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Biomedical subjects

J Goebel

Publications and source records attributed to J Goebel.

At least 19 recordsLinked to original sources
PubMed2001

STAT5 pathway: target of anti-CD4 antibody in attenuation of IL-2 receptor signaling.

BACKGROUND: Anti-CD4 antibodies induce long-term graft survival by incompletely understood mechanisms, and CD4-ligation with HIV gp120-derivatives attenuates interleukin (IL)-2 receptor signaling. We examined the latter in the context of the CD4-modulating antibody 16H5. MATERIALS AND METHODS: We performed immunoblots to assess the IL-2-induced phosphorylation of signal transducer and activator of transcription (STAT)5 and Akt in the presence or absence of 16H5. Furthermore, we documented the effects of 16H5 on the induction of STAT5, activating protein (AP)-1, and myc by IL-2 in DNA-binding assays. 3H-thymidine incorporation of the human lymphoid cell line CMO, which exhibits constitutive activation of the STAT5 pathway and IL2-independent growth, was also measured during 16H5 treatment. RESULTS: In human T lymphocytes, 16H5 attenuated both the tyrosine phosphorylation of STAT5 by IL-2 and the IL-2-induced DNA-binding of this transcription factor. In contrast, 16H5 had no effect on the serine phosphorylation of Akt by IL-2 or on the IL-2-induced DNA-binding of myc. Signal transduction involving AP-1 was unaffected by 16H5 and IL-2. 16H5 also attenuated CMO cell proliferation. CONCLUSIONS: 16H5 targets the STAT5 signaling pathway to attenuate IL-2 receptor signal transduction in human T cells. This observation provides a molecular explanation for the immunomodulatory actions of anti-CD4 antibodies.

Antibodies↗
PubMed2001

Interstitial nephritis, hepatic failure, and systemic eosinophilia after minocycline treatment.

This report describes a 15-year-old white boy who presented with fever, back pain, a disseminated exanthematous rash, renal failure, and hepatopathy 3 weeks after the initiation of oral minocycline therapy for facial acne. Marked peripheral and urine eosinophilia were noted. A bone marrow aspiration showed more than 50% eosinophils without any evidence of malignancy, and a simultaneous kidney biopsy showed acute interstitial nephritis (AIN). The patient's symptoms and laboratory findings improved after high-dose steroid therapy was initiated, worsened when it was withheld, and improved again after it was reinitiated in view of the biopsy findings. The patient recovered completely, and steroids were tapered to discontinuation over 3 months. Over a year later, the patient's peripheral blood mononuclear cells (PBMCs) were cultured for 2 weeks in the presence or absence of minocycline ex vivo, and minocycline was found to induce the emergence of CD4(+) cells after 1 week in culture. In conclusion, this article shows for the first time several new aspects of minocycline-induced morbidity: renal and hepatic failure can occur together, and AIN and elevated blood eosinophil counts can be accompanied by marked bone marrow eosinophilia, suggesting a systemic allergic response as the underlying pathomechanism. Furthermore, the initial phase of such a response appears to involve CD4(+) T cells detectable ex vivo. Lastly, high-dose treatment with corticosteroids appears to be beneficial in this setting.

Acne Vulgaris↗
PubMed2001

The meaning of the word "vertigo".

OBJECTIVE: To determine whether otologists see a need to further define the word "vertigo" and assess the variety of meanings that are meant in using the word. METHODS: A questionnaire was mailed to 720 members of the American Otological Society (AOS) and American Neurotological Society (ANS) to assess the need for further definition and the current understanding of the meaning of "vertigo." RESULTS: The response rate was 42%. Significant variability in the intended meaning of the word "vertigo" was found suggesting that the definition is inconsistent among experts. Three quarters of the respondents indicated that the word needs further definition. The word was most commonly used to indicate sensations that include spinning or turning only. CONCLUSION: The definition of the term "vertigo" is inconsistent among otolaryngologists. Refinement of the definition is desirable for accurate history taking and should be limited to false illusions of circular motion.

Humans↗
PubMed2000

Daclizumab (Zenapax) inhibits early interleukin-2 receptor signal transduction events.

Daclizumab, a humanized antibody against the interleukin-2 (IL-2) receptor (R) alpha-chain, is a promising new immunosuppressant in transplantation. As its exact mechanism of action has remained unclear, we examined its short-term effects on primary human T lymphocytes expressing the high-affinity IL-2R. Daclizumab exposure for 20 min neither affected T cell viability nor their surface expression of the IL-2R alpha-, beta-, or gamma-chains. However, after IL-2 stimulation (200 U/ml, 20 min), immunoblots of cell lysates demonstrated attenuation of the IL-2-induced tyrosine phosphorylation of 65-75 kDa proteins by Daclizumab, but not by isotype controls. Since this is the molecular weight of the IL-2R beta- and gamma-chains, which are both tyrosine-phosphorylated by IL-2, we next examined the effect of Daclizumab on their IL-2-induced tyrosine phosphorylation. In immunoblots of IL-2R beta- and gamma-chain-immunoprecipitates the tyrosine phosphorylation of both chains by IL-2, but not by IL-15, was attenuated in the presence of Daclizumab. Furthermore, co-immunoprecipitation experiments showed that Daclizumab inhibited the IL-2-induced association of these chains, a prerequisite for their mutual tyrosine phosphorylation. Lastly, we demonstrated that Daclizumab inhibits the receptor-downstream induction of the IL-2-activated DNA-binding protein STAT5 in gel shift assays. We conclude that Daclizumab directly and specifically interferes with IL-2 signaling at the receptor level by inhibiting the association and subsequent phosphorylation of the IL-2R beta- and gamma-chains induced by ligand binding. Under our experimental conditions, Daclizumab had no effects on cell viability, and it did not modulate the surface expression of the IL-2R alpha-, beta-, or gamma-chains.

Animals↗
PubMed2000

Solitary hepatic abscess with associated glomerulonephritis in a neonate.

A full-term neonate with a history of umbilical venous catheterization followed by coagulase-negative staphylococcal sepsis is presented. The infant developed a solitary hepatic abscess with saprophytic organisms. Her liver abscess resulted in acute glomerulonephritis characterized by hypertension, proteinuria, oliguria, and azotemia. Surgical drainage and antibiotic treatment of the abscess was associated with resolution of the glomerulonephritis. Glomerulonephritis due to solitary liver abscess in a neonate has not been reported previously. Acute onset of glomerulonephritis should prompt a search for occult sources of infection.

Abscess↗
PubMed2000

Pups' tails saved.

Explore the source record for details and available documents.

Animal Welfare↗
PubMed2000

Prednisolone plus albuterol versus albuterol alone in mild to moderate bronchiolitis.

To evaluate combination therapy of mild to moderate bronchiolitis with bronchiodilators and corticosteroids, we treated 51 young children with first-time wheezing and symptoms of respiratory tract infection with albuterol plus either prednisolone or placebo for 5 days. Disease severity was scored on days 0, 2, 3, and 6. On day 2, prednisolone resulted in significantly lower scores (2.7 +/- 1.4 vs. 4.0 +/- 1.5 in all patients evaluated, p < 0.05) than placebo, whereas there was no detectable difference on day 6, suggesting that addition of prednisolone to albuterol transiently accelerates recovery from bronchiolitis. The clinical significance of this effect needs to be evaluated in further studies.

Albuterol↗
PubMed2000

Evaluation and treatment of severe hyperacusis.

A 52-year-old male was evaluated by the authors after initially reporting fullness in his left ear while traveling on an airplane. A unique feature of the patient's complaint was the development of severe bilateral hyperacusis (loudness discomfort levels of between 20-34 dB HL) in spite of the fact that the hearing loss was initially reported in the left ear. To achieve loudness comfort, the patient was initially fit with ER-25 musician earplugs that proved to be unsuccessful. The patient next purchased earplugs and earmuffs from a gun shop in order to obtain relief from the pain and discomfort caused by his exposure to everyday environmental sounds. This paper describes the use of hearing devices that proved to be effective in providing attenuation sufficient that the patient rarely needs to rely on earplugs and earmuffs for relief from his hyperacusis.

Anti-Inflammatory Agents↗
PubMed1999

Hemodiafiltration for vancomycin overdose in a neonate with end-stage renal failure.

We describe continuous venovenous hemodiafiltration (CVVHD) with a high-flux membrane as a novel treatment modality for vancomycin overdose associated with renal insufficiency. CVVHD was used in a 6-day-old male with a solitary hypodysplastic kidney, suspected sepsis, and anuric renal failure who subsequently received an accidental tenfold overdose of vancomycin. We furthermore present evidence for the importance of countercurrent dialysis in addition to continuous hemofiltration for optimal vancomycin removal.

Drug Overdose↗
PubMed1995

Four cases of acoustic neuromas with normal hearing.

In 95 percent of the cases, patients with acoustic neuromas will have some magnitude of hearing loss in the affected ear. This paper reports on four patients who had acoustic neuromas and normal hearing. Results from the case history, audiometric evaluation, auditory brainstem response (ABR), electroneurography (ENOG), and vestibular evaluation are reported for each patient. For all patients, the presence of unilateral tinnitus was the most common complaint. Audiologically, elevated or absent acoustic reflex thresholds and abnormal ABR findings were the most powerful diagnostic tools.

Adult↗
PubMed1994

Intersubject variability of real-ear sound pressure level: conventional and insert earphones.

Measures of the sound pressure level (SPL) near the eardrum were determined at discrete frequencies between 500 and 4000 Hz on 50 ears using TDH-39P and ER-3A earphones with the attenuator of an audiometer fixed at 90 dB HL. Results revealed significant differences in the measured SPL between the two earphones at all test frequencies. Results also revealed large intersubject differences in the SPL measured near the eardrum for both earphones. The results of this study highlight the large intersubject variability associated with measuring the SPL at the eardrum and point out the difficulty in accurately predicting individual performance from averaged group data.

Amplifiers, Electronic↗
PubMed1992

High-frequency thresholds: sound suite versus hospital room.

Benefits of high-frequency audiometry in monitoring hearing sensitivity of patients administered ototoxic medications are well established. Thresholds obtained within a sound suite have been proven reliable. It may, however, often be necessary for the audiologist to evaluate the patient at bedside. The primary purpose of this study was to determine if significant differences are present between high-frequency thresholds measured in a sound suite versus thresholds measured in a hospital room. In addition, the test-retest reliability of high-frequency thresholds was determined when measured in a hospital room. For 25 normal hearing subjects, results revealed that significant differences were not observed between thresholds measured in a sound suite versus those measured in a typical hospital room. In addition, differences between the initial and repeated thresholds obtained in the hospital room were not significant, and the differences were, for the most part, within +/- 10 dB at all test frequencies.

Adult↗
PubMed1992

High-frequency thresholds: circumaural earphone versus insert earphone.

Benefits of high-frequency audiometry in monitoring hearing sensitivity of patients administered ototoxic medications are well established. High-frequency thresholds have been reported to be variable, due in part to small differences in the placement of the earphone diaphragm over the opening of the ear canal. Reliability may be improved by using insert earphones (ER-2) when obtaining high-frequency thresholds. The purposes of this study were to determine high-frequency threshold test-retest reliability using Koss HV/1A+ and ER-2 earphones and to determine if significant differences are present between high-frequency thresholds obtained using these two earphones. Results obtained on 40 ears of 20 normal hearing adults revealed that differences between the test and retest thresholds for each earphone were not significant. Intrasubject threshold differences between the test and retest thresholds for each earphone were, for the most part, within +/- 10 dB at all test frequencies. Further, significantly greater intensity was required to measure threshold when using the ER-2 earphone when compared to the Koss HV/1A+ at all test frequencies.

Acoustic Stimulation↗
PubMed1991

Reliability and intersubject variability of the real ear unaided response.

Intratester test-retest reliability of the real ear unaided response (REUR) was determined on 49 ears using the Frye 6500 real ear analyzer. Results revealed mean differences of less than 1 dB for repeat measurements at seven test frequencies between 250 and 4000 Hz. The average peak resonant frequency of the repeated measure was within 16 Hz of the initial measure. In addition, the intersubject variability of the amplitude of REUR was quite large. A range of 7 dB was found at 250 to 500 Hz with the range expanding to 15 to 20 dB at 2000 to 4000 Hz. Also, the peak resonant frequency varied between 2100-4800 Hz. These results are discussed in terms of those dispensers who use the REUR to "custom" order hearing aids.

Acoustics↗