Tissue Distribution of Coenzyme and other Forms of Vitamin B12 in Control Subjects and Patients with Pernicious Anaemia

1974 ◽  
Vol 46 (2) ◽  
pp. 163-172 ◽  
Author(s):  
J. C. Linnell ◽  
A. V. Hoffbrand ◽  
H. A-A. Hussein ◽  
Irene J. Wise ◽  
D. M. Matthews

1. Methylcobalamin (Me-B12), adenosylcobalamin (Ado-B12), hydroxocobalamin (OH-B12) and cyanocobalamin (CN-B12) have been estimated by a chromatographic—bioautographic technique in plasma, erythrocytes, leucocytes and bone marrow from normal subjects, hospital controls and patients with untreated pernicious anaemia. 2. Estimates of concentrations of cobalamins have also been obtained in bile, cerebrospinal fluid, liver biopsies and in autopsy samples of liver, kidney, spleen, brain and pituitary. 3. In normal and control subjects, Ado-B12 predominated in all samples except plasma, in which Me-B12 was the predominant form. Me-B12, Ado-B12, OH-B12 and CN-B12 were found in normal erythrocytes, leucocytes and bone marrow and the proportion of each cobalamin was fairly similar in all these tissues. In liver, kidney, spleen, brain and pituitary, the proportions of the cobalamins were more variable. No CN-B12 was detected in these organs. 4. In untreated pernicious anaemia, Me-B12 was disproportionately reduced in plasma, but not in erythrocytes, leucocytes or bone marrow. There was a small increase in the proportion of CN-B12 in plasma, blood cells and bone marrow in untreated pernicious anaemia.

1995 ◽  
Vol 89 (6) ◽  
pp. 591-599 ◽  
Author(s):  
Roger J. W. Truscott ◽  
Anthony J. Elderfield

1. Cataract is the single major cause of blindness worldwide; however, the reasons for the development of this condition remain unknown. It has been suggested that the essential amino acid tryptophan may be implicated in the aetiology but definitive evidence has been lacking. 2. The serum levels of tryptophan and seven of its metabolites have been measured in both cataract patients and control subjects, after administration of tryptophan, in order to determine the typical response profile and to discover whether differences could be found in tryptophan metabolism in the two groups. 3. Tryptophan, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, 5-hydroxyanthranilic acid, 5-hydroxytryptophan and anthranilic acid were measured by HPLC with dual electrochemical and programmable wavelength fluorescence detection. Fasting cataract patients (n = 42) and control subjects (n = 37) were given an oral dose of l-tryptophan and sera were sampled at 0, 1, 2, 4 and 6 h. 4. Statistically significant differences in the distribution of data between the two groups were observed. The responses of kynurenine and 5-hydroxyanthranilic acid were higher in cataract patients, but those of kynurenic acid and total tryptophan were lower than in control subjects. No statistically significant differences in free tryptophan, anthranilic acid, 3-hydroxyanthranilic acid, xanthurenic acid or 5-hydroxytryptophan levels were noted. 5. We conclude that there is a major subgroup of age-related cataract patients with a dysfunction in the metabolism of tryptophan. This may be related to the onset of cataract. The mechanism remains to be established but may operate via the action of tryptophan metabolites, such as 5-hydroxyanthranilic acid, which become reactive towards protein upon oxidation.


2005 ◽  
Vol 84 (2) ◽  
pp. 133-137 ◽  
Author(s):  
S. Miyawaki ◽  
Y. Araki ◽  
Y. Tanimoto ◽  
A. Katayama ◽  
A. Fujii ◽  
...  

Patients with open bite often show a weak occlusal force and temporomandibular disorders (TMDs). If these are the main cause of open bite, it may be hypothesized that both pre-pubertal and adult open-bite patients would show a weak occlusal force and abnormal condylar motion. The purpose of this study was to test this hypothesis. Test group subjects consisted of 13 consecutive pre-pubertal and 13 adult patients with anterior open bite. They were compared with age-matched normal subjects. The adult open-bite group showed a weaker occlusal force and a shorter range of condylar motion compared with the control subjects. In the pre-pubertal subjects, however, there were no significant differences in the occlusal force and range of condylar motion between the open-bite and control groups. Therefore, these results suggest that a weak occlusal force or TMDs may not be the main cause of open bite.


1967 ◽  
Vol 10 (3) ◽  
pp. 496-505 ◽  
Author(s):  
Robert H. Brookshire ◽  
Richard R. Martin

One hundred normal subjects, divided into five groups, read aloud for 40 minutes. For the first 10 minutes (Baserate), subjects read without interruption. For the next 20 minutes (Conditioning), verbal stimuli contingent upon disfluency were delivered to three groups. One group received “wrong”; the second, “no”; and the third “huh-uh” for disfluency. A fourth group received “wrong” on a random schedule during Conditioning, while the fifth (control) received no verbal stimuli. During the last 10 minutes (Extinction), no verbal stimuli were delivered to any group. Random and Control subjects did not change disfluency rates, while subjects in all contingent conditions decreased disfluency in Conditioning. Contingent “wrong” produced the greatest decrement in disfluency, “no” the least, and “huh-uh” occupied a midpoint.


1984 ◽  
Vol 18 (12) ◽  
pp. 1336-1339 ◽  
Author(s):  
Richard C Boucher ◽  
Dennis W Ross ◽  
Michael R Knowles ◽  
John T Gatzy ◽  
John C Parker

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1665-1672 ◽  
Author(s):  
A Velardi ◽  
P Varese ◽  
A Terenzi ◽  
C Dembech ◽  
N Albi ◽  
...  

Abstract T cells recovering after bone marrow transplantation (BMT) were analyzed for their phenotypic and functional features by two-color immunofluorescence and a high efficiency cloning technique. A predominance of cells co-expressing natural killer (NK)-related surface antigens, such as Leu 7 (CD57) and CD11b, was detected within both the CD4+ and CD8+ subsets from 5 months postgrafting onward. Such cells are virtually absent among normal circulating CD4+ cells and account for a minority (approximately 30%) of normal CD8+ cells. Postgrafting T cells representative of the whole range of NK-related antigen co-expression were selected from six patients for clonal analyses. In control subjects, 63% and 41% of the CD4+ and CD8+ clones, respectively, produced interleukin-2 (IL-2) whereas approximately 30% of either CD4+ or CD8+ control clones produced interferon (IFN)-gamma. At variance, and irrespective of their CD4+/CD8+ phenotype, lower proportions of BMT recipient-derived clones produced IL-2 (20% and 12%, respectively), whereas the majority of both CD4+ and CD8+ clones (75% and 71%, respectively) released high amounts of IFN-gamma. Purified populations of CD57+/CD11b+ v negative cells from two BMT recipients and two control subjects were cloned and subsequently evaluated for IL-2 and IFN-gamma production. CD57+/CD11b+ cell-derived clones were poor IL-2 producers in both normal subjects and BMT patients. In contrast, IL-2- producing clones were frequent (62% to 79%) among those derived from CD57-/CD11b- cells from normal subjects, whereas they were still represented at lower than normal proportions, ie, 25% to 41%, among clones generated from BMT recipients. CD57+/CD11b+ cells gave rise to comparably high proportions of IFN-gamma producing clones in both normal subjects and BMT recipients (approximately 80%). In contrast, IFN-gamma producing clones were approximately 25% to 50% of CD57-/CD11b- cell-derived clones in both normal subjects and BMT patients. Therefore, while the predominance of NK-related antigen-positive T cells may be predictive of poor IL-2 and high IFN-gamma production, the immune derangement in long-term BMT recipients is further enhanced by the finding that all T cells may be poor IL-2 producers. It is also suggested that IL-2 production is a preferential function of T cells that do not express CD57 and CD11b, whereas IFN-gamma production is attributable to T cells that express CD57 and CD11b.


1978 ◽  
Vol 55 (1) ◽  
pp. 73-80 ◽  
Author(s):  
J. Lyngsøe ◽  
J. P. Clausen ◽  
J. Trap-Jensen ◽  
L. Sestoft ◽  
O. Schaffalitzky de Muckadell ◽  
...  

1. Exchange of metabolic substrates was studied across the leg at rest and during a bicycle exercise demanding 50% of the maximal oxygen uptake in seven patients with juvenile diabetes and six control subjects. The leg blood flow and the femoral arterial and venous substrate concentrations were measured in the fasting state and, in the diabetic subjects, 24 h after the last administration of insulin. 2. At rest a close correlation was seen in the control subjects between the leg glucose uptake and the arterial insulin concentration. The diabetic subjects, including three patients in whom it could be shown that the insulin concentrations were extremely low, had a resting glucose uptake in the same order of magnitude as the control subjects. The glucose uptake was inversely related to the arterial concentrations of non-esterified fatty acids in both groups. 3. During exercise the glucose uptake increased in both patients and control subjects, but the increase was not related to arterial concentrations of insulin or non-esterified fatty acids. 4. The release of lactate, pyruvate, alanine and glycerol from the leg was not different in diabetic and control subjects neither at rest nor during exercise. 5. The ketonaemia was increased in the diabetic subjects, but the uptake of total ketone bodies was not different in the two groups. No increase in the uptake of total ketone bodies in control and diabetic subjects was found during exercise. The leg uptake of acetoacetate was a function of the substrate load and tended to be higher in diabetic subjects during exercise, when no net uptake of β-hydroxybutyrate was found. 6. The above results suggest that the glucose uptake in human skeletal muscle at rest depends on the concentration of insulin and possibly also of non-esterified fatty acids in arterial blood. In contrast the glucose uptake during exercise is not related to the concentration of insulin or non-esterified fatty acids, which may explain why no differences in this aspect are seen between the leg metabolism of diabetic and normal subjects.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5568-5568
Author(s):  
Jie yu Ye ◽  
Su yi Li ◽  
En yu Liang ◽  
Fan yi Meng ◽  
Beng Chong ◽  
...  

Abstract Imatinib mesylate (Gleevec or STI-571), a tyrosine kinase inhibitor, can potently block both platelet-derived growth factor (PDGF) receptor-α and β by inhibiting the receptor tyrosine kinase activity. Imatinib mesylate has been successfully used to treat patients with chronic myeloid leukemia (CML) and Ph positive acute lymphoid leukemia (ALL). However, a significant number of patients with imatinib mesylate treatment have developed neutropenia, thrombocytopenia and anemia (van Deventer, Hall et al. 2002). Our previous studies have demonstrated that PDGF/PDGFR plays an important role on thrombopoiesis, and blockage of PDGFR by imatinib inhibited the downstream signal pathway, which led to reduce of megakaryocyte production (Ye, et al. Haematologica, 2010). This may partially explain the imatinib-related thrombocytopenia. However, the role of imatinib on normal hematopoiesis remains to be investigated. In the present study, we identified the expression of PDGFR-β on the human megakaryoblastic cells: Meg-01, CHRF-288-11, Dami and M-07e, human erythromyeloblastoid leukemia cells: K-562 and human myeloblastic cells: HL-60 by RT-PCR, western blot and flow cytometry. We then demonstrated the effect of imatinib on normal hematopoiesis in the 8 wk old C57BL/6 mice model. Gleevec (25 mg/kg/day) dissolved in distilled water or water only were given orally for up to 2 wks. 15ul whole blood was taken from postorbital weekly to perform blood cell counts. The Gleevec -treated group showed a reduction of platelet count as compared to the control at day 14 (543.3±71.95×109/L vs. 330.0±62.23×109/L, n=5, P<0.05). Similarly, Gleevec caused a significant decrease in the number of white blood cells on day 14 (9.667×±0.8511×109/L vs. 6.080±0.8015×109/L, n=5, P<0.05). While no significant differences were found on red blood cell count between Gleevec and control groups. The mice bone marrow was harvested from each group to perform CFU assays. Gleevec significantly inhibited the formation of bone marrow CFU-MK (15.33±1.764 vs 3.333±0.6667, n=3), and CFU-GM(13.50±2.784 vs 6.333±0.7265, n=3) compared with the control. There were no significant differences found in CFU-GEMM and CFU/BFU-E formation between the Gleevec and control treatment. Our studies suggested that PDGFR were expressed on hematopoietic cells. Imatinib mesylate, an inhibitor of PDGFR, not only played an important role in malignant hematopoiesis, but also in normal hematopoiesis. Administration of Gleevec reduced white blood cells and megakaryocytes/platelets production, which implied its potential therapeutic role in treating myeloproliferative diseases, such as Essential Thrombocytosis. Disclosures: No relevant conflicts of interest to declare.


1988 ◽  
Vol 67 (1) ◽  
pp. 233-234 ◽  
Author(s):  
Kathleen O'Dea Dooley ◽  
Alvirda Farmer

Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.


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