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Biomedical subjects

A Frenkel

Publications and source records attributed to A Frenkel.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of acute hematologic and long-term pulmonary toxicities of radioimmunotherapy of Cryptococcus neoformans infection in murine models.

We evaluated acute hematological and long-term pulmonary toxicity of radioimmunotherapy in murine models of Cryptococcus neoformans infection. Activities up to 250 microCi were well tolerated by healthy A/JCr mice for (213)Bi-18B7 and (188)Re-18B7 monoclonal antibodies. In infected mice, doses up to 150 microCi produced only transient toxicity. The lungs of treated mice had no evidence of radiation fibrosis.

Animals↗
PubMed2001

Extension of a tuned log spiral of revolution fluorescence XAFS detector, designed for optimal detection of a particular element Z, to XAFS of elements other than Z.

Recently, it has been demonstrated that an x-ray detector in the form of a log spiral of revolution, covered with highly oriented pyrolytic graphite, is an excellent device for obtaining the fluorescence XAFS of an element of interest in the presence of competing fluorescence from other elements. In the present work we investigate the capabilities of a log spiral of revolution (LSR) detector, with a geometry optimized for one element (in this case Cr), if used for XAFS of other elements.

Journal Article↗
PubMed2001

Time-dependent XAS studies of trapped enzyme-substrate complexes of alcohol dehydrogenase from Thermoanaerobacter brockii.

The understanding of structure-function relationships in proteins has been significantly advanced with the advent of the biotechnological revolution. A goal yet to be realized for many metalloenzyme systems is to characterize the dynamic changes in structure that bridge the static endpoints provided by crystallography. We present here a series of edge and EXAFS spectra of the metalloenzyme alcohol dehydrogenase from Thermoanaerobacter brockii (TbADH) complexed with its substrate. The enzyme-substrate complexes were trapped by fast freezing at various times, following their enzyme activity. Our edge and EXAFS analyses both reveal the time-dependent changes in the structure of the active site of TbADH.

Alcohol Dehydrogenase↗
PubMed2001

The fusion of anatomic and physiologic imaging in the management of patients with cancer.

Imaging is of major clinical importance in the noninvasive evaluation and management of patients with cancer. Computed tomography (CT) and other anatomic imaging modalities, such as magnetic resonance imaging (MRI) or ultrasound, have a high diagnostic ability by visualizing lesion morphology and by providing the exact localization of malignant sites. Nuclear medicine provides information on the function and metabolism of cancer. Over the last decade, there have been numerous attempts to combine data obtained from different imaging techniques. Fused images of nuclear medicine and CT (or to a lesser extent, MRI) overcome the inherent limitations of both modalities. Valuable physiologic information benefits from a precise topographic localization. Coregistered data have been shown to be useful in the evaluation of patients with cancer at diagnosis and staging, in monitoring the response to treatment, and during follow up, for early detection of recurrence. Time-consuming and difficult realignment and computation for fusion of independent studies have, until now, limited the use of registration techniques to pilot studies performed in a small number of patients. The development of the new technology of single photon emission computed tomography/CT and positron emission tomography/CT that allows for combined functional and anatomic data acquisition has the potential to make fusion an everyday clinical tool.

Diagnostic Imaging↗
PubMed2000

Structural characterization of the catalytic active site in the latent and active natural gelatinase B from human neutrophils.

Matrix metalloproteinases are endopeptidases that have a leading role in the catabolism of the macromolecular components of the extracellular matrix in a variety of normal and pathological processes. Human gelatinase B is a zinc-dependent proteinase and a member of the matrix metalloproteinase family that is involved in inflammation, tissue remodeling, and cancer. We have conducted x-ray absorption spectroscopy, atomic emission, and quantum mechanics studies of natural and activated human gelatinase B. Our results show that the natural enzyme contains one catalytic zinc ion that is central to catalysis. In addition, upon enzyme activation, the catalytic zinc site exhibits a conformation change that results in the expansion of the bond distances around the zinc ion and the replacement of one sulfur with oxygen. Interestingly, quantum mechanics calculations show that oxygen ligation at the catalytic zinc ion exhibits a greater affinity to the binding of an oxygen from an amino acid residue rather than from an external water molecule. These results suggest that the catalytic zinc ion plays a key role in both substrate binding and catalysis.

Binding Sites↗
PubMed2000

Spectroscopic studies of inhibited alcohol dehydrogenase from Thermoanaerobacter brockii: proposed structure for the catalytic intermediate state.

Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) catalyzes the reversible oxidation of secondary alcohols to the corresponding ketones using NADP(+) as the cofactor. The active site of the enzyme contains a zinc ion that is tetrahedrally coordinated by four protein residues. The enzymatic reaction leads to the formation of a ternary enzyme-cofactor-substrate complex; and catalytic hydride ion transfer is believed to take place directly between the substrate and cofactor at the ternary complex. Although crystallographic data of TbADH and other alcohol dehydrogenases as well as their complexes are available, their mode of action remains to be determined. It is firmly established that the zinc ion is essential for catalysis. However, there is no clear agreement about the coordination environment of the metal ion and the competent reaction intermediates during catalysis. We used a combination of X-ray absorption, circular dichroism (CD), and fluorescence spectroscopy, together with structural analysis and modeling studies, to investigate the ternary complexes of TbADH that are bound to a transition-state analogue inhibitor. Our structural and spectroscopic studies indicated that the coordination sphere of the catalytic zinc site in TbADH undergoes conformational changes when it binds the inhibitor and forms a pentacoordinated complex at the zinc ion. These studies provide the first active site structure of bacterial ADH bound to a substrate analogue. Here, we suggest the active site structure of the central intermediate complex and, more specifically, propose the substrate-binding site in TbADH.

Absorptiometry, Photon↗
PubMed2000

A new Klebsiella planticola strain (Cd-1) grows anaerobically at high cadmium concentrations and precipitates cadmium sulfide.

Heavy metal resistance by bacteria is a topic of much importance to the bioremediation of contaminated soils and sediments. We report here the isolation of a highly cadmium-resistant Klebsiella planticola strain, Cd-1, from reducing salt marsh sediments. The strain grows in up to 15 mM CdCl(2) under a wide range of NaCl concentrations and at acidic or neutral pH. In growth medium amended with thiosulfate, it precipitated significant amounts of cadmium sulfide (CdS), as confirmed by x-absorption spectroscopy. In comparison with various other strains tested, Cd-1 is superior for precipitating CdS in cultures containing thiosulfate. Thus, our results suggest that Cd-1 is a good candidate for the accelerated bioremediation of systems contaminated by high levels of cadmium.

Anaerobiosis↗
PubMed2000

Aggressive non-Hodgkin lymphoma: early prediction of outcome with 67Ga scintigraphy.

PURPOSE: To evaluate use of gallium 67 scintigraphy early during chemotherapy to predict the outcome in patients with aggressive non-Hodgkin lymphoma. MATERIALS AND METHODS: Among 118 patients, 67Ga scintigraphy was performed after one cycle of chemotherapy in 51 patients, after a median of 3.5 cycles in 97 patients, and both in 30 patients. Computed tomography (CT) was performed after a median of 3.5 cycles of treatment in 87 patients. The failure-free survival was compared between patients with positive or negative 67Ga or CT scans by using the log-rank test. Multivariate analysis helped determine the relation between 67Ga scintigraphic and CT findings and the outcome. RESULTS: The differences in failure-free survival between patients with positive versus negative 67Ga scans after one cycle of treatment (P < .001) and at midtreatment (P < .001) were significant. There was no statistically significant difference in failure-free survival between patients with positive versus negative CT findings during treatment. In multivariate analysis, 67Ga scintigraphy after one cycle (P < .045) and at midtreatment (P < .006) was an independent factor associated with outcome. CONCLUSION: Gallium 67 scintigraphic findings after one cycle of chemotherapy and at midtreatment are predictive of outcome in patients with aggressive non-Hodgkin lymphoma. CT findings are not predictive. Early 67Ga scintigraphy during chemotherapy is a good indicator of patients who may benefit from a change to a more aggressive treatment. A future study is necessary to investigate the potential effect of early change of treatment.

Adolescent↗
PubMed2000

Quantitative bone single-photon emission computed tomography for prediction of pain relief in metastatic bone disease treated with rhenium-186 etidronate.

PURPOSE: To calculate radiation doses of rhenium-186 ((186)Re) etidronate in painful bone metastases using quantitative bone single-photon emission computed tomography (SPECT) and to determine the threshold dose for predicting pain relief. We also wanted to determine whether technetium-99m ((99m)Tc) methylene diphosphonate (MDP) concentrations predict radiation doses of (186)Re etidronate in painful lesions. MATERIALS AND METHODS: Forty-eight patients with breast and prostate cancer were evaluated. Patients received therapeutic doses of (186)Re etidronate. The area under the pain over time curve (AUPC) was measured for 8 weeks after treatment. Response was calculated as the percentage of change in AUPC. Quantitative bone SPECT (QBS)-measured concentration of (186)Re etidronate was used for calculating radiation doses. Receiver operating characteristics curve analysis determined the radiation dose threshold that best separated responders from nonresponders. SPECT-measured concentration of (186)Re etidronate in the urinary bladder was correlated with its concentration in the voided urine. Concentration of (99m)Tc MDP was compared with radiation doses to painful metastases. RESULTS: The radiation dose threshold was 2.10 Gy. For a decrease of 50% in the AUPC, the positive predictive value (PPV) of this value was 75% and the negative predictive value (NPV) was 88%. For a decrease in pain of 33%, the PPV was 84% and the NPV was 81%. In prostate cancer patients only, the PPV was 81% and the NPV was 92%. The correlation between in vivo/in vitro measured urine concentration was 0.90. The correlation between (99m)Tc MDP concentration and radiation doses of (186)Re etidronate was 0.92. CONCLUSION: QBS-measured radiation doses of (186)Re etidronate in painful metastases are a good predictor of pain relief. Bone SPECT using (99m)Tc MDP predicts radiation doses delivered by (186)Re etidronate.

Adult↗
PubMed1999

Hodgkin disease: prediction of outcome with 67Ga scintigraphy after one cycle of chemotherapy.

PURPOSE: To investigate gallium 67 scintigraphy performed early during treatment as a means to predict outcome and thus to optimize treatment of Hodgkin disease (HD) in the future. MATERIALS AND METHODS: Ninety-eight patients with HD were examined. Thirty-one patients underwent 67Ga scintigraphy after one chemotherapy cycle and 83 patients after a mean 3.5 cycles (range, 2-5 cycles). Sixteen patients underwent 67Ga scintigraphy both after one cycle and at midtreatment. Patients underwent whole-body scintigraphy and single photon emission computed tomography of the torso. Torso computed tomography (CT) was performed after a mean 3.5 cycles (range, 2-6 cycles). Failure-free survival was compared between patients with positive and patients with negative test findings (Kaplan-Meier method), and the significance of the difference was calculated. The association of failure-free survival with various prognostic clinical factors before treatment was compared (log-rank test univariate analysis). RESULTS: Failure-free survival differed significantly (P < .002) between patients with positive and patients with negative 67Ga scintigrams after one chemotherapy cycle but not at midtreatment. Failure-free survival was not significantly different between patients with positive and patients with negative CT scans at midtreatment. Twenty-two (92%) of 24 patients with negative 67Ga scintigrams after one cycle and 64 (82%) of 78 patients with negative scintigrams at midtreatment remained in complete response. In four (57%) of seven patients with positive 67Ga scintigrams after one cycle, treatment failed. CONCLUSION: 67Ga scintigraphy after one cycle of chemotherapy is a good early predictor of outcome of HD.

Adult↗
PubMed1998

Quantitative bone SPECT in young males with delayed puberty and hypogonadism: implications for treatment of low bone mineral density.

UNLABELLED: Constitutional delayed puberty (DP) and idiopathic hypogonadotropic hypogonadism (IHH) lead to osteoporosis in adult men. We were interested in whether response to treatment of these conditions by testosterone could be predicted by in vivo quantitative bone SPECT (QBS) measurement of bone turnover and whether testosterone administration affects bone mineral density (BMD) in these subjects. METHODS: In vivo QBS and BMD measurements were performed in the lumbar spine (LS) and femoral neck (FN) of 29 young men with DP and 16 young men with IHH. In vivo QBS and BMD values in these patients were compared to the values obtained from 27 age-matched normal controls. The effect of testosterone treatment was determined by measuring changes in QBS and BMD, before and after treatment of 22 patients with DP and of all 16 patients with IHH. Seven patients with DP were not treated. RESULTS: In vivo QBS values in patients with DP were significantly higher than those in controls (8.44% +/- 2.55%ID/ml compared to 5.63% +/- 1.12%ID/ml x 10(-3), p < 0.001, for the LS; and 7.86% +/- 3.01%ID/ml compared to 4.29% +/- 1.25%ID/ml, p < 0.001, for the FN). One year after testosterone treatment, QBS values in DP were significantly reduced. Pretreatment BMD values in patients with DP were significantly lower than those in normal subjects (0.77 +/- 0.11 g/cm2 compared to 1.03 +/- 0.14 g/cm2, p < 0.0001, for the LS; and 0.89 +/- 0.11 g/cm2 compared to 1.08 +/- 0.18 g/cm2, p < 0.006, for the FN). One year after treatment, BMD values increased significantly (0.91 +/- 0.14 g/cm2, p < 0.0001, for the LS; and 0.97 +/- 0.11 g/cm2, p < 0.0001, for the FN). The seven untreated young men with DP still had significantly lower-than-normal BMD values (0.82 +/- 0.08 g/cm2, p < 0.008, for the LS; and 0.89 +/- 0.05 g/cm2, p < 0.04, for the FN). In patients with IHH, QBS values were not significantly different from those found in normal controls. The values for BMD were significantly lower for both the LS (p < 0.0001) and the FN (p < 0.001). After treatment, BMD values in patients with IHH were still significantly lower than those of normals (p < 0.009 for the LS; and p < 0.006 for the FN). CONCLUSION: Young men with maturation abnormalities show low bone density. Patients with DP and high bone turnover, as revealed by high QBS values, respond to testosterone treatment. Patients with IHH have normal bone turnover and do not respond to testosterone.

Adolescent↗
PubMed1996

Diffuse lung uptake of Ga-67 after treatment of lymphoma: is it of clinical importance?

PURPOSE: To determine if diffuse lung uptake (DLU) of gallium-67 at scintigraphy in patients with lymphoma is indicative of lymphomatous involvement of the lungs. MATERIALS AND METHODS: Thirty-eight patients (24 male, 14 female; aged 15-76 years) with DLU were examined. The relation between DLU and lymphoma was investigated. Radiographic and computed tomographic findings and the persistence of Ga-67 uptake were investigated to detect lymphomatous involvement of the lungs. The relations between chemotherapy and radiation therapy, previous lung or heart disease, and DLU were also examined. RESULTS: DLU appeared only during or after chemotherapy. No clinical, radiologic, or follow-up evidence indicated that patients with DLU had active lymphomatous involvement of the lungs. The difference in survival between patients with persistent and patients with transient DLU was not statistically significant. No statistically significant correlation between DLU and any possible inductive factor was indicated at multivariate analysis. CONCLUSION: DLU after treatment does not indicate lymphomatous involvement of the lungs.

Adolescent↗
PubMed1995

Ga-67 scintigraphy with a dual-head camera.

High quality images are necessary for correct interpretation of Ga-67 studies in lymphoma. The authors were interested if there is a significant change in the quality of the Ga-67 images using a newly introduced dual-head camera compared with a conventional single-head camera. The tomographic spatial resolution, full width at half maximum, was found to be 9.63 mm compared with 13.7 for a single-head camera. The volume sensitivity was 380 cps/microCi/ml per axial cm as compared with 333 cps/microCi/ml, and point source sensitivity was 5.6 cps/microCi compared with 3.8. There was a significant difference (P < 0.001), when using the threshold technique, in the number of counts per pixel over a wide range of volumes and concentrations in phantoms when the two cameras were compared. There was also a significant difference (P < 0.001) in Ga-67 uptake in lymphoma lesions in patients when the same parameters were used for both cameras when using SPECT. The average uptake in lymphoma lesions, using a dual-head camera, was 529 counts/pixel with a range of 112 to 1275 counts/pixel in different tumors. With a single-head camera, the average for the same tumor was 216 counts/pixel with a range of 59 to 469 counts/pixel. The high sensitivity of the dual-head camera enabled high-quality, whole body scintigraphy, including the limbs, in 20 minutes compared with the 35 minutes necessary for the single-head camera for images which did not include the legs. Whole body Ga-67 scintigraphy is shown to be important in patients with lymphoma of the upper and lower limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Bone loss in patients with chronic renal disease: prediction with quantitative bone scintigraphy with SPECT.

PURPOSE: To determine whether quantitative bone scintigraphy (QBS) with single-energy photon emission computed tomography (SPECT) can help predict which patients with chronic renal disease will show bone mineral density (BMD) loss. MATERIALS AND METHODS: In 18 patients, the percentage of injected dose of technetium-99m methylene diphosphonate per cubic centimeter of bone was measured with QBS SPECT in the lumbar vertebrae and femoral neck. The differences in BMD over an average of 20 months were measured and compared with SPECT measurements. QBS values were also compared with serum bone turnover markers. RESULTS: There was a negative correlation (r = -.54, P < .05 for the lumbar spine and r = -.60, P < .01 for the femoral neck) between QBS values and bone loss. Positive and negative predictive values, sensitivity, and specificity of QBS for bone loss in the lumbar spine were 78%, 71%, 78%, and 71%, respectively, and in the femoral neck, 82%, 100%, 100%, and 78%, respectively. Differences between predictive values of serum bone turnover markers were not statistically significant. CONCLUSION: QBS with SPECT enabled prediction of rapid bone loss in patients with renal disease.

Absorptiometry, Photon↗
PubMed1995

Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake.

PURPOSE: To assess the role of quantitative gallium citrate (Ga 67) single-photon emission computed tomography (SPECT) in differentiating lymphoma from benign hilar uptake, concentrations of Ga 67 in 29 sites of documented lymphoma and in 75 benign lesions were compared. PATIENTS AND METHODS: One hundred seven thoracic Ga 67 SPECT studies obtained in 101 consecutive lymphoma patients were reviewed. Fifty-nine studies detected Ga 67 uptake in the hilar and or mediastinal regions. Forty-eight studies showed no such abnormality. The concentration of Ga 67 in the thoracic lesions was measured using a quantitative SPECT technique and its nature was determined by correlation with computed tomographic (CT) scans and follow-up evaluation of the sites. RESULTS: In 20 of 59 abnormal studies (34%), there was lymphoma in the hilar and or mediastinal regions. In the remaining 39 abnormal studies (66%), Ga 67 uptake was benign. There were 29 sites of lymphoma and 75 benign lesions. The concentration of Ga 67 in lymphoma was significantly higher than in benign hilar uptake (13.2 +/- 5.4 %ID/mL x 10(-3) v 5.6 +/- 1.5 % injected dose (ID)/mL x 10(-3); P < .001). A concentration value of 8.3 %ID/mL x 10(-3) was found to best separate lymphoma and benign uptake, with a sensitivity of 90%, a specificity of 93%, a positive predictive value of 84%, and a negative predictive value of 96%. CONCLUSION: Lymphoma and benign hilar uptake differ significantly in their concentration of Ga 67. The present study shows that quantitative Ga-67 SPECT reliably differentiates lymphoma and benign uptake.

Adolescent↗