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Biomedical subjects

P Jacobs

Publications and source records attributed to P Jacobs.

At least 397 records · Page 22Linked to original sources
PubMed1985

Molecular cloning, sequencing, and expression in Escherichia coli of human preprourokinase cDNA.

A cDNA library derived from human carcinoma cells was used to isolate a clone, pULB1000, coding for the preproenzyme form of human urokinase. This clone carries the full-length sequence coding for the signal peptide and for the A chain (157 amino acids) and B chain (253 amino acids) of urokinase in tandem. The sequence of the cDNA predicts the presence of a single lysine residue between the last amino acid of the mature A polypeptide (Phe-157) and the first amino acid of the mature B polypeptide (Ile-1). The amino acid sequence deduced from the cDNA sequence fits the published amino acid sequence data with three exceptions, the reported cysteine residue at position 131 in the A chain is a tryptophan, and glycine 366 and alanine 410 in the B chain are, respectively, a cysteine and a valine in our clone. A large Bgl I fragment (1482 bp), derived from the clone pULB1000 coding for most of the signal peptide and for the A and B chains, has been subcloned into the expression vector pCQV2. Heat induction of E. coli cells carrying the recombinant plasmid leads to the production of urokinase-like polypeptides having the expected molecular weights and being specifically recognized by antibodies raised against natural human urokinase.

Base Sequence↗
PubMed1985

Cyclosporin A in the treatment of severe acute aplastic anaemia.

Twelve consecutive adults with severe acute aplastic anaemia, not having a bone marrow transplantation option, were prospectively randomized to receive either cyclosporin A alone or an equivalent amount of this immunosuppressive agent in combination with antilymphocyte serum. The minimum follow-up is 36 months, with half the patients developing nephrotoxicity, which was easily reversible in all but one. No response could be attributed to either regimen. Cyclosporin A does not appear to have a place as primary form of treatment for adults with severe acute aplastic anaemia, either on its own or in combination with antilymphocyte serum.

Acute Disease↗
PubMed1985

Cyclosporin A pretreatment of both donor and recipient undergoing allogeneic bone marrow transplantation.

51 patients received allogeneic marrow from histocompatible and MLR non-reactive siblings. Post-transplantation methotrexate was associated with acute refractory graft-versus-host disease (GVHD) in 10/23 (43%) and caused death in 6. When cyclosporin was substituted for the methotrexate fulminating GVHD occurred in 2/28 (28%): both responded to methylprednisolone. When both donor and recipient were pretreated with cyclosporin GVHD of only mild degree developed in 6/20 (30%): 2 responded rapidly to methylprednisolone and in the remaining 4 mild cutaneous lesions persisted. The latter regimen was associated with no donor morbidity and approximately 50% of the recipients had easily reversible renal dysfunction. Thus, cyclosporin A appears to marginally reduce the incidence of acute GVHD and to facilitate response when additional methylprednisolone is required: additional pretreatment of the donor appears to reduce the severity of the acute syndrome. In none of these regimens was a beneficial effect observed on de novo GVHD.

Bone Marrow Transplantation↗
PubMed1985

Microbial and immunological investigations of chronic non-ulcerative blepharitis and meibomianitis.

Concentrations of tear lysozyme, lactoferrin, ceruloplasmin, IgG, and IgA have been measured by enzyme linked immunosorbent assay (ELISA) in patients with chronic non-ulcerative blepharitis and meibomianitis at the same time as the lid and conjunctivae were cultured for bacteria and fungi by a semiquantitative method. A group of normal controls aged 20 to 80 were similarly sampled, when strains of Staphylococcus epidermidis from their eyes and the patients' eyes were biotyped according to Baird-Parker's scheme. 5% of blepharitis cases had increased numbers of Staph. aureus present on the lids, compared with only a scanty growth obtained from 5% of normals. 7% of blepharitis cases had increased numbers of Staph. epidermidis type VI (coagulase-negative, mannitol-fermenting) present compared with a scanty growth obtained from 6% of normals. Isolation rates of other types of Staph. epidermidis did not differ from those in normals; no types were associated with meibomianitis. Tear protein profiles were normal in most patients, and there was no increase in tear IgA or IgG, which is expected with chronic infection. Overall our evidence suggests that in 88% of cases these lid conditions have an inflammatory aetiology not associated with infection. Staphylococcal isolates often found in the eye usually represent a normal commensal rather than pathogenic flora.

Adult↗
PubMed1985

Splenic pathology in immune thrombocytopenia.

Splenic pathology was analysed in 73 patients with immune thrombocytopenic purpura who underwent splenectomy for bleeding that had been resistant to adrenocorticosteroids. The mean splenic weight was 100 g. The only notable macroscopic feature was the prominence of Malpighian corpuscles in 15 cases. Microscopic examination showed formation of germinal centres in the lymphoid tissue of the white pulp in 40 cases, prominence of the histiocytes in the red pulp in 18 cases, and infiltration with neutrophils in the same area in 49 cases. Myeloid metaplasia throughout the splenic tissue was minimal in 58 cases, moderate in 15, and extreme in two. No distinguishing features were found in the spleen from patients who had not received previous immunosuppressive treatment (n = 3), those treated with prednisone (1 mg/kg/day) for a median of 14 days (n = 62), or those who had received the same dose of prednisone and additional azathioprine or cyclophosphamide (2 mg/kg/day) for a median of four weeks (n = 8). No correlation could be shown between histological features and the age of the patient or titre of antiplatelet antibodies. Similarly, no distinguishing features were found in patients with associated systemic lupus erythematosus (n = 8), hyperthyroidism (n = 6), immune haemolysis (n = 3), or recent viral illness (n = 3).

Adrenal Cortex Hormones↗
PubMed1985

Pyoderma gangrenosum in myelodysplasia and acute leukaemia.

Pyoderma gangrenosum is a rare occurrence in patients with haematological malignancy. This characteristic but nonspecific inflammatory process with skin destruction occurred in 4 patients with myelodysplasia, in one with acute leukaemic transformation of myelofibrosis, and in de novo acute myeloblastic leukaemia in another. Clinically, the cutaneous lesion in these patients differed from that associated with inflammatory bowel disease, arthritis, or the idiopathic type of pyoderma gangrenosum by having the vesiculo-bullous borders. Histopathological differences were also evident since more superficial layers of the skin were involved in the ulceration than typically encountered in patients with non-malignant systemic disease. Despite the less penetrating nature of this variant, treatment of the pyoderma gangrenosum is unsatisfactory and in the absence of effective therapy for the underlying disease, healing occurred only in the patient with acute leukaemia who achieved complete remission in response to chemotherapy.

Acute Disease↗
PubMed1985

Granulocytic sarcoma preceding leukaemic transformation in myelofibrosis.

A granulocytic sarcoma expanded the malar region in a patient with proven myelofibrosis over a 22 month period before undergoing rapid increase in size concomitantly with transformation to acute granulocytic leukaemia in the marrow and the widespread appearance of subcutaneous tumour deposits. Rapid response was obtained with local radiotherapy, and the systemic disease manifestations were controlled on combination courses of oral 4'-demethoxydaunorubicin and the epipodophyllotoxin VP16-213. This appears to be the first example of a granulocytic sarcoma occurring in a patient with myelofibrosis.

Cell Transformation, Neoplastic↗
PubMed1985

Myelofibrosis, splenomegaly, and portal hypertension.

A patient with chronic myelofibrosis and massive splenomegaly developed portal hypertension with haematemesis occurring from radiologically proven oesophageal varices. Transjugular liver biopsy showed only myeloid metaplasia, and radiological evaluation of the portal vascular system was undertaken to establish a diagnosis of hyperkinetic portal hypertension as a basis for therapeutic splenectomy. The alternative and rare situation of splenic and portal vein occlusion was demonstrated and therefore removal of the spleen was not an appropriate procedure for relief of portal hypertension. The variceal bleeding was successfully controlled with injection sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1985

Interhospital variations in hospital pharmacy markups.

The relationship between pharmacy pricing policies and overall hospital objectives was analyzed for 64 South Carolina hospitals in 1980. Using published hospital data, a linear regression model was developed to test the relationship between a pricing variable (the charge-to-cost ratio for each pharmacy) and five independent variables: demand (defined as hospital occupancy rate), industry structure (defined as affiliation or nonaffiliation with a multihospital system), level of hospital use by Medicare and Medicaid patients (defined as the proportion of hospital admissions for which reimbursement was based on costs), the contribution of nonoperating revenue, or subsidization (defined as the proportion of hospital nonoperating revenue to total expenses), and the contribution of operating revenues of departments other than pharmacy (defined as the proportion of non-pharmacy charges to total charges). In these predominantly nonprofit hospitals, the mean (+/- standard deviation) pharmacy markup was 1.99 +/- 0.49, with considerable inter-hospital variation. The level of hospital use by Medicare and Medicaid patients had the greatest influence on variation in markup, indicating that hospitals were responding to cost-based payer reimbursement practices by raising charges in areas with a high cost base, such as pharmacy. Nonoperating revenue and operating revenue of departments other than pharmacy also were significantly related to the charge-to-cost ratio. The relationship between the charge-to-cost ratio and either occupancy rate or affiliation with a multihospital system was not significant. The hospitals studied set pharmacy revenues to contribute to overall target income, but pharmacy prices were not set to achieve maximum profits by responding to changes in demand.

Costs and Cost Analysis↗
PubMed1985

[Hemodynamic effects of phentolamine in acute and chronic mitral insufficiency after myocardial infarction].

The haemodynamic effects of phentolamine, a selective alpha blocker, were studied in patients with severe mitral regurgitation and cardiac failure in the acute (Group I, 7 cases) or chronic (Group II, 7 cases) phase of myocardial infarction. After 1 hour's treatment a rise in cardiac index (+29 p. 100, p less than 0.001 and +36 p. 100, p less than 0.01), and systolic index (+19 p. 100, p less than 0.001 and +19 p. 100, p less than 0.05) were observed; the V wave of the pulmonary capillary pressure recording decreased (-32 p. 100, p less than 0.005; -26 p. 100, p less than 0.01). Oxygen transport also increased by an average of 36 p. 100, p less than 0.001, without a significant change in arterial pp O2. These results show that phentolamine improves the haemodynamics and decreases mitral regurgitation in the acute and in the chronic phases of myocardial infarction.

Acute Disease↗
PubMed1985

Pricing objectives in nonprofit hospitals.

This article reports on a survey of 60 financial managers of nonprofit hospitals in the eastern United States relating to the importance of a number of factors which influence their pricing decisions and the pricing objectives which they pursue. Among the results uncovered by the responses: that trustees are the single most important body in the price-setting process (doctors play a relatively unimportant role); that hospital pricing goals are more related to target net revenue than profit maximizing; and that regional factors seem to play an important role in management differences.

Economics, Hospital↗
PubMed1985

Cyclosporin-A radioimmunoassay: a modified method for whole blood determination.

Cyclosporin-A levels were determined by radioimmunoassay in plasma or whole blood, using split samples collected from patients receiving this agent as the only form of immunosuppression following allogeneic bone marrow transplantation. In the plasma assay the temperature at which centrifugation took place was critical since the mean levels were approximately 30% higher with separation at 37 degrees C in comparison to 20 degrees C or lower. Furthermore, the level in whole blood samples was 2.4 times higher than that from the matching serum. In addition, anticoagulated blood that had been frozen and then thawed was technically more difficult to pipette and resulted in a recovery of only 83% of the cyclosporin when compared with assay using fresh blood. In contrast, consistent measurements were obtained either when whole blood was stored at 4 degrees C and then well mixed and diluted in buffer immediately prior to use or when such buffered samples were frozen and thawed immediately before analysis. The latter modifications render the whole blood assay a practical and reliable means for monitoring cyclosporin-A concentrations and may avoid excessive and the potentially nephrotoxic levels achieved when plasma levels are held in ranges previously considered therapeutic.

Animals↗
PubMed1984

Fanconi's anemia. A family study with 20-year follow-up including associated breast pathology.

A brother and sister with Fanconi's anemia, having typical skeletal deformity and characteristic chromosomal breaks in their lymphocytes and who followed the typical clinical course, with progressive bone marrow insufficiency beginning late in the first decade, are described. The natural history of the disease before chemotherapy was available is contrasted with the response to intermittent courses of anabolic steroids during a continuous 20-year follow-up. The female patient developed a carcinoma of the breast at the age of 26, from which she died 5 years later. This neoplasm may reflect increased susceptibility of cells with proven chromosomal abnormality to the influence of carcinogens. Her brother required repeated surgery for painful, but benign, breast masses. The explanation for the latter lesion is unknown but may be related to endocrine disturbances occurring in patients with Fanconi's anemia.

Anemia, Aplastic↗
PubMed1984

Human T-cell leukemia virus (HTLV-I) antibodies in Africa.

Antibodies specific for human T-cell leukemia-lymphoma virus type I (HTLV-I) were demonstrated in serum samples from various groups of people in South Africa, Uganda, Ghana, Nigeria, Tunisia, and Egypt. The samples had been collected for other purposes and were presumably selected without bias toward clinical conditions associated with HTLV infections. Regional differences in antibody positivity were observed, indicating widely distributed loci of occurrence of HTLV on the African continent in people of both black and white ancestry. Two patients with high titers of antibody to HTLV-I had some signs of adult T-cell leukemia-lymphoma. In several groups a high frequency of false positive serum reactions was indicated when specific confirmation steps were included in the assay. Further characterization of these sera revealed highly elevated immunoglobulin levels, possibly due to polyclonal activation of immunoglobulin synthesis in these subjects. The possibility that related cross-reactive human retroviruses coexist in the same groups was not eliminated.

Adult↗
PubMed1984

Megakaryoblastic transformation in myeloproliferative disorders.

Megakaryoblastic transformation, with cells showing characteristic morphology and ultrastructural cytochemistry, developed in two patients with agnogenic myeloid metaplasia or myelofibrosis, and in one with chronic granulocytic leukemia. From the onset of the leukemic phase, all three have followed a relatively benign clinical course, surviving for 48, 29, and 24 months, respectively; only hydroxyurea has been necessary to control thrombocytosis. This experience emphasizes that it is possible for a patient to have an improved quality of life with minimum chemotherapy. In contrast, megakaryoblastic leukemia or acute myelofibrosis, where splenomegaly and a leukoerythroblastic blood picture are typically absent, responds poorly to any form of chemotherapy, and survival is short.

Blood Cell Count↗