Search PubMed⌕ Search

Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Mechanisms and treatment of primary type I hyperoxaluria].

Type I primary hyperoxaluria is an uncommon disease related to alanine glyoxylate aminotransferase (AGT) deficiency, an exclusively hepatic enzyme. AGT deficiency leads to an overproduction of oxalate in the liver and consequent hyperoxalemia and massive hyperoxaluria with renal failure. The diagnosis is confirmed by needle biopsy of the kidney showing the exact nature of the enzyme deficiency. When terminal renal failure has developed there are two therapeutic possibilities: kidney graft or a double liver-kidney graft. Kidney graft alone is often insufficient and carries the risk of recurrent disease in the graft since the liver disorder has not been corrected. Inversely, combined liver-kidney graft can not only replace the destroyed kidneys but also correct the metabolic disorder through the effect of the AGT in the donor liver. Although this approach may be successful, it is a very aggressive procedure with high mortality.

Genetic Therapy↗
PubMed1996

Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases.

NK cells express cell surface receptors for MHC class I proteins (KIR). Engagement of these receptors inhibits NK cell cytotoxic programs. KIR can be expressed on T cells, and their engagement also results in inhibition of effector functions initiated by the CD3/TCR complex. While human KIR genes belong to the Ig gene superfamily, mouse KIR belong to a family of dimeric lectins. Despite these distinct evolutionary origins, we show here that both HLA-Cw3-specific human p58.183 receptors and H-2D d/k-specific mouse Ly49A receptors recruit the same protein tyrosine phosphatases, PTP1C and PTP1D, upon phosphorylation of critical intracytoplasmic tyrosine residues. These results document a common pathway by which diverse KIR can down-regulate NK and T cell activation programs, and further define the sequence of the immunoreceptor tyrosine-based inhibitory motif (ITIM), initially described in FcgammaRIIB1, and expressed in both human and mouse KIR.

Amino Acid Sequence↗
PubMed1996

Rho proteins are localized with different membrane compartments involved in vesicular trafficking in anterior pituitary cells.

In order to explore the role of certain GTP binding proteins in the rat anterior pituitary, we have analyzed the subcellular distribution of the proteins rho and rab. They were found in both membrane and cytosolic fractions. Rab1 and rab2 were localized in both Golgi and endoplasmic reticulum (ER) membranes, while rab4 and rab6 were found in fractions enriched with Golgi and plasma membranes, implicating these proteins in the control of vesicular intracellular trafficking as described in other systems. Rab3 was localized like a fraction of synaptophysin, suggesting a role for rab3 in the targeting of "synaptic-like' microvesicles. We have identified three substrates of C. botulinum exoenzyme C3. A 26-kDa substrate with an isoelectric point (pI) of 5.2, probably rhoB, was localized in the lightest fractions such as rab3 and synaptophysin proteins. Two other 23-24 kDa substrates with pI of 5.5-5.8, probably rhoA and/or rhoC, were found in both fractions enriched with ER and secretory granules. Rho proteins have been implicated in the control of actin polymerization. Their localization in anterior pituitary suggests that rhoB could control the association of synaptic-like microvesicles and plasma membrane, and that rhoA/rhoC could play a role in secretory granule exocytosis; these two pathways being involved in cytoskeleton protein reorganisation in response to extracellular signals.

ADP Ribose Transferases↗
PubMed1996

Diabetes mellitus after renal transplantation: characteristics, outcome, and risk factors.

The incidence and risk factors of posttransplant diabetes mellitus were evaluated in 1325 consecutive renal transplant recipients. Thirty-three (2.5%) patients developed diabetes mellitus requiring insulin therapy. Onset occurred a mean of 5.7 +/- 1.5 months following transplantation. The patients were compared with 33 paired-control kidney recipients. The patients were significantly older than the controls (46.8 +/- 1.9 vs. 40.6 +/- 2.1 years) (P<0.05), and chronic renal failure was more often related to interstitial nephritis (P<0.05). A family history of diabetes mellitus, the body mass index, ethnic origin, HLA phenotype, and the total doses of steroids and cyclosporine were similar in the two groups. The number of patients with at least one rejection episode was significantly higher among the diabetic patients (21 versus 9) but the number of episodes was similar. Diabetes occurred a mean of 1.1 +/- 0.3 months following rejection treatment. Intravenous pulsed prednisolone was always used for anti-rejection therapy. Insulin was withdrawn in 16 cases after a mean of 4 +/- 1 months, independently of steroid dosage reductions. Actuarial patient and graft survival rates were not significantly different, although 6-year outcome tended to be better in the controls (86% versus 93% for patient survival and 67% versus 93% for graft survival). This study suggests that pulsed steroid therapy might be the critical factor in the onset of posttransplant diabetes and that the risk is increased in older patients with chronic interstitial nephrititis.

Adult↗
PubMed1996

Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes.

We have observed that stimulation of human natural killer cells with dibutyryl cAMP (Bt2cAMP) reproduced the effects of ADP ribosylation of the GTP binding protein RhoA by Clostridium botulinum C3 transferase: both agents induced similar morphological changes, inhibited cell motility and blocked the cytolytic function. We demonstrate here that cAMP-dependent protein kinase A (PKA) phosphorylates RhoA in its C-terminal region, on serine residue 188. This phosphorylation does not affect the ability of recombinant RhoA to bind guanine nucleotides, nor does it modify its intrinsic GTPase activity. However, treatment of cells with Bt2cAMP results in the translocation of membrane-associated RhoA towards the cytosol. Experiments using purified membrane preparations indicated that Rho-GDP dissociation inhibitor, which can complex phosphorylated RhoA in its GTP-bound state, was the effector of this translocation. Taken together, these data suggest that PKA phosphorylation of RhoA is a central event in mediating the cellular effects of cAMP, and support the existence of an alternative pathway for terminating RhoA signalling whereby GTP-bound RhoA, when phosphorylated, could be separated from its putative effector(s) independently of its GTP/GDP cycling.

ADP Ribose Transferases↗
PubMed1996

Monitoring neovascularity as an indicator to response to chemotherapy in osteogenic and Ewing sarcoma using magnetic resonance angiography.

Histologic studies on resected specimen have shown that tumor neovascularity is related to prognosis and response to therapy in a variety of human neoplasms. In nine patients with osteogenic or Ewing sarcoma, we evaluated the use of magnetic resonance angiography (MRA) to assess neovascularity non-invasively in vivo and to monitor response to chemotherapy. Seven patients with osteosarcoma and two patients with Ewing sarcoma were studied before and after chemotherapy by MRA (2-D time-of-flight gradient-echo sequence, TR = 50 msec, TE = 9.5 msec, theta = 50 degrees, acquisition time 13 min). MR angiograms were assessed for chemotherapy-induced changes in neovascularity. MRA showed both feeder vessels and neovascularity. Six patients responded to chemotherapy ( > or = 90% histologic tumor necrosis). MRA demonstrated marked reduction in neovascularity in all responders. Three patients did not respond to chemotherapy ( < 90% histologic tumor necrosis). MRA demonstrated persistent or increased neovascularity in the non-responders. MRA provides a unique opportunity to study tumoral neovascularity noninvasively in vivo and helps to assess response to chemotherapy in patients with osteogenic or Ewing sarcoma. These general principles may be applicable to other human tumors.

Adolescent↗
PubMed1996

Pulmonary hypertension in patients with chronic pulmonary thromboembolism: chest radiograph and CT evaluation before and after surgery.

The purpose of this study was to assess the value of morphometric data on conventional radiography and CT predicting the presence and degree of pulmonary hypertension and to assess the reversibility after surgery. On preoperative X-ray films and CT scans of 50 patients with pulmonary hypertension secondary to chronic thromboembolism, we measured the cardiothoracic ratio, basal diameter, length of cardiac contact to sternum, pulmonary trunk, right and left descending pulmonary artery, and the septum angle. These data were correlated with pulmonary arterial pressure. In 14 X-ray patients and 18 CT patients, with follow-up after surgical thromboendarterectomy the reversibility of these changes was assessed. A dilated pulmonary trunk was the most common abnormality (96% each on X-ray and CT). Pulmonary arteries were dilated on X-ray in 40% (right) and 14% (left), and on CT in 92% (right) and 96% (left). The best correlation with mean arterial pressure was found measuring the pulmonary trunk on CT (r = 0.43, p < 0.01). After surgery, reversibility was most significant for the pulmonary trunk on CT (p < 0.0001). In patients with chronic pulmonary embolism, pulmonary hypertension can best be predicted by assessing the diameter of the pulmonary trunk both on X-ray and CT. No close correlation is present between the extent of any parameter and the level of pulmonary pressure.

Adult↗
PubMed1996

Helper virus-free transfer of herpes simplex virus type 1 plasmid vectors into neural cells.

Herpes simplex virus type 1 (HSV-1) plasmid vectors have promise for genetic intervention in the brain, but several problems caused by the helper virus have compromised their utility. To develop a helper virus-free packaging system for these vectors, the DNA cleavage/packaging signals were deleted from a set of cosmids that represents the HSV-1 genome. Following cotransfection into cells, this modified cosmid set supported replication and packaging of vector DNA. However, in the absence of the DNA cleavage/packaging signals, the HSV-1 genome was not packaged, and consequently vector stocks were free of detectable helper virus. In the absence of helper virus, the vectors efficiently infected rat neural cells in culture or in the brain with minimal cytopathic effects. beta-galactosidase-positive cells were observed for at least 1 month in vivo, and vector DNA persisted for this period. This system may facilitate studies on neuronal physiology and potential therapeutic applications.

Animals↗
PubMed1996

Distal radius: in vivo assessment with quantitative MR imaging, peripheral quantitative CT, and dual X-ray absorptiometry.

PURPOSE: To evaluate in vivo the relationship between magnetic resonance (MR) imaging relaxation time and bone mineral density (BMD) at the distal radius. MATERIALS AND METHODS: The 1/T2* MR imaging relaxation rates and dual X-ray absorptiometry (DXA) measurements were evaluated in the trabecular bone of the distal 5 cm of the radius in 14 healthy premenopausal women and 11 healthy postmenopausal women and in 11 women with osteoporosis. Trabecular and total BMD were measured with peripheral quantitative computed tomography (CT). RESULTS: In healthy women, 1/T2* values and trabecular BMD at peripheral quantitative CT were significantly correlated but 1/T2* and total BMD were not. Statistically significant (P = .03) correlations between 1/T2* and DXA were found only in the most distal area covered with DXA. The 1/T2* values were more closely correlated with age and showed higher relative annual decreases (0.47%-0.81%) than peripheral quantitative CT (0.20%-0.59%) or DXA (0.10%-0.39%). Pre- and postmenopausal healthy subjects could be distinguished only with MR imaging, and postmenopausal healthy and osteoporotic subjects only with CT and DXA. CONCLUSION: MR imaging relaxation rates correlate well with trabecular BMD in vivo.

Absorptiometry, Photon↗
PubMed1996

Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density.

PURPOSE: To determine the relationship between capillary density, a recognized surrogate of tumor angiogenesis, and magnetic resonance (MR) imaging-derived estimates of plasma volume (PV) and microvascular permeability in two mammary carcinoma models. MATERIALS AND METHODS: Dynamic spin-echo imaging was performed by using albumin-(gadolinium-diethylenetriaminepentaacetic acid)34, a prototype blood-pool contrast medium, in 14 rats with a subcutaneously implanted slow- or fast-growing subtype of R3230 mammary carcinoma. Data were fitted to an established two-compartment kinetic model to estimate PV and permeability. RESULTS: MR imaging-derived tumor PVs and permeabilities increased exponentially with increasing capillary density. MR imaging-derived microvascular characteristics correlated strongly with histologic capillary density, with an r2 of .85. CONCLUSION: Contrast medium-enhanced MR imaging may prove useful in estimating angiogenic activity in carcinomas. MR imaging may be superior to histologic assay because it is noninvasive, can be used to "sample" the entire tumor, and reflects both anatomic and physiologic characteristics.

Albumins↗
PubMed1996

Indirect MR arthrography: optimization and clinical applications.

PURPOSE: To evaluate and optimize a method for producing magnetic resonance (MR) images similar to MR arthrograms of multiple synovial joints with intravenous gadopentetate dimeglumine injection. MATERIALS AND METHODS: The authors examined the effects of joint motion, dose of gadopentetate dimeglumine (0.1, 0.2, and 0.4 mmol/kg), and fat saturation on the enhancement rate of the joint cavity and the degree of image contrast generated among articular structures on MR images in 14 healthy volunteers. Shoulder, elbow, wrist, hip, knee, and ankle joints of 10 volunteers were imaged with optimized parameters. Indirect MR arthrographic findings in 17 patients with joint disorders (eg, rotator-cuff tears, meniscal tears, and osteoarthritis) were compared with arthroscopic findings. RESULTS: Fat-saturated images obtained after 10 minutes of exercise and administration of 0.1 mmol/kg gadopentetate dimeglumine were similar to those obtained after intraarticular injection of contrast medium. Exercising the joint yielded the strongest joint-cavity enhancement. Increasing the dose of contrast medium in the unexercised joint did not statistically significantly improve the contrast-to-noise ratio. Rotator cuff tears, meniscal tears, and cartilage defects were better delineated with this method than with unenhanced MR imaging and showed good correlation with arthroscopic results. CONCLUSION: Indirect MR arthrography of an exercised joint provides homogeneous enhancement and improved delineation of soft-tissue structures.

Adult↗
PubMed1996

[Retroperitoneal technique of laparoscopic adnexectomy after previous hysterectomy for prevention of intraoperative organ ruptures].

OBJECTIVE: The possibility of the reduction of organ ruptures during laparoscopic adnexectomy for cystic adnexal masses after previous hysterectomy with retroperitoneal techniques was studied. PATIENTS AND METHODS: Twenty-five patients with cystic adnexal masses after previous hysterectomy enetered the study. The danger of intraoperative organ ruptures was diminished by using the retroperitoneal operative technique and a 'salvage bag' (Endopouch). RESULTS: The laparoscopic operation was successfuly performed in 23 of 25 patients. In 2 patients a laparotomy was performed. The frequency of intraoperative ruptures decreased with increasing experience (1992 in 7 of 8; 1995 in 1 of 6 patients). CONCLUSION: The frequency of intraoperative organ ruptures during laparoscopic adnexectomy after previous hysterectomy can be significantly decreased by using the retroperitoneal operative technique and the Endopouch.

Adult↗
PubMed1996

Generation of high-titer defective HSV-1 vectors using an IE 2 deletion mutant and quantitative study of expression in cultured cortical cells.

Vectors based on herpes simplex virus type 1 (HSV-1) show promise for gene transfer into mammalian cells because of their wide host range, efficient infection and ability to deliver genes to nondividing cells. Defective HSV-1 vectors, or amplicons, are plasmid vectors which are unable to propagate on their own but contain specific HSV-1 sequences that, in the presence of helper virus, support DNA replication and subsequent packaging into virus particles. We compared three replication-incompetent HSV-1 mutants (KOS strain 5dl1.2, strain 17 D30EBA, KOS strain d120) as the helper virus for packaging the prototype defective HSV-1 vector, pHSVlac, which uses the HSV-1 immediate-early (1E) 4/5 promoter to regulate expression of the Escherichia coli lacZ gene. Use of 5dl1.2, which contains a deletion in the IE 2 gene, consistently produced virus stocks that contained a high level of vector, undetectable levels of wild-type HSV-1 and a ratio of vector to helper greater than 1. Virus stocks prepared using 5dl1.2 were superior to those prepared using helper viruses that harbor a deletion in the IE 3 gene, either D30EBA or dl20, and supported more efficient gene transfer than possible with previously published procedures. Lactate dehydrogenase efflux assays in rat cortical cultures showed that 5dl1.2 was no more cytotoxic than either D30EBA or dl20, despite the expression of more viral genes. Rat cortical cultures infected with pHSVlac packaged with either 5dl1.2 or D30EBA were used to quantify the stability of vector expression. Our results show a decrease in the number of cells with detectable levels of beta-galactosidase to 30% of peak levels after one week, irrespective of the helper virus used. However, simultaneous superinfection with 5dl1.2, but not with either D30EBA or dl20, produced a transient increase in the number of cells expressing beta-galactosidase. Superinfection with 5dl1.2 at 9 days after gene transfer increased the number of cells expressing detectable beta-galactosidase back to peak levels, most probably because of reactivation of the IE 4/5 promoter in pHSVlac. These results thus provide the first quantitative demonstration of long-term persistence of defective HSV-1 vectors in neurons.

3T3 Cells↗
PubMed1996

Quantitative CT assessment of the lumbar spine and radius in patients with osteoporosis.

OBJECTIVE: We undertook this study to quantify the relationship between bone mineral assessments of the lumbar spine using quantitative CT (QCT) and of the radius using peripheral QCT (pQCT) and to test the sensitivity of both techniques in detecting changes in bone mass that are related to age and osteoporosis. SUBJECTS AND METHODS: Forty-two healthy premenopausal, 38 healthy postmenopausal, and 97 osteoporotic postmenopausal women were examined with pQCT of the distal radius and with QCT of the lumbar spine (L1-L4). The bone mineral density (BMD), bone mineral content (BMC), and a cross-sectional area of cortical bone were assessed at the distal radius. The BMD of trabecular and total bone and the BMC of total bone were assessed at the midvertebral bodies of the lumbar spine. RESULTS: In the healthy women, correlations of radial BMD with spinal trabecular and total BMD were modest (r = .39 and r = .49, respectively) but were higher for total BMC (r = .79). All correlations in osteoporotic women (r = .19 for trabecular BMD, r = .31 for total BMD, and r = .47 for total BMC) were lower than those in healthy women. For measurement of spinal bone mass in healthy women, trabecular BMD showed a higher correlation with age (r = .81) and a larger relative annual decrease (1.2%) than did total BMD (r = .75, .78%) or total BMC (r = .54, .55%). At the radius, the highest correlations with age were found for total BMC (r = .57, .53%), cortical area (r - .52, .67%), and cortical BMC (r = .48, .78%). Age-adjusted odds ratios for prevalent vertebral fractures were highest for total (4.5) and trabecular (4.4) spinal BMD. For radial measurements, odds ratios were highest for both total BMD (2.3) and cortical area (2.3). CONCLUSION: QCT of spinal trabecular bone showed the strongest capability for assessment of age-related bone loss and for discrimination of osteoporotic vertebral fractures. In comparison, pQCT of radial trabecular bone showed the weakest capability for these applications, and pQCT of radial cortical or total bone showed intermediate capability.

Aged↗
PubMed1996

Long-term persistence of defective HSV-1 vectors in the rat brain is demonstrated by reactivation of vector gene expression.

Wild-type HSV-1 is known to persist indefinitely in neurons in the latent state; however, defective HSV-1 vectors, or amplicons, contain only approximately 1% of the HSV-1 genome and persistence of these HSV-1 vectors has not been studied even semiquantitatively in the adult rat brain. Defective HSV-1 vectors contain both an HSV-1 origin of replication and a packaging site, and in the presence of helper virus can undergo DNA replication and packaging into HSV-1 particles. Our prototype defective HSV-1 vector, pHSVlac, uses the HSV-1 immediate-early (IE) promoter to regulate expression of the Escherichia coli lacZ gene. Using cultured neuronal cells, we have previously shown that expression from pHSVlac can be augmented by superinfection with a helper virus. In this study, pHSVlac was delivered into the adult rat striatum or hippocampus, and 2-3 months after gene transfer we utilized superinfection with several replication-incompetent HSV-1 mutants to reactivate expression from pHSVlac in approximately 30% of the number of cells observed at 4 days after gene transfer. Thus, HSV-1 plasmid vectors can persist for at least 2-3 months in at least approximately 30% of the cells which are initially infected.

Animals↗