Search PubMed⌕ Search

Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 343 records · Page 19Linked to original sources
PubMed1987

The immunocompromised host.

The immunocompromised patient, with or without superimposed granulocytopenia, provides a wide range of life-threatening challenges for the primary medical and nursing care management group. In the context of haematological malignancy, particularly leukaemia and bone marrow transplantation, special expertise needs to be developed which includes competence in many aspects of general medical, nursing, and intensive care techniques. Clearly, the range of essential knowledge extends to other disciplines including respiratory, cardiac, and renal medicine, with important contributions from microbiology, virology, dietetics and parenteral nutrition. The increasing cure rate achieved in haematological malignancy and the ever-widening indications for bone marrow transplantation require a dedicated and experienced group, able to handle all challenges. Integral to managing the complete patient, both through the acute phase and into periods of recovery and long-term rehabilitation, is inclusion of the paramedical specialists--social workers, occupational therapists, physical medicine physicians and physiotherapists. Proper balance in the cost-effective use of expertise from each of these groups and the provision of a suitable physical facility with protected environment and intensive care facilities are the cornerstones on which individual patient survival and ultimately increase in cure rates depend.

Agranulocytosis↗
PubMed1987

Lack of short-term effects on the donor during continuous-flow selective mononuclear cell collection.

In 50 individuals, intensive harvesting of relatively pure mononuclear cell fractions from the peripheral circulation was carried out in 195 procedures. Serial collections from bone marrow donors (group 1: n = 35) or isolated procedures from volunteers (group 2: n = 15) were without morbidity. A median yield of 4.0 X 10(9) mononuclear cells were recovered in a final volume of 104 ml of cell-rich plasma, for which 4,300 ml of venous blood was processed in 107 minutes. In neither group were changes documented in donor white cell count or lymphocyte numbers. In group 1, a statistically significant but clinically unimportant and transient fall occurred in the platelet count at the end of the 5-day intensive schedule. It is concluded that mononuclear fractions can efficiently be collected from normal donors without the development of relevant cell depletion.

Blood Donors↗
PubMed1987

Aluminium loading during therapeutic plasma exchange.

Graphite furnace atomic absorption spectroscopy was used to demonstrate a fivefold increase in the median plasma aluminium levels of four patients undergoing therapeutic plasmapheresis. This plasma aluminium loading resulted from contamination of albumin incorporated in the replacement fluids and took place during its preparation, with albumin aluminium levels of 646, 669, and 715 micrograms/liter present in three representative samples. Aluminium overload may result in the development of encephalopathy and osteomalacia in patients with renal impairment, indicating the need to monitor aluminium levels in the albumin-containing replacement fluids to avoid this potential hazard.

Aluminum↗
PubMed1987

Waldenstrom macroglobulinaemia treated with sequential hemibody irradiation.

A 40-year-old man presented with symptoms of anaemia and blurred vision. Waldenstrom macroglobulinaemia was diagnosed on the basis of plasmacytoid lymphocytes in the peripheral blood, extensive bone marrow involvement, and an IgM kappa monoclone in the plasma of 48 g/liter. Symptoms were immediately reversed by isovolaemic continuous-flow plasmapheresis coupled with red cell transfusion. Specific therapy was undertaken with sequential hemibody irradiation. At two years of follow-up the patient enjoys excellent health, has improved haematopoietic reserve in the bone marrow, and the only therapy required is intermittent plasmapheresis to control symptoms relating to rising viscosity. Thus, systemic irradiation, which is well tolerated and objectively reduces marrow tumour bulk, offers an alternative to chemotherapy in the palliative management of active macroglobulinaemia and may diminish but not prevent the need for intermittent plasmapheresis.

Adult↗
PubMed1987

Diets realistic for westernized people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B6 and haematology in vervet monkeys.

This report describes measurements of 50 variables in adult, female, reproductively inactive Vervet monkeys during prolonged nutrition realistic for westernized people. Dietary treatments consisted of an atherogenic Western diet (WD) and a prudent Western diet (PD). Ingredients were normal foods for man and no extra cholesterol was added. Fortification of both diets with vitamin C after cooking was necessary to prevent deficiency. Randomised groups of Vervet monkeys received either the PD or WD for 47 months, while a third group was fed WD for 20 months and then PD for 27 months (WD-PD). Before the dietary treatments nourishment was by a high carbohydrate diet (HCD) and baseline and reference values (RV) apply to this nutritional status. Plasma total cholesterol (mg/dl) was increased from 147 (HCD) to 174 (PD) and 376 (WD). Individual cholesterolaemio response ranged from mild to severe and was stable (PD and WD). Dietary reversal (WD-PD) reduced cholesterolaemia promptly. Statistically significant increases in calcium, zinc and vitamin E and decreased vitamin B6 were associated with the WD relative to the PD (in serum and plasma). Two cholesterol metabolising microsomal enzymes in liver were notably increased and one unchanged (WD). There were no dietary effects on triglycerides, vitamin A and glucose in plasma; insulin, glucagon, electrolytes, copper, magnesium or enzymes reflecting liver, muscle or brain cell damage in serum. Red blood cells, platelets and directly associated parameters increased (WD), haemoglobin was the same and haemoglobin per red cell decreased. Bleeding time was not affected. Bivariate correlations across the diets confirmed that Western nutrition promoted inherent individual susceptibility to cholesterolaemia. There were notable differences from RVs in total cholesterol, calcium, packed cell volume and haemoglobin, which emphasise excesses and deficiencies of the WD and PD.

Animal Nutritional Physiological Phenomena↗
PubMed1987

Porcine D-amino acid oxidase: determination of the mRNA nucleotide sequence by the characterization of genomic and cDNA clones.

Oligodeoxynucleotide probes derived from the published amino acid (aa) sequence for D-amino acid oxidase (DAO) [Ronchi et al. J. Biol. Chem. 259 (1982) 8824-8834] were used to screen cDNA libraries made from porcine kidney cortex and liver. Whereas no clones were obtained from kidney mRNAs, 20 independent ones were isolated from the liver library. Surprisingly, all of them carried only partial cDNAs for DAO starting around aa 100 in the coding sequence and extending for up to 250 bp in the 3'-noncoding sequence. One of these clones, pULB9103, was used to screen a porcine genomic library and allowed the isolation of DAO gene clone phULB001. Four exons encoding aa 1-151 were identified and sequenced, as well as the relevant exon-intron junctions. The mRNA sequence coding for DAO has been reconstituted from the genomic and cDNA sequences; its analysis by computer did not reveal any significant secondary structure, or particular feature, which could explain the failure to obtain full-length cDNAs.

Amino Acid Sequence↗
PubMed1987

The effect of iron and folate therapy on maximal exercise performance in female marathon runners with iron and folate deficiency.

Of the 85 female marathon runners examined in this study, 14 (16%) had serum ferritin levels below 40 ng/ml but only two (2%) had iron deficiency anaemia (haemoglobin below 12 g/dl); 28 (33%) had serum folate levels below 4.8 ng/ml and of these two (2%) had haemoglobin levels below 12 g/dl and 13 (15%) had mean corpuscular volumes greater than 95 fl. One week after treatment with oral folate (5 mg/day) or iron (50 mg of elemental iron/day), serum ferritin and folate levels were normal but maximum oxygen uptake, maximum treadmill running time, peak blood lactate levels and the running speed at the blood 'lactate turnpoint' were not changed from values measured during an identical test performed 1 week earlier. These parameters were also unchanged in a third exercise test performed after a further 10 weeks of treatment. Serum folate or serum ferritin levels in a control (placebo-treated) group with initially high serum ferritin or folate levels fell with placebo treatment but maximum treadmill running time, maximum oxygen uptake values, peak blood lactate levels and the running speed at the blood 'lactate turnpoint' were unchanged. We conclude that biochemical evidence of iron and folate deficiency is relatively common in female distance runners; that 1 week of treatment corrects the biochemical evidence of folate and iron deficiency but that such treatment does not influence maximal exercise performance nor does it alter blood lactate levels during exercise. In the absence of iron deficiency anaemia, iron therapy for reduced serum ferritin levels, or folate therapy for low serum folate levels, may not improve maximal treadmill performance even in trained runners.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hypochromic↗
PubMed1987

Congenital dyserythropoietic anaemia (type II) presenting with haemosiderosis.

A 39-year-old female with type II congenital dyserythropoiesis presented with iron overload. The clinical and haematologic features were an anaemia of variable severity, splenomegaly, numerous bizarre and binucleate normoblasts in the bone marrow, with prominent submembranous cisternae in the late forms, a positive Ham's acid lysis test and aberrant expression of the I and i red cell antigens. The iron overload resulted from gross ineffective erythropoiesis, with accelerated plasma iron turnover and increased absorption aggravated by inappropriate replacement therapy for past episodes of anaemia.

Adult↗
PubMed1987

Evidence for the involvement of DNA topoisomerase II in neutrophil-granulocyte differentiation.

Agents that slow cellular proliferation usually stimulate myeloid differentiation. The demonstration in this report of an anomalous inhibitory behavior of the epipodophyllotoxin VP16-213, an agent known to inhibit the enzyme DNA topoisomerase II, prompted us to investigate the role of this enzyme in both changes in DNA supercoiling and in DNA strand breakage and reunion events occurring during the induction of neutrophil-granulocyte differentiation. We recently reported that retinoic acid, an inducer of granulocytic differentiation, stimulates transient relaxation of DNA supercoiling. We now show that this is associated with the formation of small numbers of protein-linked DNA breaks (a characteristic of topoisomerase reactions). Both events are perturbed by VP16-213, and since this agent inhibits subsequent differentiation, these observations raise the possibility of a role for DNA topoisomerase II in granulocytic differentiation. The possible relevance of these findings to mechanisms of leukemogenesis is discussed.

Cell Differentiation↗
PubMed1987

High-level production of fully active human alpha 1-antitrypsin in Escherichia coli.

The human alpha-1-antitrypsin (A1AT) gene expressed in Escherichia coli as a full-length, non-fusion gene product accumulates to a relatively low level approaching less than or equal to 0.1% of total cellular protein. In contrast, deletion of the first 5, 10 or 15 codons leads to production of truncated A1AT derivatives at levels between 10 and 30% of total cellular protein. The protein with the largest truncation was insoluble and inactive following solubilization by chaotropic agents. In contrast, the two derivatives with the smaller truncations were found to be soluble, and exhibit identical specific activities in both trypsin and elastase inhibition assays to authentic human A1AT. The expression of the full-length A1AT was also optimized by making silent third position mutations within its first 15 codons. These mutations were chosen to optimize codon usage and minimize the possibility of RNA secondary structure formation in this region. Via this approach, expression of full-length, authentic, fully active A1AT was increased at least 20-fold to 2% of total cellular protein. Optimal expression was obtained using as few as three silent mutations in the first five codons, confirming the importance of this 5'-terminal region as had been defined by our deletion mutants. Both the full-length derivatives as well as the small N-terminal deletion derivative can be readily purified from bacterial extracts in fully active form suitable for the examination of their potential therapeutic application.

Base Sequence↗
PubMed1987

A randomized prospective comparison of chemotherapy to total body irradiation as initial treatment for the indolent lymphoproliferative diseases.

One hundred eight consecutive patients with indolent lymphoproliferative diseases were stratified into chronic lymphocytic leukemia (CLL), stage III and IV well-differentiated lymphocytic lymphoma (WDLL), and stage III and IV follicular lymphoma (FL). Within each stratum, patients were prospectively and randomly assigned to receive chemotherapy with chlorambucil and prednisone (CP) or fractionated total body irradiation (TBI). Morbidity from both regimens was negligible. Complete response (CR) was defined as the resolution of organ enlargement and the return of blood count to normal. The CR rate for the entire CP group (n = 54) was 59% and that for the TBI group (n = 54), 52%; median survivals were 53 and 57 months respectively. In the 41 patients with CLL the CR rate for CP (n = 17) was 47% and that for TBI (n = 24), 50%; the median survival for CP was 48 months, and for TBI it was 51 months. In the 21 patients with WDLL the CR rate for CP (n = 15) was 53% and that for TBI (n = 6), 67%; the median survival for CP was 42 months and has not yet been reached for TBI. For the 46 patients with FL the CR rate for CP (n = 22) was 72% and that for TBI (n = 24), 50%; the median survival was 55 months, and for TBI it was 56 months. None of the differences in CR or survival are statistically significant (P greater than .05). In these indolent lymphoproliferative diseases, CP and TBI are equally effective forms of initial treatment irrespective of the end point being defined as CR or survival.

Adult↗
PubMed1987

Equivalent bioavailability of iron from ferrous salts and a ferric polymaltose complex. Clinical and experimental studies.

In both experimental animals and human subjects iron absorption over a wide dosage range was quantitatively equivalent from ferrous salts and a ferric polymaltose complex under basal conditions. The comparable bioavailability was maintained when demand was increased by iron depletion or erythroid stimulation and depressed by expansion of body stores or impaired erythropoiesis. This common pattern for iron retention from both salt and complex supports the interchangeable use of these products in therapy of absolute iron deficiency.

Animals↗