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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 19 recordsLinked to original sources
PubMed1995

Structure/function analysis of the periplasmic histidine-binding protein. Mutations decreasing ligand binding alter the properties of the conformational change and of the closed form.

The periplasmic histidine-binding protein, HisJ, is a receptor for the histidine permease of Salmonella typhimurium. Receptors of this type are composed of two lobes that are far apart in the unliganded structure (open conformation) and drawn close together in the liganded structure (closed conformation). The binding of the ligand, in a cleft between the lobes, stabilizes the closed conformation. Such receptors have several functions in transport: interaction with the membrane-bound complex, transmission of a transmembrane signal to hydrolyze ATP, and receiving a signal to open the lobes and release the ligand. In this study the mechanism of action of HisJ was further investigated using mutant proteins defective in ligand binding activity and closed form-specific monoclonal antibodies (Wolf, A., Shaw, E. W., Nikaido, K., and Ames G. F.-L. (1994) J. Biol. Chem. 269, 23051-23058). Y14H is defective in stabilization of the closed form, does not assume the closed empty form, and assumes an altered closed liganded form. T121A and G119R are similar to Y14H, but assume a normal closed liganded form. S72P binds the ligand to the open form, but does not assume a recognizable closed form. S92F is defective in the ability to undergo conformational change and to stabilize the closed form. All other mutant proteins appear to fall within one of these four categories. The biochemical characterization of these mutant proteins agrees with the structural analysis of the protein. We suggest that mutant proteins that do not assume the normal closed form, in addition to their defect in ligand binding, fail to interact with the membrane-bound complex and/or to transmit transmembrane signals.

Antibodies, Bacterial↗
PubMed1995

Panic attacks as ictal manifestations of parietal lobe seizures.

Although most panic attacks appear to be primary psychiatric disturbances, some evidence suggests a biologic basis for panic disorder, possibly associated with temporal lobe dysfunction. Fear is a common affective change associated with some complex partial seizures (CPS) originating from the right temporal lobe. We describe a previously unreported association between panic attacks and seizures originating from the parietal lobe in 2 patients with right parietal lobe tumors. Intracranial monitoring documented correlations between the symptoms of fear and restricted regional parietal cortical discharges. Surgical resections of the lesions (one total, one subtotal) resulted in complete recovery or improvement.

Adult↗
PubMed1995

Radiologic appearance of the dysembryoplastic neuroepithelial tumor.

PURPOSE: To evaluate the computed tomographic (CT) and magnetic resonance (MR) imaging features of dysembryoplastic neuroepithelial tumor (DNT). MATERIALS AND METHODS: Six CT studies (four with contrast material enhancement) and 10 MR imaging studies (seven with gadolinium enhancement) obtained in 10 patients with a history of seizures and pathologically proved DNT were retrospectively reviewed. RESULTS: All tumors were intracortical or subcortical. CT showed a low-attenuation mass in all cases except one of mixed isoattenuation and low attenuation. The DNT had decreased signal intensity on T1-weighted MR images and well-demarcated increased signal intensity on T2-weighted images without peritumoral edema. Prominent MR imaging features were a gyriform configuration on T1- or T2-weighted images in 10 patients (100%), well-demarcated lobular tumor margins on T2-weighted images in eight (80%), and a high rate of bone remodeling of the adjacent calvaria on MR (60% [n = 6]) and CT (67% [n = 4]) images. CONCLUSION: Diagnosis of DNT with imaging modalities alone may be difficult, but these radiologic features may aid in differentiating DNT from other gliomas.

Adolescent↗
PubMed1995

Reduced pancreatic insulin release and reduced peripheral insulin sensitivity contribute to hyperglycaemia in cystic fibrosis.

Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded conflicting results. We studied 18 patients with CF (9 male, 9 female, age 15-29 years) and 17 healthy control subjects (8 male, 9 female, 20-32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's "Minimal Model" was used to quantitate both peripheral insulin sensitivity (SI) and insulin-independent glucose disposal (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic (22%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0-10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls; P < 0.0001), with no difference between the CF-NGT and CF-IGT/DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, SI was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97 +/- 0.16 x 10(-4) l/min/pmol; control group: 1.95 +/- 0.25; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The histidine-binding protein undergoes conformational changes in the absence of ligand as analyzed with conformation-specific monoclonal antibodies.

The periplasmic histidine-binding protein, HisJ, and the lysine-, arginine-, ornithine-binding protein (LAO) are receptors for histidine transport via the histidine permease of Salmonella typhimurium. The receptors have similar structures, being composed of two lobes held together by two peptide segments, with the ligand-binding site located in a cleft between the lobes. The two lobes are far apart in the unliganded structure (open conformation) and are drawn close together in the liganded structure (closed conformation). The tight binding of the ligand via protein side chains as well as the peptide backbone from both lobes stabilizes the closed conformation (Oh, B.-H., Pandit, J., Kang, C.-H., Nikaido, K., Gokcen, S., Ames, G. F.-L., and Kim, S.-H. (1993) J. Biol. Chem. 268, 11348-11353; Oh, B.-H., Kang, C.-H., De Bondt, H., Kim, S.-H., Nikaido, K., Joshi, A., and Ames, G. F.-L. (1994) J. Biol. Chem. 269, 4135-4143). In this study two conformation-specific monoclonal antibodies (mAbs) that trap the protein in the closed empty form have been characterized and used to provide evidence that HisJ can assume the closed empty form in the absence of ligand. Several pieces of evidence were provided to demonstrate that these mAbs are specific for HisJ in the closed form. Histidine improves the interaction of these mAbs with immobilized HisJ. The mAbs inhibit both the exchange and the dissociation of histidine from HisJ, indicating that they are able to trap the protein in the closed liganded form. The characterization of the epitopes of the conformation-specific mAbs shows that they include residues that are located in both lobes and that are far apart in the open form but close to each other in the closed form, so that the mAbs must be sensitive to their spatial orientation. Two mAbs that are not conformation-specific according to these criteria were also identified.

Antibodies, Monoclonal↗
PubMed1994

Release of angiotensin in the paraventricular nucleus in response to hyperosmotic stimulation in conscious rats: a microdialysis study.

Angiotensin peptides are thought to act as neurotransmitters or neuromodulators in central osmoregulation. We tested the hypothesis that angiotensin peptides are released in the paraventricular nucleus (PVN) of the hypothalamus upon local osmotic stimulation. Brain microdialysis and radioimmunoassay (RIA) techniques were used to measure the release of immunoreactive angiotensin II (irANG II) in the PVN following direct stimulation of this area with hyperosmotic solutions. In conscious rats, perfusion of the PVN with 0.3 M and 0.6 M NaCl in artificial cerebrospinal fluid (aCSF) elicited concentration-dependent increases in irANG II release to 5.52 +/- 0.53, (P < 0.01, n = 8) and 9.01 +/- 1.03 pg/100 microliters, (P < 0.001, n = 7), respectively, from basal values of 3.04 +/- 0.46 pg/100 microliters. Local perfusion of the PVN with 1.2 M glucose in aCSF also resulted in an increased release of irANG II from 3.07 +/- 0.87 to 6.24 +/- 0.45 pg/100 microliters (P < 0.05, n = 5). Fractionization of angiotensin peptides by HPLC followed by RIA revealed that ANG II (1-8) and ANG III (2-8) were released in similar amounts in the perfusate collected during 0.6 M NaCl stimulation (4.79 +/- 0.69 and 3.45 +/- 0.76 pg/100 microliters, respectively). Our results show that both, ANG II and ANG III are released in the PVN in response to local hyperosmotic stimulation. They support the concept that angiotensin peptides in the PVN are involved as neurotransmitters in central osmotic control.

Angiotensin II↗
PubMed1994

Successful treatment of meningitis due to multiply resistant Enterococcus faecium with a combination of intrathecal teicoplanin and intravenous antimicrobial agents.

Following neurosurgery necessitated by intractable seizures, Enterococcus faecium meningitis that was resistant to ampicillin, a high-level aminoglycoside (MIC, > 2,000 micrograms/mL), and vancomycin developed in a 6-year-old boy. Treatment with intrathecal teicoplanin in combination with intravenous clindamycin, rifampin, and ampicillin was successful. The role of intravenous and intrathecal antibiotics in treatment of this infection is discussed. This case is illustrative of the safety and potential usefulness of intrathecally administered teicoplanin.

Child↗
PubMed1994

Continuous-wave Doppler investigation of uteroplacental vessels in high-risk pregnancies as predictor of fetal growth retardation and pregnancy-induced hypertension.

Continuous-wave Doppler sonography of uteroplacental vessels and the umbilical artery was used as an additive method in the management of risk pregnancies. Its major advantage lies in permitting noninvasive access to placental perfusion. In a sample of 650 singleton pregnancies considered at risk, flow patterns of the right and left uterine and arcuate arteries and of the umbilical artery were obtained. Increased resistance in uteroplacental circulation alone (90th percentile of resistance index and/or notching) was seen in 62 of 100 patients with confirmed growth retardation, proving the key role played by uteroplacental perfusion disorders. Early diastolic notching as well as incomplete vascular flow patterns were also found significantly more often in the growth-retarded group compared to the controls, especially in pregnancies additionally beset by hypertensive disorders. Doppler study of both utero- and fetoplacental circulation increased the sensitivity to 76% in pregnancies with intrauterine growth retardation, and to 90% in those cases with an additional risk of pregnancy-induced hypertension, while the false-positive rate (100-specificity) remained acceptable (17%).

Female↗
PubMed1994

[Treatment of lumbar facet joint syndrome by CT-guided infiltration of the intervertebral joints].

INTRODUCTION: Lumbar facet joint syndrome is a common condition, involving about 79% of patients suffering from low back pain. Denervation by scalpel or electrofrequency is a well-known method of treating it. An alternative method for longer lasting pain relief is CT-guided intraarticular infiltration of facet joints with local anaesthetics and cortisone. METHODS: In 62 patients with facet syndrome a total of 205 joints were infiltrated, CT monitoring being used in all cases. Each facet joint was infiltrated with 0.3 ml bupivacaine and 0.8 ml methylprednisolone. The patients were divided into three groups. Group 1 consisted of 24 persons who had undergone lumbar disc surgery, group 2 of 23 patients with spondylarthrosis of the facet joints, and group 3 of 15 patients who had undergone lumbar disc surgery but had additional spondylarthrosis. Very good results were defined as pain relief for longer than 4 weeks, good results as pain relief for up to 4 weeks and poor results as brief pain relief or none at all. In 27 patients facet infiltration was performed for the purpose of diagnosis. RESULTS: Results were significantly in group 2 than in group 1 (Fisher's exact test P < 0.012). In group 3 results were better than in group 1, but worse than in group 2. These differences were not statistical by significant (Table 3). Seven patients in the diagnostic group had no pain relief, and facet syndrome was excluded. CONCLUSIONS: CT-guided facet joint infiltration is a good method for treatment and diagnosis of lumbar facet joint syndrome. It can be repeated and has no severe side effects. The best results were seen in patients with spondylarthrosis of the facet joints. After lumbar disc surgery the pain relief was shorter, though it also yielded good results. For patients with unspecific low back pain, facet joint injections are a very good diagnostic method, allowing definite exclusion of lumbar facet syndrome.

Bupivacaine↗
PubMed1994

Epidural infusions of sufentanil with and without bupivacaine: comparison with diamorphine-bupivacaine.

The requirements for supplementary 3 ml epidural injections of bupivacaine 0.5% (top-ups) were used in a randomized double-blind study to compare the effects of five types of thoracic epidural infusions given at 2.5 ml h-1 for the first 24 h after major surgery to the upper abdomen in 99 patients and the lower abdomen in 72. The infusions were: bupivacaine 0.167% alone; diamorphine 0.167 mg ml-1 (0.417 mg h-1) in bupivacaine 0.167%; sufentanil 2 micrograms ml-1 (5 micrograms h-1) in 0.167% bupivacaine; sufentanil 4 micrograms ml-1 (10 micrograms h-1) in 0.167% bupivacaine; and sufentanil 4 micrograms ml-1 (10 micrograms h-1) in normal saline. The patients who had upper abdominal surgery were on average older than those having lower abdominal surgery and a larger proportion of them were female. They received on average fewer top-ups. After both upper and lower abdominal surgery, epidural infusions of bupivacaine alone required the most frequent supplementation (inter-quartile range 6-14 top-ups in 24 h) and the two sufentanil-bupivacaine mixtures required the fewest (interquartile range 0-12 top-ups in 24 h). The infusions of sufentanil without bupivacaine were significantly less effective than the sufentanil-bupivacaine mixtures after upper (but not lower) abdominal surgery. Although the two sufentanil-bupivacaine mixtures were indistinguishable in analgesic effectiveness after either upper or lower abdominal surgery, the lower (5 micrograms h-1) dose rate of sufentanil gave a significantly higher average breathing rate and lower average PaCO2 for the first 24 h after lower (but not upper) abdominal surgery. Blood samples were taken (as an afterthought) from 11 patients receiving sufentanil 10 micrograms h-1, just before the epidural infusion was stopped. The concentrations were mostly above the range for systemic analgesia, but below the values that would have been expected if a steady state had been achieved.

Abdomen↗
PubMed1994

Cruciate retained and excised total knee arthroplasty. A comparative study in patients with bilateral total knee arthroplasty.

A comparative study of posterior cruciate ligament retention and excision was conducted in patients who underwent bilateral total knee arthroplasty using the total condylar modifier prosthesis. The posterior cruciate ligament was excised in one knee and was retained in the other knee in 28 patients. Postoperative results were assessed using the Hospital for Special Surgery Knee Evaluation Score. In addition, stair activity was tested to determine whether there was preferential dependence on one of the two knees. There was no significant difference between the posterior cruciate ligament retained or excised knees in terms of postoperative Hospital for Special Surgery Knee Evaluation Score. Patients who ascended and descended stairs with one leg at a time tended to prefer the posterior cruciate ligament retention side. Those who could use each leg in sequence to go up and down stairs, however, did not show preferential dependence on either knee.

Activities of Daily Living↗
PubMed1993

Cataractogenic effects in rats following chronic administration of SDZ ICT 322, a selective 5-HT3 antagonist.

SDZ ICT 322, an indole-3-carboxylic acid scopine ester developed for the treatment of delayed gastric emptying, was administered in feed to four groups of 14 male and 14 female Wistar rats at daily doses of 0, 5, 25 or 125 mg/kg/day for 26 weeks. Clinical and periodic ophthalmic examinations, hematology, clinical biochemistry, and urinalysis were performed. Eyes were examined for histopathologic and electronmicroscopic alterations as well as for reduced glutathione (GSH) and oxidized glutathione (GSSG) levels. Skin effects with hair loss, hyperemia, and desquamation were found in the majority of the high-dose rats. At study termination, bilateral posterior lens opacities had developed in 26 of the 28 high-dose rats. Histopathologically, grossly irregular and fragmented lens fibres were observed. Severe vacuolization of the lens epithelium was seen electronmicroscopically. The GSH/GSSG ratio was statistically significantly reduced in lenses of mid- and high-dose animals. Since decreased GSH/GSSG ratio is an established indicator for increased oxygen radical generation, these data suggest a possible role of oxidative stress in cataracts induced by SDZ ICT 322.

Animals↗
PubMed1993

[Diagnostic value of continuous wave (cw) Doppler sonography in maternal diabetes mellitus].

Doppler studies of umbilical, uterine and arcuate artery velocity wave forms were performed in 40 insulin-dependent diabetic women in the first and second half of pregnancy. Using a continuous-wave Doppler device, the resistance index (RI) was calculated to determine the degree of vascular resistance in utero-placental and foeto-placental compartment. The 90th percentile was used to classify flow velocity profiles. In addition, diastolic notching and incomplete registration of uterine and arcuate arteries were considered as an abnormal result in utero-placental perfusion. The prevalence of abnormal velocity wave forms in this risk group was higher than in a non-diabetic population. No significant correlation was found between abnormal Doppler studies and White's classification. Patients with vasculopathy represent a high-risk group for foetal growth retardation, which may be detected early by umbilical and especially uterine artery Doppler studies. Abnormal uterine and arcuate artery wave forms allowed identification of patients who developed pregnancy-induced hypertension/preeclampsia.

Asphyxia Neonatorum↗
PubMed1993

Efficacy and tolerability of galactosamino-glycuronoglycan-sulfate in osteoarthritis of the knee: an 11-month experience.

Chondroprotective agents represent a model for basic therapy of osteoarthritis (OA), thanks to their activity directed towards the protection and repair of articular cartilage. One of the most recent compounds capable of interfering with the pathogenic mechanisms of OA is galactosamino-glycuronoglycan-sulfate (GGGS), a highly depolymerized glycosaminoglycan with favourable chondroprotective and anti-inflammatory properties. The present paper describes the experience with GGGS given to a group of patients with symptomatic OA of the knee as compared to a parallel group treated with placebo. The drug (or placebo) was administered in two series of 25 intramuscular injections each over a period of 11 months, and four successive evaluations of treatment were made at various times during this period, and a fifth evaluation one month after the suspension of treatment to better evaluate the permanence of the therapeutic effect. The results obtained showed significant improvements on pain, algofunctional index and consumption of NSAIDs only in the group treated with GGGS. The drug was well tolerated and no reduction of dosage or drop-out from therapy were required. The favourable clinical effects and the patients' good compliance make GGGS a useful drug for successful chondroprotective treatment of OA.

Aged↗
PubMed1993

Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome.

The cardiovascular response of the patient with acute spinal cord injury (SCI) is known to be altered secondary to the cord injury. Our current protocol of managing the acute phase of patients with SCI includes invasive hemodynamic monitoring (with arterial line and Swan-Ganz catheter) and support with fluids and dopamine and/or dobutamine, titrated to maintain a hemodynamic profile with adequate cardiac output (to be determined by oxygen consumption and delivery) and a mean blood pressure of > 90 mm Hg. We feel that this protocol provides two benefits: 1) maintaining the mean blood pressure improves the morbidity of these patients by deterring ischemia and accompanying secondary insults; 2) aggressive monitoring and hemodynamic intervention help stabilize the hemodynamic status of these patients and make it possible to consider early surgery in selected cases. Our hypothesis is that the pulmonary vascular bed is more sensitive to the sympathectomized effect of acute complete cervical SCI. We analyzed the demographic, neurologic, and hemodynamic data of 50 consecutive patients during their first week postinjury. All had signs of myelopathy; 31 (62%) were considered clinically complete. Of the 50 patients, 9 (18%) died, 20 did not improve functionally, and 21 improved. The mean heart rate (82.1 +/- 13.3), blood pressure (94.4 +/- 9.4), pulmonary artery pressure (22 +/- 5) and wedge (12.7 +/- 3.4), cardiac index (4.5 +/- 0.9), systemic vascular resistance index (SVRI) (1637 +/- 399), pulmonary vascular resistance index (PVRI) (181 +/- 80), and oxygen transport (694 +/- 156) showed good response to the treatment. Because the measurements were obtained during treatment, they differ from the expected "classic sympathectomized" response, but they provide a database for further analysis of hemodynamic manipulation in SCI. An analysis of the hemodynamic parameters did not differentiate between complete and incomplete lesions or between patients with functional improvement. We determined, on the basis of the initial hemodynamic measurements, that no patient with a clinically complete motor deficit (Frankel Grade A+B) improved of the 10 who had measurements compatible with either: 1) PVRI < 100 with SVRI < 1200; or 2) PVRI < 115 with SVRI < 1300 or PVR/SVR ratio of < 0.08 when SVRI was < 1600. These patients could not have other measurements that showed low SVRI < 1350 with PVRI > 139. At odds with this unique group, 13 of 29 patients with the same clinical picture and without the above physiological criteria of severe hemodynamic deficit eventually improved (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗