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Biomedical subjects

E McDonald

Publications and source records attributed to E McDonald.

At least 73 records · Page 4Linked to original sources

Persistence of pneumococcal antibodies after immunization in patients with systemic lupus erythematosus.

Antibody levels to 12 different pneumococcal capsular polysaccharides as well as the combined mean antibody level were measured in 19 patients with systemic lupus erythematosus (SLE) at 1, 2 and 3 years after immunization with a polyvalent pneumococcal vaccine and compared to 5 normal control subjects immunized at the same time. The mean levels in the 19 SLE patients were lower in all 3 years but the difference reached significance only in Year 1. At 3 years, 8 of the 19 SLE patients had levels below that considered to be protective and one such patient developed a pneumococcal pneumonia.

Antibodies, Bacterial↗

The esophageal motility disorder of polymyositis. A prospective study.

A prospective study of 12 patients with the diagnosis of polymyositis or dermatomyosiois was initiated to determine the characteristics of the esophageal manometric patterns in this group. All of the patients were women between the ages of 30 to 80 years and met three of four of Bohan's diagnostic criteria for these diseases. The patients' conditions were classified according to Rose and Walton's muscle weakness index. Almost two thirds of our patients exhibited distal esophageal dysfunction by manometry. Based on our roentgenographic and manometric data, we conclude that in addition to the well-described abnormalities in the striated portion of the esophagus, smooth-muscle dysfunction occurs with a high frequency in this patient population.

Adult↗

Purification of porphobilinogen deaminase from Euglena gracilis and studies of its kinetics.

1. Porphobilinogen deaminase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] from Euglena gracilis was purified more than 200-fold. 2. The enzyme has a molecular weight of 41 000 +/- 2000, does not contain a chromophoric prosthetic group, and appears not to require metal ions for activity. 3. The stoicheiometry of the overall reaction at pH 7.4 was shown to be: 4 Porphobilinogen leads to uroporphyrinogen-I + 4 NH4+. This stoicheiometry for porphobilinogen and uroporphyrinogen was also observed over a wide range of pH values. 4. Initial-velocity studies showed a hyperbolic dependence of velocity on substrate concentration, demonstrating the existence of a displacement-type mechanism. 5. Vmax. varied with pH as a typical bell-shaped curve, indicating that two ionizable groups with pK values of 6.1 and 8.9 are important for catalysis. A plot of Vmax./Km against pH showed a single ionization (pK 8.2) to influence binding of substrate.

Ammonia-Lyases↗

Biosynthesis of the pigments of life: formation of the macrocycle.

The organic nuclei of chlorophylls, haems, cytochromes and vitamin B12 are biosynthesised from a single tetrapyrrolic intermediate which has an unexpected, rearranged structure. The mechanism of biosynthesis of this key intermediate has now been characterised in detail. Some of the information thereby obtained is also of use in the investigation of human diseases such as the porphyrias.

Ammonia-Lyases↗

Geriatrics in family practice. A comparison of data from Wisconsin and Virginia.

For 109 Wisconsin family practices, 18% of all contacts were with patients 65 years of age and older. Of these contacts, 45% took place in the office and 40% in the hospital; the patient was female in 58.7%. The number of problems or diagnoses was 2.28 per patient contact. Comparison of the geriatric problem profile from the Wisconsin study with similar data from Virginia showed striking similarity. The diagnostic category "diseases of the circulatory system" contained more than 30% of patient problems. No other category contained 10% or more problems in either study. The problem profiles for men and women were almost identical, suggesting little difference in medical care needs according to sex.

Age Factors↗

A study of family practice in Wisconsin.

Studies of family practice in Wisconsin and elsewhere show that the clinical content of family practice has about 20 to 45 patient contacts per day and about two to six diagnoses per patient contact. Seventy-five percent of patient contacts are in the office and on the telephone, 15 to 20 percent in the hospital, and 5 to 10 percent elsewhere. There is a broad array of patient problems. Special Conditions and Examinations Without Illness contain the largest number of patient problems. About 60 percent of patients are female and present more endocrine and genitourinary problems. Men present more trauma, circulatory, and respiratory problems, and less health maintenance care. Well-baby and well-child examinations stop at age 15 years. Pre and postnatal care decline sharply at age 35 years, at which time surgical care increases. Infectious disease and trauma, ranking high in the young, are low in the elderly. Circulatory problems, obesity, diabetes, and arthritis increase greatly with age. There is no major difference in type of patient problems related to town size (ie, population). However, comparative studies may uncover different disease occurrence rates between regions.

Adolescent↗

Biosynthesis of porphyrins and corrins.

Haem, chlorophyll and vitamin B12 are all derived ultimately from four molecules of the pyrrole porphobilinogen (PBG) and the initial enzyme catalysed condensation of PBG leads to the unsymmetrical type III isomer of uroporphyrinogen. On the basis of straightforward chemical considerations the type I isomer should be formed and so the porphyrinogen-forming enzymes of all living systems must catalyse a highly specific rearrangement process. The nature and chemical mechanism of this rearrangement poses one of the most fascinating problems in the porphyrin field and so it is not surprising that over 20 hypothetical schemes have been proposed to account for it. Analysis of the problem suggested that the incorporation of doubly 13C-labelled precursors into the rearranged macrocyclic rings would give valuable new information on the nature of the rearrangement process. In this approach the meso=bridge atoms are of crucial importance, and several unambiguous syntheses of 13C-labelled pyrroles and porphyrins were developed to allow rigorous n.m.r. assignments to be made, and also to provide substrates for enzymic experiments. Studies carried out with enzymes from both avian blood and from Euglena gracilis have revealed the precise nature of the assembly of four PBG molecules into the type-III macrocycle: it is the same in both systems despite their vastly different evolutionary development. Complementary studies are in progress in order to determine the intermediates involved in the conversion of PBG into uroporphyrinogen III. The synthesis of amino methyl pyrromethanes and their interaction in the presence of PBG with the appropriate enzyme systems are described. It is important for the work to be able to separate not only isomeric pyrromethanes but also the four isomeric coproporphyrins. Powerful methods are described which make use of high pressure liquid chromatography for both types of separation process. Once uroporhyrinogen III has been built enzymically, there is a stepwise enzymic decarboxylation of the four acetic acid residues. A heptacarboxylic porphyrin shown to be a type-III porphyrin is isolated from the action of avian blood enzymes on porphobilinogen. Spectroscopic studies with 13C-labelling limit the possible structures to two and total synthesis of these substances shows that the natural product carries its methyl group on ring D. An isomeric heptacarboxylic porphyrin having its methyl group on ring C is of particular interest in relation to the biosynthesis of vitamin B12. This substance is synthesized together with uroporphyrin III, 14C-labelled specifically in ring C. This latter product is used to settle one of the key questions concerning nature's route to vitamin B12 - that is, does the corrin macrocycle arise from uroporphyrinogen III? Incorporation studies and specific degradations prove specific incorporation of uroporphyrinogen III into cobyrinic acid, which is the known precursor of vitamin B12.

Models, Biological↗

The relation between physician and patient age in family practice.

A study of 100 selected Wisconsin family physicians demonstrated that younger physicians generally had more contact with younger patients, middle-aged physicians had an even distribution of patient age contacts, and older physicians had more contact with older patients. The increase in older patients became pronounced for 56 to 60-year-old physicians. Generally a ten-year increase in physician age was accompanied by a five-year increase in patient age. The rising average age of the American population, combined with the direct physician-patient age relationship demonstrated here suggest that geriatrics will become increasingly relevant not only in the continuum of medical education but also for the individual practicing physician.

Age Factors↗