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Biomedical subjects

C Bernasconi

Publications and source records attributed to C Bernasconi.

At least 73 records · Page 4Linked to original sources
PubMed1997

The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol.

Ethambutol (EMB), a frontline antituberculous drug, targets the mycobacterial cell wall, a unique structure among prokaryotes which consists of an outer layer of mycolic acids covalently bound to peptidoglycan via the arabinogalactan. EMB inhibits the polymerization of cell wall arabinan, and results in the accumulation of the lipid carrier decaprenol phosphoarabinose, which suggests that the drug interferes with the transfer of arabinose to the cell wall acceptor. Unfortunately, resistance to EMB has been described in up to 4% of clinical isolates of Mycobacterium tuberculosis and is prevalent among isolates from patients with multidrug-resistant tuberculosis. We used resistance to EMB as a tool to identify genes participating in the biosynthesis of the mycobacterial cell wall. This approach led to the identification of the embCAB gene cluster, recently proposed to encode for mycobacterial arabinosyl transferases. Resistance to EMB results from an accumulation of genetic events determining overexpression of the Emb protein(s), structural mutation in EmbB, or both. Further characterization of these proteins might provide information on targets for new chemotherapeutic agents and might help development of diagnostic strategies for the detection of resistant M. tuberculosis.

Amino Acid Sequence↗
PubMed1997

Treatment with recombinant human erythropoietin (rHuEpo) in a patient with paroxysmal nocturnal haemoglobinuria: evaluation of membrane proteins CD55 and CD59 with cytofluorometric assay.

We describe a 28-year-old man with paroxysmal nocturnal haemoglobinuria (PNH) and a high transfusion requirement. Prior to and during therapy with recombinant human erythropoietin (rHuEpo), we evaluated the levels of 'decay-accelerating-factor', CD55, and 'membrane-inhibitor-of-reactive-lysis', CD59, as markers of the disease, whilst CD58, a marker present on leucocytes, was utilized to monitor normal haemopoietic activity. The patient became transfusion independent 1 month after beginning rHuEpo and remains well. The analysis of CD55, CD59 and CD58 suggests that the efficacy of rHuEpo was due to a selective rHuEpo action on normal erythroid clones.

Adult↗
PubMed1997

Genotypic assessment of isoniazid and rifampin resistance in Mycobacterium tuberculosis: a blind study at reference laboratory level.

Progress in understanding the basis of resistance to isoniazid (INH) and rifampin (RMP) has allowed molecular tests for the detection of drug-resistant tuberculosis to be developed. Consecutive isolates (n = 95) of Mycobacterium tuberculosis, from a Spanish reference laboratory investigating outbreaks of multidrug-resistant tuberculosis, were coded and sent to two external laboratories for genotypic analysis of INH and RMP resistance by PCR-single-strand conformation polymorphism (SSCP) analysis of specific regions of four genes: part of the coding sequence of katG and the promoter regions of inhA and ahpC for INH and the RMP resistance region of rpoB. After correction for the presence of outbreak strains and multiple isolates from single patients, RMP resistance was detected successfully by PCR-SSCP in > 96% of the RMP-resistant strains. PCR-SSCP had a sensitivity of 87% for INH resistance detection, and mutations in katG, inhA, katG-inhA, ahpC, and katG-ahpC were identified in 36.8, 31.6, 2.6, 13.2, and 2.6%, respectively, of the unique strains. Specificity was 100%. Molecular detection of resistance to the two main antituberculous drugs, INH and RMP, can be accomplished accurately by using a strategy which limits analysis to four genetic regions. This may allow the expedient analysis of drug resistance by reference laboratories.

Antibiotics, Antitubercular↗
PubMed1997

Heterogeneity and clonality among isolates of Mycobacterium kansasii: implications for epidemiological and pathogenicity studies.

The reservoir and transmission route of Mycobacterium kansasii are largely unknown. In addition, culturing of M. kansasii from human sources is not proof of disease because it may represent colonization rather than infection. Unfortunately, investigation of the epidemiology and pathogenicity of M. kansasii is complicated by evidence of heterogeneity within the species. A comprehensive study by detailed genotypic analysis of a large collection of M. kansasii isolates (n = 276) from various geographical sources within Europe was conducted. Five defined subtypes of M. kansasii were identified; of these subtypes, type I represents the most common isolate from humans. Although phylogenetic analysis confirmed its relationship to the other M. kansasii types, significant sequence divergence was found at the 16S-23S intergenic spacer. Analysis of the chromosomal polymorphism of type I demonstrated a marked clonal structure for this particular organism. Because M. kansasii is becoming a significant pathogen among immunodeficient hosts, future epidemiological and pathogenicity studies should take into consideration both the heterogeneity within the species and the apparent clonality of the most prevalent M. kansasii isolates infecting humans.

Bacterial Proteins↗
PubMed1997

Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients.

PURPOSE: To define clinicopathologic features, response to treatment, and prognostic factors of primary mediastinal B-cell lymphoma (MBL), a CD20+ tumor recognized as a distinct entity among non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: One hundred six patients presented with disease confined to thorax (86%), bulky mediastinum (73%), superior vena cava syndrome (47%), and contiguous infiltration (57%). Ninety-nine received doxorubicin-containing chemotherapy (CHT). RESULTS: Thirty-five of 99 patients were primarily CHT-resistant, and 64 responded: 23 achieved complete response (CR) and 41 achieved response with residual mediastinal abnormality. Seventy-seven percent of responders received mediastinal radiotherapy (RT). Of 64 responders, 18 (28%) relapsed: none of 23 CR patients and 18 of 41 (44%) with residual mediastinal abnormality. Relapse-free survival rate of responders was 71% at 3 years. Actuarial 3-year survival rate was 52% for all patients and 82% for responders. Predictive factors of poor outcome were identified by logistic regression; Cox survival analysis was performed on death and relapse. Pericardial effusion (P < .001) and Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 (P = .009) predicted nonresponse (NR) and affected survival. Less than partial midway response to CHT predicted NR to subsequent therapies. Bulky disease was related to persistent mediastinal abnormality and risk of relapse (P = .025). CONCLUSION: MBL is an aggressive NHL with unique clinicopathologic aspects, often refractory to current CHT designed for high-grade NHL. Poor performance status and pericardial effusion predict NR and poor survival. Inadequate response after the first courses of front-line CHT predicts failure of subsequent treatment. Responders with bulky mediastinum or residual mediastinal abnormality after CHT are at risk of relapse. These factors should help to select high-risk patients for intensive treatments.

Adolescent↗
PubMed1997

Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence.

We evaluated the presenting clinical characteristics and outcome of 68 patients with nodular lymphocyte predominance Hodgkin's disease (NLP-HD), in order to delineate the pattern of evolution of the disease. The male to female ratio was 46/22 and median age 35 yrs (range, 14-86). Eight patients had a history of benign hyperplasia on lymph node biopsies performed 6 to 36 months before the diagnosis of NLP-HD. Early stage disease accounted for 75% of cases. One patient had a coexistent non-Hodgkin's lymphoma (NHL). Treatment was as follows: radiotherapy in 26, chemotherapy in 23, combined modality in 19. CR rate was 93% (63/68). 18 patients relapsed as HD and 5 developed NHL. The cumulative risk of NHL was 9% at 10 yrs. During remission, 4 patients had 5 episodes of follicular hyperplasia histologically documented. Overall survival rate was 71% at 10 yrs and and 63% at 15 yrs. Freedom from progression (FFP) declined from 67% at 5 yrs to 45% at 10 yrs, because of late relapses. Localized disease predicted for a better FFP (p = 0.01), but was not associated with a reduced risk of recurrence over time. NLP-HD is characterized by an indolent course with a constant pattern of relapse over time, also in patients with early stage disease at diagnosis. In addition to relapse as NLP-HD, patients may evolve into a NHL or develop benign lymph nodal hyperplasia. Careful long-term follow up is needed for these patients.

Adolescent↗
PubMed1997

Growth factors in the therapy of myelodysplasia: biological aspects.

Growth factors (GF) are reported to play an important role in the therapy of myelodisplastic syndromes (MDS). After in vitro administration a consistent group of MDS may respond to GF but the possibility of differentiation, regulation or expansion of myelodisplastic clones following GF therapy is still a question to be answered as their optimum dose and combinations. To validate if in vivo treatment with GF, may promote the regulation or the recovery of myelopoiesis and/or modify the clonality of the responses, we gave G-CSF after intensive chemotherapy in high risk MDS and acute leukemia evolving from MDS patients. According to our data the use of G-CSF after intensive chemotherapy may improve the CR rate without increase of leukemic transformation. However the answer were clonal and the remission duration remained very short so we suggest to utilize this time to perform other therapeutic strategies such as, when possible, the BMT.

Adult↗
PubMed1997

Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.

The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.

Biomarkers, Tumor↗
PubMed1996

Organisation of the tmb catabolic operons of Pseudomonas putida TMB and evolutionary relationship with the xyl operons of the TOL plasmid pWW0.

In Pseudomonas putida (Pp) TMB the genes involved in the catabolism of methyl-substituted aromatic hydrocarbons 1,2,4-trimethylbenzene, m- and p-xylene (tmb operon), are functionally and genetically homologous to the xyl genes of the plasmid pWW0, but are chromosomally encoded. We have analysed by cloning. Southern blotting and sequencing of selected regions the organisation of the tmb cluster. This analysis shows that the structural and regulatory genes of the tmb and xyl systems exhibit a high degree of homology and are similarly organised in operons. However the operons are differently arranged on the Pp TMB chromosome and on the pWW0 plasmid. Comparison of the two systems suggests that the operon arrangement found in pWW0 may have originated from that found in Pp TMB via cointegration mediated by replicative transposition or by intermolecular recombination between two copies of the insertion element IS1246.

Base Sequence↗
PubMed1996

Use of V-Y flap for vulvar reconstruction.

Less extensive surgical treatment has become possible for limited vulvar cancer. However, primary closure is advisable only when the defect is minimal and tissue replacement is always needed in radical excisions. Local flaps are always considered the first choice because of their characteristics of similarity to the resected area. The V-Y island flaps from the medial side of thigh constitute one of the numerous options. Clinical experience and anatomical studies demonstrate that this procedure is extremely safe thanks to the rich subcutaneous vascular network. After illustrating the theoretical bases and the indications of this surgical procedure, we report our experience. The V-Y technique is reliable, ensures good healing, and provides almost normal sensation. We conclude that, in most instances, it can be considered a good option for vulvar reconstruction for its versatility and rapidity of execution.

Aged↗
PubMed1996

A new mumps virus lineage found in the 1995 mumps outbreak in western Switzerland identified by nucleotide sequence analysis of the SH gene.

We determined the nucleotide sequence of the SH gene its flanking regions over a range of 380 nucleotides for three distinct mumps virus (MUV) isolates. Two isolates from the 1992 mumps epidemic in Western Switzerland and one MUV isolated in 1995 in the same geographic area have been analyzed and compared to 16 recently published SH nucleotide sequences and their presumed amino acid sequences. The nucleotide sequences from the 1992 MUV isolates were identical and closely related to two MUV strains from Eastern Switzerland and strains from the U.K. The MUV isolated in 1995 is clearly different from all other strains.

Amino Acid Sequence↗
PubMed1996

Responses of fetal sheep to reduced maternal renal blood flow and maternal hypertension.

In 16 chronically catheterized fetal sheep the effects of reducing and restoring maternal renal blood flow (RBF) and thus inducing and reversing hypertension were studied in uninephrectomized pregnant ewes; controls were 3 fetuses that were carried by uninephrectomized ewes in which RBF was not reduced and that did not become hypertensive. Within 24-72 h of maternal RBF reduction, fetal arterial PO2 had fallen (P < 0.001) and PCO2 had increased (P < 0.025); fetal arterial pressure also increased (P < 0.005). These effects persisted, despite restoration of maternal RBF and reversal of maternal hypertension. Within 24-72 h of reduction of maternal RBF, fetal urine flow had increased (P < 0.005), and it remained elevated over the first 3 h after RBF was restored; 24-72 h later it was lower (P < 0.025) and returned to control levels. The excretion of sodium, potassium, and chloride showed a similar increase when maternal RBF was reduced (P < 0.001), with return to control values 24-72 h after RBF had been restored. Fetal glomerular filtration rate did not change; thus the natriuresis and diuresis that occurred were due to reduced tubular solute and water reabsorption (P < 0.025). These changes in fetal renal function may be related, in part, to changes in fetal PO2 and PCO2, but they are most likely due to reduced maternal renal function due to the restriction in maternal RBF, inasmuch as they were reversed when RBF was restored.

Animals↗
PubMed1996

Clinical and cytologic characteristics of blastic phase in Ph-positive chronic myeloid leukemia treated with alpha-interferon.

We report 72 blastic crises (BC), occurring in 238 Ph+ chronic myeloid leukemia (CML) patients treated in chronic phase (CP) with alpha-interferon (IFN) for a median time of 51 months (range 7-96). The 238 patients were grouped by Sokal's risk at diagnosis in low- (LR), intermediate- (IR) and high-risk (HR), and by CP treatment. Group 1: 160 patients (57% LR, 31% IR, 12% HR) given IFN alone in early CP. Group 2: 31 patients (65% LR, 32% IR, 3% HR) given IFN alone in late CP. Group 3: 23 patients (78% LR, 22% IR) given IFN before and after autologous stem cell transplantation (ASCT). Group 4: 24 patients (83% LR, 17% IR) given IFN after ASCT. Of the 72 BC, 52 (72%) were myeloid (My), and 20 (28%) lymphoid (Ly). Overall BC incidence was similar in all CP treatment groups, although with a prevalence of Ly BC in groups 3 + 4 vs groups 1 + 2, (p = NS); the incidence of BC was higher in HR patients (P = NS), but on the whole it was lower than expected on the basis of historical controls. Lymphoid BC was more frequent in LR than in IR + HR patients (P < 0.05), and was more frequent in responders to IFN, than in non-responders (P < 0.05). In conclusion, a subset of patients with low risk at diagnosis, better response to IFN and proneness to evolve into Ly BC can be identified. The role played by IFN in this context remains to be defined.

Adolescent↗
PubMed1996

Effects of inhibition of the maternal renin-angiotensin system on maternal and fetal responses to drainage of fetal fluids.

To find out which of the effects of angiotensin converting enzyme (ACE) inhibitors on the fetus are due to their actions in the mother and which are direct effects due to blockade of the fetal renin-angiotensin system, enalapril (150 mg twice daily i.v.), which does not readily cross the sheep placenta, was given for 3 days to nine chronically catheterized pregnant ewes, 5 days after fetal urine and lung liquid had been continuously drained and while drainage of these fetal fluids continued. Drainage of fetal fluids was carried out so that a net sodium deficit would be incurred, and the dependency of the ewe on the activity of her renin-angiotensin system (RAS) for maintenance of her arterial pressure and fluid and electrolyte balance would be increased. During drainage of fetal fluids ewes drank more and increased their net water balance (p < 0.025). With enalapril, ewes became hypotensive (p < 0.005), but heart rate did not change. Maternal plasma potassium (K) levels increased (p < 0.05) and the plasma sodium to potassium ratio (Na:K) decreased (p < 0.005). Enalapril did not reduce maternal water intake nor change her urine output. After 5 days of drainage, fetal plasma K levels (p < 0.05) were higher and plasma Na:K (p < 0.025) was lower. After maternal enalapril, lung liquid flow and electrolyte excretion were transiently reduced (p < 0.05). Fetal plasma K levels increased further (p < 0.025) and plasma Na:K ratio decreased (p < 0.025 - p < 0.01). Fetal arterial PO2 was reduced 2 h after enalapril (p < 0.005) and was low on the last 2 days of treatment. Although fetal fractional reabsorption of K fell (p < 0.01) by the last day of enalapril treatment, the increase in fetal K excretion was not significant, because by this time sufficient enalapril was present in the fetal circulation to reduce glomerular filtration rate (GFR, p < 0.025 - p < 0.001). It is concluded that the toxicity of ACE inhibitors may be related to those effects in the ewe that lead to reduced fetal arterial oxygen levels and increased fetal plasma K levels. In the latter case it is postulated that inhibition of the maternal RAS may leave ewe and fetus deficient in aldosterone, leading to the rise in K levels. Thus the toxic effects of ACE inhibitors can be mediated through their effects on the mother, but their ability to cause fetal renal failure and oligohydramnios is due to their direct effects on the fetal RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

A single heparin binding region within the fibrinogen-like domain is functional in chick tenascin-C.

Tenascin-C binds to cell surface and matrix proteoglycans and to heparin. Two heparin binding regions have recently been localized per tenascin-C monomer, one in the C-terminal fibrinogen-like domain and the other in fibronectin type III repeats 3-5. Here we show that a single region in each subunit is necessary and sufficient for heparin binding by whole tenascin-C at physiological ionic strength. First, native tenascin-C was bound to heparin-agarose and digested with Pronase. A 29-kDa fragment retained on the heparin column was recognized by a monoclonal antibody against the fibrinogen-like domain. In contrast, small fragments labeled by an antibody against fibronectin type III repeats 2-5 were released. Second, mild tryptic digestion of tenascin-C yielded two related fragments of 180 and 170 kDa. The latter missed part of the fibrinogen domain and had lost affinity for heparin, in contrast to the former. Finally, chick tenascin-C constructs were recombinantly expressed in human cells. Whereas the complete protein and a mutant lacking fibronectin type III repeats 1-5 bound to heparin-agarose, recombinant tenascin-C missing the C-terminal fibrinogen-like globe did not. Thus, whole chick tenascin-C contains one essential heparin binding region per subunit, located in the fibrinogen-like domain within 10 kDa from the C terminus.

Amino Acid Sequence↗