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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 325 records · Page 18Linked to original sources
PubMed1988

B-cell prolymphocytic leukaemia--clinical and haematological features.

Prolymphocytic leukaemia is an unusual but distinctive variant of chronic lymphocytic leukaemia which generally responds poorly to chemotherapy. Four cases are described to illustrate typical clinical and haematological features and to emphasise the unsatisfactory outcome with combination chemotherapy, radiotherapy and plasma exchange in 3 patients, and to draw attention to the prolonged disease control which followed splenectomy in the fourth. These observations illustrate the relative ease with which the diagnosis can be made and also the difficulties in management, which requires exploration of alternative treatment options.

Aged↗
PubMed1988

Phenotypic expression of the HLA-linked iron-loading gene in the Afrikaner population of the western Cape.

A previous study conducted on a group of Afrikaans-speaking subjects in the south-western Cape indicated a high frequency (0.115) of the HLA-linked iron-loading gene which causes idiopathic haemochromatosis. The results of phenotypic and genotypic studies on the first degree relatives of identified homozygotes and heterozygotes are now reported. There was considerable heterogeneity of phenotypic expression in the group of heterozygotes, with overlap between the homozygous and heterozygous subjects. The heterozygous relatives of heterozygous index cases, who had been identified on the basis of a serum ferritin concentration greater than 400 micrograms/l, appeared to have more frequent and more marked abnormalities of iron measurements than the heterozygote relatives of homozygous index cases (serum ferritin value greater than 400 micrograms/l, percentage transferrin saturation greater than 60). This suggests that the screening test was identifying a group of more significantly affected heterozygotes, with biochemical abnormalities that overlapped with the identified homozygotes. The index cases were followed up over a period of 5 years and during this time the 7 subjects diagnosed as heterozygotes showed a progressive increase in serum ferritin concentrations, which suggests some iron accumulation. Individual pedigrees included instances of gene recombination within the major histocompatibility complex, and of probable false-positive genotype assignment. The overall results confirm a high frequency of the gene in this particular community.

Adult↗
PubMed1988

Response in serum ferritin and haemoglobin to iron therapy in blood donors.

Seven hundred seventeen healthy male blood donors regularly donating four or more units a year were surveyed for haemoglobin and serum ferritin levels. One hundred fifty-one (21%) had a haemoglobin less than 13.5 g/dl and were therefore disqualified from further blood donation, having a mean serum ferritin of 28 micrograms/liter. Of the remaining 566 donors with haemoglobin levels equal to or greater than 13.5 g/dl, the mean serum ferritin was 33 micrograms/liter, although in 299 (53%) the value was less than 28 micrograms/liter. To document response to iron therapy 46 donors with haemoglobin levels equal to or greater than 13.5 g/dl were stratified into those with the lowest iron stores (group 1; n = 23), defined as a serum ferritin less than 20 micrograms/liter, and controls (group 2; n = 23), with serum ferritin between 50 and 150 micrograms/liter. Within each stratum donors randomly received ferric polymaltose at a dose of 100 mg elemental iron twice daily for 56 days (groups 1a and 2a) or an identical iron-free placebo tablet administered on the same schedule (groups 1b and 2b). Iron therapy in the iron-deficient group (group 1a:n = 11) resulted in a significant rise in haemoglobin (p = .03) and iron stores reflected in serum ferritin (p = .002) compared to those receiving placebo (group 1b). In the control group iron therapy or placebo was without significant effect. Thus, ferric polymaltose preparation is bioavailable and is notable for the virtual absence of gastrointestinal tract side effects.

Blood Donors↗
PubMed1988

Vitamin and mineral status of trained athletes including the effects of supplementation.

We measured serum concentrations of thiamin, riboflavin, nicotinic acid, pyridoxine, folate, cyanocobalamin, ascorbic acid, retinol, tocopherol, zinc, magnesium, copper, iron, and ferritin as well as hemoglobin, hematocrit, percentage transferrin saturation, and total iron-binding capacity in athletes who ingested a multivitamin and mineral supplement for 3 mo. All blood variables were normal and except for pyridoxine and riboflavin there were no significant changes in the blood concentrations of any other vitamins or minerals measured. This may have been due to variable interactions between the vitamins and minerals in the supplement that prevented their being adequately absorbed. There were no signs or symptoms of serious toxic side effects. We conclude that multivitamin and mineral supplementation was without any measurable ergogenic effect and that such supplementation is unnecessary in athletes ingesting a normal diet.

Adult↗
PubMed1988

Sequential half-body irradiation as salvage therapy in chemotherapy-resistant multiple myeloma.

Fifteen patients with a median age of 58 years, having multiple myeloma resistant to conventional combinations of cytotoxic drugs, received sequential half-body irradiation as salvage therapy. Response was obtained in 53% (n = 8: group 1); this was objective in 40% (n = 6), being defined as 50% or greater reduction in paraprotein, clearance of light chains from the urine, or an unequivocal decrease in tumor bulk on an adequate marrow trephine biopsy; a further 13% (n = 2) just failed to meet these criteria but nevertheless had excellent subjective response. Median survival was 24 months. No objective or subjective improvement occurred in 47% (n = 7: group 2); median transient survival was 4 months. Short-term toxicity was limited to transient nausea in 30% (n = 5) and protracted pancytopenia in about one-half of the patients (n = 7), who remain dependent on intermittent RBC transfusions. Morbidity is only moderate, and the response rate of 53% in refractory patients suggests that sequential half-body irradiation has a definite place in managing patients with end-stage disseminated myelomatosis.

Adult↗
PubMed1988

Pure red cell aplasia. Stable complete remission following antilymphocyte globulin administration.

A 25-yr-old woman with idiopathic pure red cell aplasia achieved complete remission following a single 5-day course of antilymphocyte globulin at a dose of 50 mg/kg daily by intravenous injection as initial and sole therapy. Apart from transient arthralgia and asymptomatic thrombocytopenia there were no side effects. At 2 yr, the patient has normal peripheral blood, bone marrow and in vitro culture studies. This approach offers an alternative to conventional immunosuppressive therapy where there is evidence of an underlying immune disorder.

Adult↗
PubMed1988

Massive macroglossia, amyloidosis and myeloma.

A 74 year old man with light-chain myeloma developed amyloidosis with macroglossia after 10 years of therapy with alkylating agents. Over a 2-year period his tongue enlarged to persistently protrude from his mouth, inhibit his speech, interfere with normal swallowing and eventually threaten his airway. As a life-saving procedure the tumorous anterior two-thirds of the tongue was resected, with excellent primary healing. Within two weeks the patient's speech became comprehensible and his ability to eat returned to normal. Although rare in amyloidosis, massive macroglossia may occur and surgical correction is easily achieved.

Amyloidosis↗
PubMed1987

Mutant and chimeric recombinant plasminogen activators. Production in eukaryotic cells and preliminary characterization.

Mutant urokinase-type plasminogen activator (u-PA) genes and hybrid genes between tissue-type plasminogen activator (t-PA) and u-PA have been designed to direct the synthesis of new plasminogen activators and to investigate the structure-function relationship in these molecules. The following classes of constructs were made starting from cDNA encoding human t-PA or u-PA: 1) u-PA mutants in which the Arg156 and Lys158 were substituted with threonine, thus preventing cleavage by thrombin and plasmin; 2) hybrid molecules in which the NH2-terminal regions of t-PA (amino acid residues 1-67, 1-262, or 1-313) were fused with the COOH-terminal region of u-PA (amino acids 136-411, 139-411, or 195-411, respectively); and 3) a hybrid molecule in which the second kringle of t-PA (amino acids 173-262) was inserted between amino acids 130 and 139 of u-PA. In all cases but one, the recombinant proteins, produced by transfected eukaryotic cells, were efficiently secreted in the culture medium. The translation products have been tested for their ability to activate plasminogen after in situ binding to an insolubilized monoclonal antibody directed against urokinase. All recombinant enzymes were shown to be active, except those in which Lys158 of u-PA was substituted with threonine. Recombination of structural regions derived from t-PA, such as the finger, the kringle 2, or most of the A-chain sequences, with the protease part or the complete u-PA molecule did not impair the catalytic activity of the hybrid polypeptides. This observation supports the hypothesis that structural domains in t-PA and u-PA fold independently from one to another.

Animals↗
PubMed1987

Characterization of a recombinant fusion protein of the finger domain of tissue-type plasminogen activator with a truncated single chain urokinase-type plasminogen activator.

Human recombinant single chain urokinase-type plasminogen activator (recombinant scu-PA) and a hybrid between human tissue-type plasminogen activator (t-PA) and scu-PA, obtained by ligation of cDNA fragments encoding the NH2-terminal region (amino acids 1-67) of t-PA and the COOH-terminal region (amino acids 136-411) of scu-PA, were expressed in a mammalian cell system. The proteins were purified from conditioned culture media containing 2% fetal calf serum by chromatography on zinc chelate-Sepharose, immunoadsorption chromatography on an insolubilized murine monoclonal antibody directed against urokinase, benzamidine-Sepharose chromatography, and Ultrogel AcA 44 gel filtration. Between 180 and 230 micrograms of the purified proteins were obtained per liter of conditioned medium, with a yield of approximately 18% and a purification factor of 720-1900. On sodium dodecyl sulfate gel electrophoresis under reducing conditions, the proteins migrated as single bands with approximate Mr 50,000 for recombinant scu-PA and Mr 43,000 for the t-PA/scu-PA hybrid. Following conversion to urokinase with plasmin, the proteins had a specific amidolytic activity comparable to that of natural scu-PA. Both proteins activated plasminogen directly with Km = 0.53 and 1.4 microM and k2 = 0.0034 and 0.0027 s-1, respectively. Both proteins did not bind specifically to fibrin and had a comparable degree of fibrin selectivity as measured in a system composed of a whole human 125I-fibrin-labeled plasma clot suspended in human plasma. It is concluded that this chimeric protein, consisting of the NH2-terminal "finger-like" domain of t-PA and the COOH-terminal region of scu-PA, has very similar enzymatic properties as compared to scu-PA, but has not acquired the fibrin affinity of t-PA.

Adenocarcinoma↗