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Biomedical subjects

P Simmonds

Publications and source records attributed to P Simmonds.

At least 145 records · Page 8Linked to original sources
PubMed1995

Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes.

OBJECTIVE: To determine, using a serotyping assay, whether the occurrence of extrahepatic immunologic disorders in patients with chronic hepatitis C is dependent on hepatitis C virus serotype. DESIGN: Prospective study. SETTING: Liver unit and virology laboratory of a university hospital. PATIENTS: 59 consecutive patients with chronic hepatitis C. MEASUREMENTS: Hepatitis C virus serotype was determined using a recently developed immunoenzymatic assay that detects antibodies directed to serotype-specific immunodominant epitopes. Cryoglobulin, rheumatoid factor, and numerous antitissue antibodies were sought. Biopsies of labial salivary glands were done in 49 of the 59 patients. RESULTS: Prevalence was 59% for serotype 1, 10% for serotype 2, 12% for serotype 3, and 3% for mixed infection. Fifteen percent of patients could not be serotyped. Cryoglobulinemia was found in 36% of patients and rheumatoid factor was found in the serum of 71%. At least one antitissue antibody was found in the serum of 41% of patients; salivary gland biopsy showed lymphocytic capillaritis in 49% of patients. These immunologic abnormalities were seen in patients infected with any of the three serotypes, and prevalences of the abnormalities did not differ significantly among patients infected with different serotypes. CONCLUSIONS: We confirm that the prevalence of extrahepatic immunologic abnormalities is high in patients with chronic hepatitis C. These abnormalities may occur in patients infected with any of the three major hepatitis C virus serotypes now present in developed countries.

Adolescent↗
PubMed1995

Molecular epidemiology of hepatitis C virus infection amongst intravenous drug users in rural communities.

The prevalence of hepatitis C virus (HCV) infection amongst a group of intravenous drug users (IVDUs) resident in West Suffolk (East Anglia, England) was investigated and compared with the prevalence of infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV). In addition, both the level of HCV persistence, as defined by detection of viral RNA, and the HCV genotypes present in this population were determined. It was found that HCV antibodies were present in 59% of those tested; by comparison 22% had antibodies to HBV and 1% antibodies to HIV. HCV RNA was found in 44% of those with HCV antibody. HCV genotype 1 was the most prevalent within this population although both genotypes 2 and 3 were also represented.

Adolescent↗
PubMed1995

Comparison of genotyping and serotyping methods for the identification of hepatitis C virus types.

The usefulness of identification of hepatitis C virus (HCV) genotype has recently been investigated for the clinical management of patients infected by HCV. In the present study, the HCV genotype infecting 127 patients was determined by two different methods: HCV genotyping using a dot-blot assay with type-specific probes derived from the 5'-UTR of HCV genome and HCV serotyping using an ELISA system in which type-specific antibodies against the NS4 region were detected. Overall, a good correlation of the two methods was observed, the main discrepancy being 4 patients with sequence-confirmed HCV-2 (2 cases) and HCV-3 (2 cases) genotypes recognized as HCV-1 by serotyping. Mixed infections were not detected by either method. In 19 PCR negative sera, in which the HCV genotype could not be evaluated, no particular serotype profile was observed. In conclusion, the molecular and serological techniques are almost equivalent in determining the viral type, although in individual cases, especially in PCR negative patients, the clinical meaning of the serotyping result remains to be determined.

Base Sequence↗
PubMed1995

The genetic diversification of the HIV type 1 gag p17 gene in patients infected from a common source.

An evolutionary analysis was undertaken of HIV-1 gag p17 sequences taken from a small cohort of hemophilia B patients infected from a common batch of clotting factor concentrate. The sequence population found at seroconversion was highly homogeneous, suggesting that the infecting batch also contained little sequence variation. Genetic diversification was found in follow-up sequences taken approximately 3 years later and was generally found to be complex. Greater rates of synonymous to nonsynonymous substitution were observed, especially when comparing distantly related isolates, and the rate of synonymous substitution was used to estimate times of divergence for a number of isolates of HIV-1 including the origin of the subtypes A to H. The p17 region is therefore proposed as a useful marker for future epidemiological studies.

Amino Acid Sequence↗
PubMed1995

The molecular epidemiology of human immunodeficiency virus type 1 in Edinburgh.

Human immunodeficiency virus (HIV) type 1 sequences obtained from HIV-infected persons in different risk groups in Edinburgh were studied to determine the number and origin of virus variants and patterns of virus transmission. Phylogenetic analysis revealed that 12 of 14 hemophiliac patients who had been exposed to a single common batch of factor VIII had closely related gag gene sequences. Sequences from intravenous drug users and patients infected through heterosexual contact formed another distinct group, and 2 other hemophiliacs formed a third group. However, epidemiologic relationships inferred from analysis of the V3 region of the env gene were less conclusive, especially when the V3 loop was taken in isolation. This appears to be due to the length of time since infection and the action of selection, which has favored the independent appearance of similar V3 loop variants.

Base Sequence↗
PubMed1995

Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification. The International HCV Collaborative Study Group.

Genotypes of hepatitis C virus (HCV) present within 104 samples from HCV-infected individuals from Africa, the Middle East, the Indian subcontinent and South-East Asia were identified by sequence comparisons in the core and NS-5 regions. Relatively short sequences (such as the 222 bp fragment of NS-5) provided effective discrimination of types, subtypes and isolates, and produced equivalent relationships between genotypes as were found upon comparison of longer sequences of NS-5, of the core region, and by comparison of the limited number of complete genomic sequences currently available. Measurement of evolutionary distances in the core and NS-5 regions allowed 79 of the 104 samples to be identified as examples of known genotypes, while 17 of the remainder could be provisionally classified as new subtypes of types 1 (Nigeria), 2 (Gambia), 3 (India, Pakistan and Bangladesh) and 4 (Middle East) on the basis of sequence comparison in core and NS-5 (n = 9) or provisionally using core alone (n = 8). The remaining sequences from Thailand made up two groups showing no close similarity to any of the six major genotypes classified to date, although one corresponded to an as yet unclassified variant of HCV also found in Thailand. However, phylogenetic analysis of the core and NS-5 regions indicated a distant relationship between these sequences with variants found in Vietnam and with type 6a, and collectively they formed a diverse single phylogenetic group. The existence of great diversity within a single genotype was also found amongst type 3 sequences in the Indian subcontinent, amongst type 4 variants in Central Africa and the Middle East, and amongst type variants in Nigeria. These findings may provide clues for understanding the origins and mechanisms of transmission of HCV.

Africa↗
PubMed1995

Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5' non-coding region.

A method is described for identifying different genotypes of hepatitis C virus (HCV) by restriction endonuclease cleavage of sequences amplified by PCR from the 5' non-coding region. Using the enzymes HaeIII-RsaI and HinfI-MvaI, followed by cleavage with BstU1 or ScrFI, it was possible to identify and distinguish HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5 and 6. The method was used to investigate the prevalence of these genotypes in 723 blood donors in 15 countries, the largest survey to date, and one which covered a wide range of geographical regions (Europe, America, Africa and Asia). These results, combined with a review of the existing literature, indicate the existence of several distinct regional patterns of HCV genotype distribution, and provide the framework for future detailed epidemiological investigations of HCV transmission.

Blood Donors↗
PubMed1995

Variation of the hepatitis C virus 5' non-coding region: implications for secondary structure, virus detection and typing. The International HCV Collaborative Study Group.

Variation in the 5' non-coding region (5'NCR) of hepatitis C virus (HCV) was investigated in detail by comparing 314 5'NCR sequences of viruses of genotypes 1 to 6. Evidence was obtained for the existence of associations between particular 5'NCR sequence motifs and virus types and subtypes. No recombination was observed between the 5'NCR and coding regions of different genotypes, implying that the sequence of subgenomic regions such as the 5'NCR can be used to deduce virus genotype. The distribution of polymorphic sites within the 5'NCR is used to propose improved oligonucleotide primers for virus detection and quantification that would be equally efficient in detecting RNA of different virus genotypes. The accuracy of two different genotyping methods (RFLP and the line probe assay) based on analysis of sequence polymorphisms in the 5'NCR is predicted from the sequences surveyed to be 97% and 83% respectively for types 1 to 6, with higher accuracies for distinguishing between subtypes 1a/1b, 2a/2b or 3a/3b. Several sites of genotype-specific polymorphism were covariant and maintained the base pairings required for a secondary structure model of the 5'NCR. Other sites of variation suggest minor modifications to this model and have implications for the probable functions of the 5'NCR.

Base Composition↗
PubMed1995

Absence of hepatitis A virus transmission by high-purity solvent detergent treated coagulation factor concentrates in Scottish haemophiliacs.

Recent reports of hepatitis A virus (HAV) infection in haemophiliacs receiving high-purity solvent detergent (HP.SD) treated factor VIII concentrates have brought into question the efficacy of this virucidal method for inactivating HAV. To assess whether HAV may have been transmitted by HP.SD concentrates, we compared seroprevalence in haemophiliacs with different disease severity, sought evidence of seroconversion to HAV since introduction of HP.SD products, and directly examined concentrates for HAV RNA by PCR. Our data suggest that Scottish haemophiliacs are not being infected with HAV by HP.SD concentrates produced initially by CRTS Lille and presently by PFC Edinburgh and supplied by the Scottish National Blood Transfusion Service (SNBTS).

Adolescent↗
PubMed1995

The distribution of hepatitis C virus genotypes in Turkish patients.

The distribution of hepatitis C virus (HCV) genotypes was investigated in 89 HCV-infected Turkish patients. Blood samples were collected from haemodialysis patients (n = 45), chronic liver disease (CLD) patients (n = 38), acute non-A, non-B (NANB) hepatitis patients (n = 2) and blood donors (n = 4). HCV RNA sequences were amplified in the 5' non-coding region and were typed by restriction fragment length polymorphism analysis. The predominant genotype was 1b (75.3%), followed by 1a (19.1%), 2 (3.4%) and 4 (2.2%). While there was no significant difference in the distribution of HCV genotypes with respect to age, sex, transfusion history, alanine aminotransferase levels or liver histology (in the CLD group), type 1a-infected patients were younger than type 1b-infected patients (P < 0.05) in the haemodialysis group. Serological reactivity to recombinant HCV proteins was assessed in 58 samples using the Chiron RIBA-2 assay. The reactivity of samples from patients infected with type 1b with 5-1-1 and c100 antigens was significantly lower (P < 0.05) than the reactivity of samples from those infected with type 1a. These results, together with the results of two previous studies, indicate that HCV genotypes 1, 2, 3 and 4 are prevalent in different frequencies in the Turkish population. Determination of the genotype distribution of HCV in a geographical area may provide important clues for studying the epidemiology, transmission and pathogenesis of HCV-related diseases and may also aid in improving serological assays to detect HCV infection.

Adult↗
PubMed1995

Acute hepatitis C infection after sexual exposure.

A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two.

Acute Disease↗
PubMed1995

Liver biopsy findings in patients with alcoholic liver disease complicated by chronic hepatitis C virus infection.

OBJECTIVE: To identify the features of concurrent hepatitis C virus (HCV) infection in liver biopsies from patients thought to have alcoholic liver disease. PATIENTS: Fifty-five patients with a history of excess alcohol consumption were studied. METHODS: All patients underwent liver biopsy. RESULTS: Eight of the 55 patients studied were found to be HCV-positive. CONCLUSION: The histological features found to be most useful for identifying concurrent HCV infection were the presence of lymphoid aggregates in portal tracts (predictive value 100%), the presence of lymphocytes in the lobules (predictive value 83%), and the pattern of fibrosis, particularly periportal spurring rather than perivenular fibrosis (predictive value 75%).

Adult↗
PubMed1995

Hepatitis C virus variants and the role of genotyping.

Hepatitis C virus demonstrates considerable divergence in nucleotide sequence. This variation may affect virus detection, disease outcome, and the effectiveness of interferon treatment. For example, infection with genotype 1 is associated with a lower response rate to interferon treatment. Hepatitis C virus can be classified into six distinct types, comprising at least 74 different subtypes. Both types and subtypes are subject to geographical differences in distribution, presumably reflecting the epidemiological history of the virus. However, because this history may be blurred by migration and by commerce in blood products between regions, screening and typing assays must recognize both the major indigenous and more exotic virus genotypes. Little information exists about the role of virus sequence variation in screening for hepatitis C virus antibodies, but there is some evidence that the reactivity of current serological screening assays for hepatitis C virus is genotype dependent. In the future, screening assays may need to include antigens specific for different virus types or may need to be designed with regard to the particular types found in a certain area. Antigenic variation may also mean that an effective vaccine needs to be multivalent to protect against all genotypes present in a given region. There are several polymerase chain reaction-based methods of distinguishing between hepatitis C virus variants. These methods must be continually updated, however, as new sequence variants are discovered. Alternative genotyping assays are based on the host's serological response to virus infection, but these cannot distinguish between virus subtypes and are unsuitable for immunocompromised patients. As more countries are sampled, it is likely that more genotypes will be identified and this may help elucidate the origins of hepatitis C virus. Detailed epidemiological studies may delineate past and current routes of transmission.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Redistribution of HIV outside the lymphoid system with onset of AIDS.

The basis for many of the symptoms and pathological changes found in patients with the acquired immunodeficiency syndrome (AIDS) remains poorly understood. We have used a quantitative polymerase chain reaction technique to investigate the extent to which direct infection with human immunodeficiency virus (HIV) produces the disease manifestations of AIDS. In five patients who died with AIDS-defining illnesses (Centers for Disease Control and Prevention class IV), we found variable, but in many cases extensive, infection by HIV at various sites, including brain, lung, colon, and liver. By contrast, in three HIV-positive subjects who died without HIV-related disease (CDC class II), we found no evidence of significant infection of any non-lymphoid organ. In both groups of patients there were high levels of infection in cells of the spleen, lymph nodes, and peripheral blood. Pathological examination of tissues from the AIDS patients revealed many abnormalities, of which some, such as giant-cell encephalitis in the brain, were specifically associated with the presence of high levels of HIV infection. These findings suggest that spread of HIV outside cells of the immune system is a late event in HIV infection and is extremely sensitive to the degree of immunosuppression in the patient.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Hepatitis C virus transmission by intravenous immunoglobulin.

The polymerase chain reaction was used to detect hepatitis C virus infection in patients who had previously been reported to have developed non-A, non-B hepatitis after intravenous immunoglobulin infusion. Of the 33 patients with intravenous immunoglobulin associated non-A, non-B hepatitis studied, HCV RNA could be detected in 15 out of 17 patients (88%) who were HCV RNA negative prior to the development of non-A, non-B hepatitis after implicated intravenous immunoglobulin batches. Similarly, eight out of nine patients (89%) in whom no sample was available for polymerase chain reaction testing prior to intravenous immunoglobulin therapy, had detectable HCV RNA after intravenous immunoglobulin therapy with intravenous immunoglobulin batches implicated in non-A, non-B hepatitis transmission. Two of the three intravenous immunoglobulin preparations implicated in non-A, non-B hepatitis transmissions that were available for polymerase chain reaction testing also had detectable HCV RNA, confirming that hepatitis C virus is the implicated virus in intravenous immunoglobulin-associated non-A, non-B hepatitis.

Hepacivirus↗