Sexual transmission of GB virus C/hepatitis G virus

Tooth transposition is a positional interchange of two adjacent teeth. The most commonly transposed tooth is the permanent canine with either the first premolar or lateral incisor. The records of 54 subjects with transposed canines, both maxillary and mandibular, were collected. Pretreatment study models of these subjects were matched with a similar number of models from unaffected individuals. Bucco-lingual and mesio-distal tooth widths, arch depth and arch width were measured on each model. Thirty-four subjects (63 per cent) were female. Thirty-seven (68.5 per cent) of the cases involved the maxillary arch and thirty-three (89.2 per cent) of these upper arch transpositions were of the canine and first premolar. In cases involving the lower arch the canine was invariably transposed with the lateral incisor. Peg-shaped lateral incisors, supernumerary and/or congenitally absent teeth occurred in 19 subjects. There were some small, but significant differences in the dimensions of some teeth, however there were no statistically significant differences in arch depths, arch widths and most tooth dimensions in subjects with and without transposed canines. These factors do not appear to be related to the development of canine transposition.     

Natural history and molecular biology of hepatitis G virus/GB virus C

BACKGROUND: The hepatitis G virus (HGV) or GB virus C (GBV-C) is a new member of the Flaviviridae family. The virus is transmitted by transfusion of blood, infusion of some blood products, and by parenteral exposure to blood during intravenous drug use (IVDU) and haemodialysis. Transmission from mother to infant and by sexual contact has also been documented. Although the virus has been found in patients with acute and chronic hepatitis, evidence of disease association has not been forthcoming. The majority of patients carry the virus in the absence of liver enzyme abnormalities. OBJECTIVES: To review what is currently known about HGV/GBV-C in order to evaluate its similarity with other members of the Flaviviridae and the association of the virus with disease. RESULTS: The genomic organisation of the virus is typical for Flaviviridae, with long 5' and 3' untranslated regions (UTR). However, a clearly identifiable nucleocapsid encoding region is lacking. Polyprotein synthesis is mediated through an internal ribosome entry site (IRES) contained within the 5' UTR. Phylogenetic tree analysis of sequences derived from this region has demonstrated the existence of at least three genotypes. Apart from serum, HGV-RNA has been detected in lymphocytes also, but the quasispecies present in the two compartments appear to be different. The envelope glycoprotein E2 lacks a hypervariable region and is potentially the target of a neutralising antibody response. CONCLUSION: Molecular analysis of HGV reveals close similarity of the virus with HCV. However, an association of the virus with liver disease remains unresolved and no association of the virus with hepatocellular carcinoma has been reported.     

GB virus C/hepatitis G virus infection in autoimmune liver diseases

Cutaneous necrosis may occur as a complication of treatment with interferon. Here we report the first case of cutaneous necrosis developing in a patient receiving interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The patient developed two necrotic lesions while receiving high doses of interferon. We suggest that discontinuation of treatment may be necessary to permit healing of such lesions. Although the exact mechanism involved in cutaneous necrosis remains unknown, our observations support earlier findings suggesting that intraarterial injection may be a factor.     

Genotype of GB virus C/hepatitis G virus by molecular evolutionary analysis

We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.     

Antibodies to the E2 protein of GB virus C/hepatitis G virus: low prevalence in Asian countries

The alpha-subunit of eukaryotic initiation factor eIF2 (eIF2alpha) plays an important role in the regulation of mRNA translation through modulation of the interaction of eIF2 and a second initiation factor, eIF2B. The interaction of the two proteins is regulated in vivo by phosphorylation of eIF2alpha at Ser51. In the present study, rat eIF2alpha was expressed in Sf21 cells using the baculovirus expression system. The recombinant protein was purified to >90% homogeneity in a single immunoaffinity chromatographic step. The protein was free of endogenous eIF2alpha kinase activity and was rapidly phosphorylated by the eIF2alpha kinases HCR and PKR. A variant of eIF2alpha in which the phosphorylation site was changed to Ala was also expressed and purified. The variant eIF2alpha was not phosphorylated by either HCR or PKR, demonstrating that the kinases specifically phosphorylate the correct site in the recombinant protein even in the absence of the other two subunits of the protein. In summary, a rapid and inexpensive method for obtaining eIF2alpha has been developed. Use of the wildtype and variant forms of eIF2alpha to measure eIF2alpha kinase activity in cell and tissue extracts should greatly facilitate examination of the regulation of mRNA translation under a variety of conditions.     

GB virus C/hepatitis G virus infection: a favorable prognostic factor in human immunodeficiency virus-infected patients?

Lung disease is a rare complication of inflammatory bowel disease (IBD). Herein is a series of seven IBD patients who developed new, persistent and unexplained symptoms of respiratory disease, particularly chronic productive cough. Using a CT scan of the chest, a diagnosis of bronchiectasis was made in five patients, while the diagnosis of chronic bronchitis was made in two patients. Factors, other than IBD, that could account for pulmonary disease in these patients were absent. Several important clinical patterns for IBD-associated large airway disease were uncovered and are reviewed in light of earlier case reports in the medical literature. A discussion regarding the possible pathogenesis of IBD-associated airway disease follows.     

Gradual loss of IgG antibodies against GB virus C/hepatitis G virus in a patient with AIDS

GB virus C/hepatitis G virus (GBV-C/HGV) is a positive-sense, single-stranded RNA virus belonging to the family Flaviviridae and is distantly related to hepatitis C virus (HCV). GBV-C/HGV can be transmitted by the parenteral and the sexual route. Among individuals infected with human immunodeficiency virus type 1 (HIV-1) by the sexual route, we and others have demonstrated a high prevalence of GBV-C/HGV infection. Recently, Woolley and colleagues reported that AIDS patients co-infected with GBV-C/HGV had a significantly lower mean CD4 cell count than AIDS patients without GBV-C/HGV infection, suggesting that GBV-C/HGV antibody may be lost with progression to AIDS. To our knowledge no data are available on the loss of antibody against GBV-C/HGV in AIDS patients. We now report on an HIV-infected patient who exhibited gradual loss of IgG antibodies against GBV-C/HGV, as well as HCV, with progression of HIV disease.     

Chronic hepatitis in children after liver transplantation: role of hepatitis C virus and hepatitis G virus infections

BACKGROUND/AIMS: Chronic graft hepatitis occurs in 20-30% adults after liver transplantation but the prevalence and causes in children are not known. In adults, hepatitis C virus infection is prevalent prior to transplantation and recurrent infection is a frequent cause of graft dysfunction. The significance of the recently described hepatitis G virus infection remains unproven. The aim of this study was to examine the role of hepatitis C virus and hepatitis G virus infection in chronic graft hepatitis after paediatric liver transplantation. METHODS: The prevalence of graft hepatitis and the role of hepatitis C virus and hepatitis G virus infections in 80 children after liver transplantation have been studied, with a median follow up of 4.4 years (range 0.4 to 10.7), and the persistence of hepatitis G infection in the presence of immunosuppression has been determined. RESULTS: Chronic graft hepatitis was diagnosed in 19/80 (24%) children and was most frequently seen in children transplanted for cryptogenic cirrhosis (71%). There was no significant difference in the prevalence of chronic hepatitis in those transplanted before or after donor anti-HCV screening. Hepatitis C infection occurred in three children transplanted prior to donor screening but in only one was associated with chronic hepatitis. Hepatitis G infection was found in 22/79 (28%) transplant recipients but was not associated with graft hepatitis. In 17/21 children hepatitis G infection persisted for a median of 5.2 years after transplantation. CONCLUSION: Chronic hepatitis occurred in 24% of children after liver transplantation, a similar prevalence to that in adults. Cryptogenic liver disease predisposed to graft hepatitis, but neither hepatitis C nor hepatitis G infection was associated. Hepatitis G virus caused a frequent and usually persistent infection after transplantation.     

Prevalence, incidence, and clinical characteristics of hepatitis G virus/GB virus C infection in Scottish blood donors

The prevalence, incidence, clinical features, and natural history of hepatitis G virus (HGV) or GB virus C (GBV-C) were investigated in a non-remunerated blood donor population to determine its clinical significance and its impact on blood safety. Of 1020 regular blood donors, 23 (2.25%) were positive for plasma HGV/GBV-C RNA. Alanine aminotransferase levels were lower than in uninfected donors (median, 20 IU/mL; 32 IU/mL in controls; P=.015). Clinical examination produced no other evidence for hepatitis or for shared nonhepatic diseases. Fifteen of 17 donors excreted HGV/GBV-C in saliva (mean level, 8x103 copies of RNA/mL). Testing of previous donations indicated an incidence of 170-200 new infections with HGV/GBV-C per 100,000 donor-years. The absence of further clinicopathologic data and the limitations of current polymerase chain reaction-based methods for screening suggests that it is neither necessary nor practical to commence screening.     

Molecular evolutionary analysis of GB viruses and hepatitis G virus

Cysteine proteases have been identified in parasitic protozoa including the causative agent of Chagas' disease Trypanosoma cruzi. T. cruzi lysates subjected to substrate-containing SDS-polyacrylamide gel electrophoresis exhibit major bands of proteolytic activity in the 45-55 kDa molecular mass range (cruzipain activity). Paradoxically, addition of kininogen (a cystatin-like protease inhibitor) to the lysates before electrophoresis results in the appearance of additional bands of proteolytic activity in the 160-190 kDa molecular mass range. This inhibitor-activated protease activity depends upon the reaction conditions and exhibits novel properties. For example, a 24-48 hour preincubation at low temperature (-20 degrees C optimum) greatly enhances the proteolytic activity. The results suggest that a metastable complex forms between kininogen and a cryptic 30 kDa cysteine protease from T. cruzi and that this complex participates in the activation of proteolytic activity.     

GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze River, China

The latest meeting of the AAMC's Forum on the Future of Academic Medicine, on April 29, 1998, opened with a talk by Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute, who reviewed the significant progress that the Human Genome Project (HGP) has made and speculated on how genetic discoveries and technologies would transform health-related research and ultimately the practice of medicine. The HGP's findings will offer clear improvements in diagnosis and prevention, and eventually in treatments, and the relationship between the academic medical center and the pharmaceutical industry will change--but remain good--as that industry applies the findings of the HGP. He stressed the need for the public and health care providers to develop a greater understanding of genetic issues, and urged changes in medical education to accomplish this. Forum members and Dr. Collins discussed the ethics and economics in patient care resulting from genetic research; forum members also asked whether academic medical centers could profit from genetic research findings. The second speaker was John Eisenberg, MD, administrator of the Agency for Health Care Policy and Research, which fosters health care research and disseminates to clinicians and others the findings of such research. Among other topics, Dr. Eisenberg described the new emphasis on health care outcomes and quality and described how his agency promotes research in these areas. Forum members asked who would pay for the information systems needed to communicate the findings of health services research and also noted that there is an expanding definition of health that places new pressures on already stressed academic medical centers, their missions, and their curricula, which must change. Michael Whitcomb, MD, of the AAMC, noted that the view that medical schools can't change their curricula has been proved wrong, and that 24 medical schools are working with the AAMC's Medical Schools Objectives Project on curricular reform. The forum closed with discussion of a few broader issues affecting academic medical centers.     

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.     

Vertical transmission of hepatitis C virus infection

BACKGROUND: Cavernous carotid aneurysms are generally benign entities. Certain indications exist for their treatment, however, including transient ischemic events, subarachnoid hemorrhage or risk of subarachnoid hemorrhage, epistaxis or its risk, ophthalmoplegia, pain, and progressive visual loss. We feel certain angiographic features may indicate a greater likelihood that cavernous carotid aneurysms extend into the subarachnoid space, thus making their rupture a life-threatening event. METHODS: A case report of an intracavernous carotid aneurysm, which at surgery extended into the subarachnoid space, is described. RESULTS: In this particular case, deformation of the aneurysm (waisting) as seen at angiography was in retrospect an indication that the cavernous carotid aneurysm extended into the subarachnoid space, either through the dural ring or through the eroded dural roof of the cavernous sinus. This finding was verified at surgery when the lesion was explored and trapped. CONCLUSION: Angiographic waisting of a cavernous carotid aneurysm may indicate that the aneurysm extends into the subarachnoid space. Such extension means that rupture would be a life-threatening event. While deformation of the aneurysm may be secondary to compression against the optic nerve or anterior clinoid process with an intact layer of dura overlying the aneurysm, the neurosurgeon confronted with such findings should analyze such lesions carefully and consider surgical exploration.