Biomedical subjects

I Berger

Publications and source records attributed to I Berger.

At least 55 records · Page 3Linked to original sources

PubMed1995

Crystal structure of the T4 regA translational regulator protein at 1.9 A resolution.

The translational regulator protein regA is encoded by the T4 bacteriophage and binds to a region of messenger RNA (mRNA) that includes the initiator codon. RegA is unusual in that it represses the translation of about 35 early T4 mRNAs but does not affect nearly 200 other mRNAs. The crystal structure of regA was determined at 1.9 A resolution; the protein was shown to have an alpha-helical core and two regions with antiparallel beta sheets. One of these beta sheets has four antiparallel strands and has some sequence homology to RNP-1 and RNP-2, which are believed to be RNA-binding motifs and are found in a number of known RNA-binding proteins. Structurally guided mutants may help to uncover the basis for this variety of RNA interaction.

Amino Acid Sequence↗

PubMed1995

Stable loop in the crystal structure of the intercalated four-stranded cytosine-rich metazoan telomere.

In most metazoans, the telomeric cytosine-rich strand repeating sequence is d(TAACCC). The crystal structure of this sequence was solved to 1.9-A resolution. Four strands associate via the cytosine-containing parts to form a four-stranded intercalated structure held together by C.C+ hydrogen bonds. The base-paired strands are parallel to each other, and the two duplexes are intercalated into each other in opposite orientations. One TAA end forms a highly stabilized loop with the 5' thymine Hoogsteen-base-paired to the third adenine. The 5' end of this loop is in close proximity to the 3' end of one of the other intercalated cytosine strands. Instead of being entirely in a DNA duplex, this structure suggests the possibility of an alternative conformation for the cytosine-rich telomere strands.

Animals↗

PubMed1995

NMDA receptors are involved at the ventrolateral nucleus tractus solitarii for termination of inspiration.

The purpose of the present study was to determine whether blockade of excitatory amino acid receptors at the ventrolateral nucleus of the tractus solitarius would influence respiratory activity. This was done by microinjecting excitatory amino acid receptor antagonists into the ventrolateral nucleus of the tractus solitarius of alpha-chloralose-anesthetized animals while monitoring respiratory activity using a Fleisch pneumotachograph and arterial blood pressure and heart rate. Bilateral microinjection of the NMDA receptor antagonist, 3-[(R)-carboxypiperazin-4-yl]-propyl-1- phosphomic acid (CPP), 5.62 nmol per side, produced an increase in inspiratory duration (+4 +/- 1.6 s, n = 8) which progressed to an apneustic pattern of breathing. Similar results were obtained with CPP microinjected into the ventrolateral nucleus of the tractus solitarius of three vagotomized animals. Bilateral microinjection of a second NMDA receptor antagonist, 2-amino-7-phosphono-heptanoic acid (AP7), 562 nmol per side, produced qualitatively similar effects on respiration as seen with CPP. In contrast, blockade of non-NMDA receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNXQ), 0.125 nmol per side, had very little effect on respiration. Activation of NMDA receptors at the ventrolateral nucleus of the tractus solitarius with bilateral microinjection of NMDA, 39 pmol, produced a large increase in expiratory duration (+11 +/- 3 s, n = 8), and apnea during the expiratory phase of the respiratory cycle in half of the animals studied. Similar results were obtained with D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazol-proprionate (AMPA). These results indicate that an endogenous excitatory amino acid released at the ventrolateral nucleus of the tractus solitarius and acting at the NMDA receptor, plays a significant role in respiratory timing.

2-Amino-5-phosphonovalerate↗

PubMed1995

Extension of the four-stranded intercalated cytosine motif by adenine.adenine base pairing in the crystal structure of d(CCCAAT).

The crystal structure of d(CCCAAT), refined at 2.0 A resolution, shows a four stranded molecule in which two parallel duplexes intercalate with opposite polarity, using cytosine.protonated cytosine base pairs. The intercalation motif in this structure is extended by adenine.adenine base pairs. Two topologically distinct broad grooves are found in the lath-like central part of the molecule with the phosphate groups on one side bent over towards each other, stabilized by bridging water molecules. At the 3' ends, two arrangements of intermolecular A.A.T base triplets are found, involving both asymmetric and symmetric A.A base pairs joined to thymine residues by Watson-Crick and reverse Hoogsteen base pairing, respectively.

Adenine↗

PubMed1995

Mortality in sleep apnea patients: a multivariate analysis of risk factors.

During 1976-1988 we diagnosed sleep apnea syndrome (SAS) in 1,620 adult men and women monitored in the Technion sleep laboratories. Their age at the time of diagnosis ranged between 21 and 79 years. Fifty-seven patients (53 men and 4 women) had died by 1990, 53% due to respiratory-cardiovascular causes. The observed/expected (O/E) mortality rates, calculated for men only, revealed excess mortality of patients under 70 years old. Excess mortality was significant in the fourth and fifth decades (3.33, p < 0.002; 3.23, p < 0.0002, respectively). In patients older than 70 O/E was 0.33 (p < 0.0007). Hierarchical multivariate analysis with four fixed variables [age, body mass index (BMI), hypertension and apnea index] and four additional variables added manually one at a time (heart disease, lung disease, diabetes, apnea duration) was used to determine the predictors of death from all causes, cardiopulmonary causes and from myocardial infarction (MI). All four major variables were found to be significant predictors of mortality from all causes, in addition to lung disease and heart disease. Only age and BMI were significant predictors of cardiopulmonary deaths in addition to lung disease. Age, BMI and hypertension predicted MI deaths in addition to lung disease. These results were interpreted to suggest that SAS affects death indirectly, most probably by being a risk factor for hypertension.

Adult↗

PubMed1995

Children with asthma in the emergency department: spectrum of disease, variation with ethnicity, and approach to treatment.

The role of the pediatric emergency department (ED) in the management of acute asthma was assessed by examining patterns of referrals, admissions, clinical patient evaluation, laboratory tests ordered, and treatment instituted. The functioning of the attending physicians with different degrees of seniority was also evaluated. One thousand thirty-six children with acute asthma (5.3% of all visits) were admitted to the ED during 1990. The mean age was 5.5 years, and the male to female ratio was 2.6:1. Fifty percent of the patients reported atopic disease in their immediate family, and upper respiratory tract infection preceding the attack was reported in 27% of patients. Significant differences were observed between Arab and Jewish patients: more Arab patients presented after physician referral (90 vs 33%) in morning hours (43 vs 26%), and after a longer duration of symptoms. Experienced physicians ordered fewer laboratory tests and treated the patients less aggressively than junior physicians. Patients treated by senior physicians stayed less time in the ED, and a smaller proportion of patients was hospitalized (4 vs 19%). Patients admitted by senior physicians had a longer period of hospitalization (4.7 vs 1.2 days). This study shows that ethnicity influenced the pattern of utilization of the ED and that the approach to care differed among junior and senior physicians.

Acute Disease↗

PubMed1995

Analgesia, sedation and paralysis in the intensive care unit.

Patients admitted to the intensive care unit often experience some degree of pain and frequently are anxious, confused or delirious. Relief of pain, anxiety and agitation is important for effective patient care. Initial attention should be directed toward eliminating organic causes of delirium. Opioids are the cornerstone of analgesia, while benzodiazepines and haloperidol are commonly used for sedation and relief of agitation. When sedative agents fail to control agitation and effective ventilation of the patient is compromised, it may be appropriate to pharmacologically paralyze the patient.

Analgesics↗

PubMed1994

Crystal structure of intercalated four-stranded d(C3T) at 1.4 A resolution.

The crystal structure of d(C3T), solved at 1.4 A resolution, reveals that the molecule forms a four-stranded intercalated complex. It consists of two parallel-stranded duplexes, each of which is held together by cytosine-protonated cytosine base pairs. The two duplexes are intercalated with each other and have opposite strand orientation. The molecule has a flat, lath-like appearance, and the covalently bonded cytosines have a slow right-handed twist of 17.1 degrees. However, there is considerable asymmetry. On one of the flat sides, the phosphate groups are rotated away from the center of the molecule. They are held in this orientation by bridging water molecules that bind the NH of cytosine and a phosphate group of an opposite chain. There is also considerable microheterogeneity in the structure. The cytosine hemiprotonation occurs even at pH 7 where stable crystals form.

Crystallography, X-Ray↗

PubMed1994

Acute asthma. Single dose oral steroids in paediatric community clinics.

The treatment of an acute asthma attack usually includes bronchodilators and often steroids. We studied 70 children who were randomly assigned to receive either single dose steroids (oral prednisone: 20-40 mg) or placebo on a double blind basis. The time course of the observation was 72 h. We demonstrate that a single dose of steroids, given orally in paediatric community clinics during an acute mild to moderate asthma attack, significantly improves the patient's course; deterioration was prevented, symptoms were relieved faster, and hospitalization was not required. We encourage paediatricians in the ambulatory clinics to follow this treatment modality and to give, in addition to other conventional therapy, a single oral dose of steroids early in the asthma attack, in order to relieve and shorten the child's distress.

Acute Disease↗

PubMed1994

The human junD gene is positively and selectively autoregulated.

The junD gene is much less inducible than that of the two other members of the jun family; c-jun and junB, and is constitutively expressed in most tissues. We cloned the promoter of the human junD (hjunD) gene and found that it contains multiple cis-acting elements, most of which are conserved from chicken to human. Those included the TATA box, TRE, the CAAT box (referred to as the CTT complex), CREs, an Oct motif, and a number of GC boxes, most probably the recognition site for the SP1 transcription factor. The enhancer of the gene was localized to the -83 to -194 region that contains a GC box and an Oct motif. The CTT complex is shared by the promoters of the three jun genes, but each with a unique TRE. We show here that the hjunD TRE binds proteins that are related, but not identical, to the classical AP1 complex. We demonstrate by transfection experiments that the hjunD promoter is preferentially regulated by hjunD, through its unique TRE, generating a positive autoregulatory loop that might be responsible for its constitutive expression.

Animals↗

PubMed1993

High-dose droperidol protects against experimental coronary thrombosis in dogs and pigs and attenuates aggregation of porcine platelets and Ca2+ mobilization in human platelets.

BACKGROUND: Activation of platelets after contact with thrombogenic substrates may be an early factor leading to coronary artery thrombosis and myocardial infarction. Haloperidol, a butyrophenone, possesses weak in vitro platelet inhibitory activity. Experiments were designed to determine whether droperidol, a butyrophenone adjunct to anesthesia, protected against experimental coronary thrombosis in intravenously anesthetized open-chest dogs and pigs, attenuated ex vivo porcine platelet aggregation, and inhibited agonist-induced increases in [Ca2+]i in human platelets. METHODS: In dogs and pigs, a lesion consisting of deendothelialization, deep vessel wall injury, and critical stenosis was created in the proximal circumflex arteries, resulting in coronary thrombus formation accompanied by decreased circumflex artery blood flow. Embolization of the thrombus restored flow, but the cycle then repeated, resulting in repetitive cyclical flow reductions (CFRs). These were measured using an electromagnetic flow probe. RESULTS: In dogs, droperidol 0.2 mg/kg intravenous rapidly abolished CFRs in all ten animals, with frequency decreasing from 0.22 +/- 0.01 cycles/min to 0. Droperidol 0.8 mg/kg intravenous rapidly abolished CFRs in seven of eight pigs, with frequency decreasing from 0.15 +/- 0.01 to 0.02 cycles/min (P < 0.005). In both species, additional doses of droperidol were effective against CFRs augmented with intravenous epinephrine, a catecholamine that stimulates thrombosis. Ex vivo platelet aggregation studies were performed in platelet-rich plasma obtained from pigs before and after droperidol 0.8 mg/kg intravenous. Pretreatment with the drug resulted in marked inhibition of aggregation evoked by collagen, modest attenuation of that elicited by adenosine diphosphate (ADP), but no effect on that evoked by arachidonic acid. In human platelets, apparent [Ca2+]i was estimated using the fluorescent indicator indo-1 and flow cytometry. Droperidol 10(-7), 10(-6), and 10(-5)M had a dose-dependent inhibitory effect on the amplitude of increases in [Ca2+]i evoked by 10(-5)M serotonin (plus 10(-7)M epinephrine). The higher droperidol concentration decreased the response to as much as 30% of control (P < 0.001). Droperidol lacked effect on Ca2+ mobilization elicited with 10(-6)M ADP. CONCLUSIONS: The results from three experimental models indicate that droperidol attenuates experimental coronary thrombosis in animals and suggest that this inhibition may result, in part, from a direct droperidol depressant effect on platelet activation and aggregation.

Adenosine Diphosphate↗

PubMed1993

Referral, admission, and discharge patterns in a pediatric emergency department in Israel.

The pediatric emergency department (PED) is an important component of the medical services provided by a hospital. The purpose of the study was to describe the patterns of referrals, admissions, and discharges in a PED to determine to what extent the PED is used solely as an emergency unit, as opposed to being used as a part of a set of primary care facilities. Data were recorded from 1200 patient charts, out of 19,000 visits to a PED in Israel in 1988. Variables such as age, sex, ethnicity, and distance between residence and hospital were checked. About half of the patients arrived during the morning shift. There was an inverse relationship between the distance from the patient's home to the hospital and the rate of visits to the PED. Fifty-eight percent of the total were self-referred; this rate increased to 84% during the night shift. Only one quarter of all children had additional laboratory or x-ray tests. Most of the diagnoses did not require emergency services. Eighty-one percent of the patients were discharged from the PED to their community physician. The rate of admissions was low (11%). This study shows that a large part of the PED work is actually primary care. Some of the demographic, cultural, and ethnic reasons for these patterns are reviewed.

Adult↗

PubMed1993

Genetic and molecular analyses of the C-terminal region of the recE gene from the Rac prophage of Escherichia coli K-12 reveal the recT gene.

The nucleotide sequence of the C-terminal region of the recE gene of the Rac prophage of Escherichia coli K-12 reveals the presence of a partially overlapping reading frame we call recT. Deletion mutations show that recT is required for the RecE pathway of conjugational recombination. By cloning recT with a plasmid vector compatible with pBR322, we showed by cis-trans tests that the portion of the recE gene encoding ExoVIII DNA nuclease activity is also required for RecE pathway conjugational recombination. The recT gene can replace the redB gene of lambda for recA-independent plasmid recombination. A Tn10 insertion mutation previously thought to be in recE is located in recT and is renamed recT101::Tn10. Discrepancies between the molecular mass estimates of wild-type ExoVIII protein determined from mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and calculated from the predicted amino acid sequence are discussed. The hypothesis that wild-type ExoVIII protein results from fusion of RecE and RecT proteins is disproved genetically, thus supporting a previous hypothesis that the discrepancies are due to abnormal protein mobility in SDS-PAGE. A computer-performed scan of the bacteriophage nucleotide sequence data base of GenBank revealed substantial similarity between most of recE and a 2.5-kb portion of the b2 region of lambda. This suggests interesting speculations concerning the evolutionary relationship of lambda and Rac prophages.

Amino Acid Sequence↗

PubMed1993

The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea.

Automated ambulatory 24-h BP monitoring was made in 38 patients with obstructive sleep apnea syndrome. Stepwise multiple regression analysis revealed that diastolic, systolic, and mean BP values during sleep as well as during wakefulness were significantly related to apnea/hypopnea index and age. Minimal arterial O2 saturation and total sleep time also significantly contributed to diastolic and mean BP values during sleep. Body mass index did not significantly contribute to any of the BP values. These results support a causal relationship between the severity of sleep apnea syndrome and systemic hypertension.

Adult↗

PubMed1993

Carboplatin-liposomes as activators of hematopoiesis.

Recombinant colony stimulating factors are studied in clinical trials with the purpose being the relief of the side effects of high dose chemotherapy and to make an optimized treatment regimen possible. The broad use of such factors is hindered by their relatively high costs, their short elimination half-lives, the occurrence of mild side effects, and the limitation of their action to the stimulation of mainly neutrophils. Therefore, exogenous preparations inducing an endogenous activation of hematopoiesis are being sought. In experiments in mice we have shown that carboplatin-liposomes injected intraperitoneally in a single dose of 100 mg/kg led to a strong two-peak increase in white blood cell counts. A maximum 10-fold elevation compared to controls of free carboplatin or empty liposomes was observed on day 2 and was probably due to the release and mobilization of cells from storage compartments. The second peak of about a 6-fold increase occurred on day 7-8 and can be seen as an indicator of bone marrow stimulation. Differentiation of blood cells revealed that neutrophils, lymphocytes and platelets multiplied. We presume that this effect of carboplatin-liposomes is due to a relatively fast uptake of these vesicles by macrophages as their natural target. Within these cells carboplatin is metabolized, leading to an almost total loss of antineoplastic activity against the murine P388 leukemia. Concomitantly, cytokines are apparently induced in and released from macrophages producing secondarily hematopoietic growth factors either directly or in combination with other cytokines. An involvement of macrophages is indicated by the fact that an intraperitoneal pretreatment of mice with zymosan caused a partial but significant suppression of hematopoietic stimulation. In an in vitro colony forming assay of serum of mice treated 1, 3, or 7 days with carboplatin-liposomes, the number of colonies increased 20-fold compared to serum from saline treated animals. Additionally, a combined intraperitoneal treatment of mice with 100 mg/kg of cyclophosphamide followed by carboplatin-liposomes one hour later demonstrated that prevention of cytostatic-induced leukopenia is possible by this method. Although the mechanism of stimulation of hematopoiesis by carboplatin-liposomes is still partially unknown our results suggest that there should be further development of such a preparation for possible use in the treatment of cancer or other inherited or acquired hematopoietic disorders.

Animals↗

PubMed1992

Citrate and recurrent idiopathic calcium urolithiasis. A longitudinal pilot study on the metabolic effects of oral potassium citrate administered over the short-, medium- and long-term medication of male stone patients.

In idiopathic recurrent calcium urolithiasis (RCU) in men (n = 37) the metabolic effects of oral tripotassium citrate (PC) were investigated in a longitudinal field study. The patients were either normo- (n = 22) or hypocitraturic (n = 15). Laboratory examinations were performed before, and after 3, 6, and more than 12 months of medication. Acceptance of PC was poor, mainly because of the salty taste of the tablet preparation chosen, and a number of participants dropped out of the study. In the remaining participants, compliance was acceptable when evaluated on the basis of urinary potassium and undesired side effects did not occur. In the short term (up to 3 months), PC evoked compensated metabolic alkalosis (pH and citrate in urine increased; blood gases remained normal), a drop in urinary calcium, together with increasing oxaluria, hydroxyapatite supersaturation, and calcium phosphate crystalluria. In the long term (greater than 12 months) PC urinary pH and citrate "dissociated", in that pH returned to pretreatment baseline values, whereas citrate stayed at high levels. In normocitraturics but not in hypocitraturics, urinary urea and sodium increased with PC. Hypocitraturics appeared to be less sensitive to the effects of PC, as reflected by the relatively small rise in urinary pH and citrate, and they maintained higher mean levels of indicators of bone metabolism (osteocalcin, alkaline phosphatase, hydroxyproline) despite continuous administration of PC. It was concluded that although the PC tablet preparation was effective it may not be an ideal anti-stone drug treatment in the long term and that, especially in hypocitraturics, the intrinsic metabolic defect of RCU may not be sufficiently well controlled.

Acid-Base Equilibrium↗

PubMed1992

Citrate and recurrent idiopathic calcium urolithiasis. A longitudinal pilot study on the metabolic effects of oral potassium sodium citrate administered as short-, medium- and long-term to male stone patients.

In male patients with idiopathic recurrent calcium urolithiasis (RCU) the effects of oral potassium sodium citrate (PSC) on acid-base, citrate and mineral metabolism were investigated. There were 17 normocitraturic and 15 hypocitraturic patients. The examination time points in our clinical laboratory were prior to medication and after 3, 6 and over 12 months of medication. Urine collection periods were over 24 h, 2 h--after an overnight fast--3 h postprandially. Acceptance by the patients was poor, a large number refusing to take PSC for 12 months. Compliance of the patients continuing with the study was adequate as assessed by the urinary excretion of potassium and sodium. No unwanted side effects were observed. After 3 months of PSC medication a compensated metabolic alkalosis developed; in the urine calcium was decreased, while citrate, pH and oxalate were increased, as were hydroxyapatite supersaturation and calcium phosphate particles. After more than 12 months of PSC medication, citrate and pH tended toward the pretreatment baseline values, while hydroxyapatite supersaturation and calcium had already returned to pretreatment values. Despite ongoing PSC intake, patients with pre-existing hypocitraturia had lower urinary citrate than patients with previous normocitraturia, while the concomitant pH and hydroxyapatite supersaturation in the urine of the former remained at levels close to those of the latter. Under the influence of PSC, parathyroid gland function remained unchanged, but serum levels of bone alkaline phosphatase and osteocalcin were low, and urinary hydroxyproline was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1992

Oral ciprofloxacin in the management of chronic suppurative otitis media without cholesteatoma in children: preliminary experience in 21 children.

The current medical management of children with chronic suppurative otitis media without cholesteatoma unresponsive to local treatment and oral antibiotics is intravenous antibiotic therapy in the hospital setting. We studied the efficacy and toxicity of oral ciprofloxacin in chronic suppurative otitis media. Twenty-one children received oral ciprofloxacin, 30 mg/kg/day. Ear discharge was positive for bacteria resistant to other oral medications and susceptible to the quinolones. The mean duration of treatment was 16.7 days. In 18 children suppuration ceased and 3 failed their first course. During a mean follow-up of 15.4 months, 6 children remained free of ear, nose and throat problems. Otorrhea recurred in 12 children. Ear cultures were positive for organisms susceptible to amoxicillin in 5 of them. In 7 cases Pseudomonas aeruginosa was again isolated from otorrhea. Repeated antibiotic therapy was advocated only in 3 (2 responded to ciprofloxacin; 1 failed ciprofloxacin and was cured by ceftazidime). Adverse clinical effects were not observed. Transient neutropenia was observed in 1 child. There was no change in the height percentile. The results of this study show that children with chronic suppurative otitis media without cholesteatoma can be effectively treated with oral ciprofloxacin. This novel approach may prevent hospitalization.

Administration, Oral↗