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Biomedical subjects

M Kane

Publications and source records attributed to M Kane.

At least 19 recordsLinked to original sources

Induction of antigen-specific T and B cell immunity in colon carcinoma patients by anti-idiotypic antibody.

Polyclonal goat anti-idiotypic Abs directed against anti-human gastrointestinal carcinoma mAb GA733 were administered to 13 colon cancer patients who had their primary tumor and lymph node metastases removed before immunotherapy. Patients received four s.c. doses (0.5 to 8 mg each) of alum-precipitated anti-idiotypic Ab. Seven of the 13 patients produced anti-anti-Ids that bound specifically to the GA733 epitope on tumor cells and shared idiotopes with mAb GA733. In four of the seven responding patients, anti-Id therapy specifically modulated T cell responses. In two patients who did not demonstrate GA733 Ag/anti-Id-reactive T cells before therapy, anti-Id administration induced CD4+, MHC class II-dependent T cells that specifically proliferated in culture in response to stimulation with either anti-Id or GA733 Ag. In two other patients who did demonstrate Ag/anti-Id-reactive T cells before therapy, anti-Id administration transiently induced lymphocytes that suppressed the proliferative responses of cultured pretherapy lymphocytes to stimulation with anti-Id or GA733 Ag. Nine of the 13 treated patients showed no evidence of disease after 39 to 86 mo of observation. Five of these patients developed Ag-specific Ab3 and one had, in addition, a T cell response.

Adult

Epidemiology of hepatitis B infection in North America.

Although the USA is considered an area of 'low' endemicity for hepatitis B infection, the incidence of new cases, the prevalence of carriers, and the burden of acute and chronic disease place hepatitis B among the most important communicable diseases. It is estimated that 300,000 new cases of hepatitis B infection occur each year. These acute infections lead to 350-450 fulminant deaths, 27,000-42,000 chronic carriers and ultimately 4000-5500 deaths per year from cirrhosis and primary liver cancer. Most reported cases occur among young adults, many of whom belong to 'high risk' groups defined by lifestyle or occupation. In 1991, sexual transmission was the predominant mode of transmission (41% of cases by heterosexual activity; 14% by homosexual activity); percutaneous drug use was also important (12% of cases). Infection in healthcare workers represented only 2% of reported cases, and is the only group where falling incidence is due to vaccine use. However, 26% of cases occur in people who deny belonging to any 'high risk group'. Public health officials in the USA concluded that the 'high risk group' immunization strategy would not lead to the control of hepatitis B infection on a population basis. In 1992, it was recommended that all newborns in the USA receive hepatitis B vaccine as part of their routine immunization schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Global programme for control of hepatitis B infection.

The hepatitis B virus (HBV) has infected more than 2000 million persons alive today and 350 million persons are chronically infected carriers of the virus, at high risk of death from active hepatitis, cirrhosis and primary hepatocellular cancer. Each year approximately 1 million people die from the acute and chronic sequelae of HBV infection, making it one of the major causes of morbidity and mortality in man. In May 1992, the World Health Assembly, the governing body of the World Health Organization, endorsed recommendations stating that countries with an HBV carrier prevalence of 8% or more should have hepatitis B vaccine integrated into their national immunization programmes by 1995 and that all countries should have such immunization in place by 1997. At present, 50 countries have a national policy of including hepatitis B vaccine as a routine part of their infant immunization programme--up from 25 countries in 1990. These countries represent 32% of the world's 145 million newborns, but 56% of the world's carriers. Several countries of 'low' endemicity are also recommending hepatitis B immunization of all newborns or adolescents (or both), realising that the strategy of 'high-risk group' immunization has failed to control HBV infection even in areas of low endemicity and that addition of hepatitis B vaccine to routine immunization schedules is highly cost-effective. All countries should establish working groups to examine the burden of disease due to HBV infection and the cost-effectiveness of adding hepatitis B vaccine to routine and/or adolescent immunization programmes.

Adolescent

Implementing universal vaccination programmes: USA.

In the USA, the policy is that all infants receive vaccine against hepatitis B virus (HBV). It is considered that HBV vaccine can be readily integrated into the routine childhood immunization schedule without additional visits. Booster doses of vaccine are not currently recommended because protection lasts for at least 10 years after vaccination. As with the other universal vaccination programmes, pre- or post-vaccination screening is not undertaken. Screening of all pregnant women for HBV surface antigen (HBsAg) and immunization of all infants of HBsAg-positive mothers has been continued.

Costs and Cost Analysis

Model-based estimates of the risk of human immunodeficiency virus and hepatitis B virus transmission through unsafe injections.

BACKGROUND: Patient-to-patient transmission through contaminated medical equipment may be the principal route of nosocomial blood-borne infections globally. Quantifying cross infection risks could facilitate efforts to ensure safe injections in developing countries. METHOD: A mathematical model was developed to evaluate the risk of cross infection due to unsafe injections. The model was applied to immunization programmes with a fixed number of injections and in which unsterile needle and syringe reuse rates were specified. Risk estimates were generated using a range of human immunodeficiency virus (HIV) and hepatitis B (HBV) prevalences. RESULTS: The risk of cross infection is zero when properly sterilized equipment is used. With unsafe injections, the risk of cross infection with HBV is consistently higher than HIV for comparable levels of endemicity. A single reuse of each needle and syringe in areas with an HBeAg prevalence of 4% results in 980 cases of HBV/100,000 infants; reuse four times results in 3740 cases. When the HIV prevalence is 1% and the reuse rate is 4, 14 to 35 cases of HIV/100,000 women could occur. Contamination of multidose vaccine vials could considerably increase these estimates. CONCLUSIONS: Neither HIV nor HBV transmission has been reported with injections administered through the Expanded Programme on Immunization. However, ample evidence exists that reuse of unsterile needles and syringes is common in developing countries. Ongoing efforts to ensure safe practices and improve injection technologies are required to protect these populations from both medical and traditional skin-piercing procedures.

Adult

Cloning, sequencing and expression of the S1 gene of avian reovirus.

The S1 genome segment of avian reovirus strain S1133 was cloned and completely sequenced. The sequence comprised 1636 bp with three distinct open reading frames (ORFs), suggesting the gene was polycistronic in nature. The three ORFs from 5' to 3' were predicted to encode polypeptides of 9.8, 3.8 and 34.9 kDa, respectively. Of the three ORFs, only the third possessed the AUG initiation codon in an optimum context for translation. The third ORF-encoded protein, 326 amino acids in length, was expressed in Escherichia coli and used as antigen in immunoblots. The protein was concluded to be sigma 3 on the basis of its recognition by a chicken anti-reovirus antiserum and due to the fact that a mouse antiserum raised against it recognized specifically the viral sigma 3 polypeptide. Sequence comparison of the avian reovirus S1 gene with its mammalian counterpart did not show any significant similarity between the two. However, amino acid sequence analysis and the predicted existence of a heptapeptide repeat pattern, as well as the relatively high frequency of alpha-helix structures in the amino terminal portion of sigma 3 suggests that this protein is structurally, and probably functionally, related to mammalian reovirus sigma 1 protein.

ATP-Binding Cassette Transporters

Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.

OBJECTIVE: To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD: Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS: The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS: These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment.

Adult

Reduced doses of hepatitis B vaccines: is it a good idea?

Hepatitis B vaccines are not generic products and it cannot be assumed that all such vaccines can be used in reduced doses in order to save costs. Any use of vaccines in an unlicensed manner should only be performed in the context of a study that is approved by the national control authority and appropriate ethical review committees.

Dose-Response Relationship, Immunologic

Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer.

The human DNA mismatch repair gene homologue hMSH2, on chromosome 2p is involved in hereditary non-polyposis colon cancer (HNPCC). On the basis of linkage data, a second HNPCC locus was assigned to chromosome 3p21-23 (ref. 3). Here we report that a human gene encoding a protein, hMLH1 (human MutL homologue), homologous to the bacterial DNA mismatch repair protein MutL, is located on human chromosome 3p21.3-23. We propose that hMLH1 is the HNPCC gene located on 3p because of the similarity of the hMLH1 gene product to the yeast DNA mismatch repair protein, MLH1, the coincident location of the hMLH1 gene and the HNPCC locus on chromosome 3, and hMLH1 missense mutations in affected individuals from a chromosome 3-linked HNPCC family.

Adaptor Proteins, Signal Transducing

An evaluation of the relationship between self-report and biochemical measures of environmental tobacco smoke exposure.

To evaluate the relationship between self-reported exposure to environmental tobacco smoke and saliva cotinine concentrations, we studied 186 nonsmokers. Each participant completed an exposure questionnaire, kept a daily exposure diary for 7 days, and provided a saliva sample for cotinine analysis. Salivary cotinine concentrations were measured using gas chromatography/mass spectrometry. Of the volunteers, 30% lived with one or more smokers, and 84% were regularly exposed to smokers at work. Eighty-three percent of the volunteers had detectable saliva cotinine concentrations (> or = 0.5 ng/ml) (median = 1.1; range = 0.5-7.4 ng/ml). Cotinine concentrations were related to exposure in the household and at the workplace. Volunteers who lived with smokers had significantly higher cotinine levels (median = 1.0; range = < 0.5-7.4 ng/ml) than those who did not (median = < 0.5; range = < 0.5-4.7 ng/ml). Volunteers who reported regular exposure at work had higher cotinine levels (median = 0.8; range = < 0.5-7.4 ng/ml) than those who did not (median = < 0.5; range = < 0.5-3.0 ng/ml). Cotinine concentrations were predicted by a regression equation that included the number of smokers at home and work and the number of minutes of exposure recorded in the daily diary (r2 = 0.29).

Adolescent

Determination of ABO genotypes with DNA extracted from formalin-fixed, paraffin-embedded tissues.

The gene encoding the specific glycosyltransferases which catalyze the conversion of the H antigen to A or B antigens shows a slight but distinct variation in its allelic nucleotide sequence and can be divided into 6 genotypes when digested with specific restriction enzymes. We extracted DNA from formalin-fixed, paraffin-embedded tissues using SDS/proteinase K treatment followed by phenol/chloroform extraction. The sequence of nucleotides for the A, B and O genes was amplified by the polymerase chain reaction (PCR). DNA fragments of 128 bp and 200 bp could be amplified in the second round of PCR, using an aliquot of the first round PCR product as template. Degraded DNA from paraffin blocks stored for up to 10.7 years could be successfully typed. The ABO genotype was deduced from the digestion patterns with an appropriate combination of restriction enzymes and was compatible with the phenotype obtained from the blood sample.

ABO Blood-Group System

A framework for the evaluation of vaccines for use in the expanded programme on immunization.

Since 1974, the Expanded Programme on Immunization (EPI) has provided technical support for the immunization of the world's children and women of childbearing age. Today, the vast majority of vaccines administered to these groups are delivered through the immunization programmes that have been established in developing countries. As these national programmes share many characteristics, the global use of a new or improved vaccine could be largely dependent on its compatibility with the priorities, existing antigens and vaccine delivery system of this network. Consequently, a framework has been developed for the systematic evaluation of candidate vaccines for use in EPI.

Adult