Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined 24 C-type hepatitis specimens from Thailand and detected hepatitis C virus (HCV) RNA in all of them by RT-nested PCR for a portion of the HCV 5' non-coding (5' NC) region and a portion of the HCV core region. However, we failed to detect HCV RNA in 11 specimens by RT-nested PCR for a portion in the non-structural protein 5 (NS5) region that has been used commonly for HCV genotyping. We designed a new primer set for a separate portion of the NS5 region. Using this primer set, we succeeded in amplifying this portion in all 24 specimens. Two novel HCV genotypes, tentatively designated HCV-VII and HCV-VIII, were identified by sequencing these amplified regions. Our newly designed primers for RT-nested PCR may be useful for diagnosing infection as well as for genotyping unidentified HCV genomes.
 ...
PMID:Novel genotypes of hepatitis C virus in Thailand. 756 72

Hemophilia A is caused by a deficiency of factor-VIII procoagulant (fVIII) activity. The current treatment by frequent infusions of plasma-derived fVIII concentrates is very effective but has the risk of transmittance of blood-borne viruses (human immunodeficiency virus [HIV], hepatitis viruses). Use of recombinant DNA-derived fVIII as well as gene therapy could make hemophilia treatment independent of blood-derived products. So far, the problematic production of the fVIII protein and the low titers of the fVIII retrovirus stocks have prevented preclinical trials of gene therapy for hemophilia A in large-animal models. We have initiated a study of the mechanisms that oppose efficient fVIII synthesis. We have established that fVIII cDNA contains sequences that dominantly inhibit its own expression from retroviral as well as from plasmid vectors. The inhibition is not caused by instability of the fVIII mRNA (t1/2, > or = 6 hours) but rather to repression at the level of transcription. A 305-bp fragment is identified that is involved in but not sufficient for repression. This fragment does not overlap the region recently identified by Lynch et al (Hum Gene Ther 4:259, 1993) as a dominant inhibitor of RNA accumulation. The repression is mediated by a cellular factor (or factors) and is independent of the orientation of the element in the transcription unit, giving the repressor element the hallmarks of a transcriptional silencer.
 ...
PMID:Expression of the blood-clotting factor-VIII cDNA is repressed by a transcriptional silencer located in its coding region. 772 75

Among a total of 220 liver transplants, reduced-size liver was used in 21 cases due to discrepancies in size between recipient and donors in 19 patients. In the case of two adult patients suffering from fulminant hepatic failure and in a critical condition, only one donor organ became available, so that the graft was divided to give the two recipients an equal opportunity. The two patients with fulminant hepatic failure were admitted to the ICU requiring mechanical respiration almost at the same time. Hepatitis serologies were HBcAb+, HBsAb+, and VCA+ in one and negative in the second. They had different blood groups (A.Rh+, O.Rh-), and the only donor available was located in Milan, Italy. The graft perfused with UW. was divided into two (right side, segments IV, V, VI, VII, and VIII, and left side, segments I, II and III). The recipients were transplanted 50 and 48 hours after admission. The cold ischemia time was 7.10 and 16.50 hours. The first patient, who received the right lobe, was extubated at 48 hours and discharged on the 40th postransplant day. The second patient remained unconscious with progressive deterioration; an EEG on the 4th day revealed absence of higher cortical function.
 ...
PMID:Utilization of split liver grafts in orthotopic liver transplantation. 846 22

Virucidal methods to inactivate infectious agents are based on various methods of heating or chemically treating plasma concentrates of coagulation factors VIII and IX used in the treatment of hemophilia A and B. This clinical evaluation of the viral safety of such 'treated' concentrates is mainly based on the prospective study of previously untreated hemophiliacs by means of clinical and serological markers of viral infection. Although there have been a few focal episodes of human immunodeficiency virus (HIV) transmission by clotting factors, these have been traced to ineffective virucidal methods that are no longer used or to clerical errors during the manufacturing process. Viral inactivation by pasteurization, vapor heating, heating in the lyophilized state at 80 degrees C and addition of solvent/detergent definitely decreases the risk of infection with hepatitis B and C. The current screening of plasma units for antibody to hepatitis C virus prior to inclusion in pools for concentrate production should further decrease the risk of hepatitis C infection. Other viruses, such as parvovirus and the hepatitis A virus, may still cause infections because they are quite resistant to virucidal methods. On the whole, virucidal methods have greatly reduced the risk of new HIV infections and, to a lesser degree, hepatitis.
 ...
PMID:Clinical evaluation of viral safety of coagulation factor VIII and IX concentrates. 803 99

Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2-128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.
 ...
PMID:Acquired factor VIII inhibitors in nonhemophilic patients. 906 79

The current treatment of haemophiliacs consists of injection of concentrates of blood clotting factors VIII (haemophilia A) and IX (haemophilia B). The inconvenience of the multiple injections needed, and the risk of transmission of infectious agents (HIV, hepatitis) prompted the development of alternative therapies. Gene therapy aims at introducing functional factor VIII and IX genes into the body cells of patients in order to make these cells produce the desired clotting factors. There are two strategies for gene therapy: (a) in the laboratory cells of the patient may be provided with the desired gene, followed by reintroduction of the cells that now produce factor VIII, into the patient (ex vivo strategy); (b) vectors with the desired genes may be injected into the patient in order to induce the modification (in vivo strategy) For both routes, the formal proof-of-principle has been acquired recently in animal experiments: cells modified by factor VIII or IX genes will produce adequate concentrations of the clotting products in plasma and will correct the bleeding tendency. Before the clinical evaluation and widespread application of the technology can be considered many technical problems have to be solved.
 ...
PMID:[Gene therapy for hemophilia: feasible in principle but not yet clinically applicable]. 962 57

We have examined 93 adults HIV serum-positive (citizens of Moldova Republic), admitted in 1994-1998 (months I-VIII) to the Hospital of Infections Diseases 'T. Ciorba'--Kishinev. Since 1996 the number of HIV infected people began to grow up rapidly. Most affected group was those of 16-29 years old people--78.4%. The major way of the HIV transmission was the use of intravenous drugs (81.7%). Number of men i.v. drug users was two time greater then women's (88.9%/66.7%). At the time of HIV infection diagnosis 77.9% of patients were in the clinical category A, 16.9% in B and 5.2% in C (1993 classification system, CDC-Atlanta). During the control period seven persons were redistributed from the clinical category A to B and two from A to C. A high prevalence value for tuberculosis in AIDS (71.4%) has been observed, this infection being the first manifestation of stadium C in 57.1% of cases. The circulation of hepatitis viruses is high in the drug users community: the markers of VHC were detected in 84.2%, HBsAg in 17.1% and VHD antibodies in 9.2%.
 ...
PMID:[The clinico-epidemiological characteristics of HIV infection in 93 adults in the Republic of Moldova]. 1042 23

Known since the beginning of the first millenium, the hemophilias are among the most frequent inherited disorders of blood coagulation and definitely the most severe. In the 1970s, with the availability of concentrated preparations of the deficient coagulation factors VIII and IX and with the large-scale adoption of home treatment, hemophilia care became one of the most gratifying examples of successful secondary prevention of a chronic disease. Unfortunately, in the early 1980s It was recognized that factor concentrates prepared from plasma pooled from thousands of donors transmitted the hepatitis and the human immunodeficiency viruses. The scientific community reacted promptly to the devastation brought about by hepatitis and AIDS. The last 15 years of the second millenium have witnessed the development of methods that applied during concentrate manufacturing inactivate viruses escaping the screening procedures. The adoption of these measures has reduced dramatically the risk of transmission of bloodborne infections. The production of recombinant factors and their availability for patient treatment epitomize progress in hemophilia care through DNA technology. Methods based on the polymerase chain reaction (PCR) have unraveled an array of gene lesions associated with hemophilia, permitting improved secondary control of the disease through carrier detection in women from affected families and prenatal termination of their affected male infants. This article will review the aforementioned areas of progress and discuss unresolved problems (such as treatment of patients with antibodies, the risk of new infectious complications, and the issue of secondary tumors). Hopes and expectations for further improvement in the third millenium and particularly the prospects of hemophilia cure through gene replacement therapy will also be mentioned.
 ...
PMID:The hemophilias: progress and problems. 1059 59

A series of serum specimens obtained from two chimpanzees experimentally infected with hepatitis A virus (HAV), hepatitis C virus, and hepatitis G/GB-C virus were tested for TT virus (TTV) by polymerase chain reaction (PCR). All PCR fragments obtained from both animals were directly sequenced, and the nucleotide sequences were compared to each other and to all known TTV sequences. This comparison showed that both animals were infected simultaneously with four new TTV variants designated A, M1, M2, and M3. One chimpanzee was found to be infected with TTV only after HAV inoculation, whereas the other animal was infected with TTV before any experimental procedure was performed. A set of PCR primers specific for these four new TTV variants was used to amplify TTV-like sequences from nine naive chimpanzees. None of these animals was infected with the prototype TTV variant. Two of these animals, however, were infected with one of the new TTV variants, while one animal was infected with an additional new TTV variant designated T. Among 99 hepatitis patients, 29 were found to be infected with the prototype TTV variant. None of these human specimens was found to be positive by PCR specific for TTV variants A, M1, M2, and M3. Similarly, not a single specimen from a smaller subset of human serum samples was found to be positive for the TTV variant T. Phylogenetic analysis performed on all known TTV sequences demonstrated that TTV can be classified into 13 different, yet closely related TTV species, designated as TTV-I for the prototype variant through TTV-XIII. The new variants M1 and M2 were classified as two different genotypes of TTV-VI, variant M3 was classified as TTV-VII, variant A was classified as TTV-VIII, and variant T was classified as TTV-IX. Thus, the data obtained in this study suggest that TTV represents a large swarm of TTV-like species, some of which have not been detected in humans and circulate predominantly among chimpanzees.
 ...
PMID:Related TT viruses in chimpanzees. 1096 77

Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.
 ...
PMID:Factors predictive of death among HIV-uninfected persons with haemophilia and other congenital coagulation disorders. 1219 76


<< Previous 1 2 3 4 5 Next >>