A case of ileosigmoid knotting in a child.
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Anastomosis, Surgical↗
Biomedical subjects
B Wolf
Publications and source records attributed to B Wolf.
Biotinidase in serum and tissues.
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Amidohydrolases↗
Neurological findings in neonates with low Apgar in Zimbabwe.
OBJECTIVES: Document neurological condition of African neonates with a low apgar score. SETTING: Mpilo Hospital, Bulawayo, Zimbabwe. SUBJECTS: 165 babies with an Apgar score of 5 or less at 5 min. METHODS: Neurological examination at term age according to Prechtl. Babies were classified as normal, suspect or abnormal and compared with two reference groups, one from Groningen, the Netherlands and one from Grenada in the Caribbean. RESULTS: A higher number of Zimbabwean babies were delivered by Caesarean section compared to the Groningen group (P < 0.001). Babies delivered by vacuum extraction scored significantly lower compared to babies delivered by Caesarean section (P < 0.003). Twenty abnormal signs derived from the neonatal neurological examination proved to be predictive on the total optimality score (P < 0.001). The number of infants who were classified as abnormal was higher in the Zimbabwean population (P < 0.01). CONCLUSION: The selected abnormal signs derived from the neonatal neurological examination proved to be highly predictive on the neurological condition. The neonatal morbidity in Zimbabwean neonates with a low Apgar score was higher when compared with two reference groups from Groningen and Grenada.
Adolescent↗
Potential of microsensor-based feedback bioactuators for biophysical cancer treatment.
Solid tumors usually exhibit a poorly organized vascularization and a deviant energy metabolism which result in an acidic pH and large hypoxic areas in the tumor microenvironment. A lot of cell biological data support the hypothesis that such physico-chemical conditions are promoters of the microevolution of malignant cells, inhibitors of the immune response, and co-factors for tumor cell invasion. Our experimental in vitro analyses and computer simulations indicate that the efficiency of immunotherapies and classical methods for cancer treatment might be improved if a physico-chemical microenvironment could be restored which reflects that found in normal tissue. In order to monitor and manipulate the tumor microenvironment, we suggest utilizing silicon-based feedback bioactuators which are controlled by on-line microsensors. These miniaturized bioactuators play the role of 'pH clamps' and can be implanted directly at the sites of inoperable tumors and metastases where they can reconstitute normal physico-chemical conditions. The drug application scheme can be precisely controlled by an integrated microprocessor. The paper summarizes the current state of development of such microsensor-based feedback bioactuators and outlines their potential for biophysical cancer treatment.
Adaptation, Physiological↗
Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3' splice acceptor site within an exon of the human biotinidase gene.
Biotinidase recycles the vitamin biotin from biocytin upon the degradation of the biotin-dependent carboxylases. We have identified a novel point mutation within the biotinidase gene that encodes the signal peptide in two unrelated individuals with profound biotinidase deficiency. Sequence analysis of genomic DNA from these individuals revealed a G to A transition (G100-->A) located 57 bases downstream of the authentic splice acceptor site in exon B. Although this mutation predicts a G34S substitution, it also generates a 3' splice acceptor site. Sequence of the PCR-amplified cDNA from the homozygous child revealed that all the product was shorter than that of normal individuals and was the result of aberrant splicing. The aberrantly spliced transcript lacked 57 bases, including a second in-frame ATG, that encode most of the putative signal peptide and results in an in-frame deletion of 19 amino acids. The mutation results in failure to secrete the aberrant protein into the blood. This is the first reported example in which a point mutation creates a cryptic 3' splice acceptor site motif that is used preferentially over the upstream authentic splice site. The preferential usage of the downstream splice site is not consistent with the 5'-3' scanning model, but is consistent with the exon definition model of RNA splicing.
Amidohydrolases↗
Pigmented epithelium sustains cell proliferation and decreases expression of opsins and acetylcholinesterase in reaggregated chicken retinospheroids.
We investigated the effect of the retinal pigmented epithelium on cell proliferation and differentiation in rosetted retinospheroids, which are retina-like spheres reaggregated in the complete absence of retinal pigmented epithelium from dissociated retinal cells of 6-day-old chick embryos in a rotation culture system. In spheroids raised in the absence of retinal pigmented epithelium (controls), acetylcholinesterase was expressed in cells of an inner nuclear-like layer and their neuropil matrices. Moreover, the ratio between rods and cones was found to be approximately normal throughout the spheroid. When spheroids were cultured in the presence of retinal pigmented epithelium monolayers, cell proliferation in spheroids as determined by BrdU labelling was significantly increased and extended for 1 week, while acetylcholinesterase protein levels and specific activities in homogenates were decreased to approximately 30%. At the same time, opsin immunoreactivity was completely suppressed within the spheroid and appeared slowly in cells around its periphery; i.e. the proportion of rhodopsin-positive cells decreased from 14 to 3%. This study reveals that the retinal pigmented epithelium in vitro sustains cell proliferation but inhibits the differentiation of acetylcholinesterase-positive cells and of photoreceptors.
Acetylcholinesterase↗
Neurodevelopmental outcome in babies with a low Apgar score from Zimbabwe.
The early identification of neurological dysfunction in the neonatal period, the predictive value of single items of the neonatal neurological examination (NNE) adapted from Prechtl and the developmental outcome at 1 year of age in infants with a low Apgar score in Zimbabwe were studied. One hundred and sixty-five infants were examined with the NNE and 142 with the Bayley Scale of Infant Development (BSID) at 1 year of age. Twenty-three infants had cerebral palsy, ten had a motor delay or developmental delay, and four were mentally retarded. The NNE proved to be a sensitive instrument for detecting neurodevelopmental abnormality. Logistic regression analysis was used to investigate the relationship between the BSID and nine selected predictors from the NNE. This resulted in a correct classification of 94%. However, the number of false negatives was high. By using only the variability of movements and fixation as predictors the number of false negatives was reduced to one.
Apgar Score↗
Pulmonary manifestations in HIV seropositivity and malnutrition in Zimbabwe.
Over a 10 month period 184 children, aged 5 years or less, who died at home had their nutritional status and HIV serostatus established; necropsies were also carried out. The HIV antibody test was positive in 122/184 (66%). Of the HIV seropositive children Pneumocystis carinii pneumonia was present in 19 (16%), cytomegalovirus pneumonia in nine (7%), and lymphoid interstitial pneumonitis in 11 (9%). Opportunistic infection was therefore seen in 28/122 (23%) of the seropositive cases but in none of the seronegative cases. Tuberculosis was present in 8/184 (4%): 6/122 (5%) in HIV seropositive and 2/62 (3%) in seronegative children. Lung aspirate showed positive bacterial isolates in 106/ 122 (86%) of HIV seropositive and 46/62 (74%) of seronegative children with Gram negative organisms predominating in both groups. Malnutrition was common and affected 106/184 (58%); positive growth was obtained in 98 (92%) of the malnourished children irrespective of their HIV serostatus. Malnutrition was significantly associated with bacterial lung infection after adjustment for the confounding effect of HIV status. No association was found between HIV serostatus and bacterial lung infection that could not be attributed to malnutrition at the time of death. The importance of adequate nutrition in reducing the risk of bacterial infection in HIV infected children is apparent.
AIDS-Related Opportunistic Infections↗
Aortic changes in experimental renal failure: hyperplasia or hypertrophy of smooth muscle cells?
Cardiovascular complications are a well-known feature of chronic renal failure. Increased wall thickness of intramyocardial arterioles and elastic (aorta) and peripheral (mesenteric) arteries is seen even after normalization of blood pressure. It is currently unknown whether such increases result from hyperplasia of vascular smooth muscle cells, hypertrophy, or a combination of both or from an increase in aortic extracellular matrix. Using a recently developed unbiased stereological technique (the dissector), we investigated the aortas of subtotally nephrectomized rats and sham-operated controls after perfusion fixation. We determined aortic wall thickness, cross-sectional area of aortic media, total number of vascular smooth muscle cells per unit aortic length (1 mm), mean cell and nuclear volumes, volume density of elastic fibers, extracellular matrix, vascular smooth muscle cells, and total volumes of these structures per unit of aortic length (1 mm). Blood pressure was not significantly increased in subtotally nephrectomized rats. In contrast, wall thickness, cross-sectional media, total number of aortic vascular smooth muscle cells, and volume of extracellular matrix including collagen were significantly increased after subtotal nephrectomy, whereas cellular hypertrophy was only modest and an increase in elastic fibers did not occur. In conclusion, increased aortic wall thickness in experimental renal failure results primarily from an increase in aortic extracellular matrix. In addition, however, proliferation of aortic vascular smooth muscle cells resulting in cell hyperplasia also contributed to aortic wall thickening to a minor degree. It appears that aortic wall thickening is caused by secretory stimulation of the proliferating vascular smooth muscle cells, resulting in increased matrix production. The nature of the underlying stimulus requires further investigation.
Animals↗
Walking pattern of midfoot and ankle disarticulation amputees.
Measurements of the vertical component of ground reaction force (ORF) and dynamic center of pressure (COP) were recorded for five subjects with midfoot level amputations and six with Syme's ankle disarticulation amputations. All of the subjects underwent amputation surgery as a consequence of peripheral vascular disease and diabetes. GRF measurement was accomplished with the F-Scan system (Tekscan, Boston, MA). Each group exhibited a consistent, reproducible pattern of gait. Subjects with Syme's ankle disarticulation initiated initial loading response, i.e., heel strike, with a concentration of GRF in the center of the anatomic heel. COP progressed along the midline to the center of the anatomic forefoot, where GRF was concentrated at push-off. Midfoot amputees initiated loading at the lateral-posterior heel. COP progressed medially to the midline, where it progressed distally to the level of the distal residual limb (proximal metatarsal metaphyses). It then shifted medially under the base of the first metatarsal, where a small concentration of GRF occurred at push-off, similar to the normal foot. These findings explain the decreased magnitude of propulsion seen in midfoot level amputees and may explain the seemingly paradoxical increased metabolic cost of walking observed in midfoot amputees as compared with Syme's ankle disarticulation amputees.
Adolescent↗
Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study.
PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and potential antitumor activity of weekly paclitaxel with concurrent radiation (RT) for locally advanced pancreatic and gastric cancer. PATIENTS AND METHODS: Thirty-four patients with locally advanced adenocarcinoma of the pancreas or stomach were studied. The initial dose of paclitaxel was 30 mg/m2 by 3-hour intravenous (I.V.) infusion repeated every week for 6 weeks with 50 Gy RT. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2/wk were abdominal pain within the RT field, nausea, and anorexia. Of 23 patients with assessable disease, 11 (seven with gastric, four with pancreatic cancer) had objective responses for an overall response rate of 48%. CONCLUSION: Concurrent paclitaxel with upper abdominal RT is well tolerated at dosages that have substantial activity. A phase II trial of neoadjuvant paclitaxel and RT at the MTD of 50 mg/m2/wk is underway.
Adult↗
Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis.
Biotinidase deficiency is an autosomal recessively inherited disorder that results in the inability to recycle the vitamin biotin. The disorder can cause neurologic and cutaneous abnormalities that can be treated effectively with pharmacologic doses of biotin. We identified 21 mutations that cause profound biotinidase deficiency in 37 symptomatic children (30 different probands and 7 siblings), as well as provide relevant biochemical and clinical information for each child. The two most common mutations (G98:d7i3 and R538C) were found in 31 of 60 alleles (52%), whereas the remainder of the alleles are accounted for by the 19 other unique mutations. Serum samples were available from 18 children, of these 11 had no detectable cross-reacting material (CRM) to antibody prepared against normal human serum biotinidase, three had reduced quantities of CRM and four had normal quantities of CRM in serum. All of these mutations result in complete absence of biotinyl-transferase activity in serum. Two polymorphisms were also identified in normal individuals. It is apparent that a child who inherits any of these mutations, either in the homozygous state or in combination, can develop the clinical features of the disorder if untreated. There are, however, no clear genotype/phenotype correlations that would allow for the prediction of the type, severity, or age of onset of symptoms.
Acyltransferases↗
[Multiple sensor systems for online analysis of cellular signals: the PhysioControl microsystem].
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Cell Survival↗
Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis.
The process of lymph vessel expansion and function in the development of CCl4-induced hepatic fibrosis and cirrhosis was studied using intravital fluorescence microscopy of the rat liver. The unique aspect of our approach was the use of high molecular fluorescein-isothiocyanate-labeled dextran (MW, 150,000) as fluorescent marker, which allowed for simultaneous assessment of both 1) the macromolecular blood hepatocytic exchange from the sinusoidal microvasculature (extra-/intrasinusoidal gray level intensity at 1, 3, 5, and 10 minutes after intravenous injection) and 2) the hepatic lymph system. In animals exposed with CCl4 up to 4 weeks, macromolecular trans-sinusoidal exchange was found progressively delayed. This was strongly associated with lymph vessel expansion and function, as indicated by a continuous increase of lymph vessel density and area. Delay of macromolecular exchange and lymph vessel expansion was found not further enhanced at fibrotic and cirrhotic stages of 8- and 12-week CCl4-exposed livers. Linear regression analysis revealed a strong negative correlation between lymphatic network density development and macromolecular trans-sinusoidal exchange (r2 = 0.99; P < 0.01). Thus, our study provides for the first time direct evidence for the pivotal role of lymphatic function for macromolecular transport in case of deteriorated sinusoidal hepatocellular exchange capacity.
Animals↗
Blastic transformation of hairy cell leukemia.
OBJECTIVE: To report blastic transformation of hairy cell leukemia, an uncommon lymphoproliferative disorder of B-cell lineage. DESIGN: Routine histology, cytochemistry, and ultrastructural analysis were used to study this case. Immunoperoxidase studies for leukocyte common antigen (CD45), pan B-cell marker L26 (CD20), and hairy cell leukemia marker DBA.44 were performed. In addition, cell surface marker analysis for CD19, CD20, CD5, CD25, CD11c, and kappa and lambda light chains by flow cytometry was performed. RESULTS: The patient presented with typical clinical, morphologic, cytochemical, immunophenotypic, and ultrastructural features of hairy cell leukemia. Following splenectomy and prior to institution of any other therapy, he developed a blastic lymphoproliferative malignancy with loss of tartrate-resistant acid phosphatase activity, expression of cell surface markers CD11c and CD25, and immunoreactivity for DBA.44. CONCLUSION: We believe this to be the first report of such a transformation and recommend that the differential diagnosis of blastic transformation of chronic lymphoproliferative disorders include such a possibility.
Antigens, CD19↗
Biotinidase and its roles in biotin metabolism.
Biotinidase is the enzyme responsible for the recycling of the vitamin biotin. Biotinidase acts as a hydrolase by cleaving biocytin and biotinyl-peptides, thereby liberating biotin for reutilization. Biotinidase is also important for making biotin bioavailable from bound dietary sources. The interest in this enzyme has been increased by the discovery of biotinidase deficiency, an inherited biotin-responsive disorder that can result in neurological and cutaneous abnormalities, but can be treated effectively with biotin supplementation. Biotinidase has recently been shown to be biotinylated in the presence of biocytin, but not biotin, at neutral and alkaline pH. This raises the possibility that biotinidase acts as a biotin-binding or biotin-carrier protein. Biotinidase has also been shown to have biotinyl-transferase activity resulting in the transfer of biotin from biocytin to nucleophilic acceptors, such as histones. Transferase activity occurs at physiological pH and at physiological concentrations of biocytin and, therefore, may be the main function of the enzyme in serum and other tissues. These novel functions of the enzyme may indicate that biotinidase plays a critical role in the metabolism of biotin in nuclei, particularly of neuronal cells. The role of biotinidase in biotin metabolism may be a paradigm for better understanding the metabolism of other vitamins.
Acyltransferases↗
A colorimetric assay of lipoyl-N-epsilon-lysine hydrolysis activity using 2,6-dibromoquinone-4-chlorimide.
Lipoic acid is a coenzyme for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, branched chain-ketoacid dehydrogenase, and the glycine cleavage system. Lipoic acid is covalently attached through an amide to the epsilon-amino group of specific lysine residues of these enzymes. Lipoamidase hydrolyzes the amide bond of lipoyl-N-epsilon-lysine. Because of the difficulty in quantitating lipoic acid or lysine released by hydrolysis of lipoyl-N-epsilon-lysine, a sensitive assay of lipoamidase activity was developed based on quantitation of lipoic acid liberated from lipoyl-epsilon-lysine using 2,6-dibromoquinone-4-chlorimide (DBQC). This method involves acidification of the assay mixture with HCl and separation of lipoic acid from lipoyl-N-epsilon-lysine by extraction into ethyl acetate where it can react with DBQC. This method is as sensitive as methods based on the reaction of lipoic acid with dinitrothiobenzoate and requires only a single extraction, but does not require reduction of the disulfide and the color reagent does not need to be prepared daily. Results obtained using this assay to quantitate lipoic acid released from lipoyl-N-p-aminobenzoate correlated excellently with results obtained using the Marshall-Bratton reaction to quantitate p-aminobenzoate. We have detected lipoyl-N-epsilon-lysine hydrolysis activity that is distinct from that of biotinidase and bile salt-stimulated lipase in lymphoblasts from a patient with biotinidase deficiency. This assay can be used to measure lipoyl-N-epsilon-lysine hydrolysis activity in tissues, especially those with little or no biotinidase activity.
4-Aminobenzoic Acid↗
Electron focusing in Ag and W single crystals.
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Journal Article↗