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Biomedical subjects

S Hecht

Publications and source records attributed to S Hecht.

At least 37 records · Page 2Linked to original sources

Perineural spread of head and neck tumors: how accurate is MR imaging?

PURPOSE: Our aim was to determine the precision of MR imaging evaluation of perineural spread of head and neck tumors. METHODS: Nineteen patients had complete extirpation of head and neck tumors (10 squamous cell carcinomas, four adenoid cystic carcinomas, one poorly differentiated carcinoma, one salivary duct carcinoma, one mucoepidermoid carcinoma, one chordoma, and one meningioma) with histologic confirmation of perineural spread. Findings at presurgical contrast-enhanced MR imaging were compared with findings at pathologic examination. RESULTS: The sensitivity of MR imaging for detection of perineural spread was 95%; however, the sensitivity for mapping the entire extent of perineural spread fell to 63%. CONCLUSION: MR imaging may fail to depict microscopic foci of perineural tumor infiltration, leading to underestimation of the extent of perineural spread. Nevertheless, with careful analysis of foraminal architecture and MR enhancement patterns, one can reliably identify the presence if not the extent of perineural spread.

Adult↗

The diversity and evolutionary relationships of the pregnancy-associated glycoproteins, an aspartic proteinase subfamily consisting of many trophoblast-expressed genes.

The pregnancy-associated glycoproteins (PAGs) are structurally related to the pepsins, thought to be restricted to the hooved (ungulate) mammals and characterized by being expressed specifically in the outer epithelial cell layer (chorion/trophectoderm) of the placenta. At least some PAGs are catalytically inactive as proteinases, although each appears to possess a cleft capable of binding peptides. By cloning expressed genes from ovine and bovine placental cDNA libraries, by Southern genomic blotting, by screening genomic libraries, and by using PCR to amplify portions of PAG genes from genomic DNA, we estimate that cattle, sheep, and most probably all ruminant Artiodactyla possess many, possibly 100 or more, PAG genes, many of which are placentally expressed. The PAGs are highly diverse in sequence, with regions of hypervariability confined largely to surface-exposed loops. Nonsynonymous (replacement) mutations in the regions of the genes coding for these hypervariable loop segments have accumulated at a higher rate than synonymous (silent) mutations. Construction of distance phylograms, based on comparisons of PAG and related aspartic proteinase amino acid sequences, suggests that much diversification of the PAG genes occurred after the divergence of the Artiodactyla and Perissodactyla, but that at least one gene is represented outside the hooved species. The results also suggest that positive selection of duplicated genes has acted to provide considerable functional diversity among the PAGs, whose presence at the interface between the placenta and endometrium and in the maternal circulation indicates involvement in fetal-maternal interactions.

Amino Acid Sequence↗

Are there gender differences in neuropsychological performance in patients with first-episode schizophrenia?

To investigate gender differences in neuropsychological (NP) functioning in first episode (FE) schizophrenia, consecutively recruited patients with FE schizophrenia (37 males, 29 females) and a subsample of these patients (20 males, 20 females), individually matched for gender, age, and education to healthy controls (20 males, 20 females) were compared on a battery of standardized neuropsychological tests. Women performed better than men in tests of verbal memory and learning, and men performed better than women in spatial organization. However, no differences were present between schizophrenic patients and controls, except that male and female schizophrenic patients showed the most pronounced impairment in visual motor processing, attention and verbal memory and learning. Our data suggest that gender does not appear markedly to modify the cognitive impairment characteristic of schizophrenia. However, they underline the necessity of controlling confounding factors on NP performance such as gender and education.

Adult↗

Neuropsychological impairment in first-episode and chronic schizophrenic patients.

Patients with first-episode (FE) schizophrenia (n = 40), with chronic schizophrenia (n = 40) and healthy controls (n = 40) matched for age, gender, education and parental socioeconomic status were administered a battery of standardized neuropsychological (NP) tests. Both patient groups showed generalized impairment relative to controls and the most pronounced deficits in visual-motor processing and attention (VSM). Compared with FE patients, chronic schizophrenics performed worse in VSM and abstraction/flexibility. Our findings suggest that NP deficits are fundamental manifestations of the illness, and that mainly frontally based dysfunctions are more prominent in chronic, kraepelinian patients.

Acute Disease↗

Increase in p53 protein half-life in mouse keratinocytes following UV-B irradiation.

Exposure of mammalian cells to UV radiation and other DNA-damaging agents triggers a response known as the UV response. This induction response involves a large number of genes including c-jun, cell-cycle regulatory proteins, specific repair enzymes, and the tumor suppressor gene p53. Altered expression of these genes following DNA damage is hypothesized to result in G1 arrest, thereby allowing cells to repair DNA damage prior to cell division. In the present study, we investigated expression of the p53 gene in mouse keratinocyte cell line 308 after exposure to UV-B light at a biologically relevant dose. Irradiation of 308 cells with 40 J/m2 UV-B resulted in a 4- to 10-fold induction in the level of p53 protein, peaking at 5 h post-irradiation. Northern blot analysis of RNA from UV-B irradiated cells showed no change in the steady-state level of p53 mRNA following irradiation. However, the half-life of p53 protein in UV-B irradiated 308 cells was extended approximately 7-fold, from 30 to 200 min. Additional studies were performed with specific anti-p53 monoclonal antibodies to establish whether UV-B irradiation induced a conformational change in p53 protein in irradiated cells. Metabolic labeling with 35S-methionine followed by immunoprecipitation with p53 monoclonal antibody PAb246, which recognizes the wild-type murine p53 protein, demonstrated that the p53 protein present in 308 cells possessed the wild-type conformation both before and after UV-B irradiation. In contrast, p53 antibody PAb240, which recognizes a 'conformation-dependent' epitope, was not reactive with the p53 protein present in 308 cells. Therefore, we conclude that the induction of p53 protein in mouse keratinocytes following UV-B irradiation occurred posttranscriptionally, and was due to a significant increase in p53 protein half-life.

Animals↗

Exercise echocardiographic correlates of transient dilatation of the left ventricular cavity on exercise thallium-201 SPECT imaging.

Transient dilatation of the left ventricular cavity on exercise thallium perfusion imaging is recognized as a marker of significant coronary disease, but the mechanisms that produce this finding are not fully understood. We studied 32 patients who underwent exercise thallium imaging and exercise echocardiography to determine the changes in left ventricular cavity size that underlie transient dilatation. Left ventricular area from the apical four-chamber view was used to approximate left ventricular cavity size. There were 24 patients who did not have transient dilatation (group 1) and 8 patients who did have transient dilatation (group 2) on thallium imaging. Systolic area decreased from rest to exercise in group 1 patients but not in group 2 patients. There was no significant change in diastolic area from rest to exercise in either group 1 or group 2 patients. Thus, exercise-induced systolic dysfunction, manifested as a failure to decrease left ventricular systolic cavity size in exercise, may be an important mechanism in producing scintigraphic transient dilatation.

Echocardiography↗

Noncystic "increased" periventricular echogenicity and other mild cranial sonographic abnormalities: predictors of outcome in low birth weight infants.

The sonograms of 71 low birth weight infants were retrospectively reviewed and compared with results of neuromotor examinations at 24 months of age to determine whether mild abnormalities commonly detected on cranial sonograms (including milder grades of hemorrhage, ventricular dilation, and noncystic increases in periventricular echogenicity) were correlated with future neurologic handicaps. Of the 71 infants studied, increased periventricular echoes were noted in 20 (28%), Grade 1 or 2 intracranial hemorrhage in 31 (43%), and mild-moderate ventriculomegaly in 28 (39%). Neuromotor handicaps were detected in 15 (21%). No significant correlation was found between the above sonographic abnormalities and the incidence of future neuromotor handicaps. When those neonates with asymmetric mild-moderate ventriculomegaly were separately analyzed, this group was found to have more neuromotor handicaps (p less than 0.05) than those with normal ventricular size, and this finding warrants future study. Importantly, early cranial sonograms were completely normal in 12% of those infants with neuromotor handicaps. We conclude that the presence of mild cranial sonographic abnormalities (including mildly increased periventricular echogenicity) in these infants is not well correlated with neuromotor handicaps detected at 24 months of age.

Brain↗

Morphometric analysis of corneal endothelium following radial keratotomy.

We performed morphometric analysis of the central corneal endothelium on 24 eyes of 19 patients who had had anterior radial keratotomy. The endothelium was analyzed for a variety of parameters, including cell area, perimeter, side lengths, cell shape, and number of sides. Mean, standard deviation, and coefficient of variation were calculated for each parameter. The mean cell density decreased from 2,835 to 2,677 cells/mm2, mean cell perimeter increased from 71.4 micron to 74.3 micron, and mean side length increased from 11.8 micron to 12.3 micron following surgery. The changes in these three parameters were statistically significant (P less than 0.05). The coefficient of variation of cell area (polymegathism) changed from 0.319 to 0.307, the hexagonality changed from 62.5% to 59.6%, and the cell shape changed from 0.872 to 0.867. The changes in these parameters were not statistically different before and after surgery. The group of patients that had no reported microperforations showed only a small decrease of cell density (1.6%), while the group of patients that had microperforations showed a large decrease of cell density (14.3%). The cell perimeter and side lengths showed a similar pattern. The group of corneas with the optical zone diameter less than 3.5 mm showed a decrease in mean cell density from 2,994 to 2,725 cells/mm2, and the cell shape changed from 0.874 to 0.866 following surgery. The changes in these parameters were statistically significant (P less than 0.05) before and after surgery. Among all factors associated with radial keratotomy, microperforation and a small diameter of central optical zone appear to be the two greatest risk factors.

Adult↗

Brain radiation lesions: MR imaging.

This retrospective study was performed to assess the capability of magnetic resonance (MR) to depict and characterize diffuse and focal radiation lesions in the brain using the spin-echo technique. The MR images of 55 patients who had undergone radiation therapy were reviewed. Comparative computed tomography (CT) studies were available for all the patients. Normal white matter was chosen as reference tissue for the quantitative comparison of signal intensities. Radiation lesions (identified in eight patients) were seen as regions of high signal intensity on the sequence with a long repetition time (TR) (2.0 sec) and showed no difference in signal compared with white matter when the TR was short (0.5 sec). Nonspecific prolongation of T1 and T2 relaxation times was measured in such lesions. In one patient, subependymal tumor spread, demonstrated by contrast-enhanced CT, was missed on MR images, masked by the adjacent abnormal signal owing to radiation effects. Recurrent or residual brain tumor could not be distinguished from radiation brain necrosis either by CT or by MR imaging. It is concluded that MR can depict radiation lesions with great sensitivity but is not very helpful for discrimination between recurrent or residual brain tumor, radiation necrosis, and other brain lesions.

Adolescent↗

Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I.

Camptothecin, a cytotoxic drug, is a strong inhibitor of nucleic acid synthesis in mammalian cells and a potent inducer of strand breaks in chromosomal DNA. Neither the equilibrium dialysis nor the unwinding measurement indicates any interaction between camptothecin and purified DNA. However, camptothecin induces extensive single strand DNA breaks in reactions containing purified mammalian DNA topoisomerase I. DNA breakage in vitro is immediate and reversible. Analyses of camptothecin-induced DNA breaks show that topoisomerase I is covalently linked to the 3' end of the broken DNA. In addition, camptothecin inhibits the catalytic activity of mammalian DNA topoisomerase I. We propose that camptothecin blocks the rejoining step of the breakage-reunion reaction of mammalian DNA topoisomerase I. This blockage results in the accumulation of a cleavable complex which resembles the transient intermediate proposed for eukaryotic DNA topoisomerase I. The inhibition of nucleic acid synthesis and the induction of DNA strand breaks observed in vivo may be related to the formation of this drug-induced cleavable complex.

Animals↗

Radiographic pseudofracture of bipolar pacemaker wire.

We present a case in which the radiographic appearance of a bipolar pacing lead mimics a wire fracture. Recognition of this normal finding--due to lead construction--will help avoid erroneous diagnosis of wire fracture on chest x-ray films.

Aged↗

Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone).

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.

Antineoplastic Agents↗

Influence of chronic ethanol consumption on the metabolism and carcinogenicity of tobacco-related nitrosamines.

The effect of chronic ethanol consumption by Syrian golden hamsters (SGH) on the carcinogenicity and target tissue metabolism of N-nitroso-pyrrolidine (NPYR) and N'-nitrosonornicotine (NNN) has been examined. Ethanol-consuming hamsters treated with NPYR developed more nasal cavity and tracheal tumours than controls. Ethanol consumption did not affect the carcino-genicity of NNN. When the metabolism of NPYR and NNN by isolated tracheal rings was examined, it was observed that tracheal rings isolated from ethanol-consuming SGH metabolized NPYR at a higher rate than similar preparations from control animals. In contrast, no differences in the rates of metabolism of NNN were observed.

Alcoholism↗

Immunotherapy with oral BCG and serial immune evaluation in childhood lymphoblastic leukemia following three years of chemotherapy.

Thirty-nine children with ALL who had completed three years of chemotherapy were randomized to receive oral BCG for immunotherapy or no treatment as controls. There was not a significant difference between the two groups in the relapse rate. Among the immune parameters, only in vitro blastogenic responses to PHA and PPD rose significantly in the BCG group compared with the controls. Skin testing also revealed evidence of tuberculin sensitization. The group as a whole was studied for the kinetic recovery of immune functions after the cessation of chemotherapy, which revealed a dissociation in both cellular and humoral systems. At three weeks after therapy, only peripheral blood lymphocyte count, non T-cells, and serum IgM showed a significant abnormality. There was a rise in these parameters in the subsequent weeks, and the non-T-cell count reached normal levels sooner than the other two parameters. Children who were less than 5 years of age at the time of diagnosis showed a lesser degree of immunosuppression after long-term chemotherapy compared with those who were greater than or equal to 5 years of age. The analysis of the data indicated a relationship between the low serum immunoglobulins (IgG, IgA) and disease status.

Administration, Oral↗