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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed1998

High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer.

The purpose of this study was to evaluate the efficacy of high-dose chemotherapy (HDC) with busulfan, melphalan and thiotepa (BUMELTT) followed by autologous PBSC infusion in treating patients with advanced ovarian cancer. Thirty-one patients, 18 with stage III/IIIc and 13 with stage IV ovarian cancer, were treated with BU (12 mg/kg), MEL (100 mg/m2) and TT (500 mg/m2) and autologous PBSC rescue. Fifteen patients were in clinical complete remission (CR) at treatment; 11 had platinum-sensitive disease. Sixteen patients were not in CR; two had platinum-sensitive disease. The probabilities of overall survival (OS), event-free survival (EFS) and relapse (R) for all patients at 18 months were 0.57, 0.30 and 0.63; for patients in CR, the rates were 0.87, 0.44 and 0.49 and for patients not in CR, 0.38, 0.13 and 0.81. Two patients (6.5%) died of treatment-related causes. Among the 13 patients with platinum-sensitive disease, all are still alive, with seven having relapsed 129-1021 days after PBSC infusion. OS, EFS and R were 1.00, 0.52 and 0.48. Of the 18 patients with platinum-resistant disease, four remain alive (two in remission). Six patients did not respond and eight relapsed from days 104-429. The OS, EFS and R were 0.33, 0.11 and 0.78. We conclude that BUMELTT is well tolerated in patients with advanced ovarian cancer and results are equivalent to other published HDC regimens.

Adult↗
PubMed1998

Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening.

We present an unusual case, in which a woman presenting with markedly decreased fetal movements at 29 weeks gestation following a recent increase in fundal height was noted sonographically to have fetal hydrops consisting of scalp edema, marked hepatomegaly, ascites, and polyhydramnios. No lethal structural congenital anomaly was noted. Admission laboratory examinations revealed a negative antibody screen and a negative RPR. Emergent cesarean section was performed due to prolonged fetal bradycardia during biophysical profile testing. The acidotic hydropic neonate weighing 1825 g was resuscitated yet succumbed at 3 hr of life following intravenous administration of antibiotics. Neonatal blood was RPR positive at 1:16. Postmortem pathology examination demonstrated severe multiorgan system failure secondary to overwhelming congenital syphilis. Extensive extramedullary hematopoiesis was noted and histopathology with Dieterle stains revealed numerous hepatic spirochetes. Postpartum reexamination of the maternal blood with serial dilutions revealed a positive RPR at 1:1024. This case emphasizes that initial negative screening for syphilis may be seen despite overwhelming infection, a condition that has been termed the "prozone effect."

Adult↗
PubMed1998

Agrobacterium tumefaciens transformation and cotransformation frequencies of Arabidopsis thaliana root explants and tobacco protoplasts.

In view of the recent finding that different T-DNAs tend to ligate and integrate as repeats at single chromosomal positions, the frequency of transformation and cotransformation was determined during cocultivation of Arabidopsis thaliana root explants and Nicotiana tabacum protoplasts with two Agrobacterium strains. The transformation frequency of unselected A. thaliana shoots was lower than 1% whereas that of cocultivated tobacco protoplasts was approximately 18%. The cotransformation frequencies, defined as the frequencies with which cells transformed with a first T-DNA contained a second unselected T-DNA, were approximately 40% reproducible, irrespective of the selection, the transformation frequency, and the plant system used. Extrapolation of these results suggests that at least two independently transferred T-DNAs were present in 64% of the transformed plant cells. Molecular analysis of cocultivated N. tabacum shoots regenerated on nonselective medium showed that only a few transformants had a silenced (2/46) or truncated (1/46) T-DNA. Therefore, most integrated T-DNAs expressed their selectable or screenable markers in primary transgenic plants. Remarkably, 10 to 30% of the selected A. thaliana shoots or progenies lost the T-DNA marker they were selected on. As these regenerants contained the unselected T-DNA with a high frequency (17%), these selected plants might result from the expression of unstable, transiently expressed T-DNAs. In conclusion, a significant part of the T-DNAs is lost from the transformed cells.

Agrobacterium tumefaciens↗
PubMed1998

The conjugal intermediate of plasmid RSF1010 inhibits Agrobacterium tumefaciens virulence and VirB-dependent export of VirE2.

Agrobacterium tumefaciens causes crown gall disease by transferring oncogenic, single-stranded DNA (T strand), covalently attached to the VirD2 protein, across the bacterial envelope into plant cells where its expression results in tumor formation. The single-stranded DNA binding protein VirE2 is also transferred into the plant cell, though the location at which VirE2 interacts with the T strand is still under investigation. The movement of the transferred DNA and VirE2 from A. tumefaciens to the plant cell depends on the membrane-localized VirB and VirD4 proteins. Further, the movement of the IncQ broad-host-range plasmid RSF1010 between Agrobacterium strains or from Agrobacterium to plants also requires the virB-encoded transfer system. Our earlier studies showed that the presence of the RSF1010 plasmid in wild-type strains of Agrobacterium inhibits both their virulence and their capacity to transport VirE2, as assayed by coinfection with virE mutants. Here we demonstrate that the capacity to form a conjugal intermediate of RSF1010 is necessary for this inhibition, suggesting that the transferred form of the plasmid competes with the VirD2-T strand and/or VirE2 for a common export site.

Agrobacterium tumefaciens↗
PubMed1998

Alterations of neuropsychological function and cerebral glucose metabolism after cardiac surgery are not related only to intraoperative microembolic events.

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) during cardiac surgery are capable of causing encephalopathy and cognitive deficits. This study was undertaken to determine whether intraoperative HITS cause alterations of neuropsychological function (NPF) and/or cerebral glucose metabolism (CMRGlc), even in a low-risk patient group, and whether induced changes are interrelated. METHODS: Eighteen patients without signs of cerebrovascular disease underwent elective coronary artery bypass grafting (CABG), and two of these additionally underwent valve replacement in normothermia. Intraoperatively, HITS were recorded by means of transcranial Doppler ultrasonography (TCD). Perioperatively, NPF and CMRGlc were assessed using a standardized complex test battery and positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET), respectively. RESULTS: Intraoperatively, the number of HITS ranged from 90 to 1710 per patient and hemisphere, more on the right side than on the left (P<.05). HITS occurred primarily during cardiopulmonary bypass (71.3%) and, to a lesser extent, during aortic manipulation (22.2%). Changes in global and regional CMRGlc between first (one day preoperatively) and second (8 to 12 days postoperatively) FDG-PET scans were mild. No correlations were found between the number of HITS, age of patient, duration of cardiac ischemia or cardiopulmonary bypass and the changes in CMRGlc. In patients with recorded HITS and a postoperative decrease of regional CMRGlc (n=11), the maximal decrease of rCMR Glc in each hemisphere below the individual global change of CMRGlc correlated with the number of HITS (r= -0.46, P<.05). Limitations in NPF occurred 8 to 12 days postoperatively, resolved within 3 months, and were not found to be correlated to the absolute number of HITS or changes in CMRGlc. CONCLUSIONS: HITS during cardiac surgery can cause alterations of both NPF and CMRGlc, even in a low-risk patient group. However, the number of HITS and changes in NPF and CMRGlc are not necessarily interrelated, which indicates that (1) the location of brain damage related to HITS is more important for the development of NPF than is the absolute number of HITS, and (2) factors in addition to HITS might contribute to surgery-related brain damage.

Adult↗
PubMed1998

Seeing difference: market health reform in Europe.

The comparative literature on health care reform has identified a convergence upon market models as nations respond to similar economic, technological, social, and demographic pressures. In this article I first challenge the conventional view by comparing "market" reforms of the late 1980s and early 1990s in the United Kingdom, the Netherlands, and Sweden. Though these nations did indeed converge upon the instrument of the market incentive, there was considerable divergence in the content and aims of their reform strategies. These nations designed their respective markets to make different tradeoffs among competing values. While all three exploited the principle of provider competition, they appointed different actors to judge the contest: the cost-conscious public authority in the United Kingdom, the quality-conscious patient in Sweden, and the optimizing consumer in the Netherlands. I argue that these countries were thus using common market tools to promote different health policy goals. Distinguishing these reforms further is the fact that--particularly in the Netherlands--there was a gap between market plans and the reality of implemented change. I then ask why nations responded so differently to such similar objective pressures. My contention is that this divergence reflects, in part, the different ideological orientations of the ruling party or coalition in each nation. Yet divergence is also the result of differences in both the design of political institutions and the structure of the pre-reform health system in each country.

Economic Competition↗
PubMed1997

Green fluorescent protein as a reporter for retrovirus and helper virus-free HSV-1 amplicon vector-mediated gene transfer into neural cells in culture and in vivo.

Green fluorescent protein (GFP) is an effective marker for retrovirus and herpes virus vector-mediated gene transfer into various central nervous system-derived cells, both proliferative and non-proliferative, in culture and in vivo. Retrovirus vectors were used to stably transduce several rat and human glioma lines, and a multipotent mouse neural progenitor line in culture. Implantation of selected pools of transduced glioma cells into rodent brain allowed clear visualization of the tumor and the invading tumor edge. Helper virus-free HSV-1 amplicon vectors successfully transferred gfp into non-dividing primary neural cells in culture and in the rat brain. This study describes the versatility of GFP for: (i) labelling of glioma cells in experimental brain tumor models and neural progenitor cells by retrovirus vectors, and (ii) efficient, non-toxic delivery of genes to post mitotic cells of the nervous system using helper-virus free HSV-1 amplicon vectors.

Animals↗
PubMed1997

Therapeutic efficiency and safety of a second-generation replication-conditional HSV1 vector for brain tumor gene therapy.

A second-generation replication-conditional herpes simplex virus type 1 (HSV) vector defective for both ribonucleotide reductase (RR) and the neurovirulence factor gamma34.5 was generated and tested for therapeutic safety and efficiency in two different experimental brain tumor models. In culture, cytotoxic activity of this double mutant HSV vector, MGH-1, for 9L gliosarcoma cells was similar to that of the HSV mutant, R3616, which is defective only for gamma34.5, but was significantly weaker than that of the HSV mutant hrR3, which is defective only for RR. The diminished tumoricidal effect of the gamma34.5 mutants could be accounted for by their reduced ability to replicate in 9L cells. The MGH-1 vector did not achieve significant prolongation of survival in vivo in the syngeneic 9L rat gliosarcoma model for either single brain tumor focus or multiple intracerebral and leptomeningeal tumors, when the vector was applied intratumorally or intrathecally, respectively, and with or without subsequent ganciclovir (GCV) treatment. In identical 9L brain tumor models with single and multiple foci, application of hrR3 with or without GCV was previously shown to result in marked long-term survival. Contrary to the findings with intrathecal injection of hrR3, no vector-related mortality was observed in any animals treated with MGH-1. Thus, in these rat brain tumor models, the double mutant, replication-conditional HSV vector MGH-1 showed a higher therapeutic safety than the RR-minus vector, hrR3, but had clearly decreased therapeutic efficiency compared to hrR3. The development of new HSV vectors for brain tumor gene therapy will require a balance between maximizing therapeutic efficacy and minimizing toxicity to the brain. Standardized application in brain tumor models as presented here will help to screen new HSV vectors for these requirements.

Animals↗
PubMed1997

MRI- and MRA-guided therapy of carotid and vertebral artery dissections.

A high sensitivity and specificity has been shown for magnetic resonance imaging (MRI) and angiography (MRA) in the diagnosis of internal carotid (ICAD) and vertebral (VAD) artery dissections, where arteriography has been and still is the gold standard. Five patients (three with ICAD, two with VAD; age range 42-56 years) are presented, in whom diagnosis and follow-up management were exclusively based on non-invasive measures. In all patients, MRI demonstrated a typical intramural hematoma and MRA in 3D phase contrast technique showed loss or diminished flow. After anticoagulation (heparin) for 3 to 4 weeks follow-up, MRI showed a regression of the mural hematoma and MRA revealed reperfusion or improvement of flow. Depending on the extent of MRI-/MRA-pathology, three patients were put on antiplatelet therapy and two on Coumadin until normalization of MRI and MRA findings, which are assessed in 3-months intervals. We suggest, that with, (I) a suspicious history, symptoms and signs for cervical artery dissection (CAD), (II) typical MR-findings proven to indicate CAD, (III) improving or resolving at follow-up, (IV) in unusual location for atherosclerotic involvement, (V) in the absence of coexisting atherosclerotic lesions, the diagnosis has not to be confirmed with conventional arteriography. Therefore, safe MRI- and MRA-guided anticoagulation and antiplatelet therapy during serial follow-up measurements are possible.

Adult↗
PubMed1997

Reactivity of a new HIV-1 group O third generation A-HIV-1/-2 assay with an unusual HIV-1 seroconversion panel and HIV-1 group O/group M subtyped samples.

It was shown previously that about 97% of the anti-HIV-1 group O strain-positive samples were detected by crossreaction with native HIV-1 gp160 (Van Binsbergen et al., Evaluation of a new third generation anti-HIV-1/anti-HIV-2 assay with increased sensitivity for HIV-1 group O, J. Virol. Methods 60 (1996) 131-137). Fourteen out of 17 new anti-HIV-1 group O positive samples, selected with the Enzygnost HIV-1/2 plus assay, were already reactive when tested with HIV-1 gp160. When tested by the Vironostika HIV Uni-Form II plus O microELISA all 17 samples were reactive, demonstrating the necessity to implement an HIV-1 group O-specific antigen in the assay. On the other hand, it was surprisingly found that 40 out of 43 (93%) of anti-HIV-1 group M-positive samples, belonging to strain A, B, C, D, E or F, were detected by crossreaction with the HIV-1 group O (strain ANT70) synthetic peptide incorporated in the Vironostika HIV Uni-Form II plus O. Only HIV-1 subtype D-positive samples did not react with this peptide, presumably because of the presence of a histidine residue in the immunodominant region of HIV-1 subtype D gp41. Both crossreactions make the Vironostika HIV Uni-Form II plus O microELISA also sensitive for anti-HIV-1-positive samples originating from different geographical regions and resulting from different HIV-1 subtype infections. With an unusual seroconversion panel in which p24 Ag was present persistently, many anti-HIV-1/-2 assays produce alternating positive/negative results in anti-HIV antibody-positive bleeds. It was shown that the use of viral p24 and gp160 in a direct sandwich, allowing detection of anti-HIV IgG and IgM, explains the identification of all anti-HIV-positive bleeds by the Vironostika HIV Uni-Form II plus O. The high sensitivity of the plus O assay was confirmed with clinical samples of a so-called anti-HIV-1 low titer panel. The specificity of the Vironostika HIV Uni-Form II plus O determined in five blood transfusion centers, based on 135070 tests, was 99.97%.

AIDS Serodiagnosis↗
PubMed1997

How neural interactions form neural responses in the salamander retina.

A wide range of experimental data characterizing properties of individual salamander retinal cells and synaptic interactions are integrated to form a quantitative computational model of visual function in the salamander retina. The model is used to show how specific interactions between neurons and between networks of neurons can lead-to the integrated response behavior of individual cells deep in the retina. The model is also used to illustrate how the representation of moving and stationary stimuli is encoded in a series of layer-by-layer transformations leading to the final retinal output at the ganglion cell layer.

Animals↗
PubMed1997

T-DNA integration patterns in co-transformed plant cells suggest that T-DNA repeats originate from co-integration of separate T-DNAs.

Nicotiana protoplasts and Arabidopsis leaf discs or roots were co-cultivated with two Agrobacterium strains each carrying a different T-DNA. Co-transformed plants were selected and the integration of the different T-DNAs was analysed at the genetic and genomic level. Genetic analysis showed that the T-DNAs derived from different bacteria were frequently integrated at the same locus, independent of the plant species or transformation method used. Southern analysis revealed that 12 out of 27 Arabidopsis transformants contained the co-transferred T-DNAs linked to each other in all possible configurations but with a preference for those with at least one right border involved in linkage. Overall, our data support the hypothesis that ligation of separate T-DNAs is a dominant mechanism in formation of the frequently observed repeats of identical T-DNAs. We propose a scheme which could explain the formation of T-DNA repeats and the preferential involvement of right borders in T-DNA linkages.

Arabidopsis↗
PubMed1997

Evidence of acute demyelination around a developmental venous anomaly: magnetic resonance imaging findings.

The authors report on the occurrence of a focal demyelination showing a mass effect around a developmental venous anomaly in the cerebellum. Because the latter presented as a single lesion, the differentiation from intraparenchymal neoplasms or infarction was difficult. Follow-up magnetic resonance imaging and histology from a biopsy specimen give useful information to find the appropriate diagnosis.

Acute Disease↗
PubMed1997

Evidence for a sex-specific residual effect of cannabis on visuospatial memory.

BACKGROUND: In an exploratory study, we used a novel computerized battery of neuropsychological tests of attention to assess residual cognitive impairment in marijuana users. METHODS: We compared 25 college students who were heavy marijuana smokers (who had smoked a median of 29 days in the last 30 days) with 30 students who were light smokers (who had smoked a median of 1 day in the last 30 days). All subjects were tested after a supervised period of abstinence from marijuana and other drugs lasting at least 19 h. RESULTS: Differences between the overall groups of heavy and light smokers did not reach statistical significance on the four subtests of attention administered. However, upon examining data for the two sexes separately, marked and significant differences were found between heavy- and light-smoking women on the subtest examining visuospatial memory. On this test, subjects were required to examine a 6 x 6 'checkerboard' of squares in which certain squares were shaded. The shaded squares were then erased and the subject was required to indicate with the mouse which squares had formerly been shaded. Increasing numbers of shaded squares were presented at each trial. The heavy-smoking women remembered significantly fewer squares on this test, and they made significantly more errors than the light-smoking women. These differences persisted despite different methods of analysis and consideration for possible confounding variables. CONCLUSIONS: This observation suggests that it may be important to study the residual effects of marijuana on men and women separately-particularly since women have been greatly underrepresented in previous studies in this area.

Adolescent↗
PubMed1997

Major activity of cladribine in patients with de novo B-cell prolymphocytic leukemia.

PURPOSE: De novo B-cell prolymphocytic leukemia (B-PLL) is a distinct clinicopathologic entity usually characterized by marked lymphocytosis, massive splenomegaly, an aggressive course, and refractoriness to therapy. Cladribine (2-chlorodeoxyadenosine [2-CdA]; Ortho Biotech, Raritan, NJ) is a newer purine analog with potent activity against indolent lymphoproliferative disorders. PATIENTS AND METHODS: We treated eight patients with cladribine 0.1 mg/kg/d for 7 days by continuous infusion or 0.14 mg/kg/d over 2 hours for 5 days, every 28 to 35 days, for a median of three courses (range, two to five). There were five men and three women, with a median age of 62 years and a median pretreatment duration of 6 months; four patients were previously untreated. RESULTS: All eight patients were assessable: five achieved a complete response with a median response duration of 14 months (range, 1+ to 55+), and three achieved a partial response with a median duration of 3 months (range, 1 to 3). Of four patients who achieved a complete response and in whom a peripheral-blood immunophenotypic analysis was performed, two had no circulating B-PLL cells and one had no residual disease on Southern blot analysis. Myelosuppression and infection were the major toxicities: three patients developed grade 3 or 4 myelosuppression, four had bacterial infections, and two had herpes zoster infections. CONCLUSION: In this small study of patients with de novo B-PLL, cladribine was an active agent that induced a high overall and complete response rate. These results require confirmation in larger numbers of B-PLL patients.

Adult↗
PubMed1996

[Varicella-zoster-virus myelitis without herpes. An important differential diagnosis of the radicular syndrome].

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman was admitted with a 14-day history of general malaise, subfebrile temperature, radicular dysaesthesias in the "riding breeches" area, severe pain in the lumbar region and progressive disorders of bladder and rectal emptying. Physical examination showed a conus-cauda syndrome. Differential diagnosis was between myelitis (inflammatory or infectious), space-occupying intraspinal mass or vascular lesion. INVESTIGATIONS: Cerebrospinal fluid contained 1700/3 cells and there was intrathecal antibody synthesis against varicella zoster virus (VZV) and positive VZV-DNA analysis in the polymerase chain reaction. Magnetic resonance imaging of the lumbar spine revealed an inflamed enlarged conal and epiconal area with small haemorrhagic spots. There was no evidence of an underlying immune-modulated disease. TREATMENT AND COURSE: With the diagnosis of varicella zoster myelitis with cutaneous changes having been established the clinical signs and symptoms regressed almost completely with aciclovir administration (10mg/kg intravenously for 14 days). CONCLUSION: VZV without cutaneous involvement should be considered in the differential diagnosis of the radicular pain syndrome. When clinical signs of beginning myelitis or encephalitis are present, immediate investigations and therapy are necessary.

Acyclovir↗