved parenchyma they included hepatocytic nodules as apparent precursors to HCC and, as markers of phenotypic alterations, dysplastic hepatocytes and hepatitis B surface antigen-laden ground-glass hepatocytes. The latter were observed in eight instances and often accumulated in nodules. Parenchyma within 1 mm of the HCC exhibited increased confluent hyperplasia and frequently conspicuous necroinflammation associated with pericellular and periductular fibrosis, which contributed, in addition to fibrous connections between displaced and heavily inflamed portal tracts, to the capsule that was forming in all cases to varying degrees in the pericarcinomatous region. The HCC was uniformly trabecular and in a few specimens, a continuous transition from hyperplasia and dysplasia near the periphery of the tumor to increasing anaplasia in the center could be made out in addition to pressure effects of the HCC. The pericarcinomatous changes, including hyperplasia progressing to neoplasia and necroinflammation, are also observed in experimental models, particularly the woodchuck HCC induced by a hepadna virus related to HBV. Coordinated morphologic and molecular biologic studies on such animal models and on human HCC detected by screening, as for instance in Eskimos, neither complicated by cirrhosis, should elucidate the direction of the evolution of the HCC and the postulated promoting role of the inflammation.

Adolescent

Relation between hepatocellular carcinoma and persistent hepatitis B infection.

Epidemiologic studies indicate a close association between hepatocellular carcinoma (HCC) and chronic hepatitis B virus (HBV) infection. HCC, a most frequent malignancy, is far more common in the Far East and Africa than in the West and may be the first to be greatly eliminated because of prevention of HBV infection by vaccination. The conceptual integration of epidemiologic observations, morphologic studies of the human precursor stages and investigations of animal infections by hepadna viruses with biologic and genomic similarity to HBV as well as with clinical and molecular biologic studies contribute to the understanding of the hepatocarcinogensis. In the woodchuck model after laboratory infection, HCC develops regularly without external cocarcinogen in permanent surface antigen carriers. The hypothesis is presented that an episodic necroinflammation in the carrier stage may act as an endogenous cocarcinogen or promoter in that previous integration of hepadna viral DNA in the host chromosone may become disorganized, which induces the clonal development of HCC. This hypothesis may become important in the management of the carrier stage.

Carcinoma, Hepatocellular

[Pulmonary involvement in tuberous sclerosis].

The authors present a case of tuberous sclerosis with marked pulmonary involvement, confirmed by both radiological and pathological studies. The radiological manifestations and basic pathology of this rare condition are reviewed with emphasis on differential diagnosis.

Adult

Non-A, non-B hepatitis-related hepatocellular carcinoma in a chimpanzee.

Epidemiology has indicated the possible association of non-A, non-B hepatitis (NANBH) with hepatocellular carcinoma (HCC) in man, but there are no means for confirmation. Chimpanzees are recognized models for studying hepatitis B and NANBH, and may become carriers of both. The first case of HCC to be reported in chimpanzees was found after longitudinal study of a hepatitis B-free chimpanzee 7 years after inoculation with human plasma from a patient reported to have chronic NANBH.

Animals

[Value and indications for bronchoalveolar lavage combined with transbronchial lung biopsy].

Bronchioloalveolar lavage (BAL) enables diffuse interstitial lung disease to be divided into lymphocytic and granulocytic alveolitis. The combination of BAL and transbronchial lung biopsies using modern flexible fiberoptic bronchoscopes allows the subdivision of lymphocytic alveolitis into sarcoidosis, exogenic allergic alveolitis (synonym: hypersensitivity pneumonitis: EAA) and granulomatous pneumonias caused by infectious agents. The use of immunohistochemical surface markers of lymphocytes in conjunction with BAL provides further differentiation of lymphocytes into T- and B-, T-helper and T-suppressor types, natural killer cells (NK cells) and cytotoxic T-cells. A predominance of T-suppressor lymphocytes is an indication of EAA, whereas a predominance of T-helper lymphocytes is positively correlated with sarcoidosis. Other markers, e.g. HLA-DR, when expressed on the surface of alveolar macrophages, merely indicate activation unrelated to a specific type of lymphocytic alveolitis. BAL is also a new and promising diagnostic tool for pneumoconioses and other types of lung disease caused by inhaled industrial pollutants. Ferruginous bodies and silica crystals, free or ingested by alveolar macrophages, can be found more easily than by scraping tissue blocks or from multiple sections of transbronchial biopsies. BAL cells can easily be processed for electron microscopy and inhaled foreign material can be analysed in an electron microscope using X-ray diffraction analysis (EDAX) or electron spectroscopic imaging (ESI). BAL is also of value in the diagnosis of peripheral lung carcinomas, in addition to cytological sputum analysis, brush smears, transthoracic fine needle aspiration and transbronchial biopsies. BAL is a valuable diagnostic tool in cases of unusual pneumonia where fungi can be visualized by silver impregnation techniques and viruses by antibodies using immunofluorescence microscopy.

Alveolitis, Extrinsic Allergic

Primary liver cancer in Alaskan natives. 1980-1985.

The authors reviewed the cases of 19 Alaskan Natives (15 men, four women) with primary hepatocellular carcinoma (HCC) diagnosed during 1980-1985. Of these 19 patients, 16 were seropositive for hepatitis B surface antigen (HBsAg). Alpha-fetoprotein (AFP) was elevated in 15 patients (all were HBsAg positive). The patients ranged in age from 8 to 80 years old. Of the 19 patients, 16 were Eskimo, 13 of whom were Yupik. The annual age-adjusted (world standard) incidence of HCC for all Alaskan Natives was 9.3/100,000 for men and 2.2/100,000 for women. The tumor was resected in seven patients; six showed no recurrence of cancer 1 to 4 years after surgery. Histologic evaluation in 18 patients revealed trabecular type of HCC in 15 and acinar HCC in two others. In 16 specimens in which nontumorous liver could be studied, only six had evidence of cirrhosis; ten others showed variants of chronic persistent hepatitis.

Alaska

Giant fibroma of the lung. A morphological study.

The authors report the case of a 78-year-old male patient with an inoperable giant lung tumour diagnosed 5 years prior to death. Fine needle cytological examination at that time was interpreted as indicative of malignancy. In the following years the tumour grew very slowly without signs of infiltration or metastatic spread. On radiological examination sharp limitation of the tumour was evident. Recurrent pleural effusions occurred and the patient died from cardiorespiratory insufficiency. Autopsy revealed a giant fibroma, well vascularized but without signs of malignancy. The diagnosis was confirmed by immunohistochemical and electron microscopic examinations.

Aged

Bilateral intralobar pulmonary sequestration: therapeutic implications.

Bilateral intralobar pulmonary sequestration within the lower lobes was suggested by computed tomography and confirmed by arteriography in a 27-year-old woman. Although one side was asymptomatic, both sequestrated areas were resected using staged bilateral thoracotomies. Histopathological examination showed massive inflammation in the symptomatic as well as the asymptomatic sequestrum. To our knowledge, this is the sixth reported case of bilateral intralobar pulmonary sequestration and the third for which bilateral resection has been performed.

Adult

Malignant fibrous histiocytoma of the lung: prognosis and therapy of a rare disease. Report of two cases and review of the literature.

On the basis of 2 own patients and 18 cases reported in the literature, clinicopathological features of primary malignant fibrous histiocytoma of the lung are reviewed. Of the 20 patients (age-range: 14-75 yrs; 13 male, 7 female), 14 underwent resection. Recurrences were noted in 7 of them. 8 patients were free of disease at least 8 months postoperatively, one having undergone successful pulmonary metastasectomy. Postresection disease-free survival ranged from 8 months to 10 years. Adjuvant chemotherapy or irradiation (3/14) did not influence postoperative outcome. After chemotherapy, irradiation or conservative measures alone (6/20) survival did not exceed 12 months; remissions were not reported. The course was fatal within 12 months in 9/20 cases due to distant metastasis or local growth. 1 patient died of tumour-associated hypoglycemia. Age, sex, localization of the tumor and histologic subtype did not influence prognosis. Small tumors, asymtomatic at time of detection probably carry a better prognosis than larger ones.

Aged