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D Kahn

Publications and source records attributed to D Kahn.

At least 109 records · Page 6Linked to original sources
PubMed1996

An alternative PII protein in the regulation of glutamine synthetase in Escherichia coli.

The PII protein has been considered pivotal to the dual cascade regulating ammonia assimilation through glutamine synthetase activity. Here we show that PII, encoded by the glnB gene, is not always essential; for instance upon ammonia deprivation of a glnB deletion strain, glutamine synthetase can be deadenylylated as effectively as in the wild-type strain. We describe a new operon, glnK amtB, which encodes a homologue of PII and a putative ammonia transporter. We cloned and overexpressed glnK and found that the expressed protein had almost the same molecular weight as PII, reacted with polyclonal PII antibody, and was 67% identical in terms of amino acid sequence with Escherichia coli PII. Like PII, purified GlnK can activate the adenylylation of glutamine synthetase in vitro, and, in vivo, the GlnK protein is uridylylated in a glnD-dependent fashion. Unlike PII, however, the expression of glnK depends on the presence of UTase, nitrogen regulator I (NRI), and absence of ammonia. Because of a NRI and a sigma N (sigma 54) RNA polymerase-binding consensus sequence upstream from the glnK gene, this suggests that glnK is regulated through the NRI/NRII two-component regulatory system. Indeed, in cells grown in the presence of ammonia, glutamine synthetase deadenylylation upon ammonia depletion depended on PII. Possible regulatory implications of this conditional redundancy of PII are discussed.

Amino Acid Sequence↗
PubMed1996

Diagnostic imaging of patients with acute scrotal pain.

Common causes of acute scrotal pain include testicular torsion, epididymo-orchitis and trauma. Epididymitis in adult men is typically associated with a history of urinary tract infection or prostatitis. Testicular torsion typically presents in young adults with a sudden onset of severe scrotal pain and, frequently, a history of recurrent episodes that have spontaneously resolved. With scrotal trauma, ultrasound may demonstrate testicular fracture, hematoceles and areas of hemorrhage or testicular infarction. Since both epididymitis and testicular torsion present with scrotal pain and swelling, and may be accompanied by fever and pyuria, Doppler ultrasound or radionuclide imaging may be necessary to make the diagnosis. In acute testicular torsion, color Doppler ultrasound shows absent flow to the epididymis and testis, while nuclear imaging shows central photon-deficient areas in the ischemic hemiscrotum. In epididymo-orchitis, color Doppler ultrasound shows increased flow to the epididymis and testis, while nuclear imaging shows increased perfusion of the affected testis and hemiscrotum.

Acute Disease↗
PubMed1996

An approach to diagnostic imaging of suspected pulmonary embolism.

Risk factors for pulmonary embolism include immobilization, trauma and surgery, particularly for hip fracture. Patients may present with acute respiratory symptoms, including tachypnea, tachycardia and rales. Chest radiographs and clinical and laboratory findings alone cannot provide a firm diagnosis. A completely normal chest radiograph may be seen in up to 40 percent of patients with pulmonary embolism, and as many as 30 percent of persons with pulmonary embolism and no prior cardiopulmonary disease will have a PaO2 greater than 80 mm Hg. The ventilation/perfusion (V/Q) lung scan is central to guiding clinical decisions. V/Q scans interpreted as either normal, near normal or high probability are reasonably diagnostic. A low probability V/Q scan can exclude the diagnosis of pulmonary embolism only if the patient has a clinically low probability of pulmonary embolism. Intermediate V/Q scans are not diagnostic and call for further evaluation. Compression ultrasonography is sensitive in detecting symptomatic deep venous thrombosis in the thigh. When clinical suspicion remains high and noninvasive imaging studies are uncertain, pulmonary angiography is likely to be diagnostic.

Algorithms↗
PubMed1996

Radiation absorbed dose from indium-111-CYT-356.

UNLABELLED: Indium-CYT-356 is an agent developed by CYTOGEN Inc. (CYT) (Princeton, NJ) for the use in staging patients with prostate cancer. This investigation was performed to provide the human dosimetry needed for Food and Drug Administration approval for routine use in patients. METHODS: Biodistribution data collected from three sites were obtained from prostate cancer patients who received diagnostic doses of 111In-CYT-356. Data included blood and urine collections, and the organ uptake value was measured from sequential conjugate whole-body and planar images over a 7-10 day period. Dose contributions from radioactivity in transit through the GI tract were estimated using a compartmental model. The calculations used the MIRD methodology and MIRDOSE 3. RESULTS: The total-body dose observed was 0.14 mGy/MBq, and the effective dose was found to be 0.25-0.29 mSv/MBq. The largest organ doses were found for the liver (1.0 mGy/MBq), kidneys (0.67 mGy/MBq) and spleen (0.88 mGy/MBq). CONCLUSION: The radiation dose to the patient from a typical 185 MBq administration of 111In-CYT-356 is comparable to the dose from other 111In-labeled whole antibodies used in the diagnosis and management of cancer patients. The inclusion of the GI tract as a source organ increases the effective dose by 18%.

Antibodies, Monoclonal↗
PubMed1995

An additional PII in Escherichia coli: a new regulatory protein in the glutamine synthetase cascade.

The PII protein in the glutamine synthetase cascade transduces the nitrogen signal, as sensed by uridylyltransferase, both to the NRII/NRI two-component system and to adenylyltransferase, to regulate the activity of glutamine synthetase. Here we describe the amplification of a chromosomal DNA fragment from Escherichia coli which contains the sequence of a PII homologue. The derived amino acid sequence of this DNA fragment is 67% identical to E. coli PII. It contains the conserved tyrosine residue which is known to be the site of uridylylation in PII. E. coli is the first organism in which two different PII proteins have been detected.

Amino Acid Sequence↗
PubMed1995

Utility of SPECT imaging for determination of vertebral metastases in patients with known primary tumors.

Determining the etiology of a focal lesion seen on bone scan in patients with primary tumors usually requires the use of other imaging procedures or biopsy. Single positron emission computed tomography (SPECT) with high resolution multidetector systems can localize the specific site of a vertebral lesion and in this way potentially differentiate between benign and metastatic disease. SPECT images of the lower thoracic and lumbar spine were reviewed for lesion location and intensity by two experienced interpreters. Follow-up data were adequate to ascertain the cause of 71 lesions seen on SPECT in 29 patients. Twenty-six of these lesions were not seen on planar images. Of the 71 lesions, 44 were benign and 27 metastatic. Of the 15 lesions where the pedicle was involved, 11 were found to metastatic. There were a total of 14 facet lesions, 9 of which were present in vertebra with no lesions at sites other than the facets. All 9 of these isolated facet lesions turned out to be benign. Lesion intensity did not distinguish benign from malignant disease. We conclude that SPECT imaging is useful in determining the etiology of focal lesions seen on bone scan in patients with a known primary tumor referred for evaluation of metastatic disease.

Colonic Neoplasms↗
PubMed1995

Detectability of simulated brain activation using dual radioisotope SPECT based on size and intensity of the focal hyperactivity.

RATIONALE AND OBJECTIVES: Simultaneous single-photon emission computed tomography (SPECT) neuroimaging with both technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and iodine-123 (123I) N-isopropyl-iodoamphetamine is a recently introduced method with potential for assessing activation phenomena in the brain. However, there is limited information on the accuracy of the technique for detecting focal cortical sites of neuroactivation. We determined, in vitro, what levels of activation could be detected as a function of the size of the activated region. METHODS: A Lucite brain phantom was filled with both 123I and 99mTc so as to simulate both a nonactivated state (123I) along with focal sites of activation (99mTc). Simulated activations ranged from 0 to 18% in volumes of 7, 14, 20, and 27 cm3. Imaging was performed with a triple-detector gamma camera using a 10% symmetric window at 140 keV and 10% asymmetric window around 159 keV. No correction was made for gamma cross-talk. To determine whether a simulated activation was "detected," the 99mTc: 123I count ratios in the activated regions were compared by t test with ratios in nonactivated regions of similar volume. Detection sensitivities also were calculated as the fraction of the activated 99mTc: 123I ratios that were greater than the mean + 2 standard deviations of the corresponding nonactivated ratios. RESULTS: All sites of simulated activations of 10% or greater were detected. The detection sensitivity was 100% (95% confidence interval, 90-100%) for the two largest chambers with simulated activations of 13-18%. Activations in the 3-6% range, in the same-sized chambers, were detected with a limited sensitivity (67% with a confidence interval of 45-84%). In the 14-cm3 chamber, simulated activations in the 13-18% range were detected with 90% sensitivity (confidence interval, 74-98%). In general, the detection sensitivity was greater for larger chambers and higher levels of simulated activation. CONCLUSION: We conclude that the dual-radioisotope technique using triple-detector SPECT systems and low-energy all-purpose (LEAP) collimators should be highly reliable for identifying focal brain activations above 13% that cover at least 14 cm3 of brain cortex. Smaller, less intense sites of activation will be detected with reduced frequency. These conclusions are based on our assessment of only the physical parameters involved in this methodology and other factors (e.g., the possibility that the relation between cerebral radiotracer concentration and regional cerebral blood flow) may affect the results obtained with patients.

Brain↗
PubMed1995

Emphysematous pyelonephritis in diabetic patients.

OBJECTIVE: To determine the clinico-pathological profile of patients with emphysematous pyelonephritis (EPN). PATIENTS AND METHODS: The records of 22 diabetic patients who presented with EPN were reviewed. RESULTS: EPN occurred predominantly in female diabetic patients without evidence of ureteric obstruction. The ages of the patients and the duration of the diabetes were variable. EPN occurred in insulin-dependent as well as non-insulin-dependent patients. The patients presented following a prodromal illness of urinary sepsis, with an acute severe illness with symptoms and signs on the affected side. Dehydration and ketoacidosis were common. The diagnosis was made by recognizing gas in the kidney on an X-ray or ultrasound. Eighteen patients were subjected to emergency nephrectomy. CONCLUSIONS: EPN is an uncommon, life-threatening condition characterized by the production of intraparenchymal gas. We believe that vigorous resuscitation and emergency nephrectomy is the treatment of choice.

Adult↗
PubMed1995

Haemostatic and immunological sequelae of portacaval shunt in rats.

We have evaluated the link between haemostatic abnormalities and immune dysfunction in liver disease by evaluating parameters of cellular and humoral immunity in conjunction with coagulation profiles in rats following portacaval anastomosis, induction of portal hypertension by portal vein stenosis or by sham surgical procedures. Twelve weeks following surgery, portacaval shunted rats were markedly anaemic (8.9 +/- 0.6 g/dl; controls 12.3 +/- 1.4 g/dl, p < 0.05), had low plasma fibrinogen levels (0.6 +/- 0.3 g/l, controls 2.5 +/- 0.2 g/l p < 0.05) and markedly elevated fibrin(ogen) degradation products (FDP) titres (1/40-1/80; controls < 1/10. p < 0.05). Portal vein stenosed rats were less anaemic (11.5 +/- 0.8 g/dl), had near normal fibrinogen levels (2.1 +/- 0.3 g/l) but elevated FDP levels (1/40-1/80). Both portacaval shunted and portal vein stenosed rats had elevated serum IgG levels (35.1 +/- 14.1 g/l; 29.2 +/- 13.9 g/l respectively; control values 20 +/- 5.9 g/l p < 0.05 for comparison with both experimental groups). Intrinsic lymphocyte proliferation to T and B cell mitogens was markedly depressed in the portacaval anastamosed rats when compared to controls. Serum factors inhibitory to control lymphocyte proliferation were noted in the shunted rats. Phagocytosis of complement and immunoglobulin sensitised sheep RBC by Kupffer cells purified from rats that had undergone portacaval shunting was markedly reduced (p < 0.05). The increased degree of phagocytosis following exposure to LPS-endotoxin (50 micrograms/ml) was proportionate in degree to the control group. Spontaneous release of bioactive lymphocyte activating factors (IL-1 and IL-6) by purified rat sinusoidal cell populations was decreased in the portacaval shunted group, and decreased still further following stimulation with LPS (50 micrograms/ml) in vitro. The observation that many of the haemostatic and immunological abnormalities associated with chronic liver disease are present in rats with surgically created portacaval shunts or with induced portal hypertension, lends credence to the hypothesis that shunting of portal blood is, at least in part, responsible for many of the systemic manifestations associated with chronic liver disease.

Animals↗
PubMed1995

Serotonin syndrome.

We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death.

Depressive Disorder↗
PubMed1995

Patients with multiple sclerosis presenting to psychiatric hospitals.

BACKGROUND: Although many neuropsychiatric syndromes are associated with multiple sclerosis, few recent studies have examined the clinical features of psychiatric illness in inpatients with multiple sclerosis. Florid psychopathology can obscure neurologic symptoms in multiple sclerosis. It is therefore important to consider the range of severe psychiatric states that can occur in multiple sclerosis and the frequency with which multiple sclerosis patients are seen in inpatient facilities. METHOD: We examined records for 2720 consecutive admissions to three psychiatric units and conducted a chart review comparing the DSM-III psychiatric diagnoses of patients with multiple sclerosis with those of the inpatient population as a whole. RESULTS: The 10 patients with multiple sclerosis were significantly more likely to present with histories of mania and manic psychosis than the inpatient population as a whole. Further, 7 of the 10 patients had psychiatric hospitalizations before the multiple sclerosis diagnosis. In 4 of these 7 patients, a review of the medical record documented neurologic symptoms that were not recognized as typical of multiple sclerosis. Three of these 4 patients were psychotic and the fourth was catatonic at the time of their admissions. CONCLUSION: While multiple sclerosis patients account for a small proportion of all psychiatric admissions, clinicians should consider the diagnosis of multiple sclerosis in patients exhibiting manic symptoms in tandem with unexplained neurologic findings.

Adult↗
PubMed1995

Repair of a massive ventral hernia in a morbidly obese patient.

Aggressive perioperative management, with progressive preoperative pneumoperitoneum, is a worthy method of repairing massive ventral hernias with associated loss of domain in morbidly obese patients. The authors present a case and its successful outcome.

Adult↗