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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 91 records · Page 5Linked to original sources

Radioimmunoscintigraphy with In-111-labeled capromab pendetide predicts prostate cancer response to salvage radiotherapy after failed radical prostatectomy.

PURPOSE: We investigated the ability of In-111-capromab pendetide to separate patients who have failed radical prostatectomy into categories of those who would versus those who would not respond to salvage radiotherapy. METHODS: Prostate-specific antigen (PSA) levels in 32 men with prostate cancer who had failed radical prostatectomy and had undergone a whole-body In-111-capromab pendetide scan were followed-up for 13 months (median) after salvage radiotherapy to the pelvis. A logistic regression model was used to determine whether the scan findings, as well as other clinical variables, were associated with a durable complete response (DCR), a nondurable response (NDR), or no response (NR). RESULTS: Sixteen of 23 (70%) men with a normal scan outside the prostatic fossa achieved a DCR after salvage radiotherapy versus two of nine (22%) who had a positive scan outside the prostate fossa and pelvis (P = .0225, Fisher's exact test). Predicted probability (95% confidence interval [CI]) that a DCR would be obtained with a normal scan was 0.88 (0.55 to 0.98); for men with a positive scan limited to the prostatic fossa it was 0.62 (0.42 to 0.79); and for men with a positive scan outside the pelvis it was 0.27 (0.09 to 0.58). No other variables before radiotherapy showed a significant association with the DCR rate. CONCLUSION: Salvage radiotherapy is statistically more likely to lead to a durable complete PSA response in men with prostate cancer who have failed radical prostatectomy and have a negative In-111-capromab pendetide scan outside the pelvis as compared with those who have a positive scan.

Aged↗

A new method of developing expert consensus practice guidelines.

To improve the quality of medical care while reducing costs, it is necessary to standardize best practice habits at the most crucial clinical decision points. Because many pertinent questions encountered in everyday practice are not well answered by the available research, expert consensus is a valuable bridge between clinical research and clinical practice. Previous methods of developing expert consensus have been limited by their relative lack of quantification, specificity, representativeness, and implementation. This article describes a new method of developing, documenting, and disseminating expert consensus guidelines that meets these concerns. This method has already been applied to four disorders in psychiatry and could be equally useful for other medical conditions. Leading clinical researchers studying a given disorder complete a survey soliciting their opinions on its most important disease management questions that are not covered well by definitive research. The survey response rates among the experts for the four different psychiatric disorders have each exceeded 85%. The views of the clinical researchers are validated by surveying separately a large group of practicing clinicians to ensure that the guideline recommendations are widely generalizable. All of the suggestions made in the guideline are derived from, and referenced to, the experts' survey responses using criteria that were established a priori for defining first-, second-, and third-line choices. Analysis of survey results suggests that this method of quantifying expert responses achieves a high level of reliability and reproducibility. This survey method is probably the best available means for standardizing practice for decisions points not well covered by research.

Bias↗

The Rhizobium meliloti PII protein, which controls bacterial nitrogen metabolism, affects alfalfa nodule development.

Symbiotic nitrogen fixation involves the development of specialized organs called nodules within which plant photosynthates are exchanged for combined nitrogen of bacterial origin. To determine the importance of bacterial nitrogen metabolism in symbiosis, we have characterized a key regulator of this metabolism in Rhizobium meliloti, the uridylylatable P(II) protein encoded by glnB. We have constructed both a glnB null mutant and a point mutant making nonuridylylatable P(II). In free-living conditions, P(II) is required for expression of the ntrC-dependent gene glnII and for adenylylation of glutamine synthetase I. P(II) is also required for efficient infection of alfalfa but not for expression of nitrogenase. However alfalfa plants inoculated with either glnB mutant are nitrogen-starved in the absence of added combined nitrogen. We hypothesize that P(II) controls expression or activity of a bacteroid ammonium transporter required for a functional nitrogen-fixing symbiosis. Therefore, the P(II) protein affects both Rhizobium nitrogen metabolism and alfalfa nodule development.

Bacterial Proteins↗

Consciousness in waking and dreaming: the roles of neuronal oscillation and neuromodulation in determining similarities and differences.

State-dependent aspects of consciousness are explored with particular attention to waking and dreaming. First, those phenomenological differences between waking and dreaming that have been established through subjective reports are reviewed. These differences are robustly expressed in most aspects of consciousness including perception, attention, memory, emotion, orientation, and thought. Next, the roles of high frequency neuronal oscillation and neuromodulation are explored in waking and rapid eye movement sleep, the stage of sleep with which the most intense dreaming is associated. The high frequency neuronal oscillations serve similar functions in the wake and rapid eye movement states sleep but neuromodulation is very different in the two states. The collective high frequency oscillatory activity gives coherence to spatially separate neurons but, because of the different neuromodulation, the binding of sensory input in the wake state is very different from the binding of internally perceived input during rapid eye movement sleep. An explanatory model is presented which states that neuromodulation, as well as input source and brain activation level differentiate states of the brain, while the self-organized collective neuronal oscillations unify consciousness via long range correlations.

Consciousness↗

Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice.

Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trcutrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.

Animals↗

XDOM, a graphical tool to analyse domain arrangements in any set of protein sequences.

MOTIVATION: To extract the maximum possible information from a set of protein sequences, its modular organization must be known and clearly displayed. This is important both for structural and functional analysis. RESULTS: This paper presents an algorithm and a graphical interface called XDOM which performs a systematic analysis of the modular organization of any set of protein sequences. The algorithm is an automatic method to identify putative domains from sequence comparisons. The graphical tool displays the proteins as a set of linked boxes, corresponding to its domains. The method has been tested on a family of bacterial proteins and on whole genomes. It is currently applied to the complete SWISS-PROT database to build the PRODOM database. AVAILABILITY: XDOM is available free of charge by anonymous ftp:¿¿ftp://ftp.toulouse.inra.fr/pub/xdom¿ ¿. The ProDom database can be consulted at ¿¿http://protein.toulouse.inra.fr/prodom.html¿¿.

Algorithms↗

Kaposi's sarcoma-associated herpesvirus and human herpesvirus 8 (KSHV/HHV8)-associated lymphoma of the bowel. Report of two cases in HIV-positive men with secondary effusion lymphomas.

This report describes two cases of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV8)-associated lymphomas that primarily involved the large bowel and that secondarily caused malignant effusions. Involvement of the gastrointestinal tract is of interest because epidemiologic evidence suggests that KSHV/HHV-8 may be transmitted via the fecal-oral route, and KSHV/HHV8 DNA has been detected in rectal samples from HIV-positive patients. This report describes two HIV-positive men who developed primary KSHV/ HHV8-associated lymphomas of the bowel. Despite similar morphology and immunophenotype, these cases differ from most KSHV/HHV8-associated primary effusion lymphomas, which present with malignant effusions in the absence of a solid tumor mass. The spectrum of KSHV/HHV8-associated lymphomas is expanded to include a subset of primary bowel lymphomas in individuals infected with human immunodeficiency virus.

AIDS-Related Opportunistic Infections↗

Mutational characterization of promoter regions recognized by the Salmonella dublin virulence plasmid regulatory protein SpvR.

The virulence plasmid-encoded spv regulon is essential for virulence of Salmonella dublin in mice. The spvR gene product belongs to the LysR family of transcriptional regulator proteins. SpvR induces the expression of the spvABCD operon and positively regulates its own expression. DNase I protection analysis with purified SpvR fusion proteins identified SpvR binding sites within the spvA and spvR promoters (P. Grob and D. G. Guiney, J. Bacteriol. 178:1813-1820, 1996). We have used PCR mutagenesis, combined with functional selection for reduced SpvR affinity, to define the DNA elements essential for SpvR binding. For the spvR promoter fragment, a screen for reduced expression was also applied. Sequence analysis of the resulting mutant fragments reveals that the base pair changes are clustered in distinct regions. Determination of the apparent dissociation constants of SpvR for the mutant promoters showed that the spvA LysR-type motif and the upstream palindromic sequences of both promoters play an important role in SpvR recognition.

Animals↗

Sequential mixed lymphocyte culture after kidney transplantation: induction of tolerance or sensitization.

Serial mixed lymphocyte culture (MLC) was used to monitor the evolution of donor-specific responsiveness over the first 2 years after cadaveric renal transplantation. Lymphocytes obtained from 37 patients at 0, 1, 3, 6, 12, 18 and 24 months following transplantation were assayed in a one-way MLC using donor lymphocytes as stimulator cells. Donor-specific hyporesponsiveness developed in 66% of the patients with functioning grafts. Donor-specific sensitization was noted in 2 patients with functioning grafts and the MLC reactivity remained unchanged compared to the pretransplant value in 8 patients. The patients with donor-specific hyporeactivity tended to remain either free of rejection episodes or experienced early rejection episodes only. Thus, using serial MLC we were able to identify patients who developed hyporeactivity or tolerance to donor antigens. These patients may require less immunosuppression.

Adult↗

Interaction between panel reactive antibodies, auto- and cold reactive antibodies, and a positive B cell cross-match in renal and cardiac allograft survival.

We analyzed the influence on allograft survival of pretransplant panel reactive antibodies (PRA) < 10%, PRA > 10%, autoantibodies, cold antibodies and a positive B cell crossmatch in 807 renal and 237 cardiac transplant recipients. Donors and recipients were predominantly of mixed ancestry (Khoi, San, Xhosa and Caucasoid). Log rank analysis showed that PRA < 10%, cold antibodies, and a positive B cell cross-match did not influence allograft survival. Autoantibodies were present only in renal recipients; they appeared to have a beneficial effect on allograft survival (P = 0.06). PRA > 10% appeared to have a detrimental effect on allograft survival in both renal (P = 0.07) and cardiac (P = 0.06) recipients. Since autoantibodies and PRA > 10% had opposing effects, the results of renal recipients were reanalyzed after omission of the recipients with autoantibodies and coexisting PRA > 10%. This resulted in augmentation of the protective effect for autoantibodies (P = 0.027) and of the detrimental effect for PRA > 10% (P = 0.020). Two-year survival curves showed that when autoantibodies coexisted with PRA > 10%, the long term, but not the short-term, detrimental effect of PRA > 10% was attenuated. Patients with a positive B cell cross-match clustered in the PRA > 10% group in both renal (PRA negative vs. PRA < 10%; P = 0.0251; PRA < 10% vs. PRA > 10%: P = 0.0011) and cardiac (PRA negative vs. PRA > 10%: P = 0.0085) recipients. We conclude that PRA > 10% is the best indicator to identify recipients at high risk for rejection, and that the influence of antibodies on graft survival can not reliably be established without taking coexisting antibodies into account.

Antilymphocyte Serum↗

The management of biliary complications following orthotopic liver transplantation.

OBJECTIVE: Review of the biliary complications following orthotopic liver transplantation (OLT) at our institution, and their management and outcome. DESIGN: Retrospective study of medical records of 63 patients who underwent 68 transplant operations. SETTING: The Liver Transplant Unit, Groote Schuur Hospital and Red Cross War Memorial Children's Hospital, Cape Town PATIENTS: Six patients treated for 9 biliary complications. INTERVENTIONS: Reoperation with biliary reconstruction, or non-operative measures by either endoscopic retrograde pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). OUTCOME MEASURES: Clinical outcome and survival following treatment for biliary complications. RESULTS: Biliary complications occurred in 8.8% of patients who underwent transplantation at our institution. These consisted of strictures in 4 patients (with leak in 2), bile leak in 1 patient, and unsuspected primary sclerosing cholangitis (PSC) of the recipient duct in 1 patient. The mean time interval of biliary complications following OLT was 8 weeks (range 3-16). Biliary reconstruction was required in 4 patients while 2 patients were treated by endoscopic stenting. After a mean follow-up period of 30 months (range 1-64), 4 patients remained stable, 1 patient developed progressive stricturing of the intrahepatic ducts requiring repeated PTC dilatations, and 1 patient experienced stent blockages requiring endoscopic stent changes (died of unrelated causes). CONCLUSIONS: The rate of biliary complications following OLT at our institution compares favourably with literature reports. While biliary reconstruction is usually needed, endoscopic stenting appears effective in selected cases of biliary stricture and leak. PSC should be excluded prior to transplantation in young patients with cryptogenic cirrhosis.

Adolescent↗

Symbiotic nitrogen fixation does not require adenylylation of glutamine synthetase I in Rhizobium meliloti.

Symbiotic nitrogen fixation is accompanied by a shift of Rhizobium nitrogen metabolism from ammonium assimilation to ammonium export, which probably involves genetic or metabolic regulation of glutamine synthetase activity. In free-living Rhizobium meliloti glutamine synthetase I (GSI) is regulated post-translationally by reversible adenylylation in response to ammonium addition. Moreover, full expression of the GSI gene glnA requires the transcriptional activator, NtrC. A glnA1 mutant synthesizing a non-adenylylatable GSI produces normal nitrogen-fixing nodules on alfalfa: GSI adenylylation is dispensable for symbiotic nitrogen fixation. This is rationalized by the observation that less GS protein is present in R. meliloti bacteroids than in free-living bacterial cells.

Adenosine Phosphosulfate↗

Venous thrombectomy in patients presenting with iliofemoral vein thrombosis after renal transplantation.

In this study 14 patients presented with 15 episodes of iliofemoral vein thrombosis after renal transplantation. Seven patients (group 1) had viable renal grafts and were treated with conventional anticoagulation. Eight patients (group 2) had non-viable renal grafts and were subjected to graft nephrectomy and simultaneous venous thrombectomy without anticoagulation. The patients in group 2 had rapid resolution of the signs and symptoms of the iliofemoral vein thrombosis, and noninvasive vascular investigation at follow-up revealed competent and patent deep veins in all patients. In contrast, only 50% of the patients in group 1 had normal venous studies at follow-up. We recommend that renal transplant recipients who develop iliofemoral vein thrombosis and nonviable allograft postoperatively should be subjected to venous thrombectomy at the time of graft nephrectomy.

Adolescent↗