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Biomedical subjects

P Lieberman

Publications and source records attributed to P Lieberman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Gamma knife pallidotomy in advanced Parkinson's disease.

Posteroventral pallidotomy as a treatment for Parkinson's disease (PD) has been the subject of increasing interest. We treated 4 nondemented patients with advanced PD, 2 with severe bradykinesia and a declining response to medication, and 2 with marked clinical fluctuations. All patients received 180 Gy delivered in one sitting to the right posteroventral pallidum site, used by Laitinen and colleagues, adjusted as needed, to avoid the optic tract. Only 1 patient changed significantly. Dyskinesia completely resolved on the side contralateral to the lesion in this patient. This same patient also became transiently demented and psychotic. The other 3 patients suffered no clearly identifiable beneficial or harmful effects. Follow-up magnetic resonance imaging scans of the brain at 1 year revealed lesions exactly where targeted although of unequal sizes. Our negative experience forces us to conclude that either larger volumes of tissue must be ablated, that physiologic monitoring is required for placing a lesion, that our subjects were poor candidates for the procedure, or that surgical ablation and radiation cause tissue damage of different types with different results.

Aged↗
PubMed1996

Dietary fatty acid composition induces comparable changes in cardiolipin fatty acid profile of heart and brain mitochondria.

The fatty acid profile of cardiolipin (CL) from brain and cardiac mitochondria was measured to determine whether CL isolated from these two tissue sources responded similarly to alterations in dietary fat composition. Male Wistar rats were fed 20% (w/w) diets containing 2 to 12% (w/w) 18:2n-6 for four weeks. Despite higher baseline levels of CL 18:2n-6 in cardiac (54 +/- 1% of total fatty acids) compared to brain (13 +/- 1%) mitochondria, CL 18:2n-6 levels increased in proportion to dietary 18:2 levels. The degree of change in 18:2n-6 was comparable with both tissues showing an approximate 1.5- to 2-fold increase. The time course of changes in CL fatty acid profile was examined in a subsequent experiment in which animals were fed 20% (w/w) fat diets containing either 3 or 15% alpha-linoleate. Changes in cardiac CL 18:1, 18:2n-6, and 22:6n-3 levels were observed within one week of feeding. While statistically significant differences were not observed in brain CL until the second week of feeding, the time course did not differ substantively from that observed in heart. The results from this study suggest that while baseline fatty acid profile of cardiac and neural CL differ, mitochondria from both tissues show comparable sensitivity to changes in dietary fat composition. Furthermore, it would appear that the turnover rate of fatty acids in CL is similar in both tissues.

Animals↗
PubMed1995

A general mechanism for transcriptional synergy by eukaryotic activators.

One of the important regulatory concepts to emerge from studies of eukaryotic gene expression is that RNA polymerase II promoters and their upstream activators are composed of functional modules whose synergistic action regulates the transcriptional activity of a nearby gene. Biochemical analysis of synergy by ZEBRA, a non-acidic activator of the Epstein-Barr virus (EBV) lytic cycle, showed that the synergistic transcriptional effect of promoter sites and activation modules correlates with assembly of the TFIID:TFIIA (DA) complex in DNase I footprinting and gel shift assays. The activator-dependent DA complex differs from a basal DA complex by its ability to bind TFIIB stably in an interaction regulated by TATA-binding protein-associated factors (TAFs). TFIIB enhances the degree of synergism by increasing complex stability. Similar findings were made with the acidic activator GAL4-VP16. Our data suggest a unifying mechanism for gene activation and synergy by acidic and non-acidic activators, and indicate that synergy is manifested at the earliest stage of preinitiation complex assembly.

DNA-Binding Proteins↗
PubMed1995

Anaphylaxis. A review of 266 cases.

BACKGROUND: A presentation of findings from a large population of anaphylaxis cases. METHODS: Retrospective chart review and follow-up questionnaire provided data on 266 subjects (113 males and 153 females) aged 12 to 75 years (mean age, 38 years) who were referred to a university-affiliated private allergy-immunology practice in Memphis, Tenn, for evaluation and management of anaphylaxis from January 1978 through March 1992. RESULTS: Of 266 subjects, 162 (61%) had three or more anaphylactic episodes, 41 (15%) had two episodes, and 63 (24%) had one episode. Atopy was present in 98 individuals (37%). Physicians thought foods, spices, and food additives caused anaphylaxis in 89 individuals (34%); crustaceans and peanut accounted for about half of these cases. Medications were thought to have caused the anaphylactic episodes in 52 individuals (20%); nonsteroidal anti-inflammatory drugs in about half of these cases. Other probable causes included exercise (n = 19), latex (n = 2), hormonal changes (n = 2), and insect bites (n = 4). A suspected cause could not be determined in 98 individuals (37%). These subjects were diagnosed as having idiopathic anaphylaxis. Of the 266 subjects, 102 responded to a follow-up survey; 68 (67%) of the 102 were thought to have identifiable causes of anaphylaxis (32 of whom [47%] failed to carry epinephrine syringes for self-administration despite instructions to do so). In contrast, of 34 subjects with idiopathic anaphylaxis who responded to the survey, only three (9%) did not carry epinephrine. CONCLUSIONS: (1) Atopy is common in subjects who experience anaphylaxis, regardless of its origin; (2) crustaceans and nonsteroidal anti-inflammatory drugs are the most common food and medication groups, respectively, thought to cause anaphylaxis; (3) causative agents can be identified for two thirds of the subjects, and recurrent attacks are the rule; and (4) subjects with idiopathic anaphylaxis are more likely to carry epinephrine for self-administration than those with identifiable causes.

Adolescent↗
PubMed1995

Speech production and cognitive deficits on Mt. Everest.

Deficits in speech motor control and in the comprehension of syntax were observed as five members of the 1993 American Sagarmatha Expedition ascended Mt. Everest. We analyzed speech recordings and cognitive test scores of the climbers at different altitudes. The mean "voice onset time" interval that differentiates "voiced" stop consonants from their "unvoiced" counterparts (e.g., a [b] from a [p]) decreased from 24.0 ms at Base Camp to 5.4 ms at Camp Three. The time needed to comprehend simple spoken English sentences increased by 50% at higher altitudes, and was correlated with speech motor deterioration. This pattern of deficits is similar to that noted for Parkinson's disease and may reflect disruption of subcortical pathways to prefrontal cortex. Similar procedures could be used to remotely assess cognitive impairments caused by hypoxia, carbon monoxide or alcohol intoxication, or drugs, in order to monitor crew behavior in aeronautics and spaceflight operations, or to evaluate the treatment of neurodegenerative diseases such as Parkinson's disease.

Adult↗
PubMed1994

A model of prenatal acquisition of speech parameters.

An unsupervised neural network model inductively acquires the ability to distinguish categorically the stop consonants of English, in a manner consistent with prenatal and early postnatal auditory experience, and without reference to any specialized knowledge of linguistic structure or the properties of speech. This argues against the common assumption that linguistic knowledge, and speech perception in particular, cannot be learned and must therefore be innately specified.

Fetus↗
PubMed1994

Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin.

We report the clinical and immunologic analysis of two patients with diabetes who had anaphylaxis to neutral protamine Hagedorn (NPH) human insulin in the absence of allergy to regular insulin. A 36-year-old woman without a recent history of local insulin reactions or interruption of insulin therapy experienced anaphylaxis within 15 minutes of her usual morning dose of subcutaneously administered NPH human insulin. A 62-year-old man with a history of generalized reactions to NPH human insulin and of anaphylaxis to intravenously administered protamine had generalized urticaria after injection of NPH human insulin. Both patients subsequently tolerated Lente human insulin. Skin test results in both patients were negative to regular and Lente insulin preparations but positive to NPH insulin and to protamine at concentrations tested. In vitro assays demonstrated that both patients had markedly elevated serum levels of IgE and IgG to protamine, but not to regular human insulin, and that their IgE antibodies to protamine recognized protamine antigenic determinants in NPH human insulin. We conclude that the anaphylactic reactions to NPH insulin in our patients were mediated by IgE to protamine, which should be a pathogenetic consideration in the evaluation of immediate-type reactions to protamine-containing insulins.

Adult↗
PubMed1994

Identification of functional targets of the Zta transcriptional activator by formation of stable preinitiation complex intermediates.

Transcriptional activator proteins stimulate the formation of a preinitiation complex that may be distinct from a basal-level transcription complex in its composition and stability. Components of the general transcription factors that form activator-dependent stable intermediates were determined by the use of Sarkosyl and oligonucleotide challenge experiments. High-level transcriptional activation by the Epstein-Barr virus-encoded Zta protein required an activity in the TFIID fraction that is distinct from the TATA-binding protein (TBP) and the TBP-associated factors. This additional activity copurifies with and is likely to be identical to the previously defined coactivator, USA (M. Meisterernst, A. L. Roy, H. M. Lieu, and R. G. Roeder, Cell 66:981-994, 1991). The formation of a stable preinitiation complex intermediate resistant to Sarkosyl required the preincubation of the promoter DNA with Zta, holo-TFIID (TBP and TBP-associated factors), TFIIB, TFIIA, and the coactivator USA. The formation of a Zta response element-resistant preinitiation complex required the preincubation of promoter DNA with Zta, holo-TFIID, TFIIB, and TFIIA. Agarose gel electrophoretic mobility shift showed that a preformed Zta-holo-TFIID-TFIIA complex was resistant to Sarkosyl and to Zta response element oligonucleotide challenge. DNase I footprinting suggests that only Zta, holo-TFIID, and TFIIA make significant contacts with the promoter DNA. These results provide functional and physical evidence that the Zta transcriptional activator influences at least two distinct steps in preinitiation complex assembly, the formation of the stable holo-TFIID-TFIIA-promoter complex and the subsequent binding of TFIIB and a USA-like coactivator.

Base Sequence↗
PubMed1993

Primary peripheral nodal lymphoma in children.

BACKGROUND: In this series of 208 pediatric patients with non-Hodgkin (NHL) studied from 1971 to 1986, 84 patients (40.4%) had nodal lymphomas; 40 (19.2%) of these patients had peripheral nodal lymphoma and 44 (21.2%) had mediastinal lymphoma. METHODS: Forty pediatric patients with primary peripheral nodal lymphoma were treated at Memorial Sloan-Kettering Cancer Center with the LSA2-L2 protocol from July 1971 to January 1986. Informed consent was obtained from all patients and/or guardians. RESULTS: There were 26 male patients and 14 female patients, with a median age of 10 years. Two patients had Stage I disease, 5 Stage II, 9 Stage III, 8 Stage IVA (< 25% blasts in the bone marrow), and 16 Stage IVB (> 25% blasts in the bone marrow). The last patient with Stage IVB disease was entered in 1977, a time when the philosophy of treatment for leukemia-lymphomas had not yet evolved completely. Most of these lymphomas were high-grade lymphoblastic lymphomas, followed by immunoblastic lymphomas and reticulosarcomas. The event-free survival rate of this group of patients was 75%, with all patients having completed therapy, and a median observation time of more than 10 years without therapy. The lymphoma-free survival rate was 80%. Sex, age, and stage were not of prognostic significance. There was no significant difference in survival between patients with lymphoblastic and histiocytic lymphomas (75% versus 64%, respectively). There was no significant difference in survival between the patients with high-grade and medium-grade lymphomas (75% versus 78%, respectively). Lactic dehydrogenase (LDH) in this primary site was not indicative of extent or bulk of disease and did not affect survival negatively. Radiation therapy and dose intensity of chemotherapy influenced survival by promoting rapid and more complete cell kill, helping prevent the emergence of resistant cells. CONCLUSIONS: Although primary peripheral nodal lymphoma usually is disseminated at diagnosis, it is still a highly curable disease when treated aggressively. The lymphoma-free survival rate for patients with primary nodal NHL with marrow involvement is 75%, and this subsequently has led to a different philosophy in the treatment of high-risk leukemias and lymphoma-leukemias with the NY-I and NY-II protocols, with excellent results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effects of cetirizine versus terfenadine in seasonal allergic rhinitis.

The purpose of this study was to compare the efficacy and safety of cetirizine, 10 mg, once daily in the morning to terfenadine, 60 mg, BID in the treatment of seasonal allergic rhinitis. The multicenter, single-blind, parallel study involved 160 patients, who were all included in the safety and efficacy analysis. The results of the study showed that both cetirizine, 10 mg, QD and terfenadine, 60 mg, BID used for 1 week are safe and effective in the management of allergic rhinitis. By repeated measures analysis, cetirizine improved symptoms more than terfenadine for the treatment period of days four to seven. Standard Cochran-Mantel-Haenszel statistics test showed the relative degree of patient satisfaction to be higher in the cetirizine group.

Adult↗
PubMed1992

Primary skeletal non-Hodgkin's lymphoma in the pediatric age group.

The authors discuss rare primary skeletal non-Hodgkin's lymphoma in 16 patients treated from 1973 to 1989. The symptoms of these patients related to bone lesions in 95% of the cases. These bone lesions were monostotic or polyostotic, with or without regional and distant metastases. The locations of these lesions were long bones in 13 patients, pelvic bones in seven patients, and skull and vertebral bodies in two patients. The anatomical locations of these lesions in the bones were diaphysis alone in one patient, epiphysis in two patients, metaphysis in three patients, and a combination of diaphyseal, epiphyseal, and metaphyseal lesions in seven patients. Extraskeletal involvement was present in nine patients; extraskeletal sites included regional or distant lymph node involvement in seven cases, the mediastinum in two, lung nodules in two patients, the skin and subcutaneous regions in four patients; bone marrow in three patients, and peripheral nervous system (PNS) in one patient. Two patients had stage I disease, three had stage II disease, eight had stage III disease, and three had stage IV disease. The majority of patients had large noncleaved cell diffuse lymphomas or DHL by Rappaport classification. All patients were treated with the LSA2-L2 protocol; six patients received radiation therapy to the affected bone, and ten patients received no radiation therapy. Three patients failed on treatment within the first 4 months of therapy. Two patients developed a second tumor, one in the radiation therapy field and the other in a patient who received no radiation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Could an autonomous syntax module have evolved?

Darwinian evolution necessitates a contribution to reproductive fitness. Recent studies of aphasia and Parkinson's disease show that functional syntactic ability involves neural structures that also are involved in speech motor control and nonlinguistic cognition. The evolution or presence of an autonomous syntax module is, therefore, implausible.

Aphasia, Broca↗
PubMed1992

Speech production, syntax comprehension, and cognitive deficits in Parkinson's disease.

Speech samples were obtained that were analyzed for voice onset time (VOT) for 40 nondemented English speaking subjects, 20 with mild and 20 with moderate Parkinson's disease. Syntax comprehension and cognitive tests were administered to these subjects in the same test sessions. VOT disruptions for stop consonants in syllable initial position, similar to those noted for Broca's aphasia, occurred for nine subjects. Longer response times and errors in the comprehension of syntax as measured by the Rhode Island Test of Sentence Comprehension (RITLS) also occurred for these subjects. Anovas indicate that the VOT overlap subjects had significantly higher syntax error rates and longer response times on the RITLS than the VOT nonoverlap subjects--F(1, 70) = 12.38, p less than 0.0008; F(1, 70) = 7.70, p less than 0.007, respectively. The correlation between the number of VOT timing errors and the number of syntax errors was significant. (r = 0.6473, p less than 0.01). VOT overlap subjects also had significantly higher error rates in cognitive tasks involving abstraction and the ability to maintain a mental set. Prefrontal cortex, acting through subcortical basal ganglia pathways, is a component of the neural substrate that regulates human speech production, syntactic ability, and certain aspects of cognition. The deterioration of these subcortical pathways may explain similar phenomena in Broca's aphasia. Results are discussed in relation to "modular" theories.

Adult↗
PubMed1992

Prevalence of dust mites in the homes of people with asthma living in eight different geographic areas of the United States.

The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.

Adolescent↗