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Biomedical subjects

R Bibi

Publications and source records attributed to R Bibi.

13 recordsLinked to original sources

A specific cadherin phenotype may characterise the disseminating yet non-metastatic behaviour of pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin, characterised by excess intra-abdominal mucin production leading to high morbidity and mortality. While histological features are frequently indolent, this tumour disseminates aggressively throughout the abdominal cavity, yet seldom metastasises. This study determined the expression of several markers of colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20 and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9 (IL-9), IL-9 receptor (IL-9Ralpha)), and cell adhesion (N- and E-cadherin, vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa (n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20-/CK7- pattern was rare in PMP (Fisher's exact test: P=0.001). Similarly, expressions of mucin-related proteins were comparable for adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible epithelial-mesenchymal transition state. Primary PMP cell cultures were successfully maintained and demonstrated marker expressions similar to those seen in in vivo tissues. These early characterisation studies demonstrate similarities between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin phenotype that may characterise the distinct non-metastasising behaviour of PMP, and form the basis for future mechanistic and therapy-targeting research.

Adult↗

Activating point mutations in cyclin-dependent kinase 4 are not seen in sporadic pituitary adenomas, insulinomas or Leydig cell tumours.

Cell cycle dysregulation is one of the defining features of cancer. Cyclin-dependent kinase 4 (CDK4), together with its regulatory subunit cyclin D, governs cell cycle progression through the G1 phase. Cyclin-dependent kinase inhibitors, including p16(INK4A) (encoded by CDKN2A), in turn regulate CDK4. In particular, dysregulation of the p16/CDK4/cyclin D complex has been established in a variety of types of human tumours. Dominant activating mutations affecting codon 24 of the CDK4 gene (replacement of Arg24 by Cys or His) render CDK4 insensitive to p16(INK4) inhibition and are responsible for melanoma susceptibility in some kindreds. However, 'knock-in' mice homozygous for the CDK4(R24C) mutation were noted to develop multiple neoplasia, most commonly including endocrine tumours: pituitary adenomas, insulinomas and Leydig cell testicular tumours. We therefore speculated that sporadic human endocrine tumours might also harbour such mutations. The aim of the current study was to analyze the CDK4 gene for the two characterized activating mutations, R24C and R24H, in sporadic human pituitary adenomas, insulinomas and Leydig cell tumours. We used DNA extracted from 61 pituitary adenomas, and paired tumorous and neighboring normal genomic DNA extracted from 14 insulinoma and 6 Leydig cell tumour samples. Genomic DNA from patients with familial melanoma harbouring the R24C or the R24H mutations served as positive controls. All samples were subjected to PCR, mutation-specific restriction digests and/or sequencing. Both methodologies failed to detect mutations at these two sites in any of the sporadic endocrine tumours including pituitary adenomas, benign or malignant insulinomas or Leydig cell tumours, while the positive controls showed the expected heterozygote patterns. Protein expression of CDK4 was demonstrated by immunohistochemistry and Western blotting in pituitary and pancreatic samples. These data suggest that the changes in the regulatory 'hot-spot' on the CDK4 gene, causing various endocrine tumours in CDK4(R24C/R24C )mice, are not a major factor in sporadic pituitary, insulin beta-cell or Leydig cell tumorigenesis.

Adolescent↗

Inappropriate expression of IgD from a transgene inhibits the function of antigen-specific memory B cells.

IgD expression has been shown to be downmodulated upon mitogenic or antigenic activation of B cells. To investigate whether this decrease is of functional significance we studied a mouse strain that expresses transgenic IgD on all B cells. The rearranged gene encoding the heavy chain of this IgD requires endogenous gene rearrangement before it can be expressed; therefore, normal B cell development is not affected. As a result, both transgenic IgD and endogenous IgM and IgD are expressed on all peripheral B cells. We show that the presence of extraneous IgD does not affect normal B cell activation by polyclonal stimulators, nor does it affect the primary IgM or IgG responses to TI or TD antigens. However, the secondary memory response is significantly diminished. The decrease is not attributable to a defective generation of memory B cells; instead the activation of memory cells appears to be compromised. Since the depressed response can be overcome by prior aggregation of the transgenic IgD with allotype-specific anti-IgD antibodies, it appears that persistence of the transgenic IgD on memory cells may influence their ability to be activated. Thus, the decrease in IgD expression on normal B cells after activation may be necessary for optimal activation of memory cells.

Animals↗

Hemodynamic consequences of cerebral vasospasm on perforating arteries: a phantom model study.

BACKGROUND AND PURPOSE: Hemodynamics of cerebral vasospasm after subarachnoid hemorrhage remain unclear, and the discrepancy between ultrasonographic or angiographic evidence of arterial narrowing and neurological ischemic deficit is still debated. Most blood flow studies have been involved with large arteries, and thus, very little is known regarding the hemodynamic behavior of small perforating vessels. Patients with symptomatic vasospasm, however, often present with neurological signs suggesting involvement of deep-sited areas of the brain supplied by perforating arteries. METHODS: A pulsatile pump was set to provide an outflow of 350 mL/min through a 10-mm-diameter C-flex tube at a perfusion pressure of 130/80 mm Hg. The perfusion fluid used was prepared to approximate blood viscosity. Perforating arteries were simulated by a 1-mm tube connected to the parent tube at a 90 degrees angle. Cylindrical stenotic devices of decreasing diameters were then introduced into the parent tube at the level of the aperture of the secondary tube and 1.5 diameters upstream of it. Velocity profiles both proximal and distal to the stenosis in the parent tube were obtained with a newly developed ultrasonographic flowmeter that allows for high spatial resolution. RESULTS: Increasing stenosis resulted in decreased outflow in the main tube, although it was significant only with severe stenosis. Whenever the simulated stenosis was placed upstream of the secondary tube, flow reduction was associated with a progressive change in the velocity profile, which gradually changed from laminar conditions to a jet stream limited to the center of the lumen. Further diameter reduction was responsible for the occurrence of flow separation with retrograde flow velocities in the periphery of the lumen. In the secondary tube, flow reduction was much more pronounced and began at a lesser degree of stenosis. Increasing fluid viscosity and decreasing perfusion pressure enhanced flow separation and prominently affected the outflow in the secondary tube. Conversely, whenever the simulated stenosis involved the branching area of the secondary tube, there was a slightly progressive decrease in the relative flow in the main tube as the stenosis became tighter. When the stenosis equaled the diameter of the secondary tube, the relative contribution of the secondary tube increased markedly at the expense of the main tube outflow. CONCLUSIONS: The present results show that local cerebral vasospasm induces changes in postvasospastic velocity profile affecting the shear rate and may eventually lead to flow separation. This phenomenon may, in turn, result in a venturi-like effect over the aperture of perforating arteries branching out of the postvasospastic portion of the affected parent artery. These alterations of cerebral hemodynamics may account for at least part of the vasospasm symptomatology, especially in the vertebrobasilar system, where vasospasm is commonly focal rather than diffuse. Furthermore, these changes proved to be affected significantly by manipulations of pressure and viscosity, supporting the use of hyperdynamic therapy in the management of cerebral vasospasm.

Blood Flow Velocity↗

Prevalence of bacterial vaginosis in antenatal women.

Bacterial vaginosis is an established risk factor in pregnant women for premature rupture of membranes and preterm delivery. This study was carried out to find out the prevalence of Bacterial Vaginosis (BV) in antenatal women with vaginal discharge and the effect of treatment with Metronidazole gel on pregnancy outcome. One hundred and fifty symptomatic and fifty asymptomatic women in second trimester of pregnancy in the age group of 20-30 years were included in the study. Gram stained smears of vaginal discharge were examined for evidence of BV with a scoring system by Nugent et al and was found to be positive in 38.5% in symptomatic antenatal women. Intravaginal metronidazole gel application was found to be an effective therapeutic option. Incidence of preterm labour was more in untreated cases.

Adult↗

[An unusual thoracic opacity].

We report a case of a paraspinal meningocele in a 37-year-old man with no other clinical manifestation. The diagnosis was established on the basis of the computed tomography and magnetic resonance imaging features.

Adult↗

Phasic firing time locked to cocaine self-infusion and locomotion: dissociable firing patterns of single nucleus accumbens neurons in the rat.

The activity of single nucleus accumbens (NAcc) neurons of rats was extracellularly recorded during intravenous cocaine self-administration sessions (0.7 mg/kg per infusion, fixed ratio 1). We reported previously that NAcc neurons showed a change, usually a decrease, in firing rate during the first 1 min after the cocaine-reinforced lever press. This postpress change was followed by a progressive reversal of that change, which began within the first 2 min after the press and was not complete until the last 1 min before the next lever press (termed the change + progressive reversal firing pattern). In the present study we documented a regular pattern of locomotion that occurred in parallel with the change + progressive reversal firing pattern. This observation suggested that discharges time locked to locomotion may determine the change + progressive reversal firing pattern. However, 55% of the neurons failed to show firing time locked to locomotion that could have contributed to the change + progressive reversal firing pattern. Moreover, for all neurons, the change + progressive reversal firing pattern was apparent even if the calculation of firing rate excluded all periods of locomotion. The present data showed that the change + progressive reversal firing pattern is not solely attributable to phasic changes in firing time locked to the execution of locomotion. The change + progressive reversal firing pattern closely mirrors changes in drug level and dopamine overflow observed by previous researchers and may thus be a component of the neurophysiological mechanism by which drug level regulates drug-taking behavior during an ongoing self-administration session.

Action Potentials↗

[Deep cerebral venous thrombosis].

Deep cerebral venous system thrombosis is uncommon and is usually encountered in children, generally in the neonatal period. In adults, this pathology is even more exceptional. We report two cases in adults. Deep cerebral venous system thrombosis mainly affects women taking oral contraception. The most common clinical pattern combines headaches and confusion. A comatose state is rather exceptional. This pathology, formerly considered to have poor prognosis, has benefited from diagnostic and therapeutic progress. Favorable outcome has been achieved in several recent cases, as one of ours, without after-effects. Diagnosis, often suggested by the CT-scan, is based on MRI associated with MRA. Thrombus formation is easily diagnosed by MRI at the subacute stage, but far less easily at the acute and chronic stages as the low signal is identical to the normal flow void. MRA, in phase contrast or time of flight sequences, is highly interesting at the acute phase. In case of doubt, an angiography can be applied. Therapy is based on heparin. The contribution of local infusion of thrombolytic agents, recently used with success, remains to be determined.

Adult↗

[MRI aspect of disk tumor infiltration].

We report a case of tumor infiltration into an intervertebral disk imaged at MR. The MRI appearance of a tumor infiltration into an intervertebral disk is the same as a spondylodiscitis: loss of the internuclear cleft, increased signal intensity of the disk on T2 weighted imaging. Other metastatic infiltration in vertebrae and a primitive tumor suggest the diagnosis. It is confirmed by percutaneous biopsy.

Aged↗

Factors affecting the detection of cytomegalovirus in urine by sandwich enzyme immunoassays.

Some factors influencing the detection of human cytomegalovirus (HCMV) in urine were investigated employing 2 enzyme-linked immunosorbent assays (ELISAs); one utilised anti-CMV DNA polymerase while the other anti-CMV mouse monoclonals as the detecting antibodies. The use of anti-CMV DNA polymerase was found to be superior in detecting HCMV in both urine and tissue culture fluids than anti-CMV monoclonals. Furthermore, alkaline phosphatase conjugates produced much lower background than did peroxidase conjugates. In reconstruction experiments, the extremes of pH in the urine clearly had an adverse effect on the detection rate of extracellular virus. pH correction of urines to neutrality improved the detection rate considerably. On the other hand, pH correction had little effect on the detection rate of intracellular HCMV in urine, although it was improved when specimens were subjected to repeated cycles of freeze-thawing, ultrasonication, and storage at 4 degrees C. It was concluded that, in addition to the factors investigated which all appear to affect virus detection rate, there may well be additional factors that interfere with CMV detection in the urine by ELISA particularly with intracellular virus.

Antibodies, Viral↗

Prevention of flap necrosis by chlorpromazine.

Chlorpromazine administered to Sprague-Dawley rats 30 minutes prior to elevation of McFarlane back flaps and continued 14 days thereafter resulted in near complete flap survival, compared with 48 percent necrosis in control animals. Chlorpromazine demonstrates a wide variety of actions that appear to meet all presently known requirements for flap preservation.

Animals↗