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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 397 records · Page 22Linked to original sources
PubMed1992

Cloning and analysis of the CD18 promoter.

CD18, the common beta chain of the leukocyte integrin adhesion proteins, is expressed exclusively by myeloid cells and lymphocytes. During myeloid differentiation, the increase in CD18 cell surface expression is paralleled by increased CD18 messenger RNA levels. Nuclear run-on studies show that CD18 expression is transcriptionally regulated during 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HL-60 monocytic differentiation. The CD18 transcriptional start site was defined by primer extension and RNAse protection. The gene encoding CD18 was cloned and a fragment that overlaps the transcriptional start site was isolated. DNA sequence analysis of this promoter fragment identified potential AP-1 elements that may mediate the TPA transcriptional response. The CD18 promoter also contains a putative binding site for PU.1, a leukocyte-specific transcription factor. DNA elements resembling those found in other myeloid and integrin promoters were identified. The CD18 promoter fragment was linked to the luciferase reporter gene, electroporated into the U937 monocytic cell line, and its expression increased after exposure to TPA. Thus, CD18 may serve as a model for identifying the cis elements and trans-acting factors that regulate gene expression during myeloid differentiation.

Antigens, CD↗
PubMed1992

Interleukin 3 is a growth factor for human follicular B cell lymphoma.

More than one-half of adults with non-Hodgkin's B cell lymphomas present with low-grade follicular lymphomas. These tumor cells are found in close association with follicular T lymphocytes and dendritic cells, suggesting that the surrounding cells may play a role in the support of follicular tumors. Supernatants from activated human peripheral blood lymphocytes were found to promote the in vitro proliferation of follicular tumor cells. This effect was entirely due to interleukin 3 (IL-3), a factor generally thought to cause the growth and differentiation of immature hematopoietic cells. IL-3 receptors were detected on fresh isolates of all primary follicular cell tumors examined. These findings suggest that follicular cell tumors may be dependent in vivo on IL-3 and that therapies directed against IL-3, its receptor, or the T cells that produce it may be effective treatment for follicular lymphoma.

Cell Division↗
PubMed1992

[Thyroid carcinoma in children and adolescents].

Of the 720 patients with thyroid cancer we saw from 1953 to 1989, 49 were younger than 20 years at diagnosis, and the female/male ratio was 4.4:1. The histologic type was papillary in 34, follicular in 14 and medullary in 1. Initial treatment in 41 was total or near-total thyroidectomy, and in 8 hemithyroidectomy. 23 underwent neck dissection in addition to thyroidectomy. 49% of those who underwent total thyroidectomy had foci of bilateral thyroid carcinoma on serial histological section. Local and distant relapse of thyroid carcinoma occurred in 4 of the 8 who underwent hemithyroidectomy, but in only 1 of the 41 who underwent total thyroidectomy. Our recommendations include total thyroidectomy, radioiodine therapy, and modified neck dissection when neck metastases are presented.

Adenocarcinoma↗
PubMed1992

Neurologic signs in Alzheimer's disease. Results of a prospective clinical and neuropathologic study.

Neurologic signs and their neuropathologic correlates were examined in a sample of 56 patients with autopsy-proved Alzheimer's disease (13 men, 43 women; mean age at death, 83.1 years; range, 67 to 96 years) from a prospective longitudinal study. Full-range regular rigidity with cog-wheeling was found in 20 patients and was significantly associated with lower neuron counts in the substantia nigra and with the presence of Lewy bodies in the brain stem and neocortex. Twelve patients with myoclonus had a younger age at onset, a lower age at death (mean, 78.6 years), and lower neuron counts in the serotoninergic dorsal raphe nucleus and in the noradrenergic locus coeruleus than did the patients without myoclonus. Generalized motor seizures were reported in six patients, and they had significantly lower counts of pyramidal cells in cortical layers III through IV of the parietal cortex (area 7) and slightly decreased pyramidal cell numbers in the parahippocampal gyrus (area 28). The 19 patients with a positive grasp reflex had an earlier onset of illness and a significantly inferior performance on the Mini-Mental State examination and Cambridge Cognitive Examination tests. They, and 25 patients with a positive snout reflex, had significantly lower counts of large pyramidal cells in layers III through V of the frontal cortex (area 32). These results indicate that different neurologic symptoms in Alzheimer's disease can be related to disproportionate neuronal degeneration in functionally different brain areas.

Aged↗
PubMed1992

Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease.

This single-blind, placebo controlled study reports on the effects of administering three acute doses of nicotine (0.4, 0.6 and 0.8 mg) subcutaneously to a group of Alzheimer's disease (DAT) patients (n = 22), young adult controls (n = 24), and normal aged controls (n = 24). The study extends our previous findings obtained using smaller groups of subjects. Drug effects were examined on three computerised tests: the first measuring rapid visual information processing, sustained visual attention and reaction time (RVIP task); a delayed response matching to location-order task measuring sustained visual attention and visual short-term memory (DRMLO task); and a finger tapping test measuring simple reaction time (FT task). The critical flicker fusion test (CFF) was used as a measure of perception and the WAIS digit span forwards (DS), of auditory short-term memory. Tests were graded in difficulty, titrated to avoid floor and ceiling effects so that meaningful, direct comparisons between groups could be made. Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task--both ascending and descending thresholds). Nicotine administration did not improve auditory and visual short-term memory. There were no consistent, overall patterns of difference in performance between smokers and non-smokers in the control groups, or between males and females in any group. Despite the absence of change in memory functioning, these results demonstrate that DAT patients have significant perceptual and visual attentional deficits which are improved by nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of exsanguination and sodium nitroprusside on compliance of the spinal canal during aortic occlusion.

To evaluate the effects of sodium nitroprusside (SNP) and partial exsanguination (EXS) on systemic hemodynamics and cerebrospinal fluid dynamics, we monitored proximal and distal blood pressure (BP), cerebrospinal fluid pressure (CSFP), spinal cord perfusion pressure (SCPP), and compliance of the spinal canal (CSC) in 10 mongrel dogs during aortic cross-clamping of the descending thoracic aorta. CSC was measured by serial injections of 2 ml of saline solution into the cisterna cerebellomedullaris via a percutaneously placed catheter with simultaneous measurements of CSFP. Data were acquired at baseline (BL), during aortic cross-clamping with proximal hypertension (AXC), and after control of proximal hypertension with EXS and SNP. During the cross-clamp interval, mean proximal aortic pressure (PxBP) rose from 114 +/- 6 to 150 +/- 3 mm Hg (P less than 0.001), whereas mean blood pressure decreased to 88 +/- 5 and 82 +/- 4 mm Hg during the SNP and EXS intervals, respectively (P less than 0.05 vs BL). EXS and SNP were equally effective in controlling PxBP (82 +/- 4 vs 88 +/- 5 mm Hg, P greater than 0.05). Mean distal aortic pressure (DsBP) decreased from systemic values to 21.5 +/- 1.9 mm Hg during AXC, and to 12.4 +/- 1.0 and to 8 +/- 0.8 mm Hg during EXS and SNP, respectively (P less than 0.05 AXC vs EXS and SNP). SNP lowered DsBP significantly more than EXS, 8 +/- 0.8 vs 12.4 +/- 1.0 mm Hg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cytokeratin polypeptide in gastrointestinal adenocarcinomas displaying squamous differentiation.

In the present study we investigated the cytokeratin (CK) polypeptide expression in gastric and colonic adenocarcinomas. A battery of monoclonal anti-cytokeratin-specific antibodies and anti-vimentin were used. While the majority of cases displayed simple epithelial characteristics, in three of 17 cases of gastric adenocarcinomas and in one of 20 cases of colonic adenocarcinomas, CK polypeptides 13 (54 kd) and 16 (48 kd) were occasionally detected. These CK polypeptides, characteristic of squamous nonkeratinizing epithelia, were found in cases in which no evidence of squamous differentiation could be demonstrated by histologic examination. We believe that the presence of these unique CK polypeptides points to the squamous differentiation potential of the tumor cells.

Adenocarcinoma↗
PubMed1992

Use of family specific leader region primers for PCR amplification of the human heavy chain variable region gene repertoire.

We have designed a set of six, non-degenerate oligonucleotide primers, corresponding to the 5' leader regions of each of the six human VH gene families. A general strategy for family specific polymerase chain reaction amplification is described using these primers and a conserved 3' primer corresponding to frame work 3, JH, or constant region. This strategy was used to isolate and sequence novel human germline VH genes belonging to the VH2 and VH4 families. Under certain conditions, chimeric VH sequences were created by a "jumping polymerase chain reaction", combining DNA segments from different germline genes, but this could be avoided by limiting the number of amplification cycles. PCR amplification with these family specific primers will facilitate studies of the repertoire of germline VH genes as well as studies on VH gene usage in normal and aberrant (B cell malignancies, autoimmune diseases, etc.) B cell populations.

Amino Acid Sequence↗
PubMed1992

[Paraplegia after spinal anesthesia].

A case of paraplegia occurring after a spinal anaesthetic is reported. The 79-year-old man was admitted for a fractured neck of femur. Twenty years previously, he had had pharyngeal surgery and a tracheostomy. He had also undergone a prostatectomy for prostate cancer, and had been on oestrogen therapy for two years. He complained of dyspnoea at rest and his chest film showed diffuse pulmonary opacities. In order to avoid possible intubation and respiratory complications, spinal anaesthesia was performed without any problems in the L4 space. After the surgery, the patient recovered all his motor and sensory functions in the lower limbs. On the second postoperative day, he suffered from a motor paralysis of the right leg, which spread to the left leg on the fourth day. NMR imaging showed several vertebral metastases, together with anterior and lateral epidural invasion responsible for cord compression. Treatment with tetracosactide was begun, but the patient died six weeks later in his home, not having recovered any neurological function at all in his lower limbs. In fact, it was only after the procedure that the anaesthetist was informed that, at the time the prostate cancer had been diagnosed, vertebral body metastases, of which the patient had not been informed, were already present. The part played by the spinal anaesthetic in the occurrence of the paraplegia is not clear. It is reminded that such a technique should be used with extreme care in patients having a neoplasm with a very often high incidence of vertebral metastases.

Aged↗
PubMed1992

Clinical and neuropathological correlates of depression in Alzheimer's disease.

Depressive symptoms have been reported in patients with mild to moderate Alzheimer's disease (AD). Recent evidence suggests that a noradrenergic deficit originating from neuronal degeneration in brainstem nuclei may represent an organic correlate of these disturbances. We examined the neuropathological changes in the locus coeruleus (LC), substantia nigra (SN), basal nucleus of Meynert and cortex of 52 patients (12 male, 40 female, mean age 83.2 +/- 6.4 years) with pathologically verified AD. Fourteen patients (1 male, 13 female) showed signs of depression. The majority of these patients suffered from severe physical disability or sensory impairment and developed persistent delusions, but had less cognitive impairment. Neuronal counts in the LC were significantly lower than in the 38 patients without depression (36.9 +/- 14.0; 51.4 +/- 28.0 neuromelanin-pigmented cells per section per nucleus; F = 3.4, df = 1, 50, P = 0.04). Neuron counts were higher in the basal nucleus of Meynert in depressed AD patients and there were no differences of the neuron numbers in the SN. Depression (main effect; F = 4.5, P = 0.04) contributed significantly to the variance of neuronal counts in the LC, even when covarying for gender, age of onset, cognitive impairment and cortical Alzheimer pathology. The observed disproportionate loss of noradrenergic and cholinergic neurons in the LC and basal nucleus of Meynert may represent an important organic substrate of depression in AD.

Aged↗
PubMed1992

Evaluation of the CELL-DYN 3000 differential.

The CELL-DYN 3000 (Unipath Corp., Mountain View, CA) differential was evaluated in a tertiary care hospital using samples with a broad range of distributional and morphologic abnormalities. Particular attention was directed to the performance of the instrument-generated suspect flags that occur as an aid to identify samples with abnormal leukocytes, as well as the estimates of abnormal cells that are made by the instrument. The CELL-DYN 3000 showed excellent quantitative results for the white blood cell differential compared with a 400-cell manual differential, in which morphologic abnormalities were absent or occurred in low numbers (< or = 5%). Specificity of the BLAST, VARIANT LYMPH, NRBC, WBC, or DIFF suspect flags (with the requirement that the blast estimate and variant lymphocyte estimate by the instrument be > or = 1%) was 82.6%. Sensitivity of these flags to detection of more than 5% "abnormal" leukocytes (blasts, malignant lymphoid cells, grossly dysplastic neutrophils, nucleated red blood cells, or reactive lymphocytes) or significant platelet clumping was 81.6%. The primary deficiency was the inability of the CELL-DYN 3000 to flag samples with small numbers (< or = 5%) of nucleated erythrocytes, lymphoid blasts, or hairy cells, or more than 5% reactive lymphocytes. Specificity of the IG flag (with immature granulocyte estimate > or = 3%) for immature granulocytes (metamyelocytes, myelocytes, or promyelocytes) was 94.9%. Sensitivity of the immature granulocyte flag varied from 41.7% for identifying IG > or = 1% to 100% for the three samples with immature granulocytes > or = 3%. Calculation of sensitivity and specificity to varying percentages of bands showed poor flagging performance, with many false-positive and false-negative results at all levels.

Blood Cells↗
PubMed1992

A study of keratin expression in benign familial chronic pemphigus.

We studied keratin expression in the involved and uninvolved skin of six benign familial chronic pemphigus (BFCP) patients, using monoclonal antibodies specific for various keratin polypeptides and immunohistopathologic techniques. Normal and psoriatic (i.e., hyperproliferative) skin specimens served as controls. The uninvolved BFCP epidermis showed keratin profiles identical to that of normal epidermis. In the acantholytic epidermal segments of the involved BFCP skin, some of the lower suprabasal acantholytic cells failed to express keratin polypeptides 10 and 11 (Moll's catalog). This delay in expression of suprabasal keratins was not accompanied by an expression of hyperproliferative keratin polypeptide 16. Also, some of the lower suprabasal acantholytic cells of the involved BFCP epidermis retained staining by the antikeratin KS-1A3 antibody, which in the normal, psoriatic, and uninvolved epidermis was limited to the basal cell layer. Staining for keratin polypeptide 18 was negative in the epidermis of all four types of specimens. We believe that the delay in suprabasal keratin expression in the involved BFCP epidermis was more likely secondary to the acantholysis (i.e., "arrest of differentiation" due to acantholysis) rather than due to a primary defect in keratin expression.

Adult↗