Search PubMed⌕ Search

Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1996

Diaschisis of specific cerebellar lobules: pontine haematoma studied with high-resolution PET and MRI.

Cerebellar glucose metabolism was studied in one patient with a hemipontine haematoma in order to investigate remote metabolic effects within the cerebellar lobules. In the patient, who suffered a circumscribed hemipontine haemorrhage, and in three normal subjects cerebellar glucose metabolisms was studied using 18F-2-fluoro-2-deoxy-D-glucose and high-resolution positron emission tomography (PET). Regions of interest were placed on sagittal brain slices of co-registered magnetic resonance images for quantitative evaluation of glucose metabolism in each cerebellar lobule. Interruption of corticopontine fibres caused inactivation of pontine nuclei with subsequent contralateral cerebellar diaschisis, mainly in the anterior lobe and the posterior portion of the quadrangular lobule. Damage within the ponto-cerebellar part of the cortico-ponto-cerebellar pathway, e.g. pontine nuclei and crossing ponto-cerebellar fibres from contralateral pontine nuclei, led to ipsi- and contralateral cerebellar diaschisis within the semilunar, gracile and biventral lobules. High-resolution PET is capable of demonstrating bilateral diaschisis involving specific cerebellar lobules to a different degree that is consistent with the pontine anatomy of the cortico-ponto-cerebellar pathway and with the location of the haemorrhagic lesion.

Adult↗
PubMed1996

Development of the multidimensional index of life quality. A quality of life measure for cardiovascular disease.

OBJECTIVES: The purpose of this study was to design a multidimensional measure of health-related quality of life appropriate for patients with cardiovascular disease that was psychometrically sound, brief, and easy to administer. METHODS: Qualitative interviews conducted with healthy subjects and patients with cardiovascular diseases identified nine major quality of life domains. Based on the responses of 129 cardiovascular disease patients recruited from hospitals and clinics, a criterion-based approach was used to select 35 questionnaire items that best tapped these domains. Psychometric properties of the Multidimensional Index of Life Quality (MILQ) were tested with a sample of 348 patients with various cardiovascular diseases. RESULTS: Cronbach's alpha was 0.76 or higher for eight of the nine MILQ domains. Test-retest reliability coefficients were 0.73 or greater in all but two domains. Individual domain scores as well as a weighted overall quality of life index were correlated highly with self-assessed health and the number of heart-related symptoms. CONCLUSIONS: The Multidimensional Index of Life Quality is a psychometrically reliable and valid instrument for measuring quality of life in patients with cardiovascular diseases. The MILQ also may be a suitable measure for other types of chronic diseases.

Adult↗
PubMed1996

Interleukin-3 plus low-dose cytosine arabinoside for advanced myelodysplasia: a pilot study. EORTC Leukemia Group.

In an attempt to reestablish normal hematopoiesis in symptomatic myelodysplasia (MDS) and to show the tolerability of a combination treatment of low-dose cytosine arabinoside (LD AraC) and interleukin-3 (IL-3), we treated 31 patients (pts., median age 65 years) who had more than 10% blasts in the bone marrow (BM) and hematopoietic failure with LD AraC (2 x 10 mg/m2 sc, day 1-14) plus IL-3 (once daily sc, day 8-21) at different dose steps (1.0, 2.5, 5.0, and 10.0 micrograms/kilogram body weight). The numbers of each 21-day cycle varied between 1 (3 pts.), 2 (6 pts.), 3 (8 pts.), 4 (1 pt.), 5 (5 pts.), and 6 (8 pts.), in total 116 cycles on an outpatient basis. Subjective tolerability was good in 20 cases (65%). Toxicities were fever (29 pts.), flu-like symptoms (17 pts.), infections (15 pts.), hepatic toxicity (10 pts.), and skin reactions (8 pts.). Overall response was seen in 13 cases (42%) and 5 complete responses (CR), while 10 pts. had stable disease (SD), 5 progressed (2 to acute leukemia), 2 were considered toxic deaths, and 1 died due to the disease. Median survival is 18 months, progression-free survival is 12.5 months (18.0 months in responding pts.), with an actuarial follow-up of 31 months. The data from this phase I/II study show that a combination of LD-AraC and IL-3 is well tolerated and that stable responses can be achieved in MDS by means of an easy outpatient therapy.

Adult↗
PubMed1996

Ovarian Cancer.

Explore the source record for details and available documents.

Combined Modality Therapy↗
PubMed1996

One-year follow-up of technetium-99m-HMPAO SPECT in mild head injury.

UNLABELLED: We evaluated the predictive capacity of 99mTc-HMPAO SPECT for clinical outcome during a follow-up period of 12 mo after mild head injury. METHODS: We prospectively evaluated 136 patients with mild head injury who underwent initial SPECT imaging (SPECTO) within 4 wk after the trauma. Re-evaluations were made 2.9-3.3 mo (T3mo), 5.7-6.3 mo (T6mo) and 11.9-12.6 mo (T12mo) postinjury. All patients with an abnormal SPECT underwent a repeat study at the subsequent time of evaluation. Patients with a previously normal SPECT scan did not undergo a repeat study. Clinical reassessments (CLIN) were performed as long as the earlier study had been positive or until patients were completely asymptomatic. RESULTS: During all follow-up evaluations, SPECT had a high sensitivity and negative predictive value, increasing from 91% and 89%, respectively, at T3mo to 100% at T6mo and at T12mo. Clinical normalization occurred earlier than scintigraphic normalization. However, at 12 mo postinjury, we observed considerable improvement in the specificity and positive predictive value of SPECT (85% and 83%, respectively). The persistent lesions on the SPECT scan were related to their severity and to localization in the frontal cortex. CONCLUSION: A normal 99mTc-HMPAO SPECT scan is a reliable tool in the exclusion of clinical sequelae of mild head injury. At 12 mo postinjury, a positive SPECT study is also a reliable predictor for clinical outcome.

Adolescent↗
PubMed1995

Intramolecular transmission of the ATP regulatory signal in Escherichia coli aspartate transcarbamylase: specific involvement of a clustered set of amino acid interactions at an interface between regulatory and catalytic subunits.

Aspartate transcarbamylase from Escherichia coli is stimulated by ATP and feedback-inhibited by CTP and UTP. Previous work allowed the identification of the hydrophobic interface between the two domains of the regulatory chain as a structural element specifically involved in the transmission of the ATP regulatory signal toward the catalytic sites. The present work describes the identification of a cluster of amino acid interactions at an interface between the regulatory chains and the catalytic chains of the enzyme as another structural feature involved in the transmission of the ATP regulatory signal but not in those of CTP and UTP. These interactions involve residues 146 to 149 of the regulatory chain and residues 242 to 245 of the catalytic chain. Perturbations of these interactions also alter to various extents the co-operativity between the catalytic sites for aspartate binding. These findings are in agreement with the idea that the primary effect of ATP might consist, in part, of a modulation of the stability of the interfaces between regulatory and catalytic subunits, thereby facilitating the T to R transition induced by aspartate binding, as was put forward in two recently proposed models, the "effector modulated transition" model and the "nucleotide perturbation" model. This does not exclude that this cluster of interactions could also act as a relay to transmit the ATP regulatory signal to the catalytic sites according to the previously proposed "primary-secondary effects" model.

Adenosine Triphosphate↗
PubMed1995

Current spectrum of cardiogenic shock and effect of early revascularization on mortality. Results of an International Registry. SHOCK Registry Investigators.

BACKGROUND: Cardiogenic shock remains the leading cause of death of patients hospitalized with acute myocardial infarction (MI). This study was conducted to examine (1) the current spectrum of cardiogenic shock, (2) the proportion of patients who are potential candidates for a trial of early revascularization, and (3) the apparent impact of early revascularization on mortality. METHODS AND RESULTS: Nineteen participating centers in the United States and Belgium prospectively registered all patients diagnosed with cardiogenic shock. Two hundred fifty-one patients were registered. The mean age was 67.5 +/- 11.7 years, and 43% were women. Acute mitral regurgitation or ventricular septal rupture was the cause of shock in 8%. Concurrent conditions contributing to the development of shock were noted in 5%, and 2% had isolated right ventricular shock. Among the remaining 214 patients, nonspecific findings on the ECG associated with "nontransmural" MI were seen in 14%. The median time to shock diagnosis after MI was 8 hours. The overall in-hospital mortality was 66%. Patients clinically selected to undergo cardiac catheterization were significantly younger and had a lower mortality than those not selected (51% versus 85%, P < .0001) even if they were not revascularized (58%). Mortality for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) was 60% (n = 55) and 19% (n = 16) for coronary artery bypass graft surgery (CABG). Sixty percent (n = 150) of registered patients were judged eligible for a trial of early revascularization. Trial-eligible patients were significantly younger (65.4 +/- 11.0 versus 70.6 +/- 11.9 years, P < .001), had an earlier median time to shock onset after MI (6.5 versus 17.5 hours, P = .003), and had lower mortality (62% versus 73%, P = .077) than ineligible patients. CONCLUSIONS: Patients diagnosed with cardiogenic shock complicating acute MI are a heterogeneous group. Those eligible for a trial of early revascularization tended to have lower mortality. Patients selected to undergo cardiac catheterization had lower mortality whether or not they were revascularized. Emergent PTCA and CABG are promising treatment modalities for cardiogenic shock, but biased case selection for treatment may confound the data. Whether PTCA and CABG reduce mortality and which patient subgroups benefit most remain to be determined in a randomized clinical trial.

Aged↗
PubMed1995

FMS mutations in patients following cytotoxic therapy for lymphoma.

Point mutations at codons 301 and 969 of the FMS proto-oncogene have been reported in both myelodysplasia (MDS) and acute myeloid leukaemia (AML). We report here the incidence of such mutations in patients at risk of developing secondary MDS and AML. Peripheral blood DNA from 70 patients in remission from lymphoma was screened for mutations by oligonucleotide (ONH) using mutant specific probes. Codon 969 mutations were detected in 11 of the 70 (15.7%) cases. No codon 301 mutations were detected. Five of these mutations were confirmed using an independent technique (single nucleotide primer extension analysis, SNPE) and a further mutation was detected in a single patient using single-stranded conformational polymorphism analysis (SSCP). No codon 969 mutations were detected in 62 lymphoma biopsy specimens from these patients or from three patients with detectable FMS mutations where pre-therapy marrow was investigated by ONH. No mutations at either codons 301 or 969 were detected by ONH in 61 normal controls. Somatic mutations at codon 969 of the FMS gene occur commonly following cytotoxic therapy for lymphoma and their detection indicates the presence of a clonally expanded population of abnormal cells.

Adult↗
PubMed1995

Occupational and environmental exposures and myelodysplasia: a case-control study.

A case-control study of newly diagnosed myelodysplastic syndrome patients investigated lifetime exposures through occupation, environment or hobby by questionnaire, structured and semi-structured interview. The exposure histories of 400 individually matched pairs were compared. Increased or possibly increased odds ratios were observed for radiation (2.05, 95% confidence interval 1.16-3.76), halogenated organics (1.57, 0.97-2.57), metals (1.40, 0.99-2.00), several specific radiation exposures and individual chemicals and for childlessness (1.46, 1.01-2.11). Since myelodysplasia generally carries a poor prognosis, whether or not individuals convert to leukaemia or to other cancer, these findings add to previous reports of exposures implicated in the aetiology of leukaemia and add to the case for minimizing exposures to radiation and halogenated organics.

Adolescent↗