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Biomedical subjects

R Haas

Publications and source records attributed to R Haas.

At least 145 records · Page 8Linked to original sources
PubMed1998

Lethal pulmonary toxicity after autologous bone marrow transplantation/peripheral blood stem cell transplantation for hematological malignancies.

BACKGROUND AND PURPOSE: Retrospective evaluation of the incidence of lethal pulmonary complications (LPC) with special emphasis on interstitial pneumonia (IP) in a large group of patients homogeneously treated with hyperfractionated total body irradiation (HTBI) before autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) for hematological malignancy. The factors influencing IP are discussed. MATERIALS AND METHODS: Of 260 patients (maximum follow-up 137 months) that were treated with ABMT or PBSCT for hematological neoplasms between 1982 and 1994, 209 patients received HTBI and could be evaluated with respect to lethal pulmonary complications and especially lethal interstitial pneumonia. For most patients (n = 155), the HTBI dose was 14.4 Gy (lung dose 9-9.5 Gy) given in 12 fractions over 4 days. Twenty-one patients received a total dose of > or =15 Gy with pulmonary doses of 9-10.5 Gy. RESULTS: The actuarial overall 5-year survival for all 209 patients evaluated was 44 +/- 4%, enabling valid evaluation with respect to lethal pulmonary toxicity. The actuarial incidence of all LPC during the first year was calculated as being 8 +/- 2%. The actuarial incidence of lethal IP is certainly lower and was estimated to be between 3 and 5% for all patients. The overall treatment-related mortality was 12% in 188 patients that received a total dose of <15 Gy and 24% among the patients treated with a total dose of > or =15 Gy. CONCLUSION: ABMT/PBSCT, like other transplant modalities without significant graft versus host disease (GvHD), has a low transplant-related mortality, a very small rate of overall LPC and a low incidence of lethal IP after HTBI. Doses up to 14.4 Gy with lung doses of 9-9.5 Gy can be administered safely. For total doses of > or =15 Gy with lung doses of 9-10.5 Gy, the risk of serious transplant-related complications cannot yet be finally assessed but such higher doses should be considered with caution because of the possibility of increasing toxicity in organs other than the lung.

Adolescent↗
PubMed1998

Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B.

Helicobacter pylori is a Gram-negative bacterial pathogen associated with gastritis, peptic ulceration, and gastric carcinoma. The bacteria express a strong urease activity which is known to be essential for colonization of gnotobiotic pigs and nude mice. UreA and UreB, two structural subunits of the active enzyme, were expressed in the attenuated Salmonella typhimurium live vaccine SL3261 strain. Evaluation of protection against H. pylori was performed in Balb/c mice by oral immunization with a single dose of the vaccine strain. Five weeks after immunization, mice were challenged orally three times with a mouse-adapted H. pylori wild type strain and, six weeks later, mice were sacrificed to determine H. pylori infection by detection of urease activity from the antral region of the mouse stomachs. In several independent experiments, we observed 100% infection with H. pylori in the non-immunized mice and no infection (100% protection) in the mice immunized with S. typhimurium expressing recombinant UreA and UreB. Specific humoral and mucosal antibody responses against UreA and UreB were observed in mice immunized as indicated by western blots and ELISA assays. These data shows that oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain induced a specific immune response and protected mice against H. pylori colonization. Single oral dose immunization with UreA and UreB delivered by a live Salmonella vaccine vector appears to be an attractive candidate for human vaccination against H. pylori infection. In addition, this model will aid to elucidate the effective protection mechanisms against H. pylori in the gastric mucosa.

Administration, Oral↗
PubMed1998

Five-year results of maxillary intramobile Zylinder implants.

We retrospectively analysed the time-dependent function of 501 Intramobile Zylinder (IMZ) implants inserted between August 1983 and December 1994 to restore partially and fully edentulous maxillae. To ensure the independence of implants when calculating level of significance, we chose one implant per patient at random. This was done 500 times to obtain a representative result. The simplified success rate was 473/501 (92%) whereas the time-related survival probability was 76% after 60 months. In 31% (156/500) of the life-table calculations, implants placed in completely edentulous maxillae showed a significantly lower probability of survival than did those placed in partially edentulous patients (P mean: 0.17; SD: 0.19). Implants, that had been placed in the anterior and premolar regions of edentulous maxillae, had a survival probability of 60%, after 60 months. The survival probability of implants placed in the molar region was 100%, over the same observation period. The patient's age, sex, and the time of placement of the implant after tooth extraction had no significant influence on the implant's prognosis. The prognosis of implants inserted for partial edentulism meets the criteria proposed for a viable implant system. Our findings indicate that in complete edentulous maxillae, implants should be placed in the posterior rather than in the anterior region, even though this necessitates augmentation procedures such as sinus lift.

Adult↗
PubMed1998

Treatment of patients with extreme maxillary atrophy using sinus floor augmentation and implants: preliminary results.

Twenty consecutive patients with extreme maxillary atrophy underwent bilateral sinus floor augmentation, either with autogenous bone from the iliac crest or with a combination of autogenous bone and hydroxyapatite. One patient was treated using autogenous bone from the chin region. After a period of three to eight months, three to four implants were placed in each posterior maxilla. Only 10 out of 155 inserted implants were located in the anterior non-augmented maxilla. During the observation period of one to six years, four implants (one of them located in the anterior maxilla) had to be removed prior to prosthetic treatment. Another three implants were lost during the follow up period. This corresponds to a Kaplan-Meier survival probability of 95.4% after 70 months. No statistically significant difference in implant success was observed between women and men (P=0.16). All prosthetic suprastructures are still in function despite these implant losses. Mean peri-implant bone resorption was 1.34 mm with no statistically significant difference between implants placed more mesially and those placed more distally in the augmented area, though a trend could be observed (P=0.058) for a more pronounced bone resorption around implants placed in the premolar region. When a mean mesial and distal bone resorption of >2 mm was considered in the calculation of the success prognosis, the survival probability dropped to 74.7% after 70 months.

Adult↗
PubMed1998

Increased risk of catheter colonization and catheter-related infections in severe immunocompromized patients with multiple myeloma undergoing high-dose glucocorticoid treatment.

Catheter-related infections (CRI) are an important problem in medicine because of major consequences for treatment, prolongation of hospitalization and increasing therapy costs. Malignancies, immunodeficiency, severe burns and malnutrition compromise host defense. Studies to quantify the increased risk of CRI in immunocompromised patients are required. We analyzed the influence of immunoglobulin deficiency and high-dose glucocorticoid treatment in patients with multiple myeloma with regard to catheter colonization and CRI. In patients with multiple myeloma, central venous catheters (CVC) were significantly more frequently colonized (> 15 CFU) as compared to patients with other malignancies undergoing chemotherapy. We found a tendency towards a higher CRI rate in the myeloma patient group. Interestingly, despite of the significantly higher incidence of catheter colonization and a tendency towards higher CRI rates in severely immunocompromised patients, the incidence of signs of local (redness of the entry site) and systemic (fever) host reactions is reduced in myeloma patients. To decrease the CRI rate in myeloma patients during chemotherapy which includes high-dose glucocorticoids, we use antibacterial (silver-coated) catheters.

Adolescent↗
PubMed1998

Bovine hydroxyapatite for maxillary sinus grafting: comparative histomorphometric findings in sheep.

This experimental study in animals examines the value of bovine hydroxyapatite as grafting material in one-stage sinus lift procedure. The Schneiderian membrane was elevated from extraorally in 54 sinuses of 27 adult female mountain sheep. Two titanium plasma-flame-spray coated cylindrical implants were placed in each sinus in the same session. In 2 groups of 18 sinuses each, the subantral hollow space was filled with bovine hydroxyapatite and autogenous cancellous bone from the iliac crest, respectively. Eighteen sinuses that were left empty served as a control group. Polyfluorochrome sequential labelling (tetracycline, calcein green, alizarin complexon) was carried out 4 weeks postoperatively, 2 weeks before the animals were sacrificed, and halfway through the observation period to assess new bone formation. The selected observation periods were 12 weeks, 16 weeks, and 26 weeks. Six sinuses per observation period and test group were available for histologic evaluation. All implants showed favourable osseointegration into local bone. New bone formation was observed in a triangular area bound by the implant surface, the local buccal antral wall, and submucous connective tissue in all implants. Bovine hydroxyapatite adjacent to local bone was mainly surrounded by bone tissue. There was a great variation in the extent of bony sheathing of the hydroxyapatite particles, irrespective of the animals' survival time. Macrophages were found around HA particles that were not surrounded by bone as well as on free implant surfaces. The mean length of the bone-implant bond was 3.86 mm in the group of empty sinuses, 4.87 mm in the group augmented with hydroxyapatite, and 5.66 mm in the group augmented with autogenous cancellous bone. During the observation period, the relative length of bone in direct contact with the implant surface increased from 20.0% to 25.1% in the control group, from 30.4% to 35.5% in the group treated with autogenous cancellous bone, and from 27.4% to 34.7% in the HA group. Autogenous cancellous bone showed a significantly greater bone-implant contact than did the control group (P = 0.0004) and the HA group (P = 0.0499). When the apical implant portions were examined separately, both HA (P = 0.006) and autogenous cancellous bone (P = 0.005) showed a significantly better bone-implant bond than did the control group.

Animals↗
PubMed1998

Bovine hydroxyapatite for maxillary sinus augmentation: analysis of interfacial bond strength of dental implants using pull-out tests.

This study examines the effect of sinus lift surgery using bovine hydroxyapatite on the bone anchorage of titanium plasma flame-spray-coated cylindrical implants. A total of 54 implants were placed in the lateral bony antral walls of 27 mountain sheep. Host site augmentation was done simultaneously using bovine hydroxyapatite and autogenous cancellous bone from the iliac crest in 18 sinuses each. The bone walls of the remaining 18 sinuses received no augmentation. Pull-out tests were carried out at 12, 16, and 26 weeks, revealing a significant influence of the implants' residence time on pull-out strength (P = 0.004). The implants of the non-augmented group and those of the group augmented using cancellous bone showed a linear increase in pull-out strength to 169.8 N and 523.7 N, respectively, until the 26th week. The implants of the group augmented with bovine hydroxyapatite exhibited the highest initial pull-out strength (325.1 N) that further increased to 521.8 N until the 26th week. All in all, this group showed a significantly greater pull-out strength tan did the negative control group (P = 0.03).

Analysis of Variance↗
PubMed1998

Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells.

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.

Adult↗
PubMed1998

The remission status before and the PCR status after high-dose therapy with peripheral blood stem cell support are prognostic factors for relapse-free survival in patients with follicular non-Hodgkin's lymphoma.

It was the aim of our study to examine the clinical significance of t(14;18)-positive cells in samples from 47 patients with follicular non-Hodgkin's lymphoma (NHL) who underwent high-dose therapy with autologous peripheral blood stem cell (PBSC) transplantation. At the time of PBSC mobilization, 25 patients were in first remission, while 22 patients had a history of previous treatment failure. At the same time, 43 patients had polymerase chain reaction (PCR)-positive cells in samples from bone marrow (BM) and/or peripheral blood (PB). Independent of the remission status, high-dose cytarabine and mitoxantrone with granulocyte colony-stimulating factor (G-CSF) support were administered for PBSC mobilization. Following high-dose conditioning therapy which consisted of cyclophosphamide (200 mg/kg) and hyperfractionated total body irradiation (TBI, 14.4 Gy) or BEAM (carmustine, etoposide, cytarabine, melphalan), 34 patients received PCR-positive and 13 patients received PCR-negative autografts. After a median follow-up time of 20 months (range, 6-50) post-transplantation, 33 patients were in remission, while 14 patients had relapsed after a median time of 14.5 months (range, 10-42). Using the Andersen-Gill proportional hazards regression model for the analysis of relapse-free survival, we found that PCR-positive findings in samples from BM and/or PB at any given time-point after transplantation were associated with an increased estimated hazard ratio of 4.5 in comparison with a PCR-negative finding (P=0.013). On the other hand, patients included while they were in first remission had a smaller estimated hazard ratio of 0.3 when compared with patients with a history of previous treatment failure (P=0.048). For the latter group of patients, this translates into a significantly smaller probability of relapse-free survival in comparison to patients who were in first remission at the time of PBSC-mobilization (P=0.012). In conclusion, the remission status of the patients before autografting and the PCR status as assessed on the occasion of follow-up examinations are significant prognostic parameters for relapse-free survival in patients with follicular lymphoma undergoing high-dose therapy with PBSC autografting.

Adult↗
PubMed1998

The dose of granulocyte colony-stimulating factor administered following cytotoxic chemotherapy is not related to the rebound level of circulating CD34+ haemopoietic progenitor cells during marrow recovery.

We report on the RmetHuG-CSF (filgrastim)-related mobilization efficiency in 120 patients with multiple myeloma who received cytotoxic chemotherapy. Three schedules of G-CSF administration starting 24h after the end of chemotherapy were used: (1) a standard dose of 300 microg/d until the completion of PBSC collection; (2) dose escalation from 300 to 600-1200 microg/d during marrow recovery; (3) 600 or 1200 microg/d starting 24 h after cytotoxic chemotherapy. As a result, the individual dose per kg bodyweight varied between 2.83 and 23.08 microg. No relationship was found between the dose of G-CSF administered and the peak level of circulating CD34+ cells or the CD34+ cell counts recorded over the entire collection period.

Adult↗
PubMed1998

Natural competence for DNA transformation in Helicobacter pylori: identification and genetic characterization of the comB locus.

The gram-negative bacterial pathogen Helicobacter pylori, an important aetiological agent of gastroduodenal disease in humans, belongs to a group of bacterial species displaying competence for genetic transformation. Here, we describe the comB gene locus of H. pylori involved in DNA transformation competence. It consists of a cluster of four tandemly arranged genes with partially overlapping open reading frames, orf2, comB1, comB2 and comB3, constituting a single transcriptional unit. Orf2 encodes a 37-amino-acid peptide carrying a signal sequence, whereas comB1, comB2 and comB3 produce 29 kDa, 38 kDa and 42 kDa proteins, respectively, as demonstrated by immunoblotting with specific antisera. For Orf2 and ComB1, no homologous proteins were identified in the database. For ComB3, the best homologies were found with TraS/TraB from the Pseudomonas aeruginosa conjugative plasmid RP1 and TrbI of plasmid RP4, VirB10 from the Ti plasmid of Agrobacterium tumefaciens and PtlG, a protein involved in secretion of pertussis toxin of Bordetella pertussis. Defined transposon knock-out mutants in individual comB genes resulted in transformation-defective phenotypes ranging from a 90% reduction to a complete loss of the natural transformation efficiency. The comB2 and comB3 genes show homology to HP0528 and HP0527, respectively, located on the cagII pathogenicity island of H. pylori strain 26695.

Amino Acid Sequence↗
PubMed1998

Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.

Autistic disorder is a complex genetic disease. Because of previous reports of individuals with autistic disorder with duplications of the Prader-Willi/Angelman syndrome critical region, we screened several markers across the 15q11-13 region, for linkage disequilibrium. One hundred forty families, consisting predominantly of a child with autistic disorder and both parents, were studied. Genotyping was performed by use of multiplex PCR and capillary electrophoresis. Two children were identified who had interstitial chromosome 15 duplications and were excluded from further linkage-disequilibrium analysis. Use of the multiallelic transmission-disequilibrium test (MTDT), for nine loci on 15q11-13, revealed linkage disequilibrium between autistic disorder and a marker in the gamma-aminobutyric acidA receptor subunit gene, GABRB3 155CA-2 (MTDT 28.63, 10 df, P=.0014). No evidence was found for parent-of-origin effects on allelic transmission. The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder.

Autistic Disorder↗
PubMed1998

Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits.

Live Salmonella typhimurium phoPc bacteria were tested as mucosal vaccine vectors to deliver Helicobacter pylori antigens. The genes encoding the A and B subunits of H. pylori urease were introduced into S. typhimurium phoPc and expressed under the control of a constitutive tac promoter (tac-ureAB) or a two-phase T7 expression system (cT7-ureAB). Both recombinant Salmonella strains expressed the two urease subunits in vitro and were used to nasally immunize BALB/c mice. The plasmid carrying cT7-ureAB was stably inherited by bacteria growing or persisting in the spleen, lungs, mesenteric or cervical lymph nodes, and Peyer's patches of immunized mice, while the plasmid carrying tac-ureAB was rapidly lost. Spleen and Peyer's patch CD4+ lymphocytes from mice immunized with S. typhimurium phopc cT7-ureAB proliferated in vitro in response to urease, whereas cells from mice given S. typhimurium phoPc alone did not. Splenic CD4+ cells from mice immunized with phoPc cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected following immunization, confirming that both Th1- and Th2-type immune responses were generated by the live vaccine. Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to be resistant to infection by H. pylori, while all mice immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected. Our data demonstrate that H. pylori urease delivered nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type responses and induce protective immunity against Helicobacter infection.

Animals↗
PubMed1998

Efficacy and toxicity of sequential high-dose therapy with peripheral blood stem cell support in patients with high-risk breast cancer.

Patients with high-risk breast cancer may benefit from dose-escalated chemotherapy. We studied toxicity and therapeutic efficacy of sequential high-dose therapy consisting of two cycles of ifosfamide 12,000 mg/m2, carboplatin 900 mg/m2, and epirubicin 180 mg/m2 (ICE) with peripheral blood stem cell support. Ninety-one patients with advanced breast cancer were included. Fifty-one patients with stage II/III disease and 10 or more tumor-positive axillary lymph nodes received high-dose therapy as adjuvant treatment; the remaining 40 patients were treated for metastatic disease. Peripheral blood stem cells were collected following granulocyte colony-stimulating factor-supported induction chemotherapy. In 68 patients, induction chemotherapy included two cycles of ifosfamide 7,500 mg/m2 and epirubicin 120 mg/m2, while 23 patients received one cycle of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 135 mg/m2, ifosfamide 6,000 mg/m2, and epirubicin 90 mg/m2. One hundred ninety-two cycles of ICE were supported with a median of 3.5 x 10(6) CD34+ cells/kg body weight (range, 1.7 to 38 x 10(6) CD34+ cells/kg body weight), which resulted in rapid hematologic reconstitution with recovery times, for a median neutrophil count of 0.5 x 10(9)/L of 13 days (range, 6 to 20 days) and for a median platelet count greater than 20 x 10(9)L of 9 days (range, 5 to 24 days). Seven patients received only one cycle of ICE because of progressive disease (in two patients with metastatic disease), central nervous system toxicity (one patient), cardiac toxicity (one patient), severe enterocolitis (one patient), development of human leukocyte antigen antibodies (one patient), and wish to withdraw from the study (one patient). Seventeen patients with metastatic disease received an additional high-dose cycle consisting of the non-cross-resistant agents thiotepa 600 mg/m2, etoposide 1,500 mg/m2, and paclitaxel 165 mg/m2. In patients treated adjuvantly, the probability of disease-free survival was 64% at 47 months, which compares favorably with results of conventional treatment protocols, with a 47% event-free probability at the same time period. The probability of progression-free survival in patients with metastatic disease was 18% at 44 months. In conclusion, sequential high-dose therapy with peripheral blood stem cell support in patients with high-risk breast cancer can be administered safely and offers a potential benefit in the adjuvant setting.

Adult↗
PubMed1998

The use of an anesthesia simulator in graduate and undergraduate education.

The use of simulation for educational training is common in many industries but is a new advancement in student instruction in anesthesia, medicine, or allied health. The Human Patient Simulator (HPS) allows students and clinicians to learn and practice a variety of technical skills as well as manage basic and complex clinical situations in a modifiable and reproducible environment. The HPS has been extensively integrated in many graduate and undergraduate Nursing and Allied Health courses at the Medical College of Georgia. Use of the HPS stems from the theory of situated cognition, which states that students best learn "what to do" and "how to do" in a real world environment. The HPS provides a real world environment for student learning in various fields. The theory of situated cognition is discussed in conjunction with the implementation of the HPS into various classes.

Anesthesia↗
PubMed1998

Leukapheresis products in multiple myeloma: lower tumor load after mobilization with cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) compared with G-CSF alone.

High-dose therapy with autografting of peripheral blood stem cells (PBSCs) has become an accepted treatment modality. However, gene-marking studies in patients with acute myeloid leukemia and neuroblastoma have revealed that malignant cells reinfused along with leukapheresis products (LPs) contribute to relapse. Thus, a reduction in the number of malignant cells in autografts is desirable. We analyzed the percentage of malignant cells and the number of CD34+ PBSCs in LPs mobilized by granulocyte colony-stimulating factor (G-CSF) alone (LP-S) compared with high-dose cyclophosphamide plus G-CSF (LP-CY) in patients with multiple myeloma (MM). A quantitative polymerase chain reaction assay involving CDR3-specific primers based on the method of limiting dilutions was used to determine the tumor loads of LPs. Sixteen LPs from eight patients with MM were analyzed intraindividually in matched pairs. The percentage of malignant cells was lower in LP-CY (p = 0.017; median 0.0067 vs. 0.009%), whereas the number of CD34+ cells was higher (p = 0.012; median 0.3 vs. 0.095%). The calculated number of malignant cells per CD34+ cell was significantly lower in LP-CY as well (p = 0.017). We conclude that mobilization by cyclophosphamide plus G-CSF leads to a lower number of malignant cells per CD34+ cell in LPs compared with G-CSF alone.

Adult↗
PubMed1998

Properties and function of the P type ion pumps cloned from Helicobacter pylori.

Three distinct P type pumps were cloned from H. pylori 69A. Two of these pumps, ATPase 439 and ATPase 948 (CopA), were isolated by gene library screening using DNA oligonucleotide primers. Amino acid similarities found for the predicted proteins were about 50% to Cd2+/Cu2+ pumps. Gene disruption mutagenesis rendered the H. pylori knockout mutants more sensitive to Zn2+ and Cd2+ (ATPase 439) or Cu2+ (CopA). Some of the ATPase 439-deficient mutants were negative for urease activity while the majority of the mutants remained positive. Functional diversity of the pumps was also reflected by the ion affinities found for N-terminal peptides of CopA to Cu2+ and of ATPase 439 to Ni2+, Cu2+ and CO2+. The membrane domain of the two pumps were experimentally shown to consist of eight membrane spans. When ATPase 439 was expressed under control of a tac promoter in Escherichia coli, vanadate-sensitive phosphate accumulation was observed cytochemically along the membrane of the host cells. The third P type pump (ATPase 115) which also exhibited homology to transition metal ATPase was identified by sequencing a library of H. pylori membrane genes. The hydropathy plot of this pump was very similar to the former H. pylori ATPases whereas the N-terminal ion binding region was distinct. It was concluded that, in H. pylori, the presence of three transition metal ATPases with distinct ion specificity contributes to the adaptive mechanisms for gastric survival.

Adenosine Triphosphatases↗