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Biomedical subjects

D Urbach

Publications and source records attributed to D Urbach.

At least 19 recordsLinked to original sources

Dynamic diversification from a putative common ancestor of scorpion toxins affecting sodium, potassium, and chloride channels.

Scorpions have survived successfully over millions of years without detectable changes in their morphology. Instead, they have developed an efficient alomonal machinery and a stinging device supporting their needs for prey and defense. They produce a large variety of polypeptidic toxins that bind and modulate ion channel conductance in excitable tissues. The binding site, mode of action, and chemical properties of many toxins have been studied extensively, but little is known about their genomic organization and diversity. Genes representing each of the major classes of Buthidae scorpion toxins, namely, "long" toxins, affecting sodium channels (alpha, depressant, and excitatory), and "short" toxins, affecting potassium and chloride channels, were isolated from a single scorpion segment and analyzed. Each toxin type was found to be encoded by a gene family. Regardless of toxin length, 3-D structure, and site of action, all genes contain A+T-rich introns that split, at a conserved location, an amino acid codon of the signal sequence. The introns vary in length and sequence but display identical boundaries, agree with the GT/AG splice junctions, and contain T-runs downstream of a putative branch point, 5'-TAAT-3'. Despite little sequence similarity among all toxin classes, the conserved gene organization, intron features, and common cysteine-stabilized alpha-helical (CSH) core connecting an alpha-helix to a three-stranded beta-sheet suggest, that they all evolved from an ancestral common progenitor. Furthermore, the vast diversity found among genomic copies, cDNAs, and their protein products for each toxin suggests an extensive evolutionary process of the scorpion "pharmaceutical factory," whose success is due, most likely, to the inherent permissiveness of the toxin exterior to structural alterations.

Amino Acid Sequence

Laparoscopic approach to hydatid liver cysts. Is it logical? Physical, experimental, and practical aspects.

BACKGROUND: In recent years attempts have been made to treat hydatid liver cysts laparoscopically. The purpose of this study was to evaluate different aspects of this approach and to examine whether a reasonable model could be developed. METHODS: Three different subjects were analyzed. In the first, physical aspects related to transmembrane pressures were analyzed to demonstrate that evacuation of the cyst under pneumoperitoneum does not carry increased risk of spillage, and may even offer an advantage when the proper technique is used. In the second subject, an isolated liver model of a goat was used to study several techniques for evacuating hydatid cysts without spillage. This was tested qualitatively by demonstrating scolices in the fluid medium around the isolated liver after surgical manipulations. In the third subject, the implication of the technique was evaluated in human patients. RESULTS: According to basic physical assumptions, the following conclusions were reached: (1) The increase in intracystic pressure is equal to or less than the increase in intraperitoneal pressure after pneumoperitoneum. (2) Aspiration of parasitic cysts by laparoscopic needle through a large cannula under "vacuum" or by sealing the cannula and adhering it to the liver by cyanoacrylate or fibrin glue was found to be very safe. Simple needle aspiration failed to prevent spillage. (3) A new transparent cannula 18 mm in diameter with a beveled tip was designed that enables good accessibility to liver cysts and safe evacuation even of huge and complex cysts. CONCLUSIONS: The novel technique to manage hydatid liver cysts, described in the study, is feasible, sensible, and safe. The isolated goat liver containing hydatid cysts can be used as a reliable animal model to test new techniques in the future.

Animals

Attentional effort modulated by task difficulty.

It has been assumed that stimulus discrimination in a visual task is performed with fixed attentive effort. Here we show that attention to the same pair of stimuli can be modulated by varying the task difficulty when a task requires the discrimination of only a small number of different stimuli. We used a matching-to-sample paradigm, where a test stimulus is presented after a sample stimulus. When both stimuli Gabor gratings have identical orientations ("matching" trial) the required response is different from when they have different orientations ("non-matching" trial). The task difficulty was manipulated by changing the orientation difference between sample and test stimuli for non-matching trials. Difficult non-matching probe trials were embedded within an easy block of trials (easy environment), and vice versa for easy probe trials. Detectability (d') differences for the same pairs of stimuli (probe trials) in the two environments were calculated as a measure for change in attentional effort, regardless of changes in likelihood ratios (beta). Our results show an increase in d' during the difficult task, for both types of probe trials, in paradigms that contained a small number of stimulus combinations. Thus a modulation in attentional effort along a single discrimination dimension is revealed. However it is restricted by the number of stimulus combinations, due to the limited capacity of the attention available for each stimulus combination.

Attention

Auditory event related potentials in simulated tinnitus.

It was previously demonstrated that noise induced tinnitus (NIT) patients have prolonged reaction times and event related potentials (ERPs) that are reduced in amplitude and prolonged in latency. This study considered whether these alterations occurred as a consequence of the competing auditory tinnitus sensation or as a result of a possible cognitive processing dysfunction in NIT patients. ERPs and reaction times (RTs) were recorded in response to a standard oddball auditory target detection paradigm, with and without simulated tinnitus. Tinnitus was simulated using a high tone narrow band noise presented at the forehead via a standard audiometric bone vibrator. The subjects consisted of 19 males suffering from noise induced hearing loss without tinnitus. The latencies and amplitudes of the ERP components N1, P2, N2, and P3, as recorded along the midline scalp sites (Fz, Cz, and Pz) and bilateral temporal sites (C3 and C4), did not differ significantly when recorded with and without simulated tinnitus. Similarly, the associated reaction times did not differ significantly. These findings suggest that the ERP alterations previously reported to exist for NIT patients cannot be explained simply as a consequence of increased task difficulty and cognitive loading due to the tinnitus sound.

Acoustic Stimulation

Auditory event related potentials in chronic tinnitus patients with noise induced hearing loss.

In order to explore a possible deficit in auditory central neural activity in tinnitus with noise induced hearing loss (NIHL), auditory event related potentials (ERP) and reaction time (RT) were recorded (measures of central processing) from tinnitus patients (N = 12) and hearing and age matched controls (N = 12). Testing procedure included oddball paradigms and 1 KHz repetitive stimulus, as well as click-induced brainstem auditory evoked potentials (BAEP). ERP amplitudes (waves N1, P2 and P3) in tinnitus patients were significantly lower than in controls in all testing paradigms. No differences were found in ERP peak latencies, BAEP, RT, or response scoring. The lower ERP amplitudes may indicate attenuated or 'abnormal' auditory central processing in NIHL tinnitus patients. It is suggested that this dysfunction reflects an adaptive brain process response to the tinnitus and points to auditory central involvement in tinnitus sensation.

Acoustic Stimulation

Eosinophilia-myalgia syndrome. Natural history in a population-based cohort.

BACKGROUND: To determine the natural history of eosinophilia-myalgia syndrome, we followed up all patients with eosinophilia-myalgia syndrome reported to the Oregon Health Division, Portland, during the recent epidemic caused by contaminated tryptophan. METHODS: Patients were interviewed by telephone from 1 to 5 months after illness onset and again at least 12 months after onset. Symptoms (type, onset, and duration), overall disability, treatment, and tryptophan lot and dose were assessed for each patient. RESULTS: Information was obtained for 55 (96%) of 57 case-patients: 53 patients completed interviews and two patients had died. For the 53 patients who were interviewed, symptoms with onset more commonly during the first 3 months of illness included severe myalgias, fatigue, generalized weakness, edema, and rash. Symptoms with later onset included paresthesias, muscle cramps, extremity weakness, and alopecia. At 12 months, 41 patients (77%) continued to report fatigue, 36 (68%) weakness, and 34 (64%) myalgias; 26 patients (49%) had difficulty climbing stairs, 23 (43%) had difficulty getting up from a chair, and 15 (28%) had difficulty holding a cup. Higher doses of tryptophan were correlated with more severe disability, both initially (rs = .33) and at follow-up (rs = .42). Although most patients reported improvement in symptoms at 12 months, only 14 (26%) patients reported that they were able to perform all normal daily activities. CONCLUSIONS: Most patients with eosinophilia-myalgia syndrome in this population-based cohort are still symptomatic 1 year after onset, primarily with the complaints reported early in the illness. The association between degree of disability and daily tryptophan dose suggests that ingestion of varying amounts of contaminant may be responsible, in part, for the severity of symptoms experienced by individual patients.

Activities of Daily Living

[Digital luminescence radiography . 2: Technical implementation and clinical application--future developments].

In the previously published Part 1 of this paper the basic principle of digital luminescence radiography (DLR) was presented and the technical implementation of the data acquisition system with its advantages and disadvantages as compared with conventional radiography were described [3]. Part 2 covers processing, display, archiving and communication of image data; in addition, suggestions for future improvements in the technique are made. Image processing research is directed towards optimal presentation of the detected data by spatial frequency filtering with unsharp masking and by gradation enhancement. Additional information can be acquired by means of dual energy investigations. The image is displayed on either monitor or transparent X-ray film. Picture archiving requires large storage capacities, and picture communication needs fast transfer rates. At present, about 450 installations for digital luminescence radiography are in clinical use worldwide. Routine use can be expected when technical improvements have been implemented.

Humans

[Digital luminescence radiography. Part 1: Basic principle, technical execution and clinical use].

Digital luminescence radiography (DLR) is a new technique in projection radiography, which enables the production of plain X-ray images and motion tomographies with high quality, and is suitable for digital image management. With this procedure the X-ray image produced by conventional roentgen devices is temporarily stored on a reusable photostimulable storage phosphor screen which is characterized by a wide dynamic range. A laser beam scans the exposed phosphor screen and recovers the stored X-ray information as photostimulated luminescence radiation. A photomultiplier converts the emitted light into electrical signals. After normalization and digitization the signals are transmitted to an image processor. The stored digital image can be individually processed and displayed, digitally archived or transferred to any location. The technique is described in two following papers. Part 1 covers the basic principle of the system and the technical implementation of the data acquisition with its advantages and disadvantages as compared with conventional film/screen radiography.

Equipment Design

Nucleotide sequence and structure analysis of a cDNA encoding an alpha insect toxin from the scorpion Leiurus quinquestriatus hebraeus.

A approximately 370 base pair cDNA encoding the alpha insect toxin Lqh alpha IT of the scorpion Leiurus quinquestriatus hebraeus was cloned and sequenced. The deduced amino acid sequence for the putative mature polypeptide is identical to the protein sequence determined chemically (Eitan et al., Biochemistry 29, 5941, 1990). A 19 amino acid signal peptide precedes the 64 amino acid long toxin. Two additional amino acid residues that do not correspond to the purified toxin are found at the COOH-terminus and may imply post-translational modification. The signal peptide region in the present clone differs obviously from that encoding the depressant insect toxin LqhIT2 derived from the same venom, but strongly resembles the leader peptide sequence of an alpha-mammal toxin from the scorpion Androctonus australis.

Amino Acid Sequence

Auditory brainstem evoked potentials peak identification by finite impulse response digital filters.

Linear phase finite impulse response (FIR) filtering can be used to differentiate auditory brainstem evoked potentials (ABEP) components. The power spectrum of ABEP at high intensities indicates that they contain 3 frequency bands that can be distinguished by applying appropriate digital filters with the following characteristics: up to 240 Hz (revealing slow components), 240-483 Hz (resulting in medium components) and above 500 Hz (leaving only fast components). The results using these filters, indicate that the medium components coincide with peaks I, III and V and that the slow filter results in a 'pedestal' whose peak coincides with peak V. These findings were used for automatic identification of ABEP peaks. A coincidence of the 'pedestal' peak with a medium component was sought and labelled peak V. The preceding medium peaks were labelled, in order of decreasing latency, III and I. Validation of this procedure was conducted on ABEP from normal subjects, using different stimulus rates and intensities, as well as from selected neurological patients with lesions affecting the brainstem. Provided the waveform included a 'pedestal', the results proved this procedure to be reliable and in very good agreement with manual identification and measurement of ABEP peaks.

Adult

Application of finite impulse response digital filters to auditory brain-stem evoked potentials.

Finite impulse response digital filtering is a linear non-distorting operation and hence can be used to differentiate ABEP components. Since the power spectrum of the ABEP indicates that it contains more than two frequency bands, they can be distinguished by applying digital filters with special characteristics: up to 200 Hz (slow components), 200-400 Hz (medium components) and above 500 Hz (fast components). The results, using these filters, indicate a different nature of components II and IV as compared to I, III and V. While II and IV are not detected under 500 Hz and thus are called 'fast components,' I, III and V are the 'middle components' and appear above 200 Hz. The slow filter results in a 'pedestal' whose peak coincides with peak V. The results of this study show that the ABEP wave form is obtained by the superposition of at least 3 major waves having distinct frequency bands.

Adult

A new skeletal dysplasia syndrome with rhizomelia of the humeri and other malformations.

An Arab family is reported in which the proband and two affected sibs had bilateral rhizomelia of the humerus and other skeletal, craniofacial and cardiac abnormalities. Since all three affected sibs died during early childhood, this may be a lethal condition. We believe this constellation of findings which has not been previously described represents a new syndrome, most probably transmitted as an autosomal recessive disorder.

Abnormalities, Multiple

Time domain analysis of VEPs. Detection of waveform abnormalities in multiple sclerosis.

Visual evoked potentials (VEPs) are a useful tool in the diagnosis of multiple sclerosis. To improve their diagnostic power in the early stages of the disease, the VEP shape, as well as its latency, were considered. The Karhunen-Loeve expansion (KLE) was used because it affords an unique advantage in classifying the VEPs by their shape, and gives a well-defined criterion based on similarity to the normative prototype. Using this criterion, it was possible to quantitatively define normative limits of waveform. We were also able to detect early changes in VEPs recorded from suspected multiple sclerosis patients. KLE promises to enable classification of waveforms in early stages of the pathology, when peak-latency comparisons are the least effective.

Adult

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism.

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.

Adolescent

The effect of once-daily minoxidil on blood pressure and plasma lipids.

Once-daily minoxidil administration was added to the treatment regimen of 11 patients with hypertension that was inadequately controlled by nadolol 160 mg and chlorthalidone 50 mg given once daily. Additional diuretic therapy was needed by five patients. During treatment without minoxidil and at three and six months of maintenance minoxidil therapy, respectively, 24-hour postdose supine blood pressure fell significantly (P less than .01) from 142 +/- 19/96 +/- 6 mm Hg to 132 +/- 16/87 +/- 4 and 131 +/- 12/87 +/- 4 mm Hg, and home recordings showed that minoxidil induced a mean increase of about 5 beats/min in heart rate. Resting plasma renin activity was not significantly altered. High-density lipoprotein (HDL) cholesterol increased from 31.6 +/- 9.9 to 35.2 +/- 10.9 mg/dL (P less than .05) and to 34.4 +/- 11.3 mg/dL (NS), and low-density lipoprotein (LDL) cholesterol decreased from 146 +/- 36 to 136 +/- 32 mg/dL (P less than .05) and to 126 +/- 35 mg/dL (P less than .01) over the same periods. At six months, approximately 20% changes in ratios of HDL cholesterol to either LDL or total cholesterol were seen. These changes occurred despite a three-pound mean increase in body weight (P less than .05); these alterations are potentially beneficial in terms of reducing the estimated risk of coronary artery disease.

Adult