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Biomedical subjects

I Millman

Publications and source records attributed to I Millman.

17 recordsLinked to original sources

'Aspira': a new sensitive assay for the detection of hepatitis B surface antigen.

A sensitive method for the detection of hepatitis B surface antigen (HBsAg) is described whereby the separation of specific antibody by affinity chromatography is incorporated into one of the assay reagents. HBsAg, which may be obtained from tissue culture fluids of a human hepatoma cell line, is first reacted with polystyrene beads. Unoccupied spaces on the plastic are next covered with a non-specific protein (e.g. albumin). The plastic is then reacted with either whole antiserum or an IgG fraction of anti-HBs. Care must be taken to cover all of the reacting sites of the first layer of HBsAg with sufficient anti-HBs. This results in a reagent of detecting antigen. No affinity purified antibody was necessary because the reagent, at this stage, contains only specific antibody on the surface. Antigen reacting with this reagent can be detected by the addition of radioactively labeled IgG fraction of anti-HBs, which will complete the 'sandwich'. This assay has been evaluated and found to be as sensitive as those commerically available.

Animals

Persistence of hepatitis B surface antigen in the bedbug Cimex hemipterus (Fabr.).

The fate of hepatitis B virus in the bedbug was investigated to assess this insect's potential as a vector. Colony-reared Cimex hemipterus (Fabr.) were fed once on blood positive for hepatitis B surface antigen (HBsAg). The insects were sampled at intervals thereafter and tested for HBsAg by radioimmunoassay. HBsAg persisted for up to six weeks in the bedbug's body after a single HBsAg-positive meal, during which time several further HBsAg-negative blood meals were taken. This result explains the high rates of field infection in bedbugs and further supports the hypothesis that bedbugs may play a role in transmission of hepatitis B virus.

Animals

Glycoproteins of natural origin with an affinity for hepatitis B surface antigen.

Sera from certain animal species contain a substance(s) which binds hepatitis B surface antigen. The hepatitis B binding substance found in animals is not antibody, but appears to be a glycoprotein which reacted with antigen-coated beads and produced a "false positive" test for antibody. This glycoprotein could be selectively and quantitatively removed by reaction with purified hepatitis B surface antigen and centrifugation. Pili fractions isolated from Neisseria gonorrhoeae and Escherichia coli bound to hepatitis B surface antigen and produced false positive anti-hepatitis B surface antigen reactions. Mouse anti-bovine hepatitis B binding substance and rabbit anti-E. coli pili were capable of neutralizing bovine hepatitis B binding substance.

Animals

Hepatitis-B virus in bedbugs (Cimex hemipterus) from Senegal.

Bedbugs of the species Cimex hemipterus (F) were collected on four separate occasions from the bedding in the huts of village dwellers in Senegal, West Africa. Hepatitis-B surface antigen (HBSAg) was detected in unengorged nymph and adult bedbugs in each of the first three collections. 3 of 28 such specimens were HBSAg(+) in the first collection and 3 of 17 specimens were positive in the second collection. In the third, 6 of 9 were HBSAg(+) when the bed occupant was known to be HBSAg(+). 2 of these 6 positive insects did not contain human serum proteins. Bedbugs in the fourth collection were captured and kept alive without a blood meal for 30 days. 3 of 89 of these samples were HBSAg(+). These are the highest field infection-rates of hepatitis-B virus reported in any insect species. The bedbug must be considered a potential vector of hepatitis-B virus.

Adolescent

Antitumor activity of Propionibacterium acnes (Corynebacterium parvum) and isolated cytoplasmic fractions.

The tumor-inhibitory effect of an intralesional injection of Propionibacterium acnes was of limited duration ("finite"). Our model was the DBA/2 syngeneic mouse injected with P815 mastocytoma cells (5 X 10(5)) into each rear footpad; only the left was treated, leaving the right as a "pseudometastasis." The finite effect occurred at approximately 21 days after the first treatment. Subsequent i.p. treatments with P. acnes did not alter this effect, although they increased mean survival time. With one footpad tumor, we achieved 22% cures with complete regression and no sign of metastatic growth. A RNA fraction from P. acnes produced inhibition of tumor growth, but crude cell walls and cell walls treated with Pronase had no effect. A P. acnes cytoplasmic fraction with tumor-inhibitory activity was pelleted by high-speed centrifugation; this fraction inhibited P815 mastocytoma as fully as whole cells injected in one-fifth the dose on a nitrogen basis and did not cause a local inflammatory reaction. The activity of the pellet also differed from whole cells in that it was equally inhibitory to the pseudometastasis in the contralateral right rear footpad. The cytoplasmic fraction apparently contained at least two active components since activity was obtained at two dilution levels. Such activity was relatively stable at 5 degrees, but it was unstable at -30 degrees.

Animals

Automated complement fixation test for the detection of antibodies against the core of hepatitis B virus (HBc).

The automated complement fixation system presented in this paper differs from those described by Studievic et al. (1971) and Vargues and Henley (1974). In the one developed here only one sampler is used with a wheel presenting a double row of cups. This system can assay 60 samples per h and can be modified to double this number. Our unit requires an incubation period of 15 min at 37 degrees C and we have nerver observed any contamination of the samples during the assay run.

Antibodies, Viral

Mycobacterial ribonucleic acid: comparison with mycobacterial cell wall fractions for regression of murine tumor growth.

Mycobacterial ribonucleic acid (RNA) and cell wall skeleton fraction isolated from H37Ra caused P-815 mastocytoma regression in DBA/2 mice provided the animals were presensitized with freshly harvested living H37Ra cells. In the absence of presensitization, only the RNA fraction inhibited. Cell wall skeleton fraction, under these conditions, stimulated tumor growth. Cell wall lipids (from H37Ra) added to H37Ra cell wall skeleton fraction did not increase the inhibitory activity of cell wall skeleton fraction alone. Mycobacterial RNA appeared to be an effective inhibitor of P-815 mastocytoma metastases as shown by (i) the inhibition of a second footpad lesion distant from the one treated and (ii) increase in survival time.

Animals

Hepatitis B surface antigen (Australia antigen) in mosquitoes collected in Senegal, West Africa.

During July and August of 1973, 9,198 mosquitoes were collected in the Republic of Senegal. Eight species of mosquitoes were found in the collections: Culex thalassius, Culex pipiens quinquefasciatus, Culex trigripes, Culex phillipi, Aedes irritans, Aedes aegypti, Anopheles gambiae, and Mansonia sp. Specimens were sorted by biological condition; those obviously engorged were designated as (E), females with swollen abdomens not conspicuously blooded were considered gravid (G), and those with normal or shrunken abdomens were considered neither blooded nor gravid (U). Representative samples of each species were tested by solid phase radioimmunoassay for hepatitis B surface antigen (HBSAg, Australia antigen). A total of 12 mosquitoes were found to be HBSAg positive out of 1,658 individuals tested. These were: 9 Culex thalassius, 1 (E), 5 (G), 3 (U); 2 Culex pipiens quinquefasciatus, 1 (E), 1 (U); and Aedes irritans, 1 (U).

Animals

[The relation of infection with the hepatitis B-agent to primary hepatic carcinoma (author's transl)].

In Asia, Africa and other tropical areas primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the post-necrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 PHC patients had hepatitis B surface antigen (HBSAg) (controls: 8 of 98) and 56 of 63 (controls: 26 of 100) had antibody against hepatitis B core antigen (anti-HBC). In earlier studies we demonstrated a maternal effect of HBSAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBSAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; p = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBSAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the African hepatoma patients showed that there is a very high frequency of HBSAg in mothers (71.6%) while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. We described a vaccine several years ago which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.

Adult

Mycobacterial RNA. A comparison with intact mycobacteria for suppression of murine tumor growth.

Our experimental data imply the following: (1) An RNA-rich fraction isolated from H37Ra, and intact H37Ra, are effective agents for suppression of tumor growth. (2) For suppression of two chemically-induced tumors with both RNA and H37Ra, direct contact with tumor is necessary. This may not be the case with other tumors in different strains of syngeneic mice. (3) The host's immunological system is a necessary component for inhibition of tumors by our test materials since there is no tumor suppression in immunologically impaired mice.

Animals

Antibody to hepatitis-B core antigen in patients with primary hepatic carcinoma.

Antibody to hepatitis-B core antigen (anti-HBc) was assayed in the serum of patients with primary hepatic carcinoma (P.H.C.) and controls from Hong Kong, West Africa, and the United States. In each region the prevalence of anti-HBc was higher in P.H.C. patients than in controls, ranging from 70 to 95% in the patients and from 20 to 68% in the controls from Asia and Africa; 24% of P.H.C. patients and 4% of controls from the U.S. had anti-HBc. These data support the hypothesis that chronic infection with hepatitis-B virus is aetiologically related to P.H.C., especially in Asia and Africa, although other factors must also be involved.

Antibodies, Viral

Investigation of the nature of Australia antigen. I: The absence of biological activity of Australia antigen in human blood leukocyte culture.

Purified and concentrated preparations of Australia antigen had no stimulating effect on leukocytes of human subjects under study when tested either on DNA-polymerase activity, 3H-thymidine uptake or chromosomal alterations. Moreover, in patients with chronic hepatitis and cirrhosis of the liver no correlation between antigenemia and chromosome aberrations in blood leukocyte cultures could be detected. On the other hand, a serum obtained from a virus hepatitis patient with Australia antigen in the blood was found to stimulate leukocyte cultures from one patient with Down's syndrome and antigenemia, one mentally retarded patient and three normal donors. This stimulating agent is obviously not associated with Australia antigen.

Adolescent

Genome of hepatitis B virus: restriction enzyme cleavage and structure of DNA extracted from Dane particles.

DNA extracted from Dane particles has been characterized by gel electrophoresis and restriction enzyme cleavage with endonuclease R-HaeIII (from Hemophilus aegyptius). Dane particle DNA is proposed to be a double-stranded circular DNA approximately 3600 nucleotides in length containing a single-stranded gap of 600-2100 nucleotides. The endogenous DNA polymerase (DNA nucleotidyl-transferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase; EC 2.7.7.7) reaction appears to repair this single-stranded gap.

DNA Nucleotidyltransferases

An association of hepatitis B (Australia) antigen with platelets.

Hepatitis B surface antigen (HBsAg, Australia antigen) was detected by radioimmunoassay in freeze-thaw lysates of washed platelets from HBsAg carriers. Incubation of platelets from an HBsAg-negative person with medium containing HBsAg resulted in the platelets becoming positive for HBsAg. We suggest that platelets may phagocytize HBsAg-coated particles, and this may be an important transport mechanism for the hepatitis B agent.

Adult

The incorporation of radioactive uridine into the hepatitis B antigen of a chimpanzee.

Radioactive (3H) uridine was incorporated into RNA isolated from the HBsAg of a chimpanzee carrier. HBsAg was purified by precipitation as an immune complex with the IgG fraction of chimpanzee anti-HBs. RNA was extracted from the washed complex with buffered phenol precipitated with alcohol and four nucleotides were identified by thin layer chromatography after alkali degradation.

Animals

The relation of infection with the hepatitis B agent to primary hepatic carcinoma.

In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.

Africa