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Biomedical subjects

S Stahl

Publications and source records attributed to S Stahl.

At least 55 records · Page 3Linked to original sources

Y2K compliance readiness and contingency planning.

As the millennium approaches, discussion of "Y2K compliance" will shift to discussion of "Y2K readiness." While "compliance" focuses on the technological functioning of one's own computers, "readiness" focuses on the operational planning required in a world of interdependence, in which the functionality of one's own computers is only part of the story. "Readiness" includes the ability to cope with potential Y2K failures of vendors, suppliers, staff, banks, utility companies, and others. Administrators must apply their traditional skills of analysis, inquiry and diligence to the manifold imaginable challenges which Y2K will thrust upon their facilities. The SPICE template can be used as a systematic tool to guide planning for this historic event.

Chronology as Topic↗

Effects of a tryptophan-free amino acid drink challenge on normal human sleep electroencephalogram and mood.

BACKGROUND: Serotonin has been implicated in the regulation of sleep and mood. In animals a tryptophan-free amino acid drink (TFD) challenge has been found to reduce brain serotonin. We hypothesized this TFD would produce alterations in electroencephalographic (EEG) sleep commonly associated with depression, i.e. an enhancement of rapid eye movement (REM) sleep, and adversely affect mood ratings in humans. METHODS: We investigated the effects of a TFD challenge in 11 healthy male subjects on EEG sleep and mood (assessed by Profile of Mood States). All subjects received on separate occasions an experimental drink containing approximately 100 g of an amino acid mixture (100% TFD) and a control drink containing one fourth strength (25% TFD) of the experimental drink 5 hours prior to sleep (6:00 PM). RESULTS: Both drinks significantly decreased plasma tryptophan levels 5 hours postchallenge (11:00 PM). Both drinks significantly decreased REM latency, and the 25% TFD also increased REM time and REM% compared to baseline. No significant changes were found in subjective ratings of depression; however, subjects reported confusion and tension and a decrease in elation, vigor, and friendliness compared with baseline. CONCLUSIONS: These TFD findings further support the involvement of serotonin deficiency in EEG sleep findings commonly seen in depression.

Adult↗

Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with remitted depression on serotonin reuptake inhibitors.

BACKGROUND: In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs. METHODS: Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram. RESULTS: The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree. CONCLUSIONS: Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients, however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.

Amino Acids↗

Midline Fasciclin: a Drosophila Fasciclin-I-related membrane protein localized to the CNS midline cells and trachea.

Drosophila Fasciclin I is the prototype of a family of vertebrate and invertebrate proteins that mediate cell adhesion and signaling. The midline fasciclin gene encodes a second Drosophila member of the Fasciclin I family. Midline Fasciclin largely consists of four 150 amino acid repeats characteristic of the Fasciclin I family of proteins. Immunostaining and biochemical analysis using Midline Fasciclin antibodies indicates that it is a membrane-associated protein, although the sequence does not reveal a transmembrane domain. The gene is expressed in a dynamic fashion during embryogenesis in the blastoderm, central nervous system midline cells, and trachea, suggesting it plays multiple developmental roles. Protein localization studies indicate that Midline Fasciclin is found within cell bodies of midline neurons and glia, and on midline axons. Initial cellular analysis of a midline fasciclin loss-of-function mutation reveals only weak defects in axonogenesis. However, embryos mutant for both midline fasciclin and the abelson nonreceptor tyrosine kinase, show more severe defects in axonogenesis that resemble fasciclin I abelson double mutant phenotypes.

Amino Acid Sequence↗

Phytoestrogens act as estrogen agonists in an estrogen-responsive pituitary cell line.

There is renewed interest in the medicinal value of natural plant products. One group of plant compounds, the phytoestrogens (PE), has been given considerable attention due to their ability to decrease the incidence of certain estrogen-dependent cancers. In this study, we evaluate the effects of PE on estrogen-dependent pituitary tumor cells by using the immortalized pituitary cell line PR1. Several PE were found to be active in PR1 cells, in that they bound to the estrogen receptor (ER), stimulated growth of PR1 cells, and induced an estrogenic response, prolactin secretion. The PE genistein, coumestrol, and zearalenone bound to the ER present in PR1 cells with an affinity 100-times lower than that of estradiol. However, resveratrol, a plant antitumor agent found in grapes, showed no significant binding to the ER. Zearalenone, coumestrol, and genistein were found to induce prolactin secretion and to stimulate growth, whereas resveratrol showed prolactin secretion but no growth stimulation. The estrogenic effects of PE in PR1 cells were ER dependent, in that addition of the antiestrogen ICI-182,780 inhibited prolactin response. Although resveratrol did not bind to the ER or stimulate growth, it induced prolactin secretion in both a dose- and time-dependent manner. The data presented here demonstrate that PE are active in lactotroph cells of the pituitary.

Animals↗

Hand infections due to non-cholera Vibrio after injuries from St Peter's fish (Tilapia zillii).

We report 49 patients with a wide variety of hand infections, which developed after injuries from St Peter's fish (Tilapia zillii). Twenty-eight of 36 patients who had been operated on had non-cholera Vibrio infections, all identified as Vibrio vulnificus. The course in these patients was characterized by rapid spread of the infection with progressive necrosis of the tendon sheath, subcutaneous tissues and the skin. Two of them required amputations but the others had satisfactory functional results. Thirteen other patients were managed nonoperatively with intravenous antibiotics and all of them recovered completely.

Adolescent↗

Specification of the Drosophila CNS midline cell lineage: direct control of single-minded transcription by dorsal/ventral patterning genes.

The Drosophila CNS consists of a bilaterally symmetric group of neurons separated by a discrete group of CNS midline cells. The specification of the CNS midline cell lineage requires transcription of the single-minded gene. Genetic evidence suggests that a group of transcription factors, including Dorsal, Snail, Twist, and Daughterless:: Scute, is required for initial single-minded transcription. Comparison of the DNA sequences of the single-minded gene regulatory regions between two Drosophila species reveals conserved sequence elements. Biochemical studies using purified proteins indicate that a number of these conserved sequences represent binding sites for Dorsal, Snail, and Twist. In vitro mutagenesis combined with germline transformation indicates that these binding sites are required in vivo for single-minded mesectodermal transcription. These results show that single-minded transcription and, thus, CNS midline specification is directly controlled by dorsal/ventral patterning transcription factors. They also suggest a model in which multiple transcriptional activators function in a cooperative, concentration-dependent mode in combination with a transcriptional repressor to restrict single-minded transcription to the CNS midline precursor cells.

Amino Acid Sequence↗

[Postoperative ulnar nerve palsy of the elbow].

Ulnar nerve neuropathy of the elbow is a recognized complication of surgery involving general anesthesia. In 13 patients, aged 21-76 years, ulnar nerve palsy developed at various times and of varying degrees of severity during the postoperative period. Diagnosis was based on clinical and electrophysiological findings. 3 patients had subclinical entrapment of the ulnar nerve. All were treated conservatively by rest, splinting and physical therapy: 10 improved slowly with time and 3 were operated on, but only 1 recovered fully. Preventive measures, such as proper positioning on the operative table, use of elbow pads, avoiding adduction of the arm, pronation of the forearm and prolonged elbow flexion, may reduce the incidence of ulnar nerve palsy. Unfortunately, treatment of established lesions has yielded mixed results.

Adult↗

The serum albumin-binding region of streptococcal protein G: a bacterial fusion partner with carrier-related properties.

In this study, we have explored the use of the serum albumin-binding region (BB) from streptococcal protein G (SpG) as a bacterial fusion partner for production of peptide immunogens. The fusion protein BB-M3, containing BB and repeated structures from the Plasmodium falciparum malaria antigen Pf155/RESA, was efficiently purified from Escherichia coli culture supernatants by affinity chromatography using BB as an affinity tag. Rabbits immunized with BB-M3 in Freund's adjuvant produced high levels of antibodies which reacted with both M3 and BB in ELISA and stained intact Pf155/RESA in the membrane of infected erythrocytes. These antibody levels were sustained for more than 30 weeks. BB-M3 also induced antibody responses to M3, BB and intact Pf155/RESA in a number of mouse strains, including several strains which are non-responders to the malaria sequences. In the latter mice, however, BB-M3 only activated BB-specific T cells, suggesting that BB has ability to provide carrier-related T cell help for antibody production. Moreover, the minimal albumin-binding motif of SpG, containing only 46 amino acids, was immunogenic in both B10.BR, B10.D2 and C57BL/6 mice (H-2k, H-2d and H-2b, respectively). These results indicate that BB has both affinity tag and carrier-related properties and suggest that fusion proteins containing BB can be efficient tools for the generation of antibody responses to peptides which are weak immunogens.

Animals↗

Ulnar nerve injury at the elbow after steroid injection for medial epicondylitis.

We describe an accidental injury to the ulnar nerve at the elbow following steroid injection for medial epicondylitis in a patient with undetected recurrent dislocation of the nerve. The chalky substance found on exploration to intermingle with the nerve fascicles was removed and the nerve was placed under the flexor-pronator mass. After surgery, complete resolution of the epicondylar pain was noted, along with significant improvement in two-point discrimination of the ulnar digits. We recommend clinical assessment of the ulnar nerve location prior to injection to avoid injury. Should recurrent dislocation of the nerve be diagnosed, injection should be given cautiously, preferably with the elbow in an extended or semiflexed position.

Adult↗

Partial lacerations of flexor tendons in children. Primary repair versus conservative treatment.

We compared the outcome of 17 partially lacerated (less than 75% of cross-sectional area) flexor tendons in children treated by surgical repair to that of 19 tendons treated conservatively by early mobilization. The outcome of both groups was similarly favourable. No complications, such as triggering or complete tendon tear, were found in either group. We advocate early mobilization in children in whom a partial division of the flexor tendon is diagnosed clinically. Exploration should be carried out only in doubtful cases to exclude complete division of the tendon.

Child↗

Ulnar nerve injury following midshaft forearm fractures in children.

We report three cases of ulnar nerve deficit in children following closed fractures of the forearm bones. Significant anterior angulation and displacement of the ulna was noted in all patients. Two patients were operated on at a later stage when no evidence of recovery was demonstrated; the ulnar nerve was found to be embedded in dense scar tissue. One patient was operated on at the time of injury; entrapment of the nerve on the anterior spike and partial transection was found. Early exploration is indicated in such cases and may result in full recovery.

Adolescent↗

Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7.

We have completed a phase I study to test feasibility and toxicity of immunotherapy of hepatic metastases from colorectal carcinoma by direct gene transfer of HLA-B7, a MHC class I gene. Eligible patients were HLA-B7 negative, immunocompetent by PHA lymphocyte stimulation and had at least two measurable hepatic lesions on CT scan for measurement of response of the injected lesion, as well as evaluation of possible distant response. Under ultrasonographic guidance the hepatic lesions were injected with Allovectin-7, a liposomal vector containing the combination of the HLA-B7 gene with beta 2-microglobulin formulated with the lipid DMRIE-DOPE. Eligible patients were injected on two schedules. On the first schedule patients received an injection on day 1 and the injected lesion was biopsied to determine transfection every 2 weeks for 8 weeks. Doses were escalated from 10 micrograms to 50 micrograms to 250 micrograms with three patients treated at each level. The second schedule included multiple injections of 10 micrograms. Three patients received injections on days 1 and 15. Three patients received injections on days 1, 15 and 29. A total of 15 patients have completed treatment. The plasmid DNA was detected in 14 of 15 patients (93%) by PCR. In five of 15 patients (33%) mRNA was also detected. The HLA-B7 protein was detected in five of eight patients (63%) by immunohistochemistry and in seven of 14 patients (50%) tested by fluorescence activated cell sorting (FACS) analysis. There has been no serious toxicity directly attributable to allovectin-7. Our results suggest that liposomal gene transfer by direct injection is feasible and non-toxic. Further studies will be necessary in order to establish the therapeutic efficacy.

Adult↗

Prognosis of intraoperative brachial plexus injury: a review of 22 cases.

A retrospective review over 6 yr of patients presenting to the hand clinic was performed to identify cases of postoperative brachial plexopathy (PBP) and to assess both prognosis and early indices of prognosis. Over this period (1989-1995), 22 patients were referred by the hospital's surgical departments to the hand clinic because of PBP. Eight cases followed open heart surgery (OHS) and 14 followed non-cardiac surgery (NCS). Median full recovery took 10 (range 4-16) weeks and 20 (8-50) weeks, respectively. Long-term follow-up revealed one OHS patient with residual tingling and three NCS patients with residual weakness. Brachial plexopathy after median sternotomy was characterized by a predominance of sensory complaint in the lower roots of the plexus. Injury after non-cardiac surgery was reflected by a predominance of motor deficit in the upper and middle roots. Brachial plexus injury after cardiac surgery carries an excellent prognosis for full functional recovery. Although the limited number of cases precludes statistical substantiation, the data suggest that the prognosis of PBP after non-cardiac surgery may be worse in males, diabetics, those with injury to all roots of the plexus and, when in addition to the motor deficit there is sensory loss and pain or dysaesthesia. At a 1 week "prognostic milestone", 79% of NCS patients with significant symptomatology enjoyed complete recovery although this took as long as 5 months to 1 yr in 50% of patients. At a 6-8 week "prognostic milestone", 50% of those who had not yet had improvement in the motor deficit suffered residual neurological deficit. All patients recovered to a significant extent even when recovery was not complete and none suffered from late deterioration or chronic pain.

Aged↗

Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and safety studies of mirtazapine versus amitriptyline in major depression.

A meta-analysis was performed on efficacy and safety data from 4 randomized, double-blind, 6-week, single-center studies comparing mirtazapine (n = 194; 5-35 mg/day) with amitriptyline (n = 193, 40-280 mg/day) and placebo (n = 193) in outpatients with a DSM-III diagnosis of major depressive episode. On all the main efficacy variables both active drugs consistently produced significantly greater improvements and significantly greater percentages of responders or remitters than placebo. The meta-analysis of adverse events shows that mirtazapine was better tolerated than amitriptyline, particularly with respect to anticholinergic and cardiac adverse events. There were no differences between mirtazapine and placebo regarding the incidence of serotonergic adverse events. In conclusion, the results of this meta-analysis demonstrate that mirtazapine is as effective as amitriptyline but has a better tolerability profile.

Adolescent↗

Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma.

PURPOSE: To determine the safety, toxicity, and efficacy of direct intratumoral injection of an allogeneic major histocompatibility complex (MHC) class I gene, HLA-B7, in a cationic lipid vector (Allovectin-7; Vical Inc, San Diego, CA) in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen HLA-B7-negative patients were treated with intralesional injection of Allovectin-7. Twelve patients received a single intralesional injection containing 10 micrograms (four patients), 50 micrograms (five patients), or 250 micrograms (three patients) of plasmid DNA. Five patients received two or three injections of 10 micrograms DNA to a single tumor site at 2-week intervals. Tumor biopsies pretherapy and 2 and 4 weeks after gene injection were obtained to determine expression of the plasmid by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, flow cytometry, and immunohistochemistry. RESULTS: Toxicities were related to technical aspects of the injections or biopsies. These included pain, hemorrhage, pneumothorax, and hypotension. Two patients were hospitalized overnight for observation. Seven patients (50%) had tumor responses insofar as the injected nodule decreased > or = 25% by radiologic or physical examination. One patient with a single site of disease achieved a complete remission. Ninety-three percent of the patients' post-gene therapy biopsies contained HLA-B7 plasmid DNA, mRNA, or protein. CONCLUSION: Intratumoral injection of the allogeneic histocompatibility gene, HLA-B7, in a lipid vector can be performed safely at plasmid DNA doses < or = 250 micrograms. The safety profile and biologic activity of this therapy warrants further studies to define the mechanism of action, predictors of response, and antitumor efficacy of this approach.

Adult↗

The Drosophila tango gene encodes a bHLH-PAS protein that is orthologous to mammalian Arnt and controls CNS midline and tracheal development.

The Drosophila single-minded and trachealess bHLH-PAS genes control transcription and development of the CNS midline cell lineage and tracheal tubules, respectively. We show that Single-minded and Trachealess activate transcription by forming dimers with the Drosophila Tango protein that is an orthologue of the mammalian Arnt protein. Both cell culture and in vivo studies show that a DNA enhancer element acts as a binding site for both Single-minded::Tango and Trachealess::Tango heterodimers and functions in controlling CNS midline and tracheal transcription. Isolation and analysis of tango mutants reveal CNS midline and tracheal defects, and gene dosage studies demonstrate in vivo interactions between single-minded::tango and trachealess::tango. These experiments support the existence of an evolutionarily conserved, functionally diverse bHLH-PAS protein regulatory system.

Amino Acid Sequence↗