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Biomedical subjects

D R Benjamin

Publications and source records attributed to D R Benjamin.

At least 19 recordsLinked to original sources
PubMed2002

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Acute Disease↗
PubMed2000

Detection and selective dissociation of intact ribosomes in a mass spectrometer.

Intact Escherichia coli ribosomes have been projected into the gas phase of a mass spectrometer by means of nanoflow electrospray techniques. Species with mass/charge ratios in excess of 20,000 were detected at the level of individual ions by using time-of-flight analysis. Once in the gas phase the stability of intact ribosomes was investigated and found to increase as a result of cross-linking ribosomal proteins to the rRNA. By lowering the Mg(2+) concentration in solutions containing ribosomes the particles were found to dissociate into 30S and 50S subunits. The resolution of the charge states in the spectrum of the 30S subunit enabled its mass to be determined as 852,187 +/- 3,918 Da, a value within 0.6% of that calculated from the individual proteins and the 16S RNA. Further dissociation into smaller macromolecular complexes and then individual proteins could be induced by subjecting the particles to increasingly energetic gas phase collisions. The ease with which proteins dissociated from the intact species was found to be related to their known interactions in the ribosome particle. The results show that emerging mass spectrometric techniques can be used to characterize a fully functional biological assembly as well as its isolated components.

Cross-Linking Reagents↗
PubMed2000

Solvent effects on the conformation of the transmembrane peptide gramicidin A: insights from electrospray ionization mass spectrometry.

The binding of sodium ions to the transmembrane channel peptide gramicidin A has permitted the use of electrospray ionization mass spectrometry to study its conformation in different solvent environments. The mass spectra of the peptide in the various solvents suggest that different conformations of gramicidin A differ in their ability to bind metal ions. The data are consistent with monomeric behavior of gramicidin A in trifluoroethanol and dimethyl sulfoxide solutions, but reveal the presence of noncovalent intermolecular interactions in ethanol solution through the observation of heterodimers formed between the naturally occurring variants of the peptide. The addition of 50% v/v of water to the ethanolic solution causes changes in the circular dichroism spectrum of the peptide, suggestive of a shift in the equilibrium mixture of conformers present toward monomeric species, a result supported by its mass spectrum. The structure of gramicidin A in trifluoroethanol has also been investigated by hydrogen exchange measurements monitored by mass spectrometry. The observation of significant protection against exchange suggests that the monomeric peptide is highly structured in trifluoroethanol. The results indicate that mass spectrometry has the potential to probe the conformational behavior of neutral hydrophobic peptides in environments that mimic their functional states.

Circular Dichroism↗
PubMed1999

Cholecystectomy is becoming an increasingly common operation in children.

PURPOSE: To determine the cause of a marked rise in cholecystectomy at a regional children's hospital. METHODS: Retrospective review of 185 patients undergoing cholecystectomy since 1984. The years 1984 to 1990 (group I) and 1991 to 1996 (group II) were compared. RESULTS: Cholecystectomy for gallbladder disease increased from 4.4/year (group I) to 16.3/ year (group II). Abdominal ultrasound examinations increased during this time. The ratio of children diagnosed with gallstones and then undergoing cholecystectomy also increased (P = 0.005). In group 11, 43% of children had no apparent etiology for gallstones, and more children developed complications of gallstones and evidence of choledocholithiasis. CONCLUSIONS: (1) The increased incidence of cholecystectomy is probably multifactorial. (2) Gallstone identification has increased owing to increased patient visits and more liberal use of ultrasonography in patients with abdominal pain. (3) More patients with cholelithiasis now undergo cholecystectomy perhaps because of a change in physician perception of the disease and an apparent increase in complications from gallstones.

Adolescent↗
PubMed1998

Mass spectrometry of ribosomes and ribosomal subunits.

Nanoflow electrospray ionization has been used to introduce intact Escherichia coli ribosomes into the ion source of a mass spectrometer. Mass spectra of remarkable quality result from a partial, but selective, dissociation of the particles within the mass spectrometer. Peaks in the spectra have been assigned to individual ribosomal proteins and to noncovalent complexes of up to five component proteins. The pattern of dissociation correlates strongly with predicted features of ribosomal protein-protein and protein-RNA interactions. The spectra allow the dynamics and state of folding of specific proteins to be investigated in the context of the intact ribosome. This study demonstrates a potentially general strategy to probe interactions within complex biological assemblies.

Escherichia coli↗
PubMed1998

Acute renal failure associated with suspected Amanita smithiana mushroom ingestions: a case series.

Mushroom poisoning leading to acute renal failure is extremely rare in North America. Cortinarius species and Amanita smithiana both can cause acute renal failure and inhabit the Pacific northwest. This article describes 4 patients who presented in acute renal failure and who ingested mushrooms described as resembling A. smithiana. Two patients (a 74-year-old Korean couple) described eating mushrooms with an approximately 6 x 0.5-inch stipe with a white cap, 1.25-1.5 inches in diameter. The other 2 patients (a 55-year-old male and a 30-year-old female) also described a white-capped mushroom. All believed they were eating the matsutake (Tricholoma magnivalere) mushroom, which can be mistaken for A. smithiana. Onset of gastrointestinal symptoms ranged from 20 minutes to 12 hours, and presentation in acute renal failure ranged from 4 to 6 days postingestion (initial BUN and creatinine were 72-91 mg/dL and 12-13.9 mg/dL, respectively). One patient had underlying mild renal insufficiency and one had hypertension that was under control, while the others had no risk factors for renal disease. None had any other explanation for the episode of acute renal failure. All underwent acute hemodialysis for at least several weeks, eventually returning to baseline renal function.

Acute Kidney Injury↗
PubMed1997

Humoral hypercalcemia due to an occult renal adenoma.

Humoral hypercalcemia refers to the elevated blood calcium levels caused by neoplasms which release a bone resorptive substance into the circulation. Previously reported infants with malignant and benign solid tumors causing humoral hypercalcemia have presented with large abdominal masses. The case we describe, a hypercalcemic infant due to an occult parathyroid hormone-related protein-containing metanephric adenoma of the kidney, shows that radionuclide bone scanning can be a useful test to identify humoral hypercalcemia. Humoral hypercalcemia stemming from a soft tissue neoplasm should be ruled out, even in the absence of clinical signs of a tumor, if bone scans show generalized uptake in the absence of hypervitaminosis D or radiological signs of bone lesions, and serum parathyroid hormone is low.

Adenoma↗
PubMed1997

EWS/FLI-1 fusion transcripts in three peripheral primitive neuroectodermal tumors of the kidney.

Although primitive neuroectodermal tumor (PNET) is a well-recognized entity, its renal localization as a primary site has not been appreciated. Only nine cases of renal PNET exist in the literature. The paucity of renal PNET could be explained by the lack of objective diagnostic techniques that would facilitate its distinction from other primitive round cell tumors of the kidney, such as the more widely recognized monophasic Wilms' tumor and clear-cell sarcoma of the kidney (CCSK), as well as renal carcinoid, or neuroblastoma invading the kidney from the adjacent adrenal gland. The recently identified specific fusion transcripts detectable by reverse transcription polymerase chain reaction (RT-PCR) have provided us with a valuable tool for the detection of renal PNET. This article reports three renal PNET that expressed EWS/FLI-1 fusion transcripts by RT-PCR, in addition to positive staining for MIC2 protein and neuron-specific enolase (NSE). One also exhibited dense core granules in cell processes by electron microscopy. Employment of such methodology will lead to a more accurate classification of renal tumors.

12E7 Antigen↗
PubMed1996

Morphologic, immunologic, and cytogenetic classification of acute myeloid leukemia and myelodysplastic syndrome in childhood: a report from the Childrens Cancer Group.

The purposes of this report are to reaffirm concordance difficulties with the acute myeloid leukemia (AML) French-American-British (FAB) classification, to present the frequency of previously delineated AML syndromes in pediatric patients and to describe additional characteristic AML profiles utilizing composite morphologic, cytogenetic and immunophenotypic data. Profiles of 124 children with acute myeloid leukemia (AML) and 13 children with myelodysplastic syndrome entered on the Childrens Cancer Group (CCG) pilot study CCG-2861 were examined. Concordance between institutions and reviewers for FAB designation was 65%. Discordance was found principally between M1 and M2, M2 and M4, and M4 and M5. In 49% of marrow specimens, leukemic blasts expressed at least one T lineage-related antigen; 24% expressed the B lineage-related antigen CD19. CDw14 correlated with FAB M4 or M5 morphology and was the only surface antigen associated with a specific FAB subtype. Normal karyotypes were found for 15% of the 75 children with satisfactory karyotype preparations. Recurring aberrations, found in 76% of children, included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), rearrangements of band 11q23, t(6;9) (p23;q34), trisomy 8 and monosomy 7. Results from this pilot study and from the current CCG randomized trial correlating morphology, immunophenotyping and cytogenetics, will help to classify AML into unique subgroups with differing clinical consequences or therapy requirements.

Adolescent↗
PubMed1995

Solution structure of the GTPase activating domain of alpha s.

We have used heteronuclear three-dimensional NMR spectroscopy to determine the solution structure of a 141 residue protein containing the GTPase activating domain from the alpha chain of the heterotrimeric G protein Gs. The domain contains six alpha-helices and is stable and structured in solution despite having been excised from the intact Gs protein. The N-terminal ten and C-terminal 11 residues of the protein are unstructured in solution while the core is well determined by the 2483 distance and torsion restraints derived from the NMR spectra. The final ensemble of 14 structures, generated with a hybrid distance geometry/simulated annealing protocol, have an average to-the-mean backbone root-mean-square deviation of 0.39 A for the core residues 89 to 201. The majority of the structure is remarkably similar to that observed for the cognate domains in crystal structures of the homologous proteins alpha t and alpha i1. However, the orientations of the second helix and the subsequent interhelical loops differ markedly among the three proteins. This structural divergence, along with functional studies of chimeric proteins, suggests that this region of the domain interacts with either the downstream effector adenylyl cyclase or with some other intermediary protein.

Amino Acid Sequence↗
PubMed1995

Complete 1H, 13C, and 15N assignments and secondary structure of the GTPase activating domain of Gs.

Complete 1H, 13C, and 15N assignments for backbone and side-chain atoms of the 145 residue GTPase activating domain of Gs are presented. The combination of gradient-enhanced versions of the HNCACB and CBCA(CO)NNH pulse sequences provided enough information to obtain sequential backbone assignments for residues 2-145 of the polypeptide, as well as assignments of asparagine and glutamine side-chain amides. HBHA(CO)NNH, HCCH-TOCSY, and 13C/15N NOESY-HSQC experiments yielded side-chain 1H and 13C assignments. Chemical shift data and 15N NOESY-HSQC experiments provided information on the secondary structure of the domain, which is similar to that observed in the cognate domain in transducin, a related G protein. The functionally essential C-terminal 15 residues are disordered in solution. These assignments provide a basis for determining the solution structure of the domain.

Amino Acid Sequence↗
PubMed1993

Nitrofen-induced congenital diaphragmatic defects in CD1 mice.

In previous clinical reports, we have documented the association of several morphologic changes with congenital diaphragmatic hernia or, perhaps more appropriately termed, congenital diaphragmatic defect (CDD). These anomalies include decreased cardiac mass with left ventricular hypoplasia in infants with left-sided CDDs (Siebert et al., '84), enlarged, asymmetric chests (Siebert and Benjamin, '87), and extrathoracic anomalies (Benjamin et al., '88), including urinary tract anomalies and elevated kidney weights in otherwise normal kidneys (Glick et al., '90; Siebert et al., '90). Hypoplastic lungs and hearts and enlarged chests are thought to result from the herniation of abdominal viscera into the thoracic cavity, but for the renal abnormalities, pathogenesis is unclear. The findings are intriguing, for they could mirror unrecognized developmental relationships between the diaphragm, lung, heart, and kidney. In order to further examine these issues and to test the applicability of experimentally produced CDDs to human disease, we administered nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether), an herbicide known to produce diaphragmatic defects in rodents, to time-mated CD1 mice by gavage feeding on gestational days 8 and 9. Dosages were 200 (low dose) or 500 (high dose) mg/kg body weight, and fetuses were studied on gestational day 18. Diaphragmatic defects occurred in a dose-response fashion: 0% (0/48) control or sham-fed, 5% (5/104) in the low-dose group, and 25% (19/75) in the high-dose group. Several fetuses with cleft palate, renal agenesis, exencephaly/encephalocele, and/or Di-George sequence were noted at the high dose, the latter a previously undescribed finding. Diaphragmatic defects were primarily right sided and only associated with herniation of abdominal viscera in animals exposed to 500 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1993

Increased expression of human leukocyte antigen-DR on pulmonary macrophages in bronchopulmonary dysplasia.

We used an immunoperoxidase method to examine the expression of the immune activation marker HLA-DR on pulmonary tissue obtained at autopsy from 14 patients dying of bronchopulmonary dysplasia. Controls consisted of 16 age-matched, sex-matched children dying of noncardiac, nonrespiratory, noninfectious illnesses or as a result of motor vehicle accidents. We did not observe aberrant expression of HLA-DR on pulmonary endothelial cells. Positive staining appeared exclusively on macrophages. We quantitated the expression of antigen by counting the number of positive macrophages and total macrophages/monocytes per high power field. Bronchopulmonary dysplasia patients displayed significantly greater numbers of both positive and total macrophages compared with the control group (p < 0.05). The percent positive macrophages also was significantly higher in the bronchopulmonary dysplasia patients (p < 0.005). We also examined a group of patients dying with infant respiratory distress syndrome. There was no significant difference in number of total macrophages in this group compared with age-matched controls.

Bronchopulmonary Dysplasia↗
PubMed1993

Relationship between epidemiologic risk factors and clinicopathologic findings in the sudden infant death syndrome.

The risk of sudden infant death syndrome (SIDS) is said to be enhanced by factors such as prematurity, low birth weight, and perinatal distress. The significance of risk factors for SIDS research was questioned because the majority of SIDS victims seem to lack them. Therefore, postmortem records of 1144 infants who died suddenly and unexpectedly in King County, Washington, over a 25-year period were studied. Deaths were classified as "explained" if a cause was apparent, "classic" SIDS if the history and autopsy were unrevealing or, where the diagnosis of SIDS was doubtful, as "probable" or "possible" SIDS. The infants' birth certificates were compared with those of 3647 infants born during a similar period. Seventy-nine deaths (7%) were explained. The 1065 previously certified as SIDS were reclassified classic SIDS (82%), probable SIDS (13%), and possible SIDS (5%). Low birth weight, small size for gestational age, prematurity, and low 5-minute Apgar scores each form a "continuum"; the possible-SIDS group had the highest proportion of such infants, followed by the probable- and classic-SIDS groups, which exhibit extensive overlap with the control population. A 5-minute Apgar score of less than 7 and delayed postnatal growth rate are not risk factors for classic SIDS. Risk factors are more prevalent in SIDS infants where the diagnosis may be doubtful. The great majority of SIDS victims possess fewer risk factors. To avoid the bias of confounding variables, SIDS research should focus on as "pure" a SIDS population as is possible.

Adult↗