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Biomedical subjects

B Ansari

Publications and source records attributed to B Ansari.

11 recordsLinked to original sources

The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis.

OBJECTIVES: To investigate HLA-DRB1, DQA1 and DQB1 allelic polymorphism in Iranian patients with pulmonary tuberculosis (PTB). METHODS: Forty patients with smear-positive PTB and 100 healthy individuals as a control group were studied for MHC class II allelic polymorphism by polymerase chain reaction with sequence-specific primers (PCR-SSP). The primer was supplied by biotest in the standard kit. DRB low resolution SSP and DQA, DQB intermediate resolution SSP was applied. RESULTS: The comparison of the patients and the control group showed a significant increase in the frequency of the HLA-DRB1*07 and DQA1*0101 alleles (OR 2.7, 95%CI 1.19-6.13, P = 0.025 and OR 2.66, 95%CI 1.15-6.44, P = 0.04, respectively) in the patient group. The frequency of DQA1*0301 and DQA1*0501 was also significantly decreased (OR 0.254, 95%CI 0.075-0.865, P = 0.033 and OR 0.53, 95%CI 0.3-0.95, P = 0.045, respectively) in the PTB patients. Concerning haplotype frequency, DRB1*11501, QDQA1*0103 and DQB1*0601 were increased, but this difference was not statistically significant. In the DQB1 locus, DQB1*0501 was non-significantly over-represented. CONCLUSIONS: HLA-DRB1*07 and HLA-DQA1*0101 appeared to be the predisposing alleles and HLA-DQA1*0301 and 0501 the protective alleles in our patients with TB.

Aged↗

Decreased bone mineral density in prepubertal children with sickle cell disease: correlation with growth parameters, degree of siderosis and secretion of growth factors.

Patients with sickle cell disease (SCD) frequently have bone disorders of multifactorial aetiology. We attempted to analyse the relationships between bone mineral density (BMD) on the one hand and auxologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein 3 (IGFBP3) axis, and calcium-phosphate balance in 28 prepubertal children with SCD and 15 age-matched children with constitutional short stature (CSS). Children with SCD had significantly decreased BMD (77.9 +/- 11.9 per cent of normal BMD for age and sex) and circulating concentrations of IGF-I (91 +/- 31 ng/ml) and IGFBP3 (1.7 +/- 0.44 mg/l) compared with the control group (BMD = 93.5 +/- 8.2 per cent of normal BMD for age and sex, IGF-I = 221 +/- 48 ng/ml, and IGFBP3 = 2.3 +/- 0.34 mg/ml). GH response to provocation was defective (peak below 10 micrograms/l) in 40 per cent of children with SCD. Those with SCD with defective GH secretion had significantly lower circulating IGF-I concentration and BMD than those with normal GH secretion. Serum calcium, phosphate and alkaline phosphatase concentrations were normal in all children with SCD. BMD was correlated significantly with height, weight, and body mass index as well as with the circulating concentrations of IGF-I and IGFBP3. It is suggested that increasing the circulating IGF-I concentration, either through increasing the caloric intake of subjects and/or via GH/IGF-I therapy, may improve growth and bone mineralization in these patients.

Anemia, Sickle Cell↗

Rapid commitment to negative selection of a thymocyte line independent of CD4 co-engagement.

Biochemical and genetic investigations of thymocyte negative selection will be facilitated by the availability of cultured cell lines representing immature thymocytes, but to date thymocyte lines have demonstrated resistance to Ag receptor-mediated death. It is shown here that a CD4+CD8+ TCR alpha beta+ cell line with a TCR of known Ag and class II MHC specificity (cytochrome c with I-Ek) undergoes Ag dose-dependent apoptotic death in a manner consistent with negative selection of normal thymocytes. In contrast to superantigen-induced selection, apoptosis in this model is unaffected by blocking co-engagement of CD4 and the TCR. At high Ag doses, a significant fraction of thymocytes becomes committed to apoptosis within 2 h of contact with antigen-pulsed APCs, while increased interaction times increase the probability of death. Longer contact periods are required at lower Ag doses. These kinetics of commitment to apoptosis suggest that, in normal negative selection, a thymocyte clone may be deleted after any of several encounters with MHC-bearing cells during progress through the thymus. They also suggest why negative selection predominates when a specific peptide is competent both to delete and to select positively.

Animals↗

Demonstration of DNA damage/repair in individual cells using in situ end labelling: association of p53 with sites of DNA damage.

We describe the development and application of in situ end labelling (ISEL) to identity sites of damaged DNA in the nuclei of individual cells. In cell culture, exposure to a variety of genotoxic agents induced a dose and time-dependent increase in nuclear labelling. In addition, examination of histological sections of human skin exposed to solar-stimulated UV light showed ISEL in both keratinocytes and superficial dermal cells, with the same spatial and temporal distribution as that of a marker of DNA repair, PCNA (proliferating cell nuclear antigen). Using co-localization techniques and confocal microscopy, we found increased levels of p53 in many ISEL-positive cells in vitro, with a similar distribution of labelling in the nucleus. This observation provides further evidence for a direct role of p53 in the recognition of damaged DNA. Thus, ISEL should prove a convenient method for demonstrating genotoxic insult in individual cells and in histological material, and may have value in toxicological screening. This high-resolution microscopy technique can also be used to compare the spatial distribution of various proteins implicated in the response to DNA damage with the sites of the lesion.

Animals↗

Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis.

The regulation of cell number in adult tissues is determined by the balance of cell production and cell loss. In the gastrointestinal tract, where there are well defined zones of proliferation and migration of both epithelial cells and associated fibroblasts, it is widely held that cell loss occurs by shedding into the gut lumen. Since the evidence for this is not compelling, we investigated the distribution and amount of apoptosis in the normal mammalian gut. In the stomach, small intestine and colon of rodents and man, there is a small number of apoptotic bodies in the epithelium and in the immediate sub-epithelial connective tissue. Engulfment by adjacent epithelial cells and sub-epithelial macrophages accounts for the removal of apoptotic bodies. Apoptotic bodies are not randomly distributed but are found towards the distal end of the known cellular migration routes of both epithelial and mesenchymal cells. Furthermore, consideration of the absolute numbers of apoptotic bodies, their rapid clearance and the dimensions of the small intestinal villi and colonic crypts indicates that the cell loss in the normal murine intestine can largely be explained on the basis of the observed apoptosis. Despite being inconspicuous in histological material, apoptosis probably accounts for the bulk of cell loss in the gut and is a central feature of the regulation of cell number in adult tissues.

Animals↗

Expression of the nuclear membrane protein statin in cycling cells.

Statin is a 57 kD protein previously reported to be expressed by cells in G0. We have studied the detailed distribution of statin immunoreactivity in normal human and rat tissues, and correlated this with investigation of in vitro model systems. By laser confocal microscopy, statin immunoreactivity is localized to the nuclear membrane. In contrast to previous reports, using in vitro model systems we found that statin was also expressed by replicating cells as judged by both co-localization with [3H]thymidine-labelled and Ki67-labelled cells. Furthermore, in a nude mouse xenograft model the number of statin-labelled cells exceeded the number of quiescent cells as assessed by both fraction of labelled mitosis methods and labelling with [3H]thymidine and Ki67. We conclude that although there is an association between expression of the 57 kD nuclear membrane protein statin and growth arrest, this is not absolute and it is expressed in a sub-population of cycling cells. The properties of statin closely resemble those of nuclear lamins, members of the intermediate filament family.

Animals↗

In situ end-labelling detects DNA strand breaks in apoptosis and other physiological and pathological states.

We have investigated the use of a novel technique, in situ end-labelling, as a means of the specific identification of apoptotic cells in formalin-fixed, paraffin-processed tissue sections. The technique relies on the presence of DNA strand breaks in apoptotic cells, caused by activation of endogenous nuclease activity during the process of cell death. These strands are labelled with a non-isotopic reporter molecule in the presence of a DNA polymerase, and labelled DNA is identified immunohistochemically. We show that in situ end-labelling stains cells with the morphological characteristics of apoptosis, and greatly simplifies their identification. Furthermore, in two model systems, the number of labelled cells parallels the number of cells undergoing apoptosis as measured by alternative techniques. The ability of the Klenow fragment of DNA polymerase to label apoptotic nuclei suggests that the characteristic DNA fragmentation seen during this process involves the formation of DNA breaks with a 5' overhang. In situ end-labelling will be valuable for the identification and quantitation of apoptosis in a range of normal tissues and in a variety of pathological states. However, the technique is not specific for programmed cell death, and results must be interpreted with caution and correlated with morphological criteria of apoptosis.

Animals↗

Epithelial proliferation in Barrett's esophagus by proliferating cell nuclear antigen immunolocalization.

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein to DNA polymerase delta and is an absolute requirement for cellular proliferation. Specialized-type Barrett's columnar-lined esophagus (CLE) is associated with adenocarcinomatous change. In the present study, the cellular proliferation of three histological types of CLE was assessed by semiquantitative evaluation of PCNA immunolocalization in 93 biopsy specimens from 45 patients using the murine monoclonal PC10. Statistical comparison was performed by the Mann-Whitney U test. Luminal surface cell labeling was uncommon in all histological types other than specialized CLE where 25 of the 43 biopsy specimens had at least occasional luminal surface cell labeling. Mean crypt labeling score of 4.06 for specialized type exceeded that for junctional (mean, 3.12; P < 0.001) and fundic types (mean, 1.6; P < 0.001). Gland cell PCNA staining scores for specialized-type CLE (mean, 3.18) exceeded that of junctional (mean, 1.97; P < 0.001) and fundic (mean, 1.04; P < 0.001). Summated PCNA scores for specialized-type, mean of 8.29, exceeded junctional mean score of 5.45 (P < 0.001) and fundic mean score of 2.76 (P < 0.001). PCNA immunolocalization reveals a high proportion of cells in cycle in the specialized-type CLE and expansion of the proliferative compartment, which may explain the association of specialized-type CLE with malignancy.

Antibodies, Monoclonal↗

[Computer-assisted navigated acetabulum placement in hip prosthesis implantation--application study in routine clinical care].

AIM: This study serves to examine the feasibility of a CAS system in clinical routine use in the field of total hip replacement. METHOD: Within a prospective study 70 total hip replacements were performed by one surgeon (KB) between March and November, 1999 using a CAS system for preoperative planning and intraoperative cup placement. RESULTS: The average operating time was 70 min. This means an average increase in total time of operation about 15-20 min. The average blood loss was 630 ml. No additional specific complications due to the use of the system were seen. There was no additional trauma created by percutaneous pointing at the spina or flxing a dynamic reference base (DRB) at the pelvis. CONCLUSION: The active application of this CAS system in clinical routine use showed very good results in feasibility and can be considered as reliable. The navigated cup placement shows the potential of improving the results in cup placement, thus improving the outcome of hip arthroplasty.

Acetabulum↗

[Using the CAS (computer-assisted surgery) system in arthroscopic cruciate ligament surgery--adaptation and application in clinical practice].

AIM AND METHOD: The anterior cruciate ligament (ACL) is of great importance for the knee joint function. In the case of a complete ligament injury there is hardly any chance for complete recovery. The clear advantages of an operative reconstruction by replacing the ACL has been shown in many trails. The accurate placement of the graft's insertions has a significant effect on the mid- and probably long-term outcome of this procedure. Reviewing the literature, there are poor long-term results of ACL replacement in 5 to 52% of all cases, depending on the score system. One of the main reasons for unacceptable results is graft misplacement. This led to the construction of a CAS system for ACL replacement. The system assists this surgical procedure by navigating the exact position of the drilling holes. The Potential deformation quantity of the transplant can be controlled by this system in real time. RESULTS: 40 computer-assisted ACL replacements have been performed under active use of the CAS system. The short-term results are encouraging, no special complications have been seen so far. Prospective long-term follow-up studies are ongoing. CONCLUSION: ACL reconstruction by manual devices has many sources of error. The CAS system is able to give the surgeon reasonable views that are unachieveable by conventional surgery. He is therefore able to control a source of error and to optimise the results. The feasibility of this device in clinical routine use has been proven.

Anterior Cruciate Ligament↗

[Computer-assisted navigated cup placement of different cup types in hip arthroplasty--a randomised controlled trial].

AIM: The position of the acetabular implant has a great influence on the outcome of total hip arthroplasty. The acetabular implants differ in their characteristics during insertion. In order to control the influence of the implant in different axes, 80 implantations of acetabular component were performed under computer-assisted control by a surogate navigation system. METHOD: Within a prospective randomised study, 70 total hip replacements were performed by one surgeon using two different uncemented implants (PPF screw cup/Hedrocel pressfit cup). The position of the cup was measured at different times during surgery and was compared to 10 cemented PE cup placements. RESULTS: During the milling procedure the anteversion of the two uncemented cups differed significantly (p = 0.026). The standard deviation of anteversion during implantation different significantly relating to the cup type: press-fit cup 3.86 degrees, screw cup 2.1 degrees and cemented PE cups 0,84 degrees. The inclination was less susceptible. CONCLUSION: The cup design of uncemented acetabular implants influences the outcome of surgery. In our trial a spherical press-fit cup showed a greater variability than the screw-cup. The CAS system can be used as a tool to minimise these effects.

Acetabulum↗