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Biomedical subjects

C A Hall

Publications and source records attributed to C A Hall.

At least 127 records · Page 7Linked to original sources

The carriers of native vitamin B12 in normal human serum.

1. After fractionation of the vitamin B12-binding proteins of ten normal sera the components containing transcobalamin II and R-type binders of vitamin B12 respectively were studied for endogenous vitamin B12 content by two distinct systems of vitamin B12 assay. 2. The measurements of total serum vitamin B12 by either bioassay with Euglena gracilis or a radioisotope dilution assay agreed closely. 3. The native vitamin B12 carried by transcobalamin II was higher as measured by bioassay than by isotope dilution assay. 4. The presence of the transcobalamin II fraction of human serum altered the key reaction between the binding reagent of the isotope dilution assay, so that this assay failed to measure vitamin B12 quantitatively. 5. Probably, the mean fraction of plasma vitamin B12 carried by transcobalamin II is in the range 20--30%.

Biological Assay↗

The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole.

Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.

Abomasum↗

Radioimmunoassay for serum transcobalamin II.

A radioimmune assay for transcobalamin II (TC II) was devised from the following: (1) TC II-57Co B12 precipitated from normal serum with (NH4)2SO4 as the labeled ligand; (2) the TC II of whole serum as the standard source of TC II; (3) rabbit anti-pure TC II as the binding agent; (4) separation of the bound and free TC II-B12 by precipitation of the antibody bound with polyethylene glycol. The assay was responsive to either TC II or TC II-B12 and to TC II either pure or in crude preparations. It was not responsive to R-type binders of B12. The median TC II of 10 normal sera was 890 pg. per milliliter and of 10 sera from 10 random hospital patients was 1,010 pg. per milliliter. There was no measurable TC II in the serum of a child with congenital absence of TC II and the assay measured levels greater than 5,000 pg. per milliliter in abnormalities of TC II metabolism.

Antigen-Antibody Complex↗

Congenital deficiency of human R-type binding proteins of cobalamin.

A family expressing the congenital absence of the R-type binders of cobalamin (Cbl), vitamin B-12, was restudied. The capacity to bind Cbl to R type binders was absent from serum, saliva, cerebrospinal fluid, gastric juice granulocytes, and granulocyte output of the propositus. Serum R did not carry Cbl in vivo. There was no immunological R binder in his saliva, but cross reacting material was detected in his serum. Evidence of a partial expression of the defect was observed in offspring of two affected persons. There were no obvious clinical consequences of the defect.

Blood Proteins↗

Improved method for the purification of biologically active transcobalamin II.

Transcobalamin II (TC II) was purified about 300,000-fold from Cohn fraction III using a modification of the procedure described by Allen and Majerus (J. Biol. Chem. 247, 7709-7717 (1972)). The simplified method incorporated isoelectric precipitation of the TC II into the purification scheme which permitted the elimination of two column chromatographic steps originally reported by the above workers. The final preparation had 26.7 mug of vitamin B12 (B12) bound per mg of protein and an A280/A361 ratio of 2.05, both of which are in good agreement with the reported values. The purified TC II was biologically active with respect to its ability to facilitate penetration of B12 into HeLa cells in tissue culture.

Blood Proteins↗

The failure of granulocytes to produce transcobalamin I TC I.

The hypothesis that transcobalamin I (TC I) originates from granulocytes was tested by comparing the isoelectric focusing (IEF) patterns of the R-type binder (cobalophilin) of vitamin B12 of: 1) lysed granulocytes, 2) 24 h granulocyte output, and 3) plasma. The preparations came from the blood of 5 normal subjects and 4 with myeloproliferative states. The cobalophilin released into a culture of granulocytes resembled the binder in the granulocytes initially. TC I, defined as the alpha1 cobalophilin with components isoelectric between pH 2.9-3.35 and as a carrier of native plasma B12, was not released by granulocytes. The granulocyte binder of leukaemic granulocytes did not differ from the normal in content per cell or amount released.

Blood Proteins↗

Cytology of bronchial washings: a study of patients with malignant neoplasms of the head and neck.

Among 18 patients with locally advanced malignant neoplasms of the head and neck region, bronchial washings failed to reveal tumor cells despite the demonstration of exfoliated tumor cells in washings from the region of the primary tumor in 13 (72 percent) of the patients. Among 17 patients with bronchogenic carcinomas, however, tumor cells were isolated from the bronchial washings in 14 (82 percent). These results indicate that, in patients with malignant neoplasms of the head and neck, tumor cells found in bonchial washings probably are not from the primary head and neck neoplasms. Thus, cytologic examination of bronchial washings may be validly employed in the differential diagnosis of the pulmonary tumors in patients with malignant neoplasms of the head and neck region.

Bronchi↗

Variation in plasma folate levels among groups of healthy persons.

Levels of plasma folate, erythrocyte folate and serum vitamin B12 were measured in 106 essentially healthy persons grouped both as to race and economic--educational status. Whereas the mean values of the three assays did not differ significantly among groups, values of plasma folate below the usual limits of normal were more prevalent in the migrant worker and urban clinic groups. Persons with low plasma folate levels did not have symptomatic deficiency as evaluated by hematocrit, peripheral blood smears and erythrocyte folate levels. The interpretation of the plasma folate requires reference values from a healthy population selected to be comparable to the study group. The diagnosis of deficiency, or at least the degree of deficiency, requires clinical and laboratory evaluations beyond the plasma folate.

Adult↗

The value of age- and sex-matched controls for coagulation studies.

Several coagulation parameters and plasminogen levels were studied in 80 normal people divided into eight paired and sex-matched age groups: prepubertal children, postpubertal children, young adults, and adults over 50. The data indicate that factor-VII and -IX activities increase with age, with a cluster of lower activity for children and higher activity for adults. Factor-VIII levels appear to decrease with age, although this effect could be due to greater anxiety in the pre- and postpubertal children at the time of venipuncture. The adults showed no significant change in factor-VIII activity with age, but partial data indicate that factor-VIII levels are higher in adults with blood group A than those with blood group O. The age-related changes in factor-VII, -IX, and possibly -VIII activities did not vary between sexes. By contrast, plasminogen increased strikingly with age in males and decreased with age in females. With fibrinogen, a similar effect was found for adults, though not for the entire population. These findings indicate the importance of using appropriate age- and sex-matched controls for coagulation and plasminogen assays, especially in patients with mild inherited or acquired coagulation disorders.

ABO Blood-Group System↗

Hereditary factor VII and IX deficiencies in a large kindred.

A large kindred with combined deficiencies of factors VII and IX is presented. The deficiencies appeared to be independent and the data were not consistent with a diagnosis of haemophilia BM. The identification of mildly affected family members, including carriers of haemophilia B and heterozygotes for factor-VII deficiency, was facilitated by comparison with the 95% confidence interval of an age- and sex-matched control population. The bleeding patterns were those of mild to moderate haemophilia B and did not appear to have been modified by the presence of factor-VII deficiency.

Factor IX↗

Transcobalamins I and II as natural transport proteins of vitamin B12.

There are two conflicting theories of how plasma vitamin B12 (B12) is transported in man: (a) by two distinct transport proteins, transcobalamins I and II (TC I and II), each having a specific role and time of function; and (b) by three active transport proteins, TC I, II, and III, that take up B12 randomly in proportion to the unsaturated amounts of each. To test these theories a man was given 1.12 mug, 229 muCi, of [57Co]B12 mixed with food. Blood samples were taken several times on the 1st day and at lengthening intervals up to day 51. The amount of TC II-B12 was measured in each sample by: gel filtration and by precipitation with (NH4)2SO4. Total serum R-B12 was then separated into TC I and TC III by: (a) a single step anion exchange system and (b) isoelectric focusing (IEF). As the B12 was being absorbed, 92-95% of that in venous blood was carried by TC II. Absolute and percentage transport by TC II declined sharply during the first 24 h; between days 7 and 51 20-33% of the label was on TC II, and the rest was carried by R-type binders. Absolute transport by TC I did not reach a maximum until after day 1 and before day 3. Transport by an alpha2 R-type binder, TC III, could not be demonstrated. TC I was isoelectrically heterogenous, with the components focusing between pH 2.9 and 3.35. It was concluded that (a) TC II is the dominant carrier of B12 immediately after absorption; (b) maximum transport by TC I requires the passage of time after absorption; (c) after the absorbed B12 reaches equilibrium with the total body B12, about one fourth of the plasma B12 is carried by TC II and three fourth by TC I; and (d) TC I and TC II are the only functional transport proteins of plasma B12.

Biological Transport↗

Release of transcobalamin II by canine organs.

The output of vitamin B12 transport proteins by canine tissues was determined from isolated, perfused organs. Transcobalamin II as identified by four techniques was released by the spleen, heart, liver, and kidney. When related to perfused weight, the greatest output occurred from the kidney.

Animals↗

Measurement of vitamin B12-binding proteins of plasma. II. Interpretation of patterns in disease.

The technique described in the preceding paper was applied to 12 abnormal sera selected for their increase in one or more B12-binding proteins. Even in the presence of large amounts of R-type binder, the ammonium sulfate technique gave a reliable separation of R binding proteins from TC II. Measurement of the TC II in abnormal sera gave results identical to those obtained by the more standard gel filtration. The R binders of four subjects with myeloproliferative disease were further separated into alpha2-R and alpha1-R. The pattern of B12 binding of polycythemia vera (PV) was an exaggeration of the normal pattern. Binding to alpha2-R was three to four times that to alpha1-R, although the total amounts bound to both were increased. In chronic myelogenous leukemia (CML), both alpha2-R and alpha1-R were also increased, but in contrast to binding in normal sera, alpha1-R predominated. In order to interpret the findings, either whole serum R or alpha1-R and alpha2-R from patients with myeloproliferative disease were subject to isoelectric focusing. Alpha2-R consisted pricipally of components isoelectric at pH 2.9, 3.0, and 3.1. These components were present in only minor amounts in normal serum and were somewhat increased in the serum of PV. These components were very much increased in the serum of CML and predominated. Alpha2-R consisted of those components isoelectric at pH 3.4,3.6, and 4.0. These components predominated in the unsaturated binding capacity of normal sera and that of PV. It was concluded that the division of plasma R binders into alpha1-R and alpha1-R by the technique described provided information useful in the study of myeloproliferative diseases.

Ammonium Sulfate↗

Fiberoptic endoscopy in the head and neck region.

The potential use of fiberoptic endoscopy in the head and neck region was evaluated by the comparison with the findings we obtained from indirect, mirror endoscopy. Fiberoptic endoscopy confirmed our clinical staging and diagnosis in 39 percent, changed our diagnosis in 41 percent, and changed our clinical staging in 20 percent of this series of patients. These findings indicate that fiberoptic endoscopy is a valuable aid for clinical staging; in some instances it may be used in preference to indirect, mirror examination; frequently, it may enable one to avoid a direct laryngoscopy. The procedure is safe, well tolerated, and may be performed on an outpatient basis. With this instrument, routine examination of the head and neck in suitable patients may lead to improved clinical evaluations.

Adolescent↗

Measurement of vitamin B12-binding proteins of plasma. I. Technique.

The unsaturated binding capacities (UBBC) of individual vitamin B12-binding proteins in plasma were measured by a two-step procedure. Transcobalamin II (TC II) was separated by precipitation with ammonium sulfate; the "R"-type binders remaining soluble were then divided into two components by bath separation with anion exchange on DEAE-cellulose. The two R components were designated alpha1-R (TC 1) and alpha2-R (third binder, fetal binder, PV binder, TC III). Ten normal sera were studied by this technique giving a separation into TC III and total plasma R identical to that obtained simultaneously by gel filtration. The mean UBBC of TC II was 969 plus or minus 204 pg of 57 Co B12 per ml of serum. The mean contamination of the precipitated TC III with plasma R was 3%. The UBBCs of alpha 2-R and alpha 1-R were 127 plus or minus 42 and 40 plus or minus 12 pg/ml, respectively. The mean contamination of the R fraction by TC II was 14% as evaluated by gel filtration. By isoelectric focusing it was found that the alpha1-R contained principally those components isoelectric at pH isoelectric at pH of 2.9-3.2, while alpha2-R was made up of those components isoelectric at pH of 3.6 or greater.

Ammonium Sulfate↗