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Biomedical subjects

J Straub

Publications and source records attributed to J Straub.

At least 37 records · Page 2Linked to original sources

[Sideropenic anemia as a manifestation of selective iron malabsorption].

The objective of the paper is to draw attention to the not very frequent and thus omitted form of sideropenic anaemia in selective iron malabsorption as the only manifestation of malabsorption syndrome in coeliac sprue. This type should be suspected when examination of blood losses is futile and oral iron administration which is usually administered empirically produces no effect. The authors present the example of two patients with severe sideropenic anaemia where the diagnosis of malabsorption was confirmed only several years after the diagnosis of sideropenic anaemia was established. Evidence of a correct conclusion was permanent normalization of haemoglobin values when the patients adhered to a gluten-free diet.

Adult↗

APC mutations in sporadic colorectal tumors: A mutational "hotspot" and interdependence of the "two hits".

Although APC mutations occur at a high frequency in colorectal cancers, few studies have performed a comprehensive analysis by screening the whole gene for mutations and assessing allelic loss. APC seems to act as a tumor-suppressor gene in a "nonclassical" fashion: data from familial adenomatous polyposis (FAP) show that the site of the germ-line mutation determines the type of "second hit" in FAP tumors, and simple protein inactivation is selected weakly, if at all. In this study, we screened the entire coding region of APC for mutations and assessed allelic loss in a set of 41 colorectal cancer cell lines. Of 41 cancers, 32 (83%) showed evidence of APC mutation and/or allelic loss. We identified several APC mutations and found a "hotspot" for somatic mutation in sporadic colorectal tumors at codon 1,554. Our results suggest that APC mutations occur in the great majority of colorectal cancers, the exceptions almost all being RER+ tumors, which may substitute for altered APC function by mutations in beta-catenin and/or at other loci. When combined with previously published data, our results show that there is interdependence of the "two hits" at APC in sporadic colorectal tumors as well as in FAP. APC mutations in the "mutation cluster region," especially those close to codon 1,300, are associated with allelic loss, whereas tumors with mutations outside this region tend to harbor truncating mutations. The causes of this phenomenon are probably selection for retained N-terminal and lost C-terminal APC functions, effects on beta-catenin levels, and APC protein stability.

Base Sequence↗

Facial palsy in cerebral venous thrombosis : transcranial stimulation and pathophysiological considerations.

BACKGROUND: Cranial nerve palsy in cerebral sinovenous thrombosis (CVT) is rare, its pathophysiology remains unclear, and data from electrophysiological examinations in such patients are missing. CASE DESCRIPTION: We report the case of a 17-year-old woman with familial protein S deficiency who was admitted with extensive multiple CVT. Two weeks after onset of symptoms, she developed isolated right peripheral facial palsy, and MR venography showed segmental occlusion of the ipsilateral transverse sinus. Complete recovery of facial palsy occurred concomitant with recanalization of the transverse sinus. Facial neurography, including transcranial magnetic stimulation of the facial nerve and related motor cortex, ruled out a coincidental idiopathic palsy and revealed conduction block proximal to the facial canal. CONCLUSIONS: Facial palsy in our patient was caused by transient neurapraxia in the intracranial segment of the nerve. We suggest that elevated venous transmural pressure in the nerve's satellite vein, which belongs to the affected drainage territory of the transverse sinus, might have caused venous blood-brain barrier dysfunction in the intrinsic vascular system of the nerve, with leakage of fluids and ions into the endoneurial space and thus an increase in interstitial resistance.

Adolescent↗

Transforming growth factor beta stimulation of colorectal cancer cell lines: type II receptor bypass and changes in adhesion molecule expression.

The type II transforming growth factor (TGF)-beta receptor gene (TGFBR2) is often mutated in nucleotide repeat sequences in colorectal cancers that are replication error positive (RER+). These mutations are thought to be selected for escape from growth inhibition by TGF-beta rather than representing bystander events because of an increased mutation rate. We investigated the role of TGFBR2 mutations in 12 colorectal cancer cell lines. Six of these were RER+, and these were shown to have homozygous TGFBR2 mutations. All cell lines then were tested for changes in proliferation in response to TGF-beta stimulation. Despite homozygous mutation of the type II TGF-beta receptor, two RER+ cell lines, Lovo and SW48, showed statistically significant growth inhibition when stimulated by TGF-beta1 in serum-free conditions. This shows that the type II TGF-beta receptor can be bypassed in certain cases to maintain growth inhibition. We next investigated whether there was any alternative mode through which TGFBR2 mutation may give a selective advantage, such as a change in adhesion molecule expression. All cell lines were stimulated with TGF-beta1 and adhesion molecules detected by ELISA. No consistent changes were identified between the RER+ and the RER- cell lines, although changes in E-cadherin, beta-catenin, and gamma-catenin were identified in individual cell lines. We conclude that (i) type II TGF-beta receptor activity can be bypassed and thus TGFBR2 mutations in RER+ cancers may, at least sometimes, be just "bystander" events and (ii) TGF-beta can affect adhesion molecule expression so that TGFBR2 mutation may give rise to a selective advantage through an effect other escape from growth inhibition.

Cell Adhesion↗

Genetic pathways in colorectal and other cancers.

Cells from cancers show aberrant behaviour such as unrestrained growth, invasion into adjacent tissue and metastasis. All these features of cancer cell behaviour can be explained in terms of genetic changes and the functional impact of these changes. In this review, colorectal cancer (CRC) is examined as a classical example of multistep carcinogenesis. First there is an overview which shows that cancers develop by a process of somatic evolution. This gives rise to preferred genetic pathways of tumorigenesis. The factors which may influence the development and ultimate choice of genetic pathways are then examined. Next, CRC is studied as a specific disease and the putative genetic pathways are described. The mutations that comprise these pathways and the possible functional sequelae of these are explored. The review concludes with a look at those avenues which may further elucidate the natural history of CRC and lead to improved therapy.

Colorectal Neoplasms↗

Genetic pathways in colorectal and other cancers.

Cells from cancers show aberrant behaviour such as unrestrained growth, invasion into adjacent tissue and metastasis. All these features of cancer cell behaviour can be explained in terms of genetic changes and the functional impact of these changes. In this review, colorectal cancer (CRC) is examined as a classical example of multistep carcinogenesis. First there is an overview which shows that cancers develop by a process of somatic evolution. This gives rise to preferred genetic pathways of tumorigenesis. The factors which may influence the development and ultimate choice of genetic pathways are then examined. Next, CRC is studied as a specific disease and the putative genetic pathways are described. The mutations that comprise these pathways and the possible functional sequelae of these are explored. The review concludes with a look at those avenues which may further elucidate the natural history of CRC and lead to improved therapy.

Cell Transformation, Neoplastic↗

Perceived health in a randomised trial of treatment for chronic venous ulceration.

STUDY OBJECTIVE: To observe changes in perceived health in patients during a clinical trial of treatments for venous leg ulceration. DESIGN: Randomised prospective factorial trial in patients with venous ulceration. Each patient randomised to a bandage, dressing and a drug. Perceived health assessed at entry and after 24 weeks. SETTING: Outpatient departments and patient's home. PATIENTS: Two hundred patients presenting to two vascular services in Falkirk and Edinburgh with chronic (duration > 2 months) non-healing venous ulceration. STATISTICAL ANALYSIS AND MAIN RESULTS: Analysis using the Nottingham Health Profile revealed that after 24 weeks there were significant improvements in all subscores (p < 0.01) with the exception of social isolation (p = 0.081). Patients with healed ulceration had improved in energy, pain, emotion, sleep and mobility compared with those whose ulceration failed to heal (p < 0.05). Patients randomised to four layer bandaging had significantly better energy (diff = 7.9, 95% CI 0.2, 15.6, p = 0.04) and mobility (diff = 4.5, 95% CI 0.0, 9.0, p = 0.046). This difference could be explained largely by the improved healing of patients randomised to this bandage system (67/97 vs. 50/103, OR = 2.37, 95% CI 1.31, 4.27). CONCLUSIONS: Improvements in perceived health were significantly greater in patients whose ulcers had completely healed. Methods of treatment which offer improved healing for patients with venous leg ulceration are likely to improve patients' perceived health status.

Adult↗

Effective contrast use in CT angiography and dual-phase hepatic CT performed with a subsecond scanner.

OBJECTIVE: To deduce an optimal injection protocol for CT angiography and fast dual-phase hepatic CT. METHODS: Fifty-two patients underwent fast dual-phase hepatic CT using one of three different injection protocols: A (0.9 g/sec iodine injection rate, 36 g dose); B (1.35 g/sec, 30 g); C (1.6 g/sec, 40 g). Aortic attenuation time curves as well as aorta-to-liver contrast and hepatic enhancement time curves obtained by region of interest measurements along the helical axis were analyzed. RESULTS: Protocol C revealed a significantly higher peak in aortic attenuation and hepatic enhancement than the other protocols. Approximately 50 seconds after the bolus injection, hepatic enhancement declined to a plateau similar to that seen with the other protocols. In terms of the areas under the curves of the aorta-to-liver contrast and hepatic enhancement dynamics, protocol C was significantly superior to the other protocols. CONCLUSIONS: A high iodine injection rate realized by a high iodine concentration in conjunction with fast dual-phase scanning (total scan time < 50 seconds) promises to enhance CT angiography and contrast of liver lesions.

Angiography↗

Triggers of overeating and related intervention strategies for women who weight cycle.

The purpose of this study was to describe overeating episodes of overweight women who weight cycle compared with women of normal weight. Repeated overeating can be a major source of excess calories that may lead to weight gain in women who have weight cycled. Interview transcripts about overeating episodes of 45 women were subjected to a content analysis in a qualitative secondary analysis of data. Four patterns emerged from the data: planned overeating, power/control, relationships with others, and unpleasant feelings. Three intervention strategies are described to assist women who have weight cycled to understand and deal with feelings that trigger overeating, including strategies to stop overeating, feel their feelings, and fight fairly.

Adult↗

[Mixed myelodysplastic and myeloproliferative syndromes].

BACKGROUND: An injury to the hemopoietic stem cell may lead to the aplasia of hemopoiesis, myelodysplasia and to an unregulated myeloproliferation. There is not a strict demarcation of them, so that mixed syndromes can develop as are hypoplastic syndromes on one side and mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) on the other side. METHODS AND RESULTS: Among our 616 pts with MDS we looked for those cases, who had beside myelodysplasia signs of myeloproliferation with increased number of blood cells. They were examined in detail including bone-marrow histology, bone marrow cultivation, cytogenetics and bcr-abl gen. Signs of MDS-MPS were found in 22 patients at the first contact with the patient (13 patients had thrombocytemia and 9 patients had leukocytosis). Further 7 patients were diagnosed as MDS, proliferative syndrome developed after several months (MDS-MPS in evolution). The level of thrombocytemia was relatively stable, the number of leukocytes was progressive. All subtypes of MDS were found. All subjects had variable degree of anemia. Ring-sideroblasts and myelofibrosis were frequent finding in MDS-MPS. Men prevailed in patients with leukocytosis. Cytogenetic and cultivation findings were similar to MDS cases, deletion of long arm of chromosome 20 was present in 3 patients. Five patients transformed to acute myeloid leukemia. CONCLUSIONS: Sings of myelodysplasia and myeloproliferation were found in 4% of our MDS patients, designated as mixed myelodysplastic and myeloproliferative syndrome (MDS-MPS). In this syndrome beside evident signs of myelodysplasia thrombocythemia or leukocytosis with the release of bone marrow precursors are present. In only one case polycythemia was encountered.

Adult↗

Nucleotide sequence of the Barmah Forest virus genome.

Barmah Forest virus (BFV) is an atypical alphavirus [Dalgarno, L., Short, N. J., Hardy, C. M., Bell, J. R., Strauss, J. H., and Marshall, I. D. (1984). Virology 133, 416-426] and has been classified as the sole known member of a seventh alphavirus serocomplex. The complete nucleotide sequence of BFV genomic RNA is 11,488 nucleotides in length excluding the poly(A) tail. Two long open reading frames in the RNA encode a nonstructural polyprotein of 2411 amino acids and a structural polyprotein of 1239 amino acids, respectively. The BFV envelope protein E2 is unique among sequenced alphaviruses in having no N-linked glycosylation sites; E1 carries two glycosylation sites. From amino acid sequence comparisons with sequenced alphaviruses BFV is most closely related to Ross River and Semliki Forest viruses. Sequence homology between BFV and other alphaviruses is relatively uniform along the length of the nonstructural and structural polyproteins, providing no evidence that BFV has arisen from recombination between ancestral alphaviruses in the coding region of the genome. The BFV 3' noncoding region of 445 nucleotides has unusual features. There are two unrelated sequence blocks of 48 nucleotides (sequence I) and 47 nucleotides (sequence II) both of which are repeated once. Sequence I is closely related to a repeat in the 3' noncoding region of Ross River and Getah viruses; sequence II is unrelated to repeat blocks in other sequenced alphaviruses. Thus, recombination between ancestral viruses may have played a role in the evolution of the BFV 3' noncoding region.

Alphavirus↗

Early high-dose intravenous methylprednisolone in acute disseminated encephalomyelitis: a successful recovery.

We describe a patient with acute disseminated encephalomyelitis (ADEM) who was treated with high-dose intravenous methylprednisolone 2 days after onset of neurologic symptoms. Despite poor prognostic factors and extensive white matter lesions, the patient recovered dramatically with no need for maintenance steroid therapy. This case report of fulminant ADEM treated successfully with early high-dose intravenous methylprednisolone, although uncontrolled, suggests that this agent should be studied in other cases.

Adult↗

[Recombinant erythropoietin (r-HuEPO) in the treatment of anemia in multiple myeloma].

BACKGROUND: Anemia is common complication in multiple myeloma (MM). Its etiology is multifactorial-bone marrow infiltration, cytokines production, renal failure and effect of chemotherapy are main contributing factors. The red cell substitution therapy, which is administrated in 34 - 53% of patients, is frequently associated with the risk of well-known side effects. The use of recombinant erythropoietin (r-HuEPO) is a novel therapy in patients with MM. METHODS AND RESULTS: We have investigated the effect of r-HuEPO (Eprex. Cilag) in the group of 8 patients with MM. The growth factor was administrated in the dose of 150 U/kg. 3 times/ week s.c. The criterium of response was the increase of Hb levels of 20 g/L. All patients responded to r-HuEPO treatment. The medium period of response was 6,5 weeks. In two patients the doses of r-HuEPO could be reduced due to excellent effect of therapy. The energy level, ability to daily activities and overall quality of life significantly improved during the course of therapy. Neither effect of growth factor on thrombopoiesis and/or leukopoiesis nor serious adverse events due to r-HuEPO therapy were observed. The activity of underlying disease did not seem to be affected by r-HuEPO. In one patient the disease rapidly progressed after the end of study. The progression had some features of plasmablastic leukemia and leads to the death of patient. CONCLUSIONS: According to our experience, r-HuEPO is highly effective in the treatment of anemia in MM. The stimulation of erythropoiesis was associated with significant improvement of quality of life of patients. The effect of r-HuEPO treatment on activity of MM was not found, however, in one patient rapid progression of disease was observed after the end of study.

Aged↗

[Recombinant human erythropoietin in the treatment of anemia associated with lymphoproliferative diseases--chronic lymphadenosis and multiple myeloma].

UNLABELLED: The etiology of anaemia associated with tumours is multifactorial. One of the mechanisms of development of anaemia in tumours are so-called chronic diseases anaemias, the main feature of which is inadequate production of endogenous erythropoietin (EPO). The objective of the investigation was to test the effect of recombinant human erythropoietin (rHuEPO) in the treatment of anaemia (rise of haematocrit, Hb) in patients with chronic lymphatic leukaemia (CLL) and multiple myeloma (MM) and the effect of this treatment on the quality of life. The authors evaluated at the same time the impact of the endogenous EPO level before treatment and its predictive value as regards the therapeutic response. PATIENTS: The investigation comprised a total of 14 patients (6 CLL, 8 MM). The basic criterion for inclusion in the group was a Ht value lower than 0.32 and Hb less than 105 g/l. The examination protocol was focused on elimination of other causes of anaemia. During the 12-week investigation the patients completed a questionnaire "Quality of life" which reflected their subjective evaluation of the effect of treatment. The patients themselves administered r-HuEPO three times a week by the s.c. route--an initial dose of 150 U/kg with the possibility to increase the dose to 300 U/kg. RESULTS: A therapeutic response was obtained in four patients with CLL and eight patients with MM. Respondents with CLL had endogenous EPO values lower than 300 U/l, seven MM respondents lower than 200 U/l, one 400 U/l. The Hb level of the patients rose and the quality of life improved. All patients tolerated treatment very well and the authors did not observe any serious undesirable effects. CONCLUSION: The investigation confirmed the therapeutic effect of r-HuEPO in patients with a lower baseline value of EPO. Subjective evaluation (questionnaire) correlated with objective evaluation (Ht, Hb). Assessment of the endogenous EPO level before treatment is according to the authors one of the important primary predictive parameters and EPO values between 200 and 300 U/l are the upper range where a therapeutic effect can be expected with the highest probability. The authors conclude also that a secondary predictive criterion of the response is evaluation of the therapeutic effect after 4-5 weeks treatment when a rise of Hb by at least 20 g/l is an argument for further treatment.

Aged↗

Inhibition of leukocyte-endothelial cell interactions and inflammation by peptides from a bacterial adhesin which mimic coagulation factor X.

Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy.

Adhesins, Bacterial↗