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Biomedical subjects

C A Hall

Publications and source records attributed to C A Hall.

At least 55 records · Page 3Linked to original sources
PubMed1987

Cyclic activity of the receptors of cobalamin bound to transcobalamin II.

The activity of receptors specific for human transcobalamin II-Cobalamin (TC II-Cbl) were measured in virus-transformed lymphoblasts, hepatocytes (hepatoma) and diploid fibro lasts. In all three types of human cells the receptor activity increased as cells went from a resting phase to the most actively dividing phase. Receptor activity declined as cell division slowed. The changes in activity of lymphoblasts and hepatocytes were produced by changes in receptor number and not by changes in affinity between receptors and TC II-Cbl. The basis of the change in fibroblasts was not clear. The Cbl-dependent methionine synthetase activity of fibroblasts, in contrast, tended to be greatest when the cultures were confluent and replication had slowed. As the fibroblasts became senescent the receptor activity for TC II-Cbl declined and the fluctuations with the phase of the cell were blunted. However, the release of apo TC II from the cells was maintained. These observations must be taken into consideration when the respective cells are used as models. Even more important are the implications of the observations of the changes in receptor activity for TC II-Cbl for the regulation of the entry of Cbl into cells.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1986

A patient with the inability to maintain in vivo levels of bound cobalamin (Cbl) and manifestations of tissue deficiency of Cbl.

A 39-year-old woman presented with mild anemia, glossitis, an increased MCV, a low serum cobalamin (Cbl) (vitamin B12), mild tissue deficiency of Cbl, but with neither malabsorption of Cbl, impaired intake, nor deficiency of or inactivity of transcobalamin II (TC II). Because of a persistently low holo-TC II (TC II carrying Cbl as the circulating complex of TC II-Cbl), much of the evaluation was focused on the patient's TC II. Her TC II promoted the uptake of Cbl, reacted with anti-TC II, and bound Cbl in vitro. A test dose of 200 micrograms of cyanocobalamin (CN-Cbl) i.m. increased her holo TC II to levels higher than those in healthy persons, but with a much more abrupt fall to a subnormal level. Two milligrams of CN-Cbl i.m. followed by 100 micrograms i.m. monthly failed to maintain normal amounts of circulating TC II-Cbl or to overcome the tissue deficiency of Cbl. One milligram i.m. weekly or daily p.o. corrected both. The low holo TC II was considered to be responsible for the clinical expression and may have been primary to the reduced amounts of total and holo R binder of Cbl in the circulation. This study of a newly recognized defect points out the need for circulating holo TC II, a rational use of pharmacologic amounts of Cbl, and a possible interrelationship between TC II and the R binder of Cbl.

Adult↗
PubMed1986

Methionine dependency of cultured human lymphocytes.

Human peripheral blood lymphocytes stimulated with phytohemagglutinin and a lymphocyte model consisting of the RPMI 6410 cell, a human virus-transformed B cell, required added methionine (Met) for growth of the cultures. This failure to meet all needs for Met via endogenous synthesis, which is characteristic of oncogenic transformation, occurred even in the presence of adequate homocysteine, methylfolate (5-CH3-H4PteGlu) and cobalamin (Cbl)-dependent methionine synthetase activity. Folinic acid (5-CHO-H4PteGlu), which provides available folate independently of Cbl, improved growth only slightly in the absence of Met. Free Cbl at 222 nM, an amount great enough to alter other intracellular events, failed to increase growth in the absence of Met, but 0.22 nM Cbl bound to transcobalamin II did, however, enhance growth.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1986

Methionine synthetase activity of human lymphocytes both replete in and depleted of vitamin B12.

The activity of the enzyme methionine synthetase (MS) (methyltetrahydrofolate:homocysteine methyltransferase) (EC 2.1.1.13) was measured in human lymphocytes of various types and cobalamin (vitamin B12) status. Total and holo MS activity was low in unstimulated peripheral blood lymphocytes from persons with tissue deficiency of cobalamin, but not in cells from those with low serum cobalamin levels for other reasons. The MS activity of the lymphocyte was increased by treatment of the patients with vitamin B12. The number of lymphocytes was often low or low normal in the circulation of those deficient in cobalamin. Holo MS activity was low in an established line of human B cells, RPMI 6410 cells, depleted of cobalamin. The total and holo MS activity of both RPMI 6410 cells, replete or depleted, and lymphocytes stimulated in culture was increased by cobalamin in vitro; 222 nmol/L free cobalamin was roughly the equivalent of 0.22 nmol/L cobalamin bound to transcobalamin II. Both lymphocytes and RPMI 6410 cells required folate for growth and could meet these needs via methylfolate, homocysteine, and the cobalamin-dependent MS reaction. Depleted RPMI 6410 cells, however, used cobalamin in some way in addition to the provision of available folate from methylfolate. The consequences of the reduced MS activity in deficient cells could include a reduction in available folate with diminished capacity for clonal expansion of lymphocytes in reaction to infection and impairment of essential methylations including those of protein synthesis. The prompt induction of MS activity by cobalamin, especially in the in vitro model, suggests an effect of therapeutic vitamin B12 well in advance of the numerical increase in cells of the blood.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1985

Synthesis of transcobalamin II by cultured human hepatocytes.

Cultured HepG2 cells, derived from a human hepatoma synthesized and released unsaturated, immunoreactive transcobalamin II. Synthesis was confirmed by the blocking with inhibitors of protein synthesis and by incorporation of tritiated leucine into transcobalamin II.

Apoproteins↗
PubMed1985

The metabolism of cobalamin bound to transcobalamin II and to glycoproteins that bind Cbl in HepG2 cells (human hepatoma).

The binding, internalization, processing and release of labeled cyanocobalamin (CN[57Co]Cbl) bound to human transcobalamin II (TC II) were studied in HepG2 cells, a line of hepatocytes derived from a human hepatoma. The cells bound the TC II-Cbl by specific, high affinity receptors. Within the cell, the CN-Cbl was promptly freed from TC II and the CN-Cbl converted to more active forms including adenosyl Cbl (AdoCbl) and methyl Cbl (MeCbl). Whereas free labeled Cbl was still present at 72 hours after entry, the cells also bound Cbl to an intracellular binder (ICB) presumed to represent the holo enzymes dependent on Cbl. At levels of TC II that saturated the receptors for TC II-Cbl, much of the Cbl entering the cells remained free and was converted to AdoCbl. Under these circumstances the cells released free Cbl, mostly AdoCbl. Human R type binders of Cbl, which are glycoproteins and some having a terminal galactose, were bound by the HepG2 cells. The binding was characteristic of the receptor system responsive to a terminal galactose, or asialoglycoproteins, but was inconsistent and of low affinity. Cbl bound to R binder was internalized and converted to coenzyme forms of Cbl, but the process was much less effective than when the Cbl entered via the TC II receptor system. It was concluded that the receptors for R-Cbl were unlikely to contribute to the physiologic transport of Cbl in man, but may function in some yet unknown way.

Asialoglycoprotein Receptor↗
PubMed1985

Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin.

A case of transcobalamin II (TCII) deficiency in which a total absence of TCII was demonstrated both functionally and immunologically is reported. Unlike previously described patients, this child has been maintained on oral hydroxocobalamin, 2 mg daily, without any parenteral supplementation for the last five years. At the age of six years her development is normal and her health is good. Plasma cobalamin levels are in the range of 3,000 ng/L and most of this appears to be bound to a molecule, which on gel filtration, elutes with albumin. In an extended family study, a clear separation of heterozygotes from both the propositus and from normal subjects suggests that the underlying defect in this condition is confined to a single gene.

Administration, Oral↗
PubMed1984

Human (semisynthetic) insulin and porcine insulin in the treatment of non-insulin-dependent diabetes. A double-blind, comparative clinical trial.

Twenty-one patients with non-insulin-dependent diabetes, who had not previously received insulin therapy, participated in a double-blind comparative trial of six months' duration to evaluate the efficacy of human (semisynthetic) insulin. Patients were allocated at random to treatment either with human (semisynthetic) insulin (10 patients) or with an equivalent porcine insulin regimen (11 patients). Sex ratio, age, body mass index, duration of diabetes, C-peptide concentrations, baseline metabolic control and initial insulin requirements were similar in both groups. After six months, no significant differences between the treatment effects of human (semisynthetic) insulin and porcine insulin, as assessed by measurements of fasting and postprandial plasma glucose levels, the concentration of glycosylated haemoglobin, serum lipid levels, insulin dose, and body weight, were found. No adverse reactions, injection-site anomalies, or drug-related biochemical abnormalities were noted in either group. It was concluded that human (semisynthetic) insulin is as effective as porcine insulin in initiating the treatment of patients with non-insulin-dependent diabetes who require insulin therapy.

Blood Chemical Analysis↗
PubMed1984

Effect of cimetidine on abomasal pH and Haemonchus and Ostertagia species in sheep.

Cimetidine, a histamine H2-receptor blocking agent which reduces gastric acid flow in simple stomach animals was administered directly into the abomasum of sheep at 100 mg kg-1 twice daily for five consecutive days and again on the eighth day. The drug caused a significant increase in the pH values of the abomasal contents and was highly effective in reducing the adult population of Haemonchus contortus (100 per cent) and Ostertagia circumcincta (70 per cent) in the abomasum of sheep. The possibility of using cimetidine as a method of treating abomasal nematode parasitism is discussed.

Abomasum↗
PubMed1984

The uptake of vitamin B12 by human lymphocytes and the relationships to the cell cycle.

The phase of the cell cycle permitting transcobalamin II (TC II) mediated entry of cobalamin (Cbl) into human lymphocytes was determined under several conditions. (1) Little was taken up by resting peripheral blood lymphocytes (PBL). (2) Uptake was enhanced by stimulation of PBL by culture with a mitogen. (3) This increase in capacity for uptake took place simultaneously during 3 days of culture with the increase in capacity to synthesize DNA. (4) Hydroxyurea inhibited both DNA synthesis and TC II-Cbl uptake. (5) As culture was prolonged and the cells passed beyond the phase of most active division, DNA synthesis and Cbl uptake declined sharply. (6) The increased capacity to take up Cbl after stimulation was determined, at least in part, by increased receptor activity for TC II-Cbl. (7) Internalization of the Cbl was also increased. (8) Simultaneously with the increasing DNA synthesis, the cells increased in the activity of the Cbl-dependent methionine synthetase (MS). (9) MS activity subsequently fell during longer culture. Thus PBL can take in Cbl only during a narrow "window" in the cell cycle. This window is associated with the period of most active DNA synthesis and at a time when one coenzyme of Cbl, MeCbl, is the most active.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1984

The availability of therapeutic hydroxocobalamin to cells.

Hydroxocobalamin (OH-Cbl), when used to treat vitamin B12 deficiency, is better retained by the body than is cyanocobalamin (CN-Cbl), but the availability to cells has not been studied systematically. In a series of experiments, we compared the uptake and internalization of OH-Cbl and CN-Cbl bound to transcobalamin II (TCII) by a human cell model, the HeLa cell. TCII-OH-Cbl was: (1) taken up in larger amounts per unit time, (2) the greater uptake was not a consequence of more effective attachment to receptors of TCII-Cbl nor to a more rapid regeneration of receptors, (3) the difference was expressed during the phase of internalization of TCII-Cbl, (4) with CN-Cbl, the stages of binding to receptors plus internalization were more readily reversed, and (5) larger amounts of OH-Cbl were internalized and converted to active coenzyme forms of Cbl. When injected into a healthy person, 200 micrograms of OH-Cbl was better retained in the circulation than 200 micrograms of CN-Cbl. When added in vitro in equivalent amounts, more OH-Cbl was bound to nonspecific plasma proteins. This greater and broader binding neither enhanced nor interfered with the uptake of Cbl by cells, which was determined by the amount of Cbl bound physiologically to TCII. It was concluded that OH-Cbl is a more efficient form of treatment of the common types of Cbl deficiency, principally because of the better retention, which requires less frequent injections, but also because of greater availability to cells.

Animals↗
PubMed1983

Influence of in vitro microwave radiation on the fertilizing capacity of turkey sperm.

Turkey sperm were exposed to 2.45-GHz microwave radiation in a temperature-controlled wave-guide apparatus. Temperature was maintained at either 25 or 40.5 degrees C. The sperm were exposed for 30 min at a specific absorption rate (SAR) of 10 or 50 mW/g. Following irradiation, the sperm were used to inseminate virgin turkey hens artificially. During the 9 weeks following the single insemination, the following were assessed: mean number of eggs, percentage of fertile eggs, rate of decrease in egg fertility, percentage of hatched eggs, and percentage of early and late deaths. These data demonstrate that, for the conditions used in these experiments, microwave radiation has no effect on the fertilizing capacity of turkey sperm.

Animals↗
PubMed1983

The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep.

The efficiency of a new benzimidazole anthelmintic, triclabendazole, was tested against cumulative infections with Fasciola hepatica aged 1 to 12 weeks in sheep and compared with that of rafoxanide. At 10 mg/kg, triclabendazole was 99% effective in eliminating both immature and adult flukes. At a lower dose rate of 5 mg/kg, triclabendazole was highly effective against adults and significantly reduced the number of early immature flukes with an 87% overall reduction of fluke burden. Rafoxanide at 7.5 mg/kg showed high efficiency against adult fluke, but its effect on immatures was not significant, and overall efficiency was 64%.

Animals↗