Hepatocyte proliferation and cell cycle phase fractions in chronic viral hepatitis C by image analysis method.

OBJECTIVE: Chronic hepatitis is characterized by necrosis of liver cells, accompanied by an inflammatory reaction and compensatory cell proliferation. The interaction of the core and non-structural proteins of hepatitis C virus (HCV) with several cellular factors suggests that cell proliferation may be influenced by HCV. The aim of this study was to investigate hepatocyte proliferation and DNA ploidy patterns in patients with chronic viral hepatitis C (CH-C) compared with chronic non-viral hepatitis (CH-N), using a TV image analysis method. METHODS: The DNA index (DI) and cell phase fractions (G1, S, G2) were measured by means of digital picture analysis method on nuclear suspensions of Feulgen stained hepatocytes. Cells were taken from the liver biopsy specimens of 71 patients with CH-C and 24 patients with CH-N. Twenty-six normal liver samples were used as controls. RESULTS: Significantly higher G1 (94 +/- 4) and lower S (3.56 +/- 3.16) phase fractions were measured in CH-C compared with CH-N (G1, 90 +/- 6; S, 6.4 +/- 5.99). The DI of moderate (1.12 +/- 0.05) and severe (1.12 +/- 0.05) CH-C showed near-aneuploid DNA content, while diploidy (DI < 1.10) was detected in cases of CH-N. CONCLUSION: The higher G1 and lower S cell cycle phase fractions in CH-C reflect decreased hepatocyte proliferation compared with CH-N. The near-aneuploid DNA content of the HCV-infected liver samples may be a sign of increased genetic instability, which may contribute to the carcinogenic potential of HCV.

Multifocal ocular histoplasmosis in a dog and cat.

In two cases of naturally occurring disseminated histoplasmosis, multifocal inflammatory lesions were seen in the posterior segment of the eyes. Histologic examination of both animals revealed lesions of active choroiditis (cat) and retinitis (dog) in association with numerous Histoplasma capsulatum.

Membrana nictitans gland cyst in a dog.

A cyst involving the gland of the 3rd eyelid was removed from an 8-year-old dog. Clinically the circumscribed mass resembled a pigmented neoplasm. Histologically the cyst was multiloculated, with homogeneous eosinophilic periodic acid-Schiff-positive content. Melanin pigment was present in epithelial cells and cystic lumens. Protective functions of the 3rd eyelid were retained following excisional biopsy.

[Treatment of methimazole-induced agranulocytosis with granulocyte-macrophage colony stimulating factor]. / Metothyrin indukált agranulocytosis kezelése granulocyta-macrophag colonia stimuláló faktorral.

The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin.

[Two cases of Richter's syndrome]. / Richter syndroma két esete.

Two cases of Richter's syndrome were observed by the authors between April and August 1987. The patients were treated previously because of chronic lymphoid leukemia. The histological findings indicated in both cases immunoblast transformation of CLL. The patients were non-respondent to intensive chemotherapy and died within a short time.

[Hepatocyte proliferation and DNA content in chronic hepatitis C]. / Hepatocyta-proliferáció és DNS-tartalom krónikus C-hepatitisben.

Apart from inflammatory reaction, the death of hepatocytes is also a characteristic of chronic hepatitis. Necroinflammation is followed by compensatory proliferation, which plays a rather important role in maintaining the liver function. Authors studied the DNA content of hepatocytes in patients with chronic hepatitis C, and determined the ratio of hepatocytes in phases G1, S and G2 to determine the hepatocyte proliferation and regeneration capacity of the liver. Liver biopsy samples were taken from 23 patients with chronic hepatitis C and from 16 with chronic hepatitis with non viral origin, from which nuclear suspension counts were done based on the histological slides. A total of 16 normal liver tissue samples served as control. The DNA index, G1, S, G2 and polyploid fraction were determined using the DNACE (Digital Image Analyzer for Nuclear Deoxyribonucleic Acid Content Estimation, KFKI/NIO, Hungary) digital imaging process. The DNA index was found to be significantly higher in the chronic hepatitis C than in the non-C group, with the verification of aneuploidy (DI > 1.10). The chronic non-C hepatitis cases showed lower G1 (88 +/- 6) and higher S (7.8 +/- 6.6) fractions. In comparison to the normal liver tissues, the chronic hepatitis C cases also revealed a significantly (p < 0.05) lower G1 (91 +/- 5) and a higher S (5.4 +/- 3.6) fraction, though staying behind the values found for the non-viral group. The deviation can be explained by the presentation of the HCV proliferation inhibitory effect. The polyploid cell fraction revealed a significantly higher value in the chronic non-viral cases as compared to the C virus group, reflecting on the decreased regeneration capacity of the liver. When comparing the HCV groups, significant differences were found between the mild and moderate cases in respect to the G1 and G2 fractions. At the same time, the moderate and severe cases showed statistical deviation regarding the DNA index. Chronic hepatitis C virus infection reduces the proliferation of hepatocytes and the regeneration capacity of the liver. The aneuploid DNA index reflects on genetic instability, which could be the basis of the malignant transformation of the cells.

[Treatment of carcinoid tumor with a long-acting somatostatin analog]. / Carcinoid tumor kezelése hosszú hatású somatostatin analóggal.

A case of carcinoid tumour of the small intestine has been reported, which caused hormone producing multiple hepatic metastases. The 45 year old man had flush syndrome several times a day, that was caused by a carcinoid tumour originated from the jejunum. After the operation of the primary tumour he was treated by Sandostatin (Sandoz, Basel), which significantly reduced the symptoms and slowed down the progression. The neural elements containing substance P, neuropeptide Y, vasoactive intestinal polypeptide, serotonin, dopamine-beta-hydroxylase and somatostatin, which are thought to cause the symptoms, were investigated in the small intestine and the liver metastasis by an immunocytochemical method. It seems to be an interesting observation, that a large number of neuropeptide Y immunoreactive nerve fibers and some substance P and vasoactive intestinal polypeptide immunoreactive nerve processes and cell bodies were observed however, no trace of somatostatin and serotonin immunoreactive nerve elements could be detected in the hepatic metastasis. That can be a novel addition to the possible aetiology of the carcinoid syndrome and to the way how the somatostatin treatment acts.

[A case of adult Gaucher disease]. / Felnöttkori Gaucher-kór esete.

The authors describe a case of an adult patient having Gaucher's disease, who had hepatosplenomegaly and pancytopenia. The diagnosis was established by the low level of leukocyte beta-glucosidase and by histology of bone marrow, liver and spleen. The patient had no bone pain, but MRI described characteristic lesions of the femur. Serum acid phosphatase was characteristically elevated. The hypersplenism was reduced after splenectomy. The patient has a daughter with central nervous system dysfunction. Her chromosome examination is normal, but she has lower leukocyte beta-glucosidase activity too. She may have a Gaucher's disease of type II, the acute neuropathic form.

Treatment of drug-induced bone marrow suppression with recombinant human granulocyte/monocyte colony stimulating factor.

The haemopoietic growth factors are relatively new additions to the treatment of drug-induced bone marrow suppression. Treatment with growth factors may induce primitive cells to enter into cell cycle. In clinical practice they have beneficial effects on the neutropenia following cytotoxic chemotherapy, bone marrow transplantation, and it may be effective in severe chronic neutropenia by cause drugs. One of the classes of drugs which cause serious agranulocytosis are the antithyroid drugs. A thyrotoxic patient with methimazole-induced agranulocytosis was treated with recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF). Seven days following treatment with daily subcutaneous injection of 270 micrograms rHu GM-CSF combined with antibiotics and glucocorticosteroids, granulocytes reappeared in the peripheral blood and the sepsis resolved. No side effects of the treatment were observed. The combination of rHu GM-CSF and glucocorticosteroids was successful in restoring normal granulocyte count.

Cryptococcosis in a phthisical eye.

A case of an enucleated phthisical eye was examined pathologically and was diagnosed as uveitis, subretinal granuloma, detached retina, phthisis bulbi. Twenty years later a more detailed study of multiple sections with differential stains revealed the existence of yeast-like bodies morphologically compatible with Cryptococcus neoformans. Systemic involvement was not found in this case, and the patient died 17 years later from an unrelated disease of the cardiovascular system. However an autopsy was not performed. Indirect fluorescent antibody staining technique on unstained deparaffinized sections of the eye tissue was positive for C. neoformans.

Unrecognized Legionnaires' disease as a cause of fatal illness.

Lungs from 224 patients, obtained at autopsy, were examined for Legionella pneumophila by fluorescent antibody (FA) staining. Of 121 patients who died with pneumonia, L pneumophila was present in eight cases (6.6%). (Two of the eight patients exhibited no important respiratory symptoms or fever, although pneumonia contributed considerably to their deaths. Preexisting underlying disease was present in all cases. Legionnaires' disease (LD), endemic in the central Ohio area, may cause up to 3.6% of the nosocomial pneumonias at the study site. Application of the local incidence of LD to the number of annual adult deaths in the United States indicates that many LD-associated deaths may occur each year. The study shows the importance of using the FA and Dieterle stains during routine pathological examination of lung tissue, especially from compromised hosts in endemic areas.

Effect of hepatitis C virus on hepatocyte proliferation and DNA ploidy in patients with chronic hepatitis C.

Hepatitis C virus infection may act as a cofactor by inducing chronic hepatitis and cirrhosis, playing a promoting role in the multistep process of hepatocarcinogenesis by maintaining liver inflammation, hepatocyte necrosis and regeneration. The aim of this study was to measure the DNA ploidy and cell proliferation of hepatocytes in patients with chronic hepatitis C. Hepatocyte nucleus suspension was analyzed from 45 patients with chronic hepatitis C and from 27 patients with chronic hepatitis non-C. The histopathological pattern of chronic hepatitis samples/grade, stage/was investigated. A significantly lower cyclin A protein expression and cytometrically measured S-phase fraction was observed in chronic hepatitis C as compared to chronic hepatitis non-C, representing suppressed cell proliferation of virus infected cells. In the chronic hepatitis C groups, the S-phase fraction depression was moderate, the grade of inflammation and cyclin A protein expression were also decreased, mainly in the severe grade group. In chronic hepatitis non-C, the number of cyclin A staining-positive cells increased parallel with severity of the inflammation. In addition, the HCV infection caused a near diploid minimally aneuploid cellular DNA content in the cases of moderate and severe histological groups. In contrast, the cellular DNA content was consequently diploid-independent of histological grades in chronic hepatitis non-C. Our results suggest that in chronic viral hepatitis C, the hepatocyte proliferation is suppressed parallel with the degree of inflammation, while the DNA content becomes aneuploid. The aneuploidy is a sign of genetic instability, predisposing the affected cells to unbalanced chromosomal abnormality which finally leads to malignant transformation.

Pathogenesis of retinal dystrophy in the Royal College of Surgeons rat.

The Royal College of Surgeons (RCS) rat is an animal with genetically transmitted progressive retinal dystrophy. We compared histopathologically the RCS rat retina with normal age-matched control retinas (Long-Evans rats) using light and scanning electron microscopy. Retinal degeneration begins with alteration of the rod outer segments. There is a progressive involvement of the entire retina, with all layers affected by 45 days. The three-dimensional view obtained with scanning electron microscopy provides another perspective on the pathogenetic changes of the RCS retina.