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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 19 recordsLinked to original sources

Nonrandom distribution of gp120 N-linked glycosylation sites important for infectivity of human immunodeficiency virus type 1.

More than 20 consensus N-linked glycosylation sites occur in the gp120 coding sequence of most isolates of human immunodeficiency virus type 1. Based on the N-linked glycosylation pattern of a well-characterized recombinant gp120, it is likely that N-linked sugars are present at most, if not all, of the consensus glycosylation sites of the heavily glycosylated gp120. In this study, we evaluated the relative importance of each of the 24 N-linked glycosylation sites of gp120 in the molecular clone HXB2 to viral infectivity. The ability of HXB2-derived mutants, each having 1 of the 24 N-linked glycosylation sites mutated by site-directed mutagenesis, to infect CD4-positive SupT1 cells was compared with that of the wild-type virus. We found that most of the individual consensus N-linked glycosylation sites are dispensable for viral infectivity. The five consensus N-linked glycosylation sites that are likely to have important roles in infectivity are all located in the amino-terminal half of gp120, indicating that the N-linked glycosylation sites that are important for infectivity of human immunodeficiency virus type 1 are not randomly distributed in gp120. We predict that a partially glycosylated gp120 with most of the dispensable N-linked glycosylation sites removed may be a better vaccine candidate than the fully glycosylated gp120.

Amino Acid Sequence

The spectrum of CFTR mutations in south-west German cystic fibrosis patients.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 110 cystic fibrosis (CF) patients from the south-west of Germany was screened for 12 different mutations. This analysis resulted in an identification of 79% of all CF mutations and a complete genotype in 66% of the families. The most common mutation found was delta F508 (67%). Another 5 mutations accounted for a further 12.5% (4% G542X; 3% R553X; 3% N1303K; 2% 1717-1 G-->A; 0.5% G551D) whereas 6 mutations (R117H, A455E, delta I507, S549I, S549N, and R1162X) were not found. Fifty-four (49%) patients were delta F508 homozygotes and 18 (16.5%) were compound heterozygotes for delta F508 and one of the rarer mutations. These frequencies differ slightly from those found in the north of Germany and considerably from those reported from the south of Europe, which seems to be consistent with a north to south decline of the relative abundance of delta F508. Two patients, age 6 and 25 years, were compound heterozygotes for G542X and N1303K. The clinical features of the 6 year old were characterised by severe gastrointestinal and as yet only mild pulmonary complications whereas the 25 year old manifested severe pulmonary and gastrointestinal symptoms indicating that the N1303K mutation of the C-terminal CFTR nucleotide binding fold significantly impairs protein function in both the pancreas and the lungs.

Adolescent

Reversal of multidrug resistance by B859-35, a metabolite of B859-35, niguldipine, verapamil and nitrendipine.

It has been shown previously that verapamil and other calcium antagonists and calmodulin inhibitors can reverse multidrug resistance. We compared the potency of the dihydropyridine derivatives (4R)-3-[3-(4,4-diphenyl-1-piperadinyl)-propyl]-5-methyl-1,4-dihydr o-2,6- dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride (B859-35), a metabolite of B859-35, niguldipine and (R)-nitrendipine to that of (RS)-verapamil in reversing multidrug resistance. The accumulation of the fluorescent dye rhodamine 123, which is transported by the P-glycoprotein, was determined by a flow cytometer. Multidrug-resistant human HeLa KB-8-5 and Walker rat carcinoma cells were incubated in the presence and in absence of the drugs indicated above. We found that 0.1 microM B859-35 increases the accumulation of rhodamine 123 in multidrug-resistant KB-8-5 and Walker cells more effectively than 1 microM (RS)-verapamil. In sensitive KB-3-1 cells addition of the drugs had no significant influence on the accumulation of rhodamine 123. IN KB-8-5 cells, 10 nM Adriamycin caused a reduction of cell growth to 85% compared to untreated controls (= 100%). If 1 microM B859-35, B859-35 metabolite, niguldipine, verapamil or (R)-nitrendipine was added to 10 nM Adriamycin, growth reduction compared with untreated controls increased to 12%, 11%, 23%, 63%, and 82% respectively. The effect of 0.1 microM B859-35 was a reduction in proliferation to 38%, that of 0.1 microM verapamil to 72%. These data illustrate that B859-35, a compound with antitumor activity in several tumors, is at least ten times more potent than racemic verapamil in reversing multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Comparison of different blood flow parameters for evaluating blood flow spectra in fetal growth retardation].

Uteroplacental and foetoplacental vascular resistance is generally high in pregnancies complicated by intrauterine growth retardation. Assessment of flow velocity curves using angle-independent indices as A/B ratio, resistance index (RI) or pulsatility index (PI) cannot classify all cases with pathological flow velocity profiles. Beneath the pulsatility the maximum frequency outline of the flow velocity waveform offers additional clinical information. The evaluation of flow velocity curves using polynome analysis (including III degrees) provides additional data including occurrence of diastolic notching and can be used as a more sensitive indicator of impaired uteroplacental blood flow. In such pregnancies accurate evaluation of the maximum flow velocity outline with polynome analysis has been shown to be an important qualitative criterion in the assessment of blood flow velocity waveforms.

Blood Flow Velocity

Frequency of intra-abdominal injury in cases of blunt trauma to the cervical spinal cord.

Historically, early management of the blunt trauma victim with hemodynamic instability and cervical spinal cord injury has been hampered by the physician's inability to perform an accurate physical examination. Invasive and time-consuming diagnostic tests are often run to check for the presence of occult intra-abdominal injuries. For this reason, we decided to study these patients by reviewing a clinical registry to assess the frequency of intra-abdominal injuries in cases of cervical spinal cord trauma. We hypothesized that intra-abdominal injury would occur infrequently in cases of blunt trauma to the cervical spinal cord. In fact, data from the Maryland Institute for Emergency Medical Services Systems revealed that blunt trauma victims with cervical cord injury rarely (2.6%) sustained intra-abdominal wounds. Further analysis of this population revealed that specific mechanisms of trauma and the presence of hemodynamic instability and other major injuries were factors strongly associated with occult intra-abdominal injury. In light of these findings, we have outlined a protocol for management of these patients that is geared toward more rapid stabilization of the injured spinal column.

Abdominal Injuries

Isolated granulocytic sarcoma of the ovary: histologic, electron microscopic, and immunohistochemical findings.

An isolated granulocytic sarcoma (myelosarcoma) of the right ovary occurred in the absence of leukemia in a 49-year-old woman. The diagnosis of this tumor, which occurs extremely rarely in the ovary, was established by light microscopic, immunohistochemical, and electron microscopic investigations. The major cell population consisted of immature myeloid cells; scattered megakaryocytes were also seen. The tumor exhibited a prominent cellular stroma with scattered follicle-like collections of B-lymphocytes and many fibroblasts, giving the initial impression that the tumor could be of mesenchymal origin. Twelve months after operation, the patient still exhibits no evidence of leukemia.

B-Lymphocytes

Optic nerve decompression surgery improves visual function in patients with pseudotumor cerebri.

Papilledema from pseudotumor cerebri can cause severe loss of visual acuity and visual field. We performed optic nerve decompression surgery on 17 patients with pseudotumor cerebri who, despite maximum conventional therapy, developed progressive loss of visual acuity and/or visual field. Postoperatively, visual acuity improved or stabilized in 33 of 34 eyes (97%). Visual fields improved in 20 of 21 eyes that underwent surgery. Optic nerve decompression surgery relieves local cerebrospinal fluid pressure on the optic nerve. Progressive loss of visual function associated with pseudotumor cerebri can be reversed or stabilized with optic nerve sheath decompression surgery.

Adolescent

Uteroplacental diastolic notching in 510 uneventful pregnancies.

In a collective of 510 patients with uneventful pregnancies and deliveries the rate of waveform notching in the uteroplacental flow velocity pattern was examined. Notching appeared to be significantly more frequent in the uterine than arcuate artery. It was unilateral and mainly affected placenta-contralateral sites. Bilateral notching or notching on placental site were the exception. In both flow patterns notching was seen to increase as pregnancy progressed and was slightly higher in the third compared to the second trimester.

Blood Flow Velocity

[Uteroplacental circulation in growth retardation--experiences with the clinical use of continuous-wave Doppler].

Doppler ultrasound measurement of blood flow velocity represents a non-invasive method of studying uteroplacental and feto-placental haemodynamics. Using a continuous-wave Doppler device, the blood flow velocity was examined in the uterine and arcuate arteries, as well as in the umbilical artery in 81 patients demonstrating fetal growth retardation. An increase in vessel resistance was found in the uterine and arcuate arteries in most of the patients. In addition, patients with fetal retardation showed a significantly higher rate of diastolic notching and incomplete registration of uterine and arcuate wave forms, especially in pregnancies complicated by hypertension. The implementation of the continuous-wave technique as a simple Doppler system allows differential evaluation of placental function and provides information on the nutritional supply to the fetus.

Blood Flow Velocity

[Evaluation of the pulsatile curve of the placental blood flow profile by polynomial analysis].

The analysis of uterine and umbilical blood flow velocities using A/B ratio, resistance index and pulsatility index has shown to be a highly specific and sufficiently sensitive method in the evaluation of high risk pregnancies. In situations of high peripheral vascular resistance diastolic velocities are low and index values are high. Additional information of flow velocities curves, as diastolic notching, is not represented in the indices commonly used. A mathematical model was established using polynom analysis of blood flow velocity curves. In a group of 78 patients with intrauterine growth retardation polynome analysis of uteroplacental flow velocity curves was more sensitive than resistance index and pulsatility index.

Blood Flow Velocity

[Obstetric cw-Doppler--results of a study of normal values. Effect of different variables on results].

Using a 4 MHz continuous wave Doppler device reference values for resistance index (RI) and pulsatility index (PI) of uterine and arcuate arteries as well as umbilical artery were established based on 510 patients with uneventful pregnancies and deliveries. Percentiles are more suitable localisation gauge than are standard deviations. Neither RI nor PI of maternal arteries proved to be dependent on gestational age in the observation period. If the heart rate are in physiological ranges no clinically relevant effect on the results were observed in either the maternal of the foetal copartment. By contrast umbilical artery shows a definite linear relation between the indices measured and gestational age. A significant effect of placental site on the measurement was found in both, uterine and arcurate arteries, but only the differences found in arcuates were of clinical value. An increase of diastolic notching was observed in both, uterine and arcuate arteries during pregnancy. Mostly only one vessel showed diastolic notching when observed in normal pregnancy. With a lateralized placenta the condition was more probable on the contralateral site.

Blood Flow Velocity

[Ovarian stimulation with clomiphene is not a risk factor for extrauterine pregnancy].

In a retrospective cohort study of 252 patients with ectopic pregnancies the possible association between use of clomiphene citrate and the occurrence of an ectopic pregnancy was examined. Seventeen out of 252 patients had been treated with clomiphene. Epidemiologic data and animal experiments suggest, that there may be a role of clomiphene in the etiology of ectopic pregnancy. Marchbanks et al. [6] reported that patients who used clomiphene were found to have a relative risk of 10.0 for ectopic pregnancy. The analysis of our own data show an accumulation of classic risk factors as history of pelvic inflammatory disease or of microsurgery for treatment of tubal disease in the clomiphene group. The higher rate of ectopic pregnancies in patients who have been treated with clomiphene is more likely associated with the diagnosis of infertility than with the use of ovulatory-inducing agents. Clomiphene treatment is no independent risk factor in the etiology of ectopic pregnancy.

Clomiphene

In vitro studies of multiple impact injury to mammalian CNS neurons: prevention of perikaryal damage and death by ketamine.

We have developed an in vitro model of rapid acceleration injury (RAI) to study the effects of multiple impact (220 g/impact, 3-5 s intervals) trauma on cultures of mammalian CNS cells. Our initial investigations have shown that: (1) multiple impacts delivered tangential to the plane of growth caused neuronal death while normal impacts did not; (2) glia were not affected by tangential or normal RAI; (3) most neuronal death occurred within 15 min; (4) the threshold for neuronal death was above 440 g (cumulative); (5) neuronal death reached a maximum of 50% at cumulative accelerations greater than or equal to 1100 g; (6) somal swelling and increased nuclear prominence were often observed after tangential RAI, and the frequency of these changes increased with the cumulative acceleration; and (7) ketamine prevented neuronal death and morphological changes during tangential RAI. We hypothesize that neuronal sensitivity to multiple impact RAI depends on the density of N-methyl-D-aspartate (NMDA) complexes in the dendrosomatic membranes. We also hypothesize that the events leading to neuronal death during multiple impact injury are: (1) calcium leakage through NMDA channels causes weakening of the cytoskeleton; (2) loss of cytoskeletal integrity allows nuclear shifting during impact; and (3) nuclear pressure disrupts the plasmalemma causing a lethal influx of calcium.

Animals

Effects of polychlorinated biphenyls in rat liver: correlation between primary subcellular effects and promoting activity.

In the present study the promoting activity of various PCB and PBB isomers and congeners in rat liver has been studied and compared with a variety of primary xenobiotic-mediated enzymatic changes in this target organ. Female Wistar rats were given diethylnitrosamine (DEN; 10 mg/kg body wt for 10 days) and were subsequently treated once weekly with polychlorinated biphenyls (150 or 15 mumol/kg body wt) for a total of 8 weeks. Additional groups of rats were administered 3,3',4,4'-tetrabromobiphenyl or 3-methylcholanthrene (8 weekly injections of 15 or 150 mumol/kg body wt, respectively) or were given phenobarbital (0.05% in the diet) until the end of the experiment. Reference groups were treated with the various test compounds without prior initiation. One week and 9 weeks after cessation of promoter treatment rats were killed and the volumetric fraction of enzyme-altered foci characterized by changes in adenosine triphosphatase and gamma-glutamyl transpeptidase activity was determined as a means to quantitatively assess the extent of preneoplastic response in this organ. Out of the series of polyhalogenated biphenyls tested, promoting effects were seen with the following compounds: 2,2',4,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 2,3,4,4',5-pentachlorobiphenyl, and 3,3',4,4'-tetrabromobiphenyl, whereas no significant effects were obtained with 4-monochlorobiphenyl. In rats not treated with DEN, the two strongly promoting agents 2,3,4,4',5-pentachlorobiphenyl and 3,3',4,4'-tetrachlorobiphenyl also significantly increased the volume fraction of enzyme-altered foci over the respective controls when analyzed at the second time point of investigation. In parallel experiments, induction of liver growth and of microsomal cytochrome P450 content in liver was found to correlate well with the promoting activity of the various xenobiotics, suggesting that these parameters may be used to predict the promoting activity of polyhalogenated biphenyls in a short term assay.

Adenosine Triphosphatases

The use of anterior Caspar plate fixation in acute cervical spine injury.

Optimal management of cervical cord injury in the presence of documented instability and/or compression of neural elements remains a controversial topic. Surgery and internal stabilization of cervical spine fracture/dislocations are effective and well accepted, but controversy exists on the relative merits of the anterior versus the posterior approach as well as the optimal timing of surgical intervention. We report our experience with the Caspar technique and instrumentation for anterior stabilization in 54 patients for acute cervical spine injury. Our series consists of 38 male and 16 female patients whose ages ranged from 16 to 68 years, with a mean age of 29.2 years. Thirty-two of these patients had complete neurological sensory/motor deficits at the time of presentation, eight were neurologically intact, and 14 had preservation of some motor and sensory function. All 54 patients had radiographic evidence of posterior instability as well as anterior disruption of either a vertebral body or intervertebral disk. We found that "early" intervention (less than 24 hours after injury) was performed frequently in the neurologically compromised patients. Twelve of the 22 patients undergoing surgery less than 24 hours after admission regained significant neurological function, with 13 of 22 developing postoperative complications. In the "delayed" group (surgery more than 24 hours after injury, mean 14.3 days), 14 patients experienced postoperative complications, with 15 of 24 demonstrating neurological improvement. The eight patients who were intact did uniformly well. There was no mortality during the follow-up. All 54 patients showed a solid fusion (clinically and radiologically) within 6 months of surgery. In two cases the plates had to be removed, without risking the fusion. Our experience suggests that although anterior cervical fusion and Caspar plating remain appropriate for patients with documented anterior compromise of the canal, it should not substitute for more traditional posterior stabilization procedures. Because this route has the potential for more serious complications, it should be reserved for the cases in which anterior decompression is deemed necessary or posterior fusion was unsuccessful. With appropriate selection of patients, no adverse effect of early surgery was demonstrated. In fact, neurologically compromised patients had the benefits of increased ease of patient care and early transfer to rehabilitation.

Adolescent

Anterior decompression in cervical spine trauma: does the timing of surgery affect the outcome?

To clarify the ideal timing of anterior decompression and stabilization for all patients with cervical spine trauma as well as its efficacy for patients with complete deficits, we reviewed the records of 103 consecutive patients with cervical spine trauma (50 incomplete deficits, Group A; 53 complete deficits, Group B) who underwent this procedure during a 5-year period at the Shock Trauma Center. We subdivided each group according to time of surgery: early and delayed (less than 24 and greater than 24 hours past injury, respectively). In Group A, 10 patients underwent early surgery and 40 patients underwent delayed surgery (range, 2 to 77 days past injury; mean, 13 days). One patient (2.5%) in the delayed group died. The following data refer to the early and delayed subgroups, respectively: average acute hospitalization, 20 and 22 days; patient motor score improvement (at discharge), 37.2 and 45.0%; functional grade improvement (at discharge), 5 (50.0%) and 9 (22.5%) patients. At 1-year follow-up, every patient who had had a deficit had progressed to a higher functional grade. In Group B, 35 patients underwent early surgery and 18 underwent delayed surgery (range, 2 to 45 days past injury; mean, 13 days). One patient (2.9%) in the early group died. The following data refer to the early and delayed subgroups, respectively: average acute hospitalization, 38.7 and 45.2 days (P less than 0.05); respiratory care (number of daily suction procedures), 6.0 and 9.86 (P less than 0.05); patient motor score improvement (at discharge), 3.9 and 4.5%; functional grade improvement (at discharge), 4 (11.4%) and 1 (5.6%) patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent