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Biomedical subjects

H Popper

Publications and source records attributed to H Popper.

At least 55 records · Page 3Linked to original sources

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

Histologic patterns of liver disease in hemophiliacs, with special reference to morphologic characteristics of non-A, non-B hepatitis.

In a retrospective study 157 liver specimens from hemophiliac patients (105 percutaneous needle and 12 wedge biopsies, 40 autopsy specimens) were read blindly and independently by four pathologists on the basis of a computer codable questionnaire asking for evaluation of individual histologic features, classification of the liver disease, and speculation on etiology. The majority of cases had histologic evidence of mild chronic viral hepatitis; 7.6% of all cases were classified as CAH, and an additional 7.6% as CPH by all four interpreters. A large number (40.8%) were on the borderline of CAH and CPH or CLH. These were classified as "possible CAH" because of a diagnosis of CAH by one to three of the pathologists. Although there was therefore some interobserver variability in the diagnostic labels applied to these cases, all four pathologists were strikingly similar in their identification of individual histologic features. Furthermore, on blind rereadings, each pathologist made the same diagnosis in more than 90% of readings. In this retrospective study, serologic data were not available in many cases. Thus, etiologic considerations were based purely on speculation from the histologic appearance. One case was identified as "definite" and 28 of 157 (18%) as "possible" HBV infection. Based on the assumption that some of the individual histologic criteria indeed might be in favor of NANB hepatitis, 21 cases (13%) were considered "definite" NANB, and "possible" NANB was suspected in 107 additional cases (68%). The addition of these figures makes clear that within the limitations of histologic assessment, double infections appear to be frequent in this setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle

Hepatitis B virus produced by transfected Hep G2 cells causes hepatitis in chimpanzees.

We have reported that clonal cells derived from Hep G2 cells transfected with a plasmid containing hepatitis B virus (HBV) DNA secrete spherical and filamentous forms of hepatitis B surface antigen (HBsAg), core particles, and virions into the culture medium. Here we describe the development of typical hepatitis in two chimpanzees following intravenous inoculation with the medium in which the transfected cells had grown. The liver biopsies from these animals showed characteristic lesions in parenchyma and portal tracts, more conspicuous at an earlier time in the chimpanzee that had received a greater number of virions. The amount of HBsAg in the serum of one infected chimpanzee increased with time after the initial inoculation and then decreased concomitantly with the appearance of antibodies against HBsAg and core antigens. HBsAg remained detectable in the other animal throughout the course of the experiment. The levels of hepatitis B "e" antigen in both animals peaked at week 5, signifying the acute phase of the infection. The activities of serum enzymes that are markers for necroinflammation also increased. The hepatitis HBsAg subtype of the virions isolated from the patient whose DNA was cloned and then used for transfection of the Hep G2 cells was the same as that found in the chimpanzees. Furthermore, the restriction enzyme analysis of the viral DNA isolated from the chimpanzees was identical to the cloned DNA. Thus, HBV DNA-transfected Hep G2 cells can support the replication of virions that, in turn, produce hepatitis in chimpanzees.

Animals

Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice.

Overproduction of the hepatitis B virus (HBV) large envelope polypeptide by transgenic mice containing the entire HBV envelope coding region leads to the formation of extremely long (up to 800 nm), occasionally branching, filamentous 22-nm-diameter hepatitis B surface antigen particles that accumulate within the endoplasmic reticulum of the hepatocyte and are not efficiently secreted. As the endoplasmic reticulum expands to accommodate the increasing cellular filament stores, the hepatocytes become enlarged, hydropic, and eosinophilic and also display the characteristic features of "ground-glass" cells. As filament storage progresses, the ground-glass cells undergo coagulative necrosis and the mice develop an age-dependent lesion, whose severity is related to the intracellular concentration of envelope polypeptide, that is characterized by focal hepatocellular degeneration and necrosis, lobular macrophagic inflammation, and increased serum transaminase activity. Advanced lesions demonstrate hepatocellular hyperplasia evident as lobular architectural disarray and microscopic hepatocellular nodules, many of which no longer contain detectable HBV envelope antigens. These changes may become extreme, producing a massively enlarged liver due to multifocal nodular regenerative hyperplasia. Overproduction of the large HBV envelope polypeptide exerts major structural constraints on HBV particle formation, leading to reduced secretion and progressive intracellular accumulation of hepatitis B surface antigen, which can reach sufficiently high concentrations to be directly cytotoxic to hepatocytes in this transgenic mouse system.

Animals

Hepatocarcinogenicity of the woodchuck hepatitis virus.

During investigations of the evolution of experimental laboratory infections of woodchucks (Marmota monax) with the woodchuck hepatitis virus (WHV), eight hepatocellular carcinomas (HCC) were observed, six in newborns and two in young adult animals, all within 17-36 months after infection. The absence of an external cocarcinogenic effect in the well-monitored woodchucks indicates the carcinogenicity of WHV and suggests the same for the genetically and biologically similar human hepatitis B virus (HBV). Laboratory infections of woodchucks with two strains of WHV, not reported here in detail, resembled human and chimpanzee HBV infections histologically and serologically. In these studies, eight woodchucks became carriers of surface antigen of WHV for greater than 1 year. All eight woodchucks developed HCC, indicating a 100% risk of HCC in experimentally infected chronic WHV antigen carriers, which is analogous to the high risk of HCC in human hepatitis B surface antigen carriers. Histologically, the absence of cirrhosis in the examined pericarcinomatous tissue permits recognition of gradual transition from normal parenchyma to neoplastic nodules to HCC of rising anaplasia, indicating a continuum of increasingly more malignant neoplastic stages, as known for chemical carcinogenesis. The HCC developed in carrier woodchucks infected as newborns with only minor, if any, hepatitic changes but is associated with antigen-carrying hepatocytes and sometimes with hyperplastic nodules. This stage was preceded in infected adults by an early, acute, weeks-long hepatitis coinciding with the appearance of surface antigen. These findings are also analogous to typical HBV infection in human newborns and young adults, respectively. At the time of HCC development in all animals with adequate histologic material, an acute recent necroinflammation appeared around the tumor, associated with abnormal hematopoietic cells around and within the tumor. A promoting role in carcinogenesis of this necroinflammation of yet unestablished pathogenesis is being postulated, to be confirmed by determination of the status of the WHV DNA in the HCC and by prospective histologic study of the inflammatory reaction.

Animals

Titration of the infectivity of hepatitis D virus in chimpanzees.

The infectivity of hepatitis D virus (HDV) was evaluated by intravenous inoculation of chimpanzees. HDV was present in the inoculum at a titer of 10(11) chimpanzee infectious doses (CID). In contrast, the titer of hepatitis B virus (HBV) in the same inoculum was 10(6) CID. All HBV-infected chimpanzees inoculated with less than or equal to 10(-11) dilutions of the HDV-positive plasma were superinfected; an animal receiving a 10(-12) dilution did not develop markers of HDV replication in serum or liver. All HDV-infected chimpanzees had marked elevations of serum alanine aminotransferase activities. The incubation period from exposure to development of hepatitis was inversely related to the dose of HDV inoculum, although the severity and duration of hepatitis were independent of it. All animals recovered and rapidly developed antibody to hepatitis D antigen.

Alanine Transaminase

Detection of hepatitis A virus by extraction of viral RNA and molecular hybridization.

Hepatitis A virus (HAV) RNA was extracted from cell culture, serum, liver, and feces and then detected by molecular hybridization with cloned HAV cDNA. Hybridization was approximately 10-fold more sensitive than immune electron microscopy or radioimmunoassay was and less sensitive than was assays of HAV infectivity in primates or in cell culture. As little as 10(3) 50% infective doses of HAV, or approximately 0.1 pg of viral RNA, was detected by this method. Analysis of fecal specimens from an experimentally infected marmoset and an epidemic of hepatitis A showed that HAV excretion could often be detected later in the illness by hybridization than by radioimmunoassay. This technique should be widely applicable for detection and analysis of HAV RNA.

Animals

Immunohistochemical and histochemical markers of primary lung cancer, lung metastases, and pleural mesotheliomas.

Sections of primary lung carcinomas, lung metastases, mesotheliomas, and lung metastases of some rare mesenchymal tumors were incubated with different cytokeratin (CK), vimentin, desmin, and tissue polypeptide antigen (TPA) antibodies and with antibodies reactive with different hormones (ACTH, PTH, alpha-HCG, Calcitonin CT), CEA, carcinoma-associated antigen (CA1), secretory component (SC), neuron-specific enolase (NSE), alpha-1-antitrypsin (alpha-1-AT), lysozyme (lyso), and S-100 protein (S 100). CK antibodies derived from a 49 kD (reactive with simple epithelia [SE]) and a 67 kD CK polypeptide fraction (reaction with complex epithelia [CE] were useful differentiation markers for the four major groups of lung carcinomas. In one half of small cell carcinomas a positive reaction with NSE antibodies was found. S 100 and SC were good markers for papillary and bronchioloalveolar adenocarcinomas, whereas CEA was less important because of its reactivity with different types of lung carcinomas. To discern clear cell carcinomas of lung and renal origin a positive reaction with vimentin antibodies (some renal but not lung types) and with CA1 (no renal but all lung types) seemed to be useful. All hormone antibodies were of no importance as markers for difficult differential diagnosis, because positive reactivities were found in cases from every major carcinoma group. In addition, a Ca2+-activated adenosine triphosphatase (ATPase) was found in mesotheliomas but not in papillary adenocarcinomas.

Adenocarcinoma

The gastric juice aspiration syndrome (Mendelson syndrome). Aspects of pathogenesis and treatment in the pig.

The gastric juice aspiration syndrome (GJA-S, Mendelson syndrome) was studied experimentally in pigs. Following instillation of gastric juice into the right main bronchus necrosis of pneumocytes and bronchiolar epithelium occurred with activation of complement and a prostaglandin E releasing system (possibly the kinin system). Cell necrosis was followed by loss of surfactant and formation of hyaline membranes, rich in immunoglobulin M. The alveolar damage organized, resulting in intraalveolar and interstitial fibrosis. The causative agents were found to be both gastric hydrochloric acid and pepsin. Pretreatment with H2-, or acetylcholine-receptor-antagonists (cimetidine or pirenzepin) as well as buffering of the gastric juice to a neutral pH did not prevent lung fibrosis. If a mixture of aluminium hydroxide, magnesium carbonate and oxethazaine was added to the aspirate, development of lung fibrosis was prevented, but severe granulomatous reaction with foreign body giant cells within both lungs evolved. Kallikrein inhibitor, when administered intravenously not later than 3 min after artificial aspiration, protected the left lung completely and large areas of the right. If infused within 60-90 s complete protection of the left lung and the right upper lobe was achieved. In the majority of the animals a mild focal fibrosis developed in the right lower lobe; in one experiment both lungs were devoid of fibrotic areas. If Kallikrein inhibitor was infused 5 min prior to aspiration, lung fibrosis was not prevented.

Anesthesia, General

Experimental eosinophilia and inflammation--the effect of various inflammatory mediators and chemoattractants.

An experimental subcutaneous inflammation was produced in guinea pigs with peripheral blood eosinophilia. The eosinophilia resulted from two subsequent infections with Trichinella spiralis larvae. One group of guinea pigs served as non-infected control. Inflammation was induced by carrageenan, bradykinin, histamine, platelet activating factor and eosinophilotactic factors of lymphocytic or neutrophilic origin. Whereas in the control group no eosinophil granulocytic response was observed, this response was seen in the group with peripheral blood eosinophilia. The inflammatory substances and mediators (carrageenan, bradykinin, histamine, platelet activating factor) did not attract eosinophils alone, but also neutrophils. Under peripheral blood eosinophilia within the time course of the inflammatory reaction a second emigration with a shifted neutrophil/eosinophil ratio in favour of eosinophils was found. This could be due to a generation of chemoattractants by the injected substances themselves or more probably, by already emigrated granulocytes. Neither histamine, bradykinin, carrageenan, nor the eosinophilotactic factors (ECF's) in the concentrations used did release the cytotoxic major basic protein from eosinophils. Platelet activating factor exhibited a release of major basic protein from some eosinophils but no release of the peroxidase under our experimental conditions. The immigration of sufficient numbers of eosinophils into inflammatory areas might be one cause of the reduction of the inflammatory edema found in a previous investigation under similar conditions.

Acid Phosphatase

Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.

Although persistent infection with hepatitis B virus and woodchuck hepatitis virus has been associated with development of hepatocellular carcinoma in the host, little has been known of such an association with ground squirrel hepatitis virus (GSHV), which is closely related to the woodchuck virus. Colonies of GSHV-infected and -uninfected Beechey ground squirrels were observed for tumors for a period of 5 years. Tumors developed in seven squirrels after a minimum of 2.4 years of observation per animal; each of the seven animals was over 4 years old when the tumor was detected. The predominant type of tumor was hepatocellular carcinoma, which appeared in 2 of 28 GSHV-bearing animals studied and in 1 of 23 squirrels with antibody to the virus. No hepatocellular carcinoma appeared in 24 GSHV marker-free squirrels. Integrated GSHV DNA was found in the hepatocellular carcinoma tissue of the one carrier animal examined, paralleling the frequent findings of integrated hepatitis B and woodchuck hepatitis viral DNA in human and woodchuck hepatocellular carcinoma. Although the incidence of liver carcinoma reported here in carrier ground squirrels is neither as great as that in carrier woodchucks nor statistically different from the incidence in noncarrier squirrels, the data presented suggest that persistent infection with GSHV may also be associated with hepatocellular carcinoma.

Animals

Protection of chimpanzees from type B hepatitis by immunization with woodchuck hepatitis virus surface antigen.

Two chimpanzees immunized with woodchuck hepatitis virus (WHV) surface antigen (WHsAg) developed antibodies cross-reactive with hepatitis B virus (HBV) surface antigen (HBsAg). After challenge with HBV, one animal was completely protected and the other experienced a subclinical infection, without evidence of liver disease. Three woodchucks immunized with HBsAg developed antibodies to HBsAg which did not cross-react with WHsAg. After challenge with WHV, all three woodchucks developed typical acute infections with associated hepatic lesions. Serological studies with the cross-reactive antibodies raised in chimpanzees suggested that the protective epitopes of WHsAg were related to the group a specificity of HBsAg. These studies indicated that cross-protective epitopes are shared by HBV and WHV; however, the humoral response to these epitopes can vary among species.

Animals

[Perioperative adjuvant chemotherapy with bleomycin in bronchogenic squamous cell cancer. A prospective randomized study].

Bleomycin (BLM) was given perioperatively and 3 and 6 months postoperatively in a dosage of 150 mg per course (total: 450 mg) to 37 patients with surgically resectable squamous-cell lung cancer. 37 randomized control patients with resectable squamous-cell lung cancer were compared to the chemotherapy-group. 5-year overall survival of the BLM group was 46.3%, that of the controls 40.5% (Mantel-Haenszel test; p greater than 0.05). BLM-treated stage I showed a 5-year survival of 47.9% (controls: 55%), BLM stage II 50% (controls: 33.3%), BLM stage III 40% (controls: 21.4%). The difference is not statistically significant. No severe adverse effects of therapy on either wound healing, or perioperative mortality of lung function were observed.

Bleomycin