M.S. / Biochemistry / This study was undertaken with the object of discovering a clinically practicable, accurate method of estimating hemoglobin. / The poor quality of the text is due to the onion skin paper the thesis was scanned from.

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Thesis Submitted to the Faculty of Medicine University of the Witwatersraiu', Johannesburg for the Degree of Doctor of Philosophy (Medicine) Johannesburg 1976 / An attempt was made to fortify sugar with iron in order to prevent the development of iron deficiency. It was possible to add various iron salts and ascorbic acid to sugar without discolouring the vehicle even after storage for many months under hot humid conditions. The absorption of iron from fortified sugar and cereal meals was then measured in human volunteers using either an "extrinsic tag" to label the iron compound or intrinsically labelled food iron. / IT2018

by Cham Pak-Meng. / Title also in Chinese. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 124-125.

Hemoglobinopathies, the disorders of hemoglobin structure and synthesis, can be divided into two forms of clinical manifestation, namely thalassemias and abnormal hemoglobins. Thalassemia appears to involve an abnormal gene which results in a reduced rate of globin synthesis and it presents clinically as a hypochromic microcytic anemia. Its cause lies in some abnormality of the regulation of globin synthesis. An abnormal hemoglobin is usually the result of a mutation of one base in a codon triplet of the structural gene for one or other hemoglobin chain which leads to an amino acid substitution in the primary structure of the globin. In this study, the biochemical characterization of five samples of abnormal hemoglobin which were obtained from patients at Vancouver General Hospital, Vancouver, B.C. and Siriraj Hospital, Bangkok is described. In the first case from V.G.H., the propositus, a 17 month old Chinese girl showed a fast (anionic) abnormal hemoglobin from birth. In a biochemical investigation of the variant from her father it was found that the glycine residue 56 in the β-chain was substituted by aspartic acid. This mutant is identical to that previously designated as HbJ Bangkok ([formula omitted]). The second case, a 21 year old Thai male in Bangkok was shown to be a double heterozygote with both a slow and a fast abnormal hemoglobin and an absence of HbA upon starch gel electrophoresis. Structural characterization of the separated globin chain of both variants indicated that the mutation in the slow variant occurred at residue 26 of β-chain where glutamic acid was replaced by lysine. This mutation is similar to that previously described as HbE ([formula omitted]). The fast variant showed an amino acid alteration at position 113 of β-chain where valine was substituted by glutamic acid. This mutation is identical with Hb New York ([formula omitted]). A double heterozygote involving both HbE and Hb New York has not been previously described. The other three samples from unrelated patients in Bangkok revealed a slow mutant on starch gel electrophoresis and biochemical studies showed that residue 74 in the α-chain was changed from an aspartyl to a histidyl residue. This mutation has not been previously described. It is proposed that this new hemoglobin ([formula omitted]) be called Hb Mahidol after Mahidol University in Bangkok. In one of the three patients showing Hb Mahidol interaction with α-thalassemia (α-thalassemia-Hb Mahidol) occurs. This results in the clinical features of chronic hemolytic anemia and a total absence of HbA which is replaced by Hb Mahidol together with some HbH([formula omitted]). / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

The chemical relationship which exists between haemoglobin and bile pigments was first established in 1933, when, after monumental studies covering a period of 24 years, Hans Fischer and his colleagues succeeded in synthesizing bile pigments and protoporphyrin. He thereby demonstrated the fundamental tetrapyrrolic structure which is common to both haem and bilirubin. Prior to this, in vivo experiments on dogs performed by Mann, Sheard, Bollman and Blades showed that haemoglobin, injected into the arterial blood of the spleen or bone-marrow, produced a rise in the bilirubin content of the venous blood. Haematin was also evident in both arterial and venous blood.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diabetic individuals have been found to have consistently higher levels of a minor hemoglobin component, HbAIc, than non-diabetic individuals. Previous investigators have suggested that variation in these high levels of HbAIc may be a reflection of the degree of diabetic hyperglycemia, of hypertriglyceridemia in diabetes, and of diabetic control. To date, evaluation of HbAIc as a clinically useful parameter has been hampered by the complexity of the method of measurement, the inconsistency in ranges of normal values reported, and the lack of a broad data base for comparison with new results. This investigation began with a critical appraisal of the methods currently in use for measurement of HbAIc, followed by a simplification and standardization of theJ assay. Then the levels of HbAIc in 16 non-diabetics and 47 diabetics were determined and the mean values for these 2 groups compared. The relationships between HbAIc levels in the diabetics and selected clinical data |fasting blood sugar, 24-hour urinary sugar, age,duration of illness, dietary record, insulin dosage, and family history of diabetes) were examined. Finally, the degree of diabetic control in each of the diabetic patients was estimated by the attending physician on a scale of 1 to 5 (1=very good, 2=good, 3=fair, 4=poor, 5=very poor) and was compared with the HbAIc measurement. Results of the investigation have shown that the chromatographic measurement of HbAIc is unusually sensitive to the pH of developers used and also somewhat variable with respect to the length of storage time and the optical density at which samples are read. The comparison of mean values of HbAIc for diabetics and non-diabetics has confirmed the approximately twofold higher concentration of HbAIc in diabetics. Significant correlations were found between HbAIc and fasting blood sugar (r = .442), fat content of diet (r=-. 300) , family history of diabetes (r=-.312) and degree of diabetic control (r=.529). Thus, HbAIc values tend to be higher in patients whose fasting blood sugar is high, whose diet contains relatively little fat, whose relatives are diabetic and /or whose diabetic control is poor. Correlations between HbAIc and duration of diabetes, HbAIc and insulin dosage or HbAIc and 24-hour urinary sugar were not statistically significant (r=-.131, r=-.264, r=„067, respectively). The HbAIc level appears to be an accurate reflection of fasting blood sugar levels averaged over a prolonged period of time (r=.587). In conclusion, HbAIc levels were found to provide an objective measure of diabetic control. The improved assay method makes it a practical and valuable tool for the clinician as well as the investigator. Measurement of HbAIc levels in diabetics presents a considerable advantage over currently available measures of diabetic control in assessing the long-term effectiveness of diabetic management. / Land and Food Systems, Faculty of / Graduate

Thesis (M.Sc. (Med.))--University of the Witwatersrand, Faculty of Health Sciences, 1998. / The issue of Malagasy ancestry has been controversial, and has still not been completely resolved. The historical, linguistic, archaeological and some genetic evidence points to the fact that modern Malagasy are the descendants of immigrants who arrived on the island over the past 2000 years, from South and Southeast Asia, Africa and the Near East. In more recent centuries, mainly in the twentieth century, there have been significant numbers of Indian, Chinese and French immigrants. In addition, archaeological and historical studies of specific regional populations of Malagasy suggest a complex pattern of internal migration within the island, extending back in time to the first European contacts with the island in the sixteenth century. The 22 Malagasy ethnic groups may be classified as "highland" or "lowland" depending on their geographic distribution on the island. Within the ethnic groups, the founding populations have made different genetic contributions: the highland groups are said to have a greater Indonesian contribution to their ancestry, while the lowlanders have a greater African contribution to their ancestry. Genetic studies on the Malagasy have been limited by small sample sizes, deficiencies in sampling procedures and in the limited number of polymorphisms studied. In light of the paucity of written records, the Department of Human Genetics, SAIMR, has undertaken a large study in Madagascar to reconstruct the biological history of its people, using genetic variation. This thesis forms a part of this study. Variation in the a- and p-globin cluster has been extensively studied in many parts of the world, and has been shown to be population specific, with specific variants having distinct geographical distributions. Thus haemoglobin and its related disorders have been the subject of extensive studies for determining the origin(s) of particular populations. In this study, some of the a- and p-globin variation present in the Malagasy was characterised. Seven RFLPs/HVRs in the a-globin gene cluster and seven RFLPs in the p-globin gene cluster were analysed. The common a- and p-globin gene cluster haplotypes differ between African and Asian populations. Frequencies also vary between populations in a specific geographical regions. The aim of this study was to characterise the haplotypes present in the Malagasy, to provide information on the relative genetic contributions of different populations to the peoples of Madagascar. DNA samples from randomly selected, haematologically normal individuals were analysed. Individuals were chosen from six Malagasy ethnic groups: two “highland” populations (Merina and Betsileo), two “lowland" populations (Antasaka and Tsimiheti) and two populations from the south-west of the island (Mahafaly and Vezo). The groups chosen cover a broad range of Madagascar and thus provide some representation of the Malagasy population as a whole. The number of individuals studied in each ethnic group are as follows: Merina: 88; Betsileo: 78; Antasaka: 67; Tsimiheti: 67; Mahafaly: 26; Vezo: 25. The frequencies of the a- and (B-globin RFLP sites and a-globin HVRs in the Malagasy vere calculated. 5' and 3’ p-globin haplotypes were constructed on the basis of homozygosity. A maximum-likelihood algorithm was used to obtain frequencies of 5’ P-globin haplotypes that could not be assigned on the basis of homozygosity. These data were then subject to statistical analysis. The frequencies of the 5’ p-globin haplotypes (consisting of the five sites Hindi 5' to e, Hindi 11 within Gy and Ay, Hindi within \|/P and 3' to it) were the most informative data set for comparing the Malagasy ethnic groups to each other and to other world populations. Unfortunately, the maximum-likelihood estimates of 5‘ p-globin haplotypes could not be used for comparative analyses due to the lack of similar data in other populations. However the strong correlation between the maximum-likelihood frequencies and the observed frequencies illustrated the ability of the algorithm to determine hapiotype frequencies from otherwise uninformative individuals. 5’ p-globin haplotypes were assigned unambiguously for 248 Malagasy chromosomes. Ten haplotypes were found; of these, nine have been reported previously in other world populations and one has not been reported and hns thus been called “rare” in this study. The frequencies of unambiguous 5’ p-globin haplotypes in the Malagasy and the proposed parental populations were initially analysed with x2 tests. For a more accurate comparison between these populations, genetic distances were calculated and used for the construction of phylogenetic trees, principle component analysis was carried out, and a study of heterozygosity versus distance from the centroid was performed. Admixture estimates of two African populations and one Indonesian population to Malagasy ancestry were calculated. Certain general trends were noted in all the analyses. The results are in agreement with the historical data which provides evidence for both African and Asian contributions to Malagasy ancestry. The highlanders were more closely affiliated to the Indonesian/Polynesian populations, while the south-west groups showed the strongest associations with the African populations. The lowlanders were consistently intermediate in position between the highlanders and the south-west groups, with the Antasaka being slightly more closely related to the African populations than the Tsimiheti. The Malagasy were shown to have high heterozygosities, similar to those of African populations, and this high degree of diversity is probably a reflection of the many sources of ancestry of the Malagasy. The south-west groups were the furthest outliers in the model of heterozygosity versus distance from the centroid, suggesting that these groups are the most genetically admixed of all the Malagasy groups that were studied. Estimates of ancestral population admixture confirmed these trends, with the highlanders having the highest proportional contribution by Indonesians (53%), but the lowest total African contribution (47%), while the south-west groups have the highest Bantu contribution (65%). The Indonesian and African contributions to the lowlanders are intermediate between those to highlanders and south-west groups. Overall the Malagasy subjects included in this study showed a 61% African admixture contribution and a 39% Indonesian admixture contribution. It is hoped that the results obtained in this study will contribute to the larger project concerning the origins of the Malagasy, and that they may be used to shed further light on the much debated issue of Malagasy ancestry.

A Thesis presented for the degree of Doctor of Philosophy in the University of the Witwatersrand. Johannesburg, January, 1967. / Although reports of the medicinal use of iron date back to ancient times it was not until the present century that the many functions of iron in the body were studied. Once started, the investigation received impetus from the seriousness of iron deficiency anaemia, a major cause of ill health throughout the world. The introduction of radio-isotope tracer techniques in 1939 greatly facilitated investigation of absorption, excretion and the metabolic pathways of iron. The tremendous amount of work already carried out has led to a fairly comprehensive knowledge of the various aspects of iron metabolism. Nevertheless, there remain wide gaps in the overall picture. In / IT2018