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PubMed1988

Molecular genetics and structure of the human immunodeficiency virus.

A novel human lymphotropic virus capable of crippling the immune system by infecting and destroying T4 antigen-positive cells is now known to be the etiologic agent of the acquired immune deficiency syndrome (AIDS). The AIDS or human immunodeficiency virus (HIV) belongs to a family of RNA viruses called retroviruses. Several strains of HIV have been molecularly cloned, and DNA sequence comparisons have established that the proviral DNA genome is 9.7 kilobase pairs. The genome possesses characteristic retrovirus features including structural genes, flanked by long terminal repeats, in the order gag, pol, and env and, in addition, four unique nonstructural genes, several of which appear to be essential in regulating virus replication. Electron microscopy has played an important role in elucidating structural, genetic, and molecular properties of HIV and has aided in its classification as a member of the Lentivirnae retrovirus subfamily. Heteroduplex mapping methodologies pertinent to these findings are described. Although the relationships show considerable divergence, the similarities between HIV and lentiviruses are profound and encompass an indistinguishable morphology, genome sequence homology and topography, genomic diversity, and overlapping biology, including a preference for infecting cells of the immune system, a cytopathic effect in vitro, and the ability to produce a persistent, slowly progressing, degenerative disease in vivo. The newest HIV class (HIV-2) has recently been molecularly characterized. HIV-2 also bears all the hallmarks of a lentivirus but is more closely related to simian immunodeficiency viruses than the previously described HIV-1, despite a similar biology. The HIV-lentivirus phylogenetic relationship has broad implications for the AIDS disease process and has given new importance to the study of the natural history and pathogenesis of animal lentiviruses in searching for clues to prevent the spread of AIDS.

Amino Acid Sequence↗
PubMed1994

[Definition and classification of liver cirrhosis].

The clinical features of liver cirrhosis are manifestation of altered hepatic hemodynamics and of reduced hepatic cell mass, represented by portal hypertension and sometimes hepatic failure. Histologically, cirrhosis is defined in general as a diffusely altered reconstruction of the lobular parenchyma with widespread connective tissue septa, which circumscribe regenerative nodules of the hepatocytes and contain anastomoses between efferent as well as afferent vascular systems linking central and portal canals. Thus, a large portion of portal blood flow bypasses the hepatocytes and reticuloendothelial cells, depleting them of their metabolic and detoxifying function. It is often impossible to make a morphologic classification of liver cirrhosis based on tiny biopsy specimens, and the histologic criteria are neither specific nor mutually exclusive. Furthermore, a frequent lack of correlation between the etiologic and morphologic types of cirrhosis has led the clinicians to classify the cirrhosis based on the main etiologic factor. According to the statistics (1991) of 40 representative medical institutes in Japan, covering approximately 8,600 liver cirrhosis cases, 16.9% of the cirrhosis is supposedly due to type B hepatitis virus infection, 54.9% to type C, 10.7% to alcoholic abuse and the remainder are of unknown etiology. It would be reasonable to apply the etiologic classification to liver biopsy specimens and morphologic classification to autopsy materials for thorough examination.

Alcoholism↗
PubMed1984

[Determination of the virucidal activity of antiseptics by a gel filtration method].

The authors propose a method for determining the virucidal potency of antiseptics, in which separation of antiseptic from virus is achieved by filtration through a gel of Sephadex LH20. The antiseptic is trapped within the gel while the virus passes through. Thus, the cytotoxic effect of the antiseptic, which usually hinders virus titration, is eliminated. Two filtration devices were developed: one is a polypropylene syringe, and the other is made of stainless steel. Determination of the effect of four products on poliovirus type I shows that this method allows classification of their activities.

Anti-Infective Agents, Local↗
PubMed1988

[Hepatic involvement in HIV 1 virus infection].

One hundred consecutive patients with serum antibodies against HIV 1 were evaluated for the prevalence and the type of liver injury. According to the CDC classification, 16 patients belonged to group II (asymptomatic patients), 47 to group III (persistent generalized lymphadenopathy) and 37 to group IV (11 constitutional disease, 19 secondary infectious diseases, 5 secondary cancers, one chronic lymphoid interstitial pneumonitis and one visceral leishmaniasis). Liver histology was studied in 32 patients. Clinical, biological and histologic abnormalities were assessed according to the clinical group and to the number of T4 lymphocytes. The prevalence of HBV infection was determined by HBV DNA and monoclonal antibodies. Clinical hepatic abnormalities were rare (13 p. 100) and no difference was found between groups. Transaminases or GGT activities were elevated in 60 p. 100 of all cases. Serum GGT activity was higher and serum albumin lower in patients in group IV. HBV infection markers were less frequently found in patients with opportunistic infection (74 p. 100) than in asymptomatic patients (100 p. 100; p less than 0.05). Prevalence of serum HBsAg detected by poly- or monoclonal antibodies was very high (29 p. 100) in all clinical groups. Prevalence of serum HBsAg detected only by monoclonal antibodies (10 p. 100) suggest infection of these patients by an HBV variant. Of the 32 patients undergoing liver histology, only 5 (16 p. 100) had signs of activity. There was no association between clinical or histologic signs and the number of T4 lymphocytes per ml. Alkaline phosphatase, ASAT and GGT activities were higher and serum albumin lower in patients with less than 200 T4 lymphocytes per ml.

Adolescent↗
PubMed2002

Genetic variability in hepatitis B viruses.

In 1988, it was reported that the full nucleotide sequences of 18 hepatitis B virus (HBV) strains clustered into four genetic groups (A to D) with more than 8% divergence between the groups. This classification of strains in terms of genome sequence has since proven to be an important tool in the understanding of HBV epidemiology and evolution and has been expanded to include three more genotypes. In parallel with the HBV genotypes described in humans, HBV strains isolated from different primates and hepadnaviruses found in woodchucks, ground squirrels, ducks and herons have been studied. Sequence differences between HBV genotypes can lead to structural differences at the level of the pregenome and can also lead to dramatic differences at the translational level when specific and commonly occurring mutations occur. There is increasing evidence that the clinical picture, the response to treatment and the long-term prognosis may differ depending on which genotype has infected the patient. The consideration of traditional serological patterns in a patient must therefore take the genotype of the infecting strain into account. Nucleotide variability between HBV strains has been used in several studies to trace routes of transmission and, since it is becoming increasingly clear that the differences between HBV genotypes are important, the need for reliable and easy methods of differentiating HBV genotypes has arisen. This review summarizes the knowledge of HBV genotypes with regard to their genetic, structural and clinically significant differences and their origin and evolution in the context of the hepadnaviruses in general.

Animals↗
PubMed1983

Immunological abnormalities in South African homosexual men.

Immunological tests of cell-mediated immunity (CMI), serological tests for antibodies to sexually transmitted and possibly immunosuppressive viruses, determination of serum immunoglobulin levels, full blood counts and serotyping for the HLA-DRw5 antigen were performed in 10 homosexual men with a mean age of 35 years (range 21-59 years). Five of these were associates of a patient who had died of confirmed acquired immunodeficiency syndrome (AIDS). At the time of investigation 9 of the men were apparently healthy and 1 had active pulmonary tuberculosis. Only in 2 subjects were no abnormalities of CMI found; they were 23 and 28 years of age and, interestingly, were also the only 2 whose sera were negative for antibodies to cytomegalovirus (CMV) and for the other viruses investigated. Of the remainder, 1 was lymphopenic, 6 had increased numbers of circulating suppressor T lymphocytes, 4 had reduced delayed-type hypersensitivity skin responses to recall antigens, and in 6 mitogen-induced lymphocyte transformation was decreased. Of these 8 subjects, 4 and 2 had antibodies to hepatitis B surface and core antigens respectively and 1 was positive for hepatitis B surface antigen and HBe antigen. The most severe abnormalities were observed in individuals who were seropositive for both CMV and hepatitis B virus. These findings indicate the existence of acquired immunosuppression in some members of the South African homosexual community. On the basis of these findings an immunological classification of potential sufferers of AIDS in the male homosexual community is proposed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Rejection, herpesvirus infection, and Ki-67 expression in endomyocardial biopsy specimens from heart transplant recipients.

We examined 164 endomyocardial biopsy specimens from 29 patients who received an orthotopic heart transplant since 1984. Rejection was graded according to the Hannover classification. Non-isotopic in situ DNA hybridization was conducted on cryostat sections with biotinylated probes for herpes simplex virus, Epstein-Barr virus, and cytomegalovirus. Serial sections of 126 biopsies were investigated immunohistochemically for the presence of activated T lymphocytes and proliferating cells, with monoclonal antibodies against interleukin 2 receptors (CD 25) and Ki-67 antigen. Relations between rejection grades, presence of proliferating cells, and presence of herpesvirus DNA were determined for the total number of biopsies. For some patients correlation of these parameters was studied over time. Herpesviral nucleic acids were detected in 25% of all biopsies: 37% of biopsies with relevant rejection (grades A 2 or A 3; 39% of all biopsies) compared to 18% of biopsies graded A 0, A 1, or A 5 (61% of all samples) (P less than 0.01). 56% of the biopsies with infection showed relevant rejection as compared with only 33% of the uninfected. Ki-67 expression was found in 41% of all biopsies, mainly in infiltrating cells: 69% of biopsies with relevant rejection compared with 23% of cases of minor/no rejection (P much less than 0.001). Ki-67 expression was also associated with herpesvirus infection: 66% of infected biopsies contained Ki-67 positive cells compared with 33% of uninfected biopsies (P less than 0.001). Herpesvirus infection was usually observed within the interstitial cell population, which, in many cases, displayed a considerable Ki-67 expression, too. In few cases only, hybridization was unequivocally found in vascular wall cells or myocytes. Viral myocarditis does not only mimic graft rejection morphologically, but it may also affect the course of rejection, via induction of antigenic changes or direct injury of cardiac tissues. Virus infections may also elicit or aggravate obliterative coronary artery disease, and thus contribute to accelerated graft atherosclerosis.

Adult↗
PubMed1997

Subacute sclerosing panencephalitis and chorioretinitis.

This is a case report of a 10-year-old boy with subacute sclerosing panencephalitis (SSPE). He initially developed visual disturbance and macular degenerative changes of the right eye at the age of 8 years, followed by chorioretinitis of the left eye, and his neurological symptoms deteriorated rapidly from the age of 10 years. He was diagnosed as having SSPE, as judged on cerebrospinal fluid examination for measles virus RNA by reverse transcription-polymerase chain reaction (RT-PCR), at the second stage of Jabbour's classification on admission. Although high intensity lesions were observed in the right occipital and temporal lobes, especially around the optic radiation, on T2-weighted brain MRI before the start of intrathecal interferon-alpha (IFN-alpha) therapy, they had disappeared at about two months after the treatment. Chorioretinitis (and/or macular degeneration) should be considered in the differential diagnosis of SSPE, permitting early IFN therapy.

Child↗
PubMed1989

Classification, management, and tracking of abnormal Papanicolaou smears.

A system of classifying, managing, and tracking abnormal Papanicolaou (Pap) smears was used at a California university where 3,289 patients were tested. Classification was based on use of the latest cytopathological techniques for identifying characteristics associated with dysplasia and human papilloma virus (HPV). The follow-up success rate was determined for 6-month repeat Pap smears, colposcopy patient contact, and biopsy results. Pathology report correlations were determined for the noncolposcopy group by using repeat Pap smear results. Biopsy results were correlated with Pap smear readings for accuracy and yielded significant statistical information for the program.

California↗
PubMed1996

Current anatomico-pathological classification of hepatitis: characteristics of HCV infection.

Better knowledge of the natural history and aetiology of chronic hepatitis and the introduction of effective treatments have lead to revising the histopathological classification of chronic hepatitis. The basic lesions observed in chronic hepatitis are intra-portal inflammatory infiltrate, piecemeal necrosis, lobular necrotico-inflammatory lesions, and fibrosis. The histological activity of chronic hepatitis is usually assessed by apply Knodell's score or histological activity index (HAI). This score includes inflammatory lesions and fibrosis. But fibrosis is in fact the consequence of portal and lobular inflammation. The current classifications, including that proposed at the 1994 world conference on gastroenterology, propose discriminating between activity, or grade, and fibrosis, or stage. The classification of chronic hepatitis has also been revised because it was ill-adapted to assessing the C virus-linked chronic hepatitis. Histologically, these are little active chronic hepatitis associated with intra-sinusoidal inflammatory infiltrates of the leukaemia type, intralobular microgranulomas, intraportal lymphoid aggregates, and lesions of the small biliary tracts. Although non-specific, these lesions are evocative enough to histologically back-up diagnosis. Liver biopsy confirms chronic hepatitis diagnosis, determines its grade and stage, sometimes its cause. Liver biopsy also permits assessing treatment response.

Antibodies, Viral↗
PubMed1995

Vasculitis.

Many cutaneous and systemic disorders are associated with inflammation and necrosis of blood vessels. Several classifications of vasculitis have been used. Internists tend to utilize the classification of Fauci with modifications such as those by Cupps. Gibson and Ryan, who are dermatopathologists, have classified vasculitis based on vessel size, leukocyte type, and presence of granulomas. A more recent classification has been developed by Jennette, a pathologist, and colleagues. The etiology of vasculitis is varied; it includes bacteria, viruses, chemicals, autoimmune disease, malignancy and abnormal exogenous and endogenous proteins. Leukocytoclastic vasculitis can be experimentally reproduced by the Arthus phenomenon. IgM and C3 are found in cutaneous blood vessels and associated with circulating immune complexes. CH50, C3 and C4 may be reduced in serum. Increased incidence of nasal carriage of staphylococci is associated with higher relapse rates in Wegener's granulomatosis and toxic shock syndrome toxin from staphylococci is associated with the Kawasaki syndrome. Additionally, at least four systemic vasculitic drug reactions can be confirmed with patch testing. Antineutrophil cytoplasmic antibodies (ANCA) are found in association with certain systemic vasculitides. These may be tested with indirect immunofluorescence and enzyme linked immunosorbent assays (ELISA) with radioimmunoassays. Originally cytoplasmic ANCA (cANCA) was identified with proteinase 3 as the antigen and perinuclear ANCA (pANCA) was related to myeloperoxidase. While cANCA is very specific for proteinase 3, pANCA is associated with a number of antigens other than myeloperoxidase. pANCA is found with alcohol fixed but not formalin-fixed neutrophils. cANCA is particularly sensitive and specific for Wegener's granulomatosis and predicts prognosis and response to therapy. pANCA is not so specific and is associated with a number of other vasculitic syndromes. Cutaneous vasculitis is managed primarily with colchicine, dapsone and prednisone, with recent studies indicating that there may be a synergistic effect of pentoxifylline with dapsone. Systemic vasculitis involves treatment with various agents. Recently it has been observed that co-trimoxazole (trimethoprim/sulfamethoxazole) is useful in many cases of Wegener's granulomatosis along with other more toxic chemotherapeutic agents.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2006

Analysis of the 5' noncoding region versus the NS5b region in genotyping hepatitis C virus isolates from blood donors in France.

The 5' noncoding region (5' NCR) of the hepatitis C virus (HCV) has become the standard for genotyping even though several reports show that its use can result in classification errors. The purpose of this study was to perform genotyping based on sequence analysis of the NS5b region in a set of 357 HCV strains isolated from blood donors in France in 2002 and 2003. Results were compared with those previously obtained using 5' NCR analysis, and HCV subtype distribution was reevaluated. Twenty-six of 120 strains (approximately 22%) initially identified as genotype 1b by 5' NCR region sequence analysis were reclassified as genotype 1a by NS5b region sequence analysis. Similarly, 14 of 23 strains (approximately 61%) initially identified as 2a/2c were reclassified as non-2a and non-2c subtypes, and 12 of 22 strains (approximately 45%) initially identified as 4c/4d subtypes were reclassified as non-4c and non-4d subtypes. Sequence analysis of the NS5b region also revealed 5 putative new subtype 2 variants and 2 putative new subtype 4 variants. Although these findings demonstrated full agreement between 5' NCR and NS5b sequence analysis with regard to type classification, genotyping based on phylogenetic analysis of the NS5b region is more accurate for subtype determination than genotyping based on analysis of the 5' NCR. Sequence analysis of the NS5b region is mandatory for epidemiologic studies.

5' Untranslated Regions↗
PubMed1991

[Materno-fetal dengue. Apropos of 5 cases observed during the epidemic in Tahiti (1989)].

During the dengue 3 epidemic which occurred in French Polynesia between September 1989 and March 1990, number of cases of Dengue Haemorrhagic Fever (DHF) were reported among children and infants. Of interest, five cases of neonatal infections were recorded and involved the transmission of the virus from mother to child as the end of the pregnancy. Detailed observations on these cases are presented in this paper. Fever in mother, when delivering or just a few days before, represents the circumstances of the diagnosis. Analysis of the clinical features shows that fever and vasomotor troubles (blotches) were the dominating traits of the disease in the newborns. Also, hepatomegaly was constantly observed. Concerning the biological results, thrombopenia (platelets count: 100,000/mm3) was reported for all cases. According to these data, all cases were classified into DHF cases. Laboratory confirmation was obtained by serological investigations (antidengue IgM immunocapture ELISA and Haemagglutination Inhibition Tests) and/or virus isolation in both mother and child. Thus, virus was recovered in two newborns while IgM were detected in all infants and in four mothers. Severity of the disease was variable. However, out of five cases one fulfills the WHO definition of Dengue Shock Syndrome (DSC). Moreover, the authors discuss about the difficulties encountered to classify the cases according to WHO criteria for the grade classification of DHF.

Dengue↗
PubMed1991

[Surface phenotypic diversity of CD4 or CD8 in ATL].

A 51-year-old woman was admitted to our hospital complaining of lymphadenopathy in June, 1987. Lymph node biopsy revealed diffuse lymphoma, mixed cell type according to the LSG classification. On hematological examinations, leukocyte has counted 12,400/microliters, of which 15% abnormal lymphocytes containing human T cell lymphotropic virus type-1 (HTLV-1) proviral DNA into the cellular DNA. She was diagnosed as adult T-cell leukemia (ATL). The abnormal lymphocytes in the peripheral blood expressed CD4 but lymph node cells expressed CD8. Thirty months after initial diagnosis, abnormal lymphocytes began to increased and reached 30,500/microliters. Surface phenotype of abnormal lymphocytes changed CD3+ CD4+ CD8- OKla1+ to CD3- CD4- CD8- OKla1-. This change is considered to show the surface phenotypic diversity in ATL cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Cutaneous signs of AIDS.

In this article, selected aspects of human immunodeficiency virus (HIV) infection are reviewed, particularly as it relates to cutaneous signs and symptoms. Included are discussions of the classification, epidemiology, and clinical manifestations of this complex infectious process.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols.

In France, more than 80% of children with Burkitt's lymphoma or Burkitt's leukemia (ALL3) are now cured with the LMB (B-cell non-Hodgkin's lymphoma and B-ALL) protocols of the Société Française d'Oncologie Pédiatrique, but so far, poor results have been obtained in the few adult studies available. We have analyzed the experience with LMB protocols in adult patients. This retrospective study involved 65 adult patients with small noncleaved cell lymphoma or ALL3 treated with the LMB protocols. They were 17 to 65 years old and not previously treated. Human immunodeficiency virus-infected patients were excluded. The diagnoses were made between September 1984 and August 1991. According to the Murphy classification, 12 patients (18%) had stage I or II disease, 25 (38%), stage III disease; 4 (6%), stage IV disease; and 24 (37%), ALL3 (> or = 25% blasts). According to the Ann Arbor classification, 9 patients had stage I disease; 8 patients, stage II; 5 patients, stage III; 21 patients, stage IV disease; and 22 patients, ALL (> or = 30% blasts). Twelve patients had central nervous system (CNS) involvement before treatment. Thirty-nine patients were treated according to the LMB 84 protocol scheme; 14 according to the LMB 86 protocol, and 12 patients received the LMB 84 induction courses followed by the LMB 86 consolidation courses. Three patients underwent bone marrow transplantation (BMT) while in second complete remission (CR) and 3 others had refractory disease. There were some protocol violations caused by empirical medical decisions: local irradiation was performed in 4 patients, 2 patients received prophylactic radiation to the brain that was not specified in the protocol, 13 patients underwent BMT in first CR, and methotrexate doses were modified in 10 patients. Fifty-eight patients (89%) achieved a CR. There were four (6%) primary induction treatment failures, and three (4%) early treatment-related deaths. Eight patients relapsed between 2 and 30 months after CR (median, 4.7 months). Forty-seven patients are alive in CR (45 first CR, 2 second CR) with a median follow-up of 57 months (24 to 93 months). There were five toxicity-related deaths among patients in CR including four BMT-related deaths and five deaths caused by refractory relapses. One patient died in CR at 62 months of rectal cancer. The 3-year overall survival rate is 74% (SE = 5). According to the stages in the Murphy classification, the 3-year survival rates are stages I and II, 100%; stage III, 80% (SE = 7); and stage IV and ALL, 57% (SE = 8). Seven of 12 patients with initial CNS disease are alive with a median survival of 56 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Chronic hepatitis C virus infection in haemophilic patients: clinical significance of viral genotype.

We have undertaken a comprehensive study of hepatitis C virus (HCV) genotype and its clinical significance in haemophilic patients. 189 HCV RNA positive were typed, using the Simmonds classification scheme, by restriction fragment length polymorphism (RFLP) in an amplified segment of the 5' non-coding region of the HCV genome. Type 1 was found in 121 (64.0%), type 2 in 23 (12.2%), type 3 in 36 (19.0%), type 4 in 3 (1.6%), type 5 in 2 (1.1%) and mixed infection in 3 (1.6%). There were no type 6 infections and one patient (0.5%) could not be typed. Genotype was not associated with diagnosis, age, or with HIV infection. Type 1 was associated with higher serum HCV RNA levels, and with a poor response to interferon. Progression to hepatic decompensation has been seen less frequently in those with type 3 compared to type 1 infection (p = 0.07). Three out of eleven patients studied over a longer time course showed a change in genotype, the remainder were persistently infected with HCV type 1. In conclusion, HCV genotype has clinical relevance in the management of haemophilic patients. Those with type 1 are probably more likely to develop serious liver disease and since they respond poorly to interferon-alpha, should be considered for new treatment strategies aimed at sustained clearance of HCV RNA.

Chronic Disease↗
PubMed1996

Parvovirus B19 infection and rheumatic diseases.

We reviewed the literature on relationships between human parvovirus B19 infection and rheumatic diseases. Parvovirus B19 causes erythema infectiosum in childhood, transient anemia in immunocompetent individuals, and potentially severe infections in fetuses; laboratory evidence that the virus is directly responsible for these disorders has been obtained. Acute arthropathy meeting American College of Rheumatology criteria for rheumatoid arthritis and disorders meeting some of the classification criteria for systemic lupus erythematosus are the most striking rheumatic manifestations of parvovirus B19 infection. Purpuric lesions have also been reported. Parvovirus B19 infection may be capable of inducing a number of manifestations that have not yet been described in the literature. Although the relationship between human parvovirus B19 infection and rheumatic diseases has been the focus of many studies, compelling evidence that the virus is directly involved in the pathogenesis of rheumatic diseases has not yet been obtained.

Humans↗