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Biomedical subjects

S Rosen

Publications and source records attributed to S Rosen.

At least 55 records · Page 3Linked to original sources

Auditory backward-masking performance by children who stutter and its relation to dysfluency rate.

The fluency of people who stutter is affected markedly when auditory feedback is altered, suggesting that stuttering may be associated with hearing. Peripheral hearing problems, however, are no more common in people who stutter than in those who do not. Performance was investigated in a task that involves central auditory processing (backward masking). Children who stuttered had deficits in backward masking (indicated by higher thresholds) compared with a group of fluent control children. The backward-masking thresholds were positively correlated with frequency of stuttering.

Acoustic Stimulation↗

RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells.

Related Adhesion Focal Tyrosine Kinase (RAFTK; also known as Pyk2), is a member of the Focal Adhesion Kinase (FAK) subfamily and is activated by TNF alpha, UV light and increases in intracellular calcium levels. However, the function of RAFTK remains largely unknown. Our previous studies demonstrated that treatment with dexamethasone (Dex), ionizing radiation (IR), and anti-Fas mAb induces apoptosis in multiple myeloma (MM) cells. In the present study, we examined the potential role of RAFTK during induction of apoptosis in human MM cells triggered by these three stimuli. Dex-induced apoptosis, in contrast to apoptosis triggered by anti-Fas mAb or IR, is associated with activation of RAFTK. Transient overexpression of RAFTK wild type (RAFTK WT) induces apoptosis, whereas transient overexpression of Kinase inactive RAFTK (RAFTK K-M) blocks Dex-induced apoptosis. In contrast, transient overexpression of RAFTK K-M has no effect on apoptosis triggered by IR or Fas. In Dex-resistant cells, Dex does not trigger either RAFTK activation or apoptosis. Finally, interleukin-6 (IL-6), a known survival factor for MM cells, inhibits both activation of RAFTK and apoptosis of MM.1S cells triggered by Dex. Our studies therefore demonstrate Dex-induced RAFTK-dependent, and IR or Fas induced RAFTK-independent apoptotic signaling cascades in MM cells.

Apoptosis↗

A problem with auditory processing?

Recent studies have found associations between auditory processing deficits and language disorders such as dyslexia; but whether the former cause the latter, or simply co-occur with them, is still an open question.

Adult↗

Arthropod parasites of Nubian ibexes (Capra ibex nubiana) and gazelles (Gazella gazella) in Israel.

In a 20-year survey the following ectoparasites were collected from Nubian ibexes: larvae of an unidentified Oestrus sp. collected from the nasal cavities, sinuses and horns, hippoboscid flies (Lipoptena chalcomelaena) specific to the Nubian ibex, blood sucking lice (Linognathus africanus) and unidentified biting lice (Damalinia sp.). Ibexes were severely infested with the cattle tick, Boophilus annulatus; a few Hyalomma anatolicum excavatum ticks were also collected. In five ibexes kept in two zoos, showing otitis, Psoroptes cuniculi, was identified, and from skin scrpaings of nine animals with severe dermatitis in three other zoos, Sarcoptes scabiei was isolated. Infestation of Nubian ibexes with sucking and biting lice as well as H. anatolicum excavatum is reported for the first time. The ectoparasites collected from gazelles were: hippoboscid flies (Lipoptena capreoli), calliphorid flies (Lucilia sericata and Calliphora sp.), sucking lice (Linognathus africanus and Solenopotes capillatus) and unidentified biting lice (Damalinia sp.), fleas (Ctenocephalides felis felis), and ticks, B. annulatus, Rhipicepahlus bursa, Rhipicephalus turanicus, H. anatolicum excavatum and H. marginatum rufipes. In skin scrapings of four gazelles with local dermatitis in the fetlocks Chorioptes bovis was identified. Neoschoengastia sp. was found in craters between the claws in three gazelles.

Animals↗

Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients.

OBJECTIVE: To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA). METHODS: Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3-4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria. RESULTS: HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT. CONCLUSION: In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.

Adult↗

Cutaneous CD8 T cell infiltrates in advanced HIV infection.

BACKGROUND: Aggressive non-Hodgkin's lymphomas are common among patients infected with HIV. Although such lymphomas are mostly of the B-cell type, various cases of cutaneous T-cell lymphoma (CTCL) have also been reported. Recent reports suggest that some HIV-related lymphoproliferative conditions may not be clonal processes, but polyclonal lymphoid proliferations. OBJECTIVE: We reviewed our experience with HIV patients seen at the dermatology clinics for possible CTCL. METHODS: A retrospective study was performed to evaluate clinical, laboratory, and histologic findings of HIV-infected patients with atypical T-cell cutaneous infiltrates. RESULTS: We observed 9 patients with advanced HIV infection and a cutaneous eruption characterized by a dense infiltrate of lymphocytes resembling mycosis fungoides histopathologically, but composed of CD8(+) cells. Although clonality was not identified in any of the 6 cases tested, 3 patients had similar CD8(+) infiltrates involving lymph nodes or bone marrow. Of the 9 patients, 8 died of AIDS wasting syndrome or infections in less than 1 year. CONCLUSION: Cutaneous and systemic infiltrates with polyclonal CD8 T lymphocytes can be seen in patients with advanced HIV infection and profound CD4 lymphopenia. The clinical presentation may resemble CTCL and is associated with a poor outcome.

Adult↗

Chorioptic mange (Acarina: Psoroptidae) in domestic and wild ruminants in Israel.

In a 20-year-survey, 9364 dairy cattle in 324 herds kept under a zero-grazing management, 1252 beef cattle in 46 herds grazing all the year round, 3347 sheep in 134 herds (only 26 are grazing herds), and 872 goats in 47 herds (only 20 are grazing) were examined. The mites collected from cattle were identified as Chorioptes texanus only, and those from sheep, goats and gazelles were identified as C. bovis. Chorioptic mange was not diagnozed in grazing beef cattle, ibexes and housed animals (as compared to grazing herds), and in rams and billy goats. Holstein-Israeli bulls kept in insemination centres were not clinically infested, whereas four Charolais bulls were infested with chorioptic mange. Infestation rate was higher in older animals than in younger ones. Hoggets and young goats over 10 months and heifers over 13 months were found clinically infested with Choriopic mites. Lesions were not usually extensive and occurred mainly in predilection sites. The ocular form in sheep and the groin form in goats are very uncommon and apparently are reported for the first time. Chorioptic mange was recorded generally throughout the year. In our study seasonal distribution could not be demonstrated in cattle, while in sheep and goats the highest infestation rate occurred in February to March and the lowest in August and September.

Animal Feed↗

Stem cell component therapy: supplementation of unmanipulated marrow with CD34 enriched peripheral blood stem cells.

Eleven patients with hematologic malignancies and two with aplastic anemia were treated using unmanipulated marrow and immunoselected CD34+ blood cells. Donors began G-CSF (10 microg/kg) injections 1 day after undergoing bone marrow harvest. Blood stem cells were collected on day 5 of G-CSF. Peripheral blood lymphocytes were depleted via CD34-positive selection. If, after marrow and blood harvest, less than 2.0 x 10(6) CD34 cells/kg were mobilized, leukapheresis was repeated on day 6. Median time to an absolute neutrophil count greater than 500 microl was day 10; transfusion-independent platelet count greater than 20,000/microl was day 13; average hospital discharge was day 14; and average inpatient hospital charges were 101,870 US dollars. Acute GVHD grade II occurred in five of 13 patients. No patient developed grade III or IV acute GVHD. At a median follow-up of 10 months, no patient has developed extensive chronic GVHD. Allografts of unmanipulated bone marrow supplemented with G-CSF-mobilized and CD34 immunoselected blood cells may prevent an increased risk of GVHD while preserving the rapid engraftment kinetics of peripheral blood. Supplementation of marrow with CD34 enriched blood cells appears to result in rapid engraftment, early hospital discharge, lower inpatient charges, decreased regimen-related toxicity, and no apparent increase in GVHD.

Adult↗

Contributions of temporal encodings of voicing, voicelessness, fundamental frequency, and amplitude variation to audio-visual and auditory speech perception.

Auditory and audio-visual speech perception was investigated using auditory signals of invariant spectral envelope that temporally encoded the presence of voiced and voiceless excitation, variations in amplitude envelope and F0. In experiment 1, the contribution of the timing of voicing was compared in consonant identification to the additional effects of variations in F0 and the amplitude of voiced speech. In audio-visual conditions only, amplitude variation slightly increased accuracy globally and for manner features. F0 variation slightly increased overall accuracy and manner perception in auditory and audio-visual conditions. Experiment 2 examined consonant information derived from the presence and amplitude variation of voiceless speech in addition to that from voicing, F0, and voiced speech amplitude. Binary indication of voiceless excitation improved accuracy overall and for voicing and manner. The amplitude variation of voiceless speech produced only a small increment in place of articulation scores. A final experiment examined audio-visual sentence perception using encodings of voiceless excitation and amplitude variation added to a signal representing voicing and F0. There was a contribution of amplitude variation to sentence perception, but not of voiceless excitation. The timing of voiced and voiceless excitation appears to be the major temporal cues to consonant identity.

Acoustic Stimulation↗

Adaptation by normal listeners to upward spectral shifts of speech: implications for cochlear implants.

Multi-channel cochlear implants typically present spectral information to the wrong "place" in the auditory nerve array, because electrodes can only be inserted partway into the cochlea. Although such spectral shifts are known to cause large immediate decrements in performance in simulations, the extent to which listeners can adapt to such shifts has yet to be investigated. Here, the effects of a four-channel implant in normal listeners have been simulated, and performance tested with unshifted spectral information and with the equivalent of a 6.5-mm basalward shift on the basilar membrane (1.3-2.9 octaves, depending on frequency). As expected, the unshifted simulation led to relatively high levels of mean performance (e.g., 64% of words in sentences correctly identified) whereas the shifted simulation led to very poor results (e.g., 1% of words). However, after just nine 20-min sessions of connected discourse tracking with the shifted simulation, performance improved significantly for the identification of intervocalic consonants, medial vowels in monosyllables, and words in sentences (30% of words). Also, listeners were able to track connected discourse of shifted signals without lipreading at rates up to 40 words per minute. Although we do not know if complete adaptation to the shifted signals is possible, it is clear that short-term experiments seriously exaggerate the long-term consequences of such spectral shifts.

Adolescent↗

Evidence for a grammar-specific deficit in children.

BACKGROUND: Specific language impairment (SLI) is a disorder in which language acquisition is impaired in an otherwise normally developing child. SLI affects around 7% of children. The existence of a purely grammatical form of SLI has become extremely controversial because it points to the existence and innateness of a putative grammatical subsystem in the brain. Some researchers dispute the existence of a purely grammatical form of SLI. They hypothesise that SLI in children is caused by deficits in auditory and/or general cognitive processing, or social factors. There are also claims that the cognitive abilities of people with SLI have not yet been sufficiently characterised to substantiate the existence of SLI in a pure grammatical form. RESULTS: We present a case study of a boy, known as AZ, with SLI. To investigate the claim for a primary grammatical impairment, we distinguish between grammatical abilities, non-grammatical language abilities and non-verbal cognitive abilities. We investigated AZ's abilities in each of these areas. AZ performed normally on auditory and cognitive tasks, yet exhibited severe grammatical impairments. This is evidence for a developmental grammatical deficit that cannot be explained as a by-product of retardation or auditory difficulties. CONCLUSIONS: The case of AZ provides evidence supporting the existence of a genetically determined, specialised mechanism that is necessary for the normal development of human language.

Adolescent↗

Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation.

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.

Activities of Daily Living↗

Generation of carbohydrate-deficient transferrin by enzymatic deglycosylation of human transferrin.

Carbohydrate-deficient transferrin (CDT) molecules are transferrin isoforms that lack one or both of the carbohydrate groups attached to a normal human transferrin molecule. CDT has been reported to be a sensitive and specific marker for diagnosing alcoholism. This report demonstrates the in vitro generation of CDT molecules that can potentially be used as the standard in measuring CDT concentrations. This was achieved by deglycosylation of human transferrin with the enzyme Endo-beta-N-acetylglucosaminidase F2 (Endo-F2). The enzyme was immobilized on sepharose beads, which were packed into a column. The immobilization of the enzyme not only eliminated the Endo-F2 contamination of CDT, but also rendered the enzyme suitable for repetitive use. In this manner, it was possible to obtain at least 200 mg of CDT over a period of more than 3 mo, without any noticeable decrease of enzyme activity, using only 3.0 micrograms of enzyme. This proved to be an efficient method for generating CDT.

Alcoholism↗

Naltrexone effects on diazepam intoxication and pharmacokinetics in humans.

The opiate antagonist naltrexone (NTX) blocks relapse drinking in alcoholics and modifies some of the subjective effects of alcohol intoxication. Benzodiazepines have demonstrated cross-dependence and cross-tolerance to alcohol. Furthermore, benzodiazepine intoxication has effects on mood and psychomotor performance that are similar to alcohol intoxication. The effects of NTX on diazepam intoxication were investigated in non-drug abusing individuals. Eighteen men and eight women were randomly assigned to receive either 50 mg NTX or placebo PO, on two different occasions in a within-subjects, crossover, double-blind protocol. Diazepam was taken by mouth, 90 min after NTX. At -90, 45, 75, 135, 210 min, subjects were tested with repeated assessments of several mood and sensation scales and a computer-generated psychomotor test battery (CTB). Blood samples were also obtained and analyzed for serum diazepam levels. Diazepam induced several sensations and mood effects similar to those induced by alcohol. Negative mood states such as sedation, fatigue, and anxiety were higher for NTX than for placebo. Positive mood states such as friendliness, vigor, liking the effects of diazepam, and feeling high from diazepam were all lower for NTX than for placebo. There were no group differences on the CTB performance. NTX delayed the time to reach peak diazepam levels, so that peak levels occurred at 75 min for placebo compared to 135 min for NTX. A sub-analysis was conducted with 14 subjects who were FHP for alcoholism, but no differences were found on these outcome measures.

Adult↗

Acute interstitial nephritis presenting as presumed minimal change nephrotic syndrome.

Nephrotic syndrome (NS) secondary to drug-induced acute interstitial nephritis (AIN) is well described in adult but is very rare in children. We report an unusual case of AIN mimicking prototypical childhood minimal change NS. A 2-year-old girl on long-standing amoxicillin therapy for vesicoureteral reflux presented with the acute onset of generalized edema, proteinuria, hypoalbuminemia, hypercholesterolemia, and an inactive urinary sediment. She was placed on empiric steroid therapy for presumed minimal change NS. When she did not respond to steroids, a renal biopsy was performed and revealed AIN. Her NS resolved completely with cessation of her amoxicillin therapy and concomitant tapering of her steroids. This patient demonstrates that the association of AIN with NS should be carefully considered in children on antimicrobials who develop NS, even in the absence of the classic clinical features of AIN. In addition to the usual work-up and care of a child with NS, in these patients consideration may also need to be given to withdrawal of the potential precipitating agent.

Acute Disease↗

Membranous glomerulonephritis and nephrosis post factor IX infusions in hemophilia B.

Children with hemophilia B who receive exogenous factor IX infusions may rarely develop inhibitors to the exogenous factor IX and require desensitization. Nephrotic syndrome has recently been described in some of these children. We report the renal clinicopathological findings in a child with severe factor IX deficiency, requiring induction of an immune tolerance protocol, who developed nephrotic syndrome. Renal biopsy revealed peripheral capillary wall thickening and a spike appearance consistent with membranous glomerulonephritis. Electron microscopy showed prominent deposits throughout the thickness of the basement membrane. Factor IX dose reduction was accompanied by reversal of the child's nephrotic syndrome without relapses.

Child, Preschool↗

Angiographic characteristics of infarct-related and non-infarct-related stenoses in patients in whom stable angina progressed to acute myocardial infarction.

BACKGROUND: In patients with coronary artery disease, angiographic and postmortem studies have shown that coronary stenoses in infarct-related arteries often have complex morphology. It is not known whether in patients with multivessel disease stenosis morphology in non-infarct-related arteries is different from those of the infarct-related arteries. METHODS AND RESULTS: In 24 consecutive patients we examined the angiographic characteristics of both the infarct-related stenoses and non-infarct-related stenoses before and after spontaneous acute myocardial infarction, by visual inspection and computerized edge detection of coronary angiograms. Before myocardial infarction, the severity of the infarct-related stenoses was <50% in 14 patients and > or =50% in 10 patients (p=not significant) and of non-infarct-related stenoses was <50% in 16 and > or=50% in 13. A significantly greater proportion of infarct-related stenoses with severity > or =50% progressed to non-Q-wave than to Q-wave myocardial infarction (71% vs 50%, p < 0.05). Before myocardial infarction, the percentage of concentric, eccentric, and irregular infarct-related stenoses was 8%, 13%, and 50%, respectively, whereas in the non-infarct-related stenoses it was 62%, 17%, and 21%, respectively (p < 0.01). A similar proportion of irregular morphology progressed to Q-wave or non-Q-wave myocardial infarction. CONCLUSIONS: In patients with stable angina who had acute myocardial infarction develop, the infarct-related and non-infarct-related stenoses on average are similar in severity but different in morphology. Nonsevere stenoses more frequently progress to Q-wave than to non-Q-wave myocardial infarction.

Adult↗