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Biomedical subjects

J Clemens

Publications and source records attributed to J Clemens.

At least 37 records · Page 2Linked to original sources

Seroprevalence of Helicobacter pylori among Egyptian newborns and their mothers: a preliminary report.

Helicobacter pylori is one of the most common human bacterial infections in the world and children in the developing countries acquire H. pylori infection early in life. We prospectively evaluated the prevalence of serum antibodies to H. pylori in a cohort of pregnant women and their offspring. Mothers' sera were collected during the third trimester of pregnancy and sera from their offspring were collected when they were 7-9 months and 18 months of age. Pylori-Stat, a commercially available ELISA kit, was used to detect antibodies to H. pylori in the serum of the subjects tested. Sera from 169 mothers were available for testing and 88% of these samples were positive for anti-H. pylori IgG. Of the 169 children tested, 13% of the infants 7-9 months of age and 25% of the children 18 months of age had serologic evidence of H. pylori infection. These data indicate that infection with H. pylori is common in Egypt and acquisition of infection occurs at a very young age.

Adolescent↗

Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice.

When administered intracerebroventricularly to mice performing various learning tasks involving either short-term or long-term memory, secreted forms of the beta-amyloid precursor protein (APPs751 and APPs695) have potent memory-enhancing effects and block learning deficits induced by scopolamine. The memory-enhancing effects of APPs were observed over a wide range of extremely low doses (0.05-5,000 pg intracerebroventricularly), blocked by anti-APPs antisera, and observed when APPs was administered either after the first training session in a visual discrimination or a lever-press learning task or before the acquisition trial in an object recognition task. APPs had no effect on motor performance or exploratory activity. APPs695 and APPs751 were equally effective in the object recognition task, suggesting that the memory-enhancing effect of APPs does not require the Kunitz protease inhibitor domain. These data suggest an important role for APPss on memory processes.

Amnesia↗

Electrocautery versus curette adenoidectomy: comparison of postoperative results.

OBJECTIVE: Identify differences in adenoidectomy performed by curettage versus electrocautery ablation. DESIGN: To receive adenoidectomy by curettage or electrocautery ablation 38 patients undergoing adenoidectomy or adenotonsillectomy were prospectively randomized. The study was completed by 24 patients. All tonsillectomy patients received electrocautery dissection of the tonsils. Preoperative and at least 1 month postoperative video-nasopharyngoscopy was performed. Video tapes were reviewed by the authors blinded to patient identity and procedure to evaluate choanal obstruction. Preoperative and postoperative lateral neck radiographs were obtained. Blood loss and postoperative complications were recorded. SETTING: A single, tertiary care pediatric facility. INTERVENTIONS: Electrocautery ablation of the adenoid was performed with suction cautery. Curettage was performed with standard adenoid curettes. MAIN OUTCOME MEASURED: A grading system for adenoid size was developed using radiographs and endoscopic parameters. The grade of preoperative and postoperative adenoid tissue was compared between the curettage and electrocautery ablation groups. Operative blood loss was compared between the groups. The postoperative course and complications were compared. RESULTS: The preoperative grade of choanal obstruction in both groups was the same. No differences could be found in the postoperative grade between the curettage and the electrocautery ablation groups. No postoperative complications were recorded in either group. The estimated blood loss in the curettage group was 54.5 ml (S.D. 50.7) while the electrocautery ablation group averaged 3.75 ml (S.D. 6.4; p = 0.0053). CONCLUSION: There are no differences in the postoperative results of adenoidectomy performed by electrocautery ablation or curettage. There are no complications recorded in either group. Estimated blood loss was lower in the electrocautery ablation group. Decreased blood loss during the procedure makes the electrocautery ablation method of adenoidectomy attractive.

Adenoidectomy↗

Brain trauma induces massive hippocampal neuron death linked to a surge in beta-amyloid levels in mice overexpressing mutant amyloid precursor protein.

Although brain trauma is a risk factor for Alzheimer's disease, no experimental model has been generated to explore this relationship. We developed a model of brain trauma in transgenic mice that overexpress mutant human amyloid precursor protein (PDAPP) leading to the appearance of Alzheimer's disease-like beta-amyloid (Abeta) plaques beginning at 6 months of age. We induced cortical impact brain injury in the PDAPP animals and their wild-type littermates at 4 months of age, ie, before Abeta plaque formation, and evaluated changes in posttraumatic memory function, histopathology, and regional tissue levels of the Abeta peptides Abeta1-40 and Abeta1-42. We found that noninjured PDAPP mice had impaired memory function compared to noninjured wild-type littermates (P < 0.01) and that brain-injured PDAPP mice had more profound memory dysfunction than brain-injured wild-type littermates (P < 0.001). Although no augmentation of Abeta plaque formation was observed in brain-injured PDAPP mice, a substantial exacerbation of neuron death was found in the hippocampus (P < 0.001) in association with an acute threefold increase in Abeta1-40 and sevenfold increase in Abeta1-42 levels selectively in the hippocampus (P < 0.01). These data suggest a mechanistic link between brain trauma and Abeta levels and the death of neurons.

Amyloid beta-Peptides↗

Transient global forebrain ischemia induces a prolonged expression of the caspase-3 mRNA in rat hippocampal CA1 pyramidal neurons.

The authors recently cloned a cDNA for an ICE/CED3-related cysteine protease from rat brain, which is closely related to human CPP32 (now designated caspase-3). In situ hybridization histochemistry revealed a profound developmental regulation of the caspase-3 transcript in rat brain, with relatively high levels of caspase-3 mRNA observed in neurons of the fetal and neonatal brain and low levels of mRNA in neurons of the adult brain. The authors report that transient forebrain ischemia, which results in a delayed apoptotic death of CA1 pyramidal neurons, results in prolonged expression of caspase-3 mRNA in these same pyramidal neurons. Up-regulation of caspase-3 mRNA in CA1 pyramidal neurons is prominent 24 hours after transient global ischemia, and expression is maintained at higher levels for at least 72 hours after ischemia. However, by 96 hours after ischemia, a marked decrease in caspase-3 mRNA expression is observed in CA1 pyramidal neurons, showing severe degenerative changes (e.g., nuclear condensation). By contrast, there is no change in the expression of a closely related member of caspase family, caspase-2, in CA1 pyramidal neurons after global ischemia. Instead, caspase-2 mRNA is induced in lamina layers of cerebral cortex 24 hours after the ischemia. A selective and prolonged induction of the caspase-3 gene in committed CA1 pyramidal neurons suggests that transcriptional activation of this caspase-3 gene may be involved in the apoptotic cell death cascade of CA1 neurons after transient global ischemia.

Animals↗

Abdominal ultra sonographic findings detected in the course of a hepatitis survey in an Egyptian rural area.

The objective of this study was to determine the prevalence of abnormal findings detected by abdominal ultrasonography (US) in an Egyptian rural area. This study was a part of a community based cross sectional survey for virus hepatitis carried out at Kalama village in Nile Delta, 40 kilometers north of Cairo. People above 10 years of age living in a 10% systemic random sample of houses in the village were subjects of this study. A member of the team carried out US examination of the liver, biliary tree, spleen, kidneys, pancreas, para aortic areas and the pelvis. Examination included morphological assessment and organometry. All results are recorded on images by videoprinter. Abnormalities in abdominal US was detected in 34% of examined cases. Abnormal liver impressions were detected in 28.3% of cases. Ascites was detected in 13 cases (1.8%). Diseases of the gall bladder and kidneys were detected in 2.7% and 2.1%, respectively. US diagnosed pregnancy in 5 women, one of them had a blighted ovum. Some of these abnormalities were detected in subjects with no complaint. It is concluded that abdominal US may be a tool for early detection of asymptomatic disease.

Cholecystitis↗

Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain.

The deposition of the beta amyloid peptide in neuritic plaques and cerebral blood vessels is a hallmark of Alzheimer's disease (AD) pathology. The major component of the amyloid deposit is a 4.2-kDa polypeptide termed amyloid beta-protein of 39-43 residues, which is derived from processing of a larger amyloid precursor protein (APP). It is hypothesized that a chymotrypsin-like enzyme is involved in the processing of APP. We have discovered a new serine protease from the AD brain by polymerase chain reaction amplification of DNA sequences representing active site homologous regions of chymotrypsin-like enzymes. A cDNA clone was identified as one out of one million that encodes Zyme, a serine protease. Messenger RNA encoding Zyme can be detected in some mammalian species but not in mice, rats, or hamster. Zyme is expressed predominantly in brain, kidney, and salivary gland. Zyme mRNA cannot be detected in fetal brain but is seen in adult brain. The Zyme gene maps to chromosome 19q13.3, a region which shows genetic linkage with late onset familial Alzheimer's disease. When Zyme cDNA is co-expressed with the APP cDNA in 293 (human embryonic kidney) cells, amyloidogenic fragments are detected using C-terminal antibody to APP. These co-transfected cells release an abundance of truncated amyloid beta-protein peptide and shows a reduction of residues 17-42 of Abeta (P3) peptide. Zyme is immunolocalized to perivascular cells in monkey cortex and the AD brain. In addition, Zyme is localized to microglial cells in our AD brain sample. The amyloidogenic potential and localization in brain may indicate a role for this protease in amyloid precursor processing and AD.

Adult↗

A comparison of changes in nucleotide-protein interactions in the striatal, hippocampus and paramedian cortex after cerebral ischemia and reperfusion: correlations to regional vulnerability.

[32P]Azido-purine analogs of ATP and GTP were used to detect changes in phosphorylation and nucleotide binding induced by ischemia and subsequent reperfusion in rat brain striatum, hippocampus and paramedian cortex (PM cortex) tissues. Major changes in phosphorylation were observed for a 130-kDa protein, tentatively identified as the Ca2+ transport ATPase, and calcium/calmodulin-dependent protein kinase II (CaM Kinase II) in all tissues. However, recovery of the phosphorylation of the 130-kDa protein occurred only in the PM cortex on reperfusion. A 200-300% increase in [32P]8N3ATP photoinsertions was observed in the striatum and hippocampus regions for a 43-kDa protein with an isoelectric point of 6.8. This protein was identified as glutamine synthetase (GS) and the increase in binding was found to be due to both increased copy number and activation by Mn2+. An increase in [32P]8N3GTP photoinsertion into a 55-kDa protein, identified as the beta-subunit of tubulin, was found only in the striatum and hippocampus. This indicates the depolymerization of microtubulin in these tissues. These changes correlate to the vulnerability of the striatum and hippocampus to ischemia-induced neuronal death.

Animals↗

Selective loss of neuronal Na+-dependent phosphate cotransporter mRNA in CA1 pyramidal neuron following global ischemia.

A recently identified neuronal Na+-dependent phosphate cotransporter (rBNPI) has been shown to import inorganic phosphate (P(i)) required for the production of high-energy phosphates which are vital to neuronal energy metabolism. In the present study, we have examined the expression of rBNPI mRNA in the hippocampus of rats subjected to 30 min of global ischemia by four-vessel occlusion. In situ hybridization reveals that transient forebrain ischemia results in a selective reduction in rBNPI mRNA expression in CA1 pyramidal neurons of the hippocampus. Expression of rBNPI is significantly reduced by 24 h and completely absent at 72 h following global ischemia when CA1 pyramidal neurons begin to show cell damage. By contrast, there is no change in the expression of Nedd2 mRNA, a developmentally regulated cell death gene, in CA1 pyramidal neurons at these same time points. The loss of rBNPI transcripts appears to be selective for CA1 pyramidal neurons since rBNPI mRNA expression is unchanged in neurons of the CA2-CA4 pyramidal cell layers following global ischemia. Our data indicate that an early reduction of rBNPI transcripts may contribute to a reduction in P(i)-dependent energy metabolism or signal transduction which has been reported in CA1 hippocampal neurons following global ischemia.

Animals↗

Ultra sonographic measurements of the normal liver and spleen among Egyptians 10-50 years old.

OBJECTIVE: To determine reference values of ultra sonographic (US) measurements of the normal liver, spleen, portal vein, right and left periportal thickness, gall bladder wall thickness and common bile duct diameter of Egyptians. DESIGN: Community-based cross sectional study. SETTING: Kalama village in Nile Delta, 40 kilometers north of Cairo. SUBJECTS: 10% systematic sample of people above 10 years of age. Selection criteria included normal clinical examination, normal liver functions by ALT, absence of hepatitis B and C virus markers and liver or spleen pathology by US. MEASUREMENTS: Organometery of the liver, spleen, portal vein, right and left periportal thickness, gall bladder wall thickness and common bile duct diameter by US. RESULTS: 217 subjects were admitted to the study out of 700 examined. All measured parameters increased with age till 20 years. There was no significant difference in measurements between males and females. The means, standard deviation and 95th percentiles of all measurements were higher than those recorded in other studies. CONCLUSION: Egyptian norms for US organometery of the liver, spleen, portal vein and gall bladder are different from those of other countries. We suggest that Egyptian sonologists use these norms in routine practice.

Adolescent↗

The WHO Global Programme for Vaccines and Immunization Vaccine Trial Registry.

In 1995, the WHO Global Programme for Vaccines and Immunization established a Vaccine Trial Registry. As of September 1996, this registry included 50 WHO-supported vaccine trials, of which 25 (50%) were completed studies. The vaccines most frequently tested have been against measles (9 trials), poliovirus (8 trials), cholera (8 trials), enterotoxigenic Escherichia coli (4 trials), and pneumococcus (4 trials). Nearly 80% of these trials have been conducted in developing countries, with the largest number being in Africa. Among the 25 completed trials, outcomes measured were immune response (24 trials), adverse reactions (13 trials), morbidity (4 trials), and mortality (1 trial). WHO's contributions to these studies include direct funding, assistance with study design, site visits, data analysis, vaccine procurement, and vaccine potency testing.

Adolescent↗

Evaluating new vaccines for developing countries. Efficacy or effectiveness?

Despite the profusion of promising new vaccines against illnesses prevalent in developing countries, uncertainties about the balance between costs and benefits of new vaccines have retarded their use in public health practice. Conventional prelicensure trials of vaccine protection exacerbate these uncertainties by focusing on measurement of vaccine efficacy--the performance of a vaccine under idealized conditions. Vaccine effectiveness trials provide a more pragmatic perspective by addressing the performance of a vaccine under the ordinary conditions of a public health program, by capturing direct as well as indirect effects of vaccination, and by comprehensively addressing outcomes of public health concern. The use of effectiveness trials should enable more rational triaging of new vaccines for developing countries and may accelerate the introduction of new vaccines into public health practice by resolving speculative debates about practical costs and benefits.

Case-Control Studies↗

Sociodemographic, hygienic and nutritional correlates of Helicobacter pylori infection of young Bangladeshi children.

BACKGROUND: By the age of 10 years most children in developing countries have been infected by Helicobacter pylori Identification of clues to modes of transmission of this organism to children, as well as evaluation of the sequelae of childhood infections, constitute important research priorities for developing countries. OBJECTIVES: To evaluate demographic, socioeconomic and hygienic factors associated with acquisition of infection by H. pylori early in childhood among Bangladeshi children ages 2 to 5 years and to assess whether infection by H. pylori was associated with poor nutritional status in these children and in an older group ages 6 to 9 years. METHODS: A random population-based survey of 257 rural Bangladeshi children ages 2 to 5 years and 312 children ages 6 to 9 years. Seropositivity for H. pylori, as manifested by the presence of serum IgG anti-H. pylori antibodies, was correlated with nutritional status of the sampled children and with sociodemographic features and access to clean water and latrine facilities among families of the children. RESULTS: Among children ages 2 to 5 years, the 123 (48%) who were infected by H. pylori were similar to the 134 noninfected children with respect to socioeconomic level, family access to tube well water and family ownership of a latrine. However, families of infected children had more persons per sleeping room in the home (3.8 vs. 3.2, P < 0.05) and were more likely to be Hindu (20% vs. 10%, P < 0.05). Infected children did not differ significantly from noninfected children in Z scores for weight-for-age (-2.66 vs. -2.78), weight-for-height (-1.17 vs. -1.28) or height-for-age (-3.58 vs. -3.56). Analysis of survey children ages 6 to 9 years also revealed similar nutritional indexes among infected vs. noninfected children. CONCLUSIONS: Household crowding and behaviors that differ between Hindus and Muslims, but not lack of access to clean water and latrines, may enhance the transmission of H. pylori to rural Bangladeshi children. Although confirming the high frequency of infections in young Bangladeshi children, our findings do not support the notion that H. pylori is responsible for the high prevalence of malnutrition in this setting.

Age Distribution↗

Impaired immune response to natural infection as a correlate of vaccine failure in a field trial of killed oral cholera vaccines.

In a field trial carried out in 1985 in Matlab, Bangladesh, the authors evaluated whether subjects who developed Vibrio cholerae 01 infections during the first year after earlier receipt of B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) oral cholera vaccines exhibited deficient serum vibriocidal immune responses to these infections. After severe V. cholerae 01 infections (n = 70) in subjects > 5 years of age, the age group in which both vaccines were efficacious, a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among vaccinees, compared with an 18.6 geometric mean-fold rise in placebo-recipients (p < 0.01). Depressions of serum vibriocidal responses among vaccinees were even more marked after asymptomatic infections (n = 30): a 1.1 geometric mean-fold rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients (p < 0.01). The authors conclude that subjects who failed to be protected by BS-WC and WC, despite being in the age group for which these vaccines were protective, exhibited poor immune responses even to the vigorous stimulus of natural infection. These findings raise the possibility that immune hyporesponsiveness may limit the potential efficacy attainable by cholera vaccines in populations with endemic cholera.

Administration, Oral↗

Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.

Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.

Alzheimer Disease↗