Biomedical subjects

A Gad

Publications and source records attributed to A Gad.

At least 19 recordsLinked to original sources

PubMed2006

The kinase-inhibitory domain of p21-activated kinase 1 (PAK1) inhibits cell cycle progression independent of PAK1 kinase activity.

p21-activated kinase 1 (PAK1) is a mediator of downstream signaling from the small GTPases Rac and Cdc42. In its inactive state, PAK1 forms a homodimer where two kinases inhibit each other in trans. The kinase inhibitory domain (KID) of one molecule of PAK1 binds to the kinase domain of its counterpart and keeps it inactive. Therefore, the isolated KID of PAK1 has been widely used to specifically inhibit and study PAK function. Here, we show that the isolated KID induced a cell cycle arrest with accumulation of cells in the G1 phase of the cell cycle with an inhibition of cyclin D1 and D2 expression. This cell cycle arrest required the intact KID and was also induced by a mutated KID unable to block PAK1 kinase activity. Furthermore, the KID-induced cell cycle arrest could not be rescued by the expression of a constitutively active PAK1-T423E mutant, concluding that this arrest occurs independently of PAK1 kinase activity. Our results suggest that PAK1 through its KID inhibits cyclin D expression and thereby enforces a cell cycle arrest. Our results also call for serious precaution in the use of KID to study PAK function.

Animals↗

PubMed2001

Intracerebroventricular administration of somatostatin prevents and attenuates adjuvant arthritis.

The effects of somatostatin on the development of adjuvant arthritis induced by Mycobacterium butyricum were studied. Somatostatin was injected into the lateral cerebral ventricle every day for 14 days beginning on the first day of mycobacteria inoculation in the preventive group. In the treatment group, somatostatin was injected from day 17 until day 30 post-mycobacteria inoculation. Arthritis was evaluated by measuring ankle joint circumference and diameter as well as microscopic examination of ankle joint sections. Somatostatin profoundly inhibited the development of adjuvant arthritis and an anti-inflammatory action was observed in the treatment group. These results suggest that somatostatin has a central action that can prevent or attenuate symptoms associated with arthritis.

Animals↗

PubMed2001

Relationship between hepatitis C virus infection and schistosomal liver disease: not simply an additive effect.

BACKGROUND: To study the association, clinical significance, and impact of hepatitis C virus (HCV) co-infection in patients with schistosomal liver disease (SLD). METHODS: A total of 240 patients with chronic liver diseases encountered consecutively were enrolled in the study. Fifty volunteer blood donors were enrolled as controls. HCV antibody determination (enzyme-linked immunosorbent assay), qualitative and quantitative HCV RNA assay (reverse transcriptase polymerase chain reaction), and HCV genotyping (line probe assay) were performed. RESULTS: Twenty-eight patients had SLD alone, 60 had both SLD and chronic hepatitis C (CH-C), 120 had CH-C alone, and 32 had other liver diseases. The positivity rates for HCV antibody (76% vs 20%; P < 0.001) and HCV RNA (59% vs 10%; P < 0.001) were significantly higher in the patients with SLD (n = 88) than in the volunteer blood donors (n = 50). Complications of liver cirrhosis were more common in patients with concomitant SLD and CH-C than in those with either SLD or CH-C alone. The mean levels of alanine aminotransferase (77 +/- 42 vs 93 +/- 55 IU/l; P = 0.049) and HCV RNA concentrations (3.5 +/- 1.0 vs 4.2 +/- 1.0 log copy/ml; P < 0.001) were significantly lower in patients with concomitant SLD and CH-C than in those with CH-C alone. HCV genotype 4 predominated in both these groups (93% and 98%). CONCLUSIONS: SLD in Egypt is significantly associated with HCV infection, with the predominance of genotype 4. Concurrent HCV infection and SLD result in much more severe liver disease than that seen with either disease alone. However, the activity of HCV infection seems to be partially suppressed in patients with SLD.

Adult↗

PubMed2001

RANTES promotes growth and survival of human first-trimester forebrain astrocytes.

We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferon-gamma (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.

Animals↗

PubMed2001

Intestinal parasitic diseases in Riyadh, Saudi Arabia: prevalence, sociodemographic and environmental associates.

Our objectives were to assess the prevalence of intestinal parasitic infections in Riyadh and to determine associated sociodemographic and environmental factors. The study was conducted through a household survey. Three health centres were chosen from each of the five Riyadh urban regions and 15 from rural areas. Based on the average family size, a random sample of households were chosen. All household members were asked to participate in the study. Data were collected using a pre-designed questionnaire eliciting data on sociodemographic and environmental factors. A stool specimen of each individual was examined microscopically for the presence of trophozoites and cysts. Six thousand and twelve participants with a mean age of 23.3 +/- 17.4 (median 19 years, 48.6% males) were studied and 32.2% were infected. The infection rate was high in urban areas (33.3%), among children < 12 years (34.4%), non-Saudis (42.2%), single persons (34.9%), illiterate individuals (33.8%), those who obtained drinking water from tankers (36.1%) and those who disposed of sewage in open channels (47.1%). Stratified analysis showed that for Saudis <12 years parasitic infections were significantly higher among tanker users (39.5%) and septic tank users (36.8%). For Saudis> or =12 years low education, water storage and open sewage disposal were statistically associated with parasitic infections (P < 0.05). Among expatriates, infections were high among males (47.6%), urban residents (48.3%), single persons (46.9%), tanker users (39.5%) and septic tank users (78.6%). Multivariate logistic regression analysis showed that age < 12 years, non-Saudi nationalities, educational level below secondary school, tanker as source of water and open sewage disposal were independently associated with high intestinal parasitic infection.

Adolescent↗

PubMed2000

Intracerebroventricular met-enkephalin administration modulates adjuvant arthritis.

The purpose of this study was to investigate the anti-inflammatory properties of intracerebroventricular met-enkephalin (met-enk) administration in an animal model of arthritis. Adjuvant arthritis was induced in rats by intradermal inoculation of mycobacterium butyricum and the effects of intraventricular met-enk+thiorphan (enkephalinase inhibitor) were studied. Treatment was initiated either simultaneously with the bacterial inoculation (preventive group) or on post-inoculation day 17 after the appearance of inflammation (treatment group). The degree of inflammation was evaluated by measuring the diameter and the circumference of the ankle joint immediately before the sacrifice (day 31) and by histologic examination of ankle joint sections. The results of this study revealed that combined intraventricular injections of met-enk+thiorphan reduced the arthritic-like inflammation in the preventive group as well as in the treatment group. These findings suggest that centrally applied met-enk+thiorphan may suppress the development adjuvant arthritis as well as the symptoms of manifest arthritis. Thus central met-enk may be involved in both hypothalamic pituitary adrenal axis and immune forms of stress-induced modulation.

Animals↗

PubMed2000

Allelic loss is heterogeneous throughout the tumor in colorectal carcinoma.

BACKGROUND: Loss of heterozygosity (LOH) at 17p and 18q in colorectal carcinoma has been depicted as a potential prognostic marker for the disease. However, conclusions vary among reports, and evidence of clinically useful genetic prognostic markers is still lacking. As a rule, single biopsies are used. In this study, the authors hypothesized that an important cause of earlier contradictory results was the heterogeneity of colorectal neoplasms. METHODS: In this study, DNA originating in each quadrant of tumors from 64 patients with colorectal carcinoma was analyzed. Microsatellite markers for chromosome 18q and 17p were amplified by polymerase chain reaction and automatically analyzed. RESULTS: The authors found that, regardless of stage, LOH and non-LOH in both 17p and 18q varied among biopsies within the tumors in a random fashion. LOH in 18q was detected in all 4 quadrants in 22% and in 1 of 4, 2 of 4, or 3 of 4 quadrants in 56% of the tumors, whereas 22% of the tumors were homogeneously without LOH in 18q. LOH 17p was distributed similarly throughout the tumors and was present in 1 of 4, 2 of 4, or 3 of 4 of the quadrants in 44%. The authors also reexamined a subset of tumors by subdividing one biopsy from each into four. Analysis of the microsatellite markers then yielded identical results. No correlation between the degree of LOH status and patient survival was observed. CONCLUSIONS: LOH status within a colorectal tumor is extensively heterogeneous. However, it is more homologous on a lower macroscopic level. For relevant genetic analysis, multiple biopsies and DNA sampling preceded by careful morphologic examination must be standard in the preparation of DNA.

Adult↗

PubMed2000

Modes of adherence of Helicobacter pylori to gastric surface epithelium in gastroduodenal disease: a possible sequence of events leading to internalisation.

We have investigated various modes of adherence of Helicobacter pylori to the human gastric epithelium, using transmission electron microscopy, in biopsies from nine patients with peptic ulcer disease and from four patients with chronic active gastritis. H. pylori was demonstrated in abundance in all cases within the surface mucous layer. In all ulcer- and in one out of four gastritis patients H. pylori was shown in close proximity to the gastric epithelium, with concurrent alterations in the configuration of microvilli and the apical cytoplasmic region of gastric cells. Previously described modes of H. pylori adherence were confirmed, such as loose attachment with fibrillar-like strands, firm attachment with pedestal formation, invasion in the intercellular spaces, and invagination with "cup" formation. Moreover, in many cases a fusion between the bacterial outer layer and gastric cell membranes was evident. In four cases (31%; three with active and one with past ulcer disease) viable H. pylori was found in the cytoplasm of gastric mucous cells. Our results support the hypothesis that the different modes of adherence of H. pylori represent a stepwise, possibly sequential, process which in a significant number of cases leads to internalisation of the organism. The invariable occurrence of adhesion and more frequent internalisation of H. pylori in ulcer patients may suggest a link with the pathogenesis of peptic ulcer disease.

Adult↗

PubMed2000

Clinical significance of TT virus infection in patients with chronic liver disease and volunteer blood donors in Egypt.

Clinical significance of TT virus (TTV) infection was investigated in Egyptian patients with chronic liver disease and volunteer blood donors by a cross sectional analysis. TTV DNA in serum was assessed by a semi-nested polymerase chain reaction. The prevalence of TTV DNA did not differ among patients with chronic hepatitis B (11/24, 46%), chronic hepatitis C (22/72, 31%), or schistosomal liver disease (14/39, 36%). No difference in prevalence was found between blood donors (32/109, 29%) and each of the patient groups. Clinical background including mean age, sex distribution, history of blood transfusion, and mean level of alanine aminotransferase did not differ between TTV DNA-positive and -negative individuals in any of the study groups. Ultrasonographic evidence of liver cirrhosis was similar between TTV-positive and -negative patients in each of the chronic liver disease groups. TTV infection was not associated with hepatitis B or C virus infection in blood donors. The only significant difference observed was the lower concentration of serum HCV RNA in TTV DNA positive compared with negative patients with chronic hepatitis C (3.0 +/- 1.4 vs. 4.0 +/- 0.9 log copies/ml, P <. 001). In conclusion, TTV infection was not associated with either past history of blood exposure or infection with bloodborne hepatitis viruses in Egypt. No clinical significance of TTV was found in the present study. However, a reciprocal interaction was suggested between TTV and HCV replication.

Adult↗

PubMed1999

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗

PubMed1999

Sensitivity and specificity of planar scintimammography with 99mTc-sestamibi.

PURPOSE: The aim of our prospective study was to determine the diagnostic accuracy of planar breast imaging with 99mTc-MIBI in detecting malignant disease. MATERIAL AND METHODS: Ninety-six consecutive patients with 121 clinically- and/or mammographically-detected breast lesions underwent preoperative planar scintimammography. Ten minutes after injection of 700 MBq 99mTc-MIBI, two lateral prone and one anterior supine projections with an acquisition time of 8 minutes each were obtained. Interpretation of scintimammographic results was made blindly and any focal accumulation of MIBI in the breasts was the criterion for an abnormal scintigram. All lesions were operated on and histologically verified. RESULTS: Histologically, 86 malignant and 35 benign lesions were found in 121 breast lesions. A sensitivity of 83.7% and a specificity of 74.2% for malignancy was achieved at planar scintimammography. CONCLUSION: Scintimammography with 99mTc-MIBI is an imaging modality of modest usefulness in the investigation of breast lesions. The method has a low sensitivity in lesions smaller than 10 mm in diameter, which decreases the clinical use of the method.

Adult↗

PubMed1998

Mechanism of contrast enhancement in breast lesions at MR imaging.

PURPOSE: The aim of the study was to explain why breast lesions are enhanced by contrast medium at MR imaging and to elucidate the histopathological basis for the overlap in the enhancement patterns of benign and malignant breast lesions. MATERIAL AND METHODS: Ten invasive breast carcinomas and 10 benign breast lesions were selected for the study. Of the 10 carcinomas, 5 showed a strong and early contrast enhancement, and 5 did not. Of the 10 benign lesions, 5 showed a strong and early contrast enhancement, and 5 showed no enhancement. The following morphometric variables were evaluated: proliferation cell index of neoplastic parenchymal cells, S-phase fraction, nuclear ploidy analysed by image DNA-cytometry, microvessel density, and the percentage proportion of the interstitial area. RESULTS: Contrast enhancement was related to the proliferating activity of the hyperplastic or neoplastic parenchymal cells and was inversely correlated with the interstitial area in carcinomas as well as in benign tumours and non-neoplastic lesions of the breast. CONCLUSION: Morphometric variables play an important role in the general mechanism of MR contrast enhancement in examinations of the breast and explain the histopathological basis for the overlap in the enhancement patterns of benign and malignant breast lesions.

Breast↗

PubMed1998

Iodine deficiency disorders among school children in upper Egypt: an epidemiologic study.

Iodine deficiency disorders (IDD) are the world's single most significant cause of preventable brain damage and mental retardation. Data regarding IDD in upper Egypt are scarce and even lacking. The aim of the present work was to study the prevalence of IDD and some potential risk factors in upper Egypt. Using a two-stage cluster sampling technique, 6750 school children aged 8-10 years were screened for IDD through clinical examination of the thyroid gland and determination of urinary iodine, from three governorates in upper Egypt, namely Al-Minya (population of 3.3 million), Assyut (population of 2.9 million), and Suhag (population of 3.1 million). Iodine was determined in samples of soil and drinking water. Overall, the prevalence rate of goitre was 34.6 per cent. The median urinary iodine level for children with goitre was 5.04 micrograms/dl compared to 14.81 micrograms/dl among children free of goitre. Multiple logistic regression analysis showed that certain groups of school children were much more likely to develop goitre. They included females (OR = 3.07, 95 per cent CI = 2.78-3.39), children in households where drinking water had an iodine content of less than 0.5 microgram/100 ml (OR = 3.44, 95 per cent CI = 3.09-3.89), and children living in places where soil content of iodine was less than 0.2 microgram/100 g (OR = 2.67, 95 per cent CI = 2.30-3.10). We conclude that IDD is a severe public health problem in upper Egypt. The present situation in upper Egypt necessitates an urgent intervention programme.

Chi-Square Distribution↗

PubMed1998

Intratendinous alterations as imaged by ultrasound and contrast medium-enhanced magnetic resonance in chronic achillodynia.

OBJECTIVES: We performed a comparative study of ultrasonography and gadolinium imaging contrast-enhanced T1-weighted magnetic resonance to evaluate tendon pathology in chronic Achilles tendon disorder. Another main issue was to evaluate the structural basis as defined by histopathology from hypoechoic compared with normoechoic areas within the same tendon. MATERIALS AND METHODS: Twenty patients (16 male, 4 females, median age 40 years) with chronic achillodynia participated in the study. Clinical examination revealed swelling and tenderness localized to the midportion of the Achilles tendon. Contrast medium-enhanced magnetic resonance imaging (CME-MRI) was performed in all patients. Ultrasonography-guided core biopsies were taken from regions with a clear widening of the tendon and a pathologic low-echo signal as well as from normoechoic areas. The specimens were analyzed with a standardized protocol giving a total tendon score (0-24), and a stereologic method for quantification of glycosaminoglycan (GAG)-rich areas. RESULTS: The volume of the intratendinous abnormality was larger in 13 of 20 when imaged by CME-MR (P < 0.05), whereas the shape and enlargement of the tendon per se were similarly imaged by ultrasound (US) and CME-MR. Tendon pathology as imaged by US was graded as severe from hypoechoic regions and moderate from normoechoic regions. The corresponding quantification of GAGs was 0.36 compared with 0.17, respectively (P < 0.001). CONCLUSION: CME-MR imaging revealed greater sensitivity in demonstrating intratendinous pathology than the ultrasound; this was documented by the larger size of the corresponding lesion and the fact that the pathology was occurring in areas that were considered normal by ultrasonography. US hypoechoic areas showed a markedly abnormal tendon structure including an increased amount of GAG-rich areas. However, moderate pathology was also found in the neighboring normoechogenous areas within the same tendon, indicating a more generalized disorder than depicted by echogenic properties.

Achilles Tendon↗

PubMed1998

Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.

Breast Neoplasms↗

PubMed1997

Ultrasonography-guided percutaneous core biopsy in Achilles tendon disorder.

Ultrasound-guided percutaneous core biopsy technique was studied in 15 consecutive patients with chronic Achilles tendon disorder defined as persisting local pain during daily activities, localized pain and swelling on palpation 2-5 cm proximal to the calcaneal insertion. Ultrasound verified widening of the tendon and low echogenous areas at the site of pain. Percutaneous biopsies were taken from both the low echogenous areas and the normoechogenic tendon tissue. Of 104 core biopsies 99 were representative. Open biopsies were taken from the macroscopically injured and normal tendon for comparison. Core and open biopsies of the low echogenous and macroscopically injured tendon showed similar histopathology. In 10 patients the core biopsy was performed under local anesthesia with limited subjective symptoms. Five of these patients were operated 18-41 days later. No adverse effect was found referring to the biopsy taken a few weeks prior to surgery. No complications occurred. We conclude that the percutaneous core biopsy, guided by ultrasound and performed under local anesthesia, can be used under clinical and experimental in vivo studies for improving knowledge on pathoanatomy and healing processes of the Achilles tendon.

Achilles Tendon↗

PubMed1997

The anterior stress fracture of the tibia: an atrophic pseudoarthosis?

Histopathological examination of biopsies from the fracture site in two cases of anterior stress fractures of the tibia demonstrated no bone remodelling activity, absence of inflammatory cells, extensive fibrotic infiltration and local avascular bone necrosis. The biopsies were taken peroperatively from two elite soccer players who earlier had to stop training due to severe exertional pain. When non-operative treatment failed to heal the fractures within 1 year and 6 months, respectively, surgery was performed in order to stabilize the fractures. Both subjects were relieved from exertional pain within 6 months of surgery. Consecutive radiographs showed the pattern of direct healing and 8 months postoperatively confirmed complete healing without callus formation. Both elite soccer players returned to pre-injury activity level. We suggest that the excessive fibrotic tissue ingrowth and hypovascularity under repetitive stress causes the delayed healing and histopathological signs similar to an atrophic pseudoarthosis. Treatment should consequently consider the pseudoarthrotic character of the anterior stress fracture of the tibia.

Adult↗

PubMed1997

Primary retroperitoneal mucinous tumor of low malignant potential: histogenetic aspects and review of the literature.

We report an unusual mucinous tumor of low malignant potential, of ovarian-like type, arising in the retroperitoneum of an otherwise healthy 33-year-old woman. This is the fifth described case of such a tumor in the world literature, and the first reported in Scandinavia or Europe. We also discuss aspects of the histogenesis of this type of tumor and review the available literature. The histological heterogeneity and metastatic potential of the tumor warrant careful histopathologic analysis and follow-up of patients presenting with such lesions.

Adult↗