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C Schwab

Publications and source records attributed to C Schwab.

At least 37 records · Page 2Linked to original sources
PubMed1999

Up-regulated production and activation of the complement system in Alzheimer's disease brain.

We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer's disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated in affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense accumulations of plaques and tangles, C1q mRNA was increased 11- to 80-fold over control levels, and C9 mRNA 10- to 27-fold. These levels were substantially higher than in the livers of the same cases. Western blot analysis of AD hippocampus established the presence of all of the native complement proteins as well as their activation products C4d, C3d, and the membrane attack complex. These data indicate that high levels of complement are being produced in affected areas of AD brain, that full activation of the classical complement pathway is continuously taking place, and that this activation may be contributing significantly to AD pathology.

Adult↗
PubMed1999

An audit of postoperative analgesia after pyloromyotomy.

Seventy-two cases of pyloric stenosis treated in our institution in the last five years were reviewed in an attempt to determine the need for postoperative analgesia after pyloromyotomy in infants. All children had their wound infiltrated with a mean dose of 2.16+/-1.43 mg x kg(-1) of bupivacaine, and first analgesia was required 9.12+/-8.04 h after surgery. Paracetamol was the main analgesic administered (average of two doses of approximately 20 mg x kg(-1)). Only three patients required postoperative opioids. In conclusion, there was a low consumption of analgesics after pyloromyotomy. Furthermore, infiltration of the wound appeared to be beneficial since time to administration of first postoperative analgesia was delayed.

Acetaminophen↗
PubMed1999

Gas embolism produced by hydrogen peroxide abscess irrigation in an infant.

The production of gaseous oxygen when hydrogen peroxide interacts with tissue is a well-known phenomenon that has been reported as a rare cause of gas embolism. We present the case of an 11-month-old infant who sustained an immediate cardiorespiratory arrest following the use of this agent during a minor surgical procedure. Clinical features, radiological findings and the rapid response to resuscitation were strongly suggestive of major gas embolism. Adverse effects of inappropriate use of hydrogen peroxide, and the diagnosis and management of these problems are discussed.

Abscess↗
PubMed1999

Development of test systems for the detection of compounds that prevent the genotoxic effects of heterocyclic aromatic amines: preliminary results with constituents of cruciferous vegetables and other dietary constituents.

Over the past decades, strong efforts have been made to identify dietary constituents that protect against the genotoxic effects of heterocyclic aromatic amines (HAAs). However, most of the methods that have been used, in particular in vitro assays that require the addition of exogenous enzyme homogenates, have only a limited predictive value because important protective mechanisms are not adequately represented and may give misleading results. Therefore, we attempted to develop improved test systems, namely assays, with human hepatoma cells and single-cell gel electrophoresis (SCGE) tests with rats. Genotoxicity tests with human derived Hep G2 cells reflect the genotoxic effects of HAAs better than other in vitro systems. They also enable the detection of protective effects since the human derived hepatoma cells possess phase I and phase II enzymes that are involved in the activation/ detoxification of the amines. The most appropriate endpoint for experiments with Hep G2 cells appears to be micronucleus induction, but protocols for other endpoints are available as well. The second promising model is the SCGE ("comet") assay with rats that was used successfully to measure protective effects of constituents of cruciferous vegetables against 2-amino-3-methylimidazo[4,5-flquinoline (IQ) in the liver and in the colon mucosa. The present study describes the experimental design of the new approaches, as well as results obtained with various dietary constituents.

Animals↗
PubMed1998

Human heart generates complement proteins that are upregulated and activated after myocardial infarction.

In human heart, we detected mRNAs and proteins for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 with the use of reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical techniques. We found an upregulation of both mRNAs and proteins in areas of recent and old myocardial infarctions. In both situations, the classical complement pathway was activated, with C4d, C3d, and the membrane attack complex (C5b-9) being deposited on damaged cardiac myocytes. These activated complement components were also identified on Western blots of infarcted tissue. Complement mRNAs in infarcted heart tissue were higher than those in liver, and liver complement mRNAs were not upregulated in cases with infarcted hearts. Our results establish that (1) complement proteins are endogenously produced by human heart; (2) the classical complement pathway is fully activated after myocardial infarction; (3) complement activation is directly involved in myocardial damage after ischemic insults; and (4) damage from complement activation may be chronically sustained. These data suggest that inhibition of the complement system should be effective in treating myocardial infarction.

Adult↗
PubMed1998

Use of metabolically competent human hepatoma cells for the detection of mutagens and antimutagens.

The human hepatoma line (Hep G2) has retained the activities of various phase I and phase II enzymes which play a crucial role in the activation/detoxification of genotoxic procarcinogens and reflect the metabolism of such compounds in vivo better than experimental models with metabolically incompetent cells and exogenous activation mixtures. In the last years, methodologies have been developed which enable the detection of genotoxic effects in Hep G2 cells. Appropriate endpoints are the induction of 6-TGr mutants, of micronuclei and of comets (single cell gel electrophoresis assay). It has been demonstrated that various classes of environmental carcinogens such as nitrosamines, aflatoxins, aromatic and heterocyclic amines and polycyclic aromatic hydrocarbons can be detected in genotoxicity assays with Hep G2 cells. Furthermore, it has been shown that these assays can distinguish between structurally related carcinogens and non-carcinogens, and positive results have been obtained with rodent carcinogens (such as safrole and hexamethylphosphoramide) which give false negative results in conventional in vitro assays with rat liver homogenates. Hep G2 cells have also been used in antimutagenicity studies and can identify mechanisms not detected in conventional in vitro systems such as induction of detoxifying enzymes, inactivation of endogenously formed DNA-reactive metabolites and intracellular inhibition of activating enzymes.

Animals↗
PubMed1998

Pyramidal neuron loss is matched by ghost tangle increase in Guam parkinsonism-dementia hippocampus.

The parkinsonism dementia complex of Guam (bodig disease) is characterized by severe neurofibrillary tangle (NFT) development without the senile plaques which characterize Alzheimer's disease. Here we analyze eight cases of bodig and three control cases from Guam, for the numbers of unaffected pyramidal neurons, intracellular NFTs (iNFTs), and extracellular NFTs (eNFTs) in hippocampal sectors CA1 and CA4. We utilized Alz50 immunostaining to identify iNFTs, amyloid P immunostaining to identify eNFTs, and cresyl violet staining to identify the surviving pyramidal neurons. We developed a modification of the Bielschowsky silver staining method which distinguished iNFTs from eNFTs and found the numbers of iNFTs and eNFTs identified by this method to be comparable to those obtained by immunohistochemical staining. In CA4, the combined total of unaffected pyramidal neurons, iNFTs and eNFTs was found to be remarkably constant in all the cases studied. The density of eNFTs correlated significantly and negatively with the density of surviving neurons, which included unaffected neurons and iNFTs. CA1 was more intensely affected than CA4. The combined total of unaffected pyramidal neurons, iNFTs and eNFTs was still relatively constant, although greater variability was recorded. Our results suggest that loss of pyramidal neurons is proportional to the appearance of eNFTs. The eNFTs accumulate, without evidence of disappearance through phagocytosis.

Adult↗
PubMed1998

Extracellular neurofibrillary tangles are immunopositive for the 40 carboxy-terminal sequence of beta-amyloid protein.

Neurofibrillary tangles (NFTs) form in a number of neurodegenerative disorders. In Alzheimer disease (AD), intracellular NFTs (iNFTs) develop along with extracellular beta-amyloid (Abeta) deposits. Reports on whether NFTs have Abeta associated with them are inconsistent. Here we study NFTs and their direct relationship with Abeta-like fragments in cases of AD, Down Syndrome, and the parkinsonism-dementia complex of Guam, using a panel of antibodies which recognize different epitopes of Abeta. In all diseases, as well as in the aged controls, the majority of extracellular NFTs (eNFTs) are stained with antibodies recognizing the 40 carboxy-terminal of Abeta, but not other epitopes. Such staining is morphologically distinguishable from the previously described Abeta positive 'tangle associated amyloid deposits' (TAADs), which surround some eNFTs, and are immunopositive for all epitopes of the Abeta molecule. Some iNFTs are immunoreactive with antibodies to the 42 carboxy-terminal epitope, and, to a lesser extent, with antibodies to midportions and more N-terminal epitopes of Abeta. These results may indicate a direct interaction between Abeta and NFTs, although secondary deposition or crossreactivity with other epitopes associated with NFTs cannot be ruled out.

Aged↗
PubMed1998

Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis.

Bacterial sepsis is still a leading cause of neonatal morbidity and mortality. Early onset sepsis in particular, presents with a different clinical course and involves other pathogens than sepsis later in life. In this study, plasma concentrations and mRNA expression of granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) of neonates with early onset sepsis were evaluated in cord blood and during the first days of life. Irrespective of prematurity, plasma levels of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8, but not sICAM-1, were excessively elevated in septic neonates when compared with both healthy infants and infants with clinically suspected but not confirmed sepsis. Compared with the corresponding maternal levels, neonatal cytokine cord plasma levels were likewise highly elevated, indicating the endogenous cytokine production by the neonate. With the exception of TNF-alpha, mRNA expression in blood cells from septic infants was, however, not more frequently detectable than in those from nonseptic patients. Cytokine levels decreased significantly within the first days of life, whereas levels of sICAM-1 and C-reactive protein increased during the same time period. In summary, in contrast to C-reactive protein and sICAM-1, cord blood plasma levels, but not the presence of mRNA, of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8 can predict neonatal early onset sepsis with a high sensitivity and specificity. Cell types other than blood cells are likely to contribute considerably to the high cytokine production in septic newborns.

Bacteremia↗
PubMed1997

Amyloid P immunoreactivity precedes C4d deposition on extracellular neurofibrillary tangles.

Extracellular neurofibrillary tangles (eNFTs) are the insoluble cytoskeletal debris left behind when neurons with intracellular neurofibrillary tangles (iNFTs) die. Reactive microglia and reactive astrocytes gather around eNFTs. Many inflammatory proteins are deposited in their vicinity, including activated components of the classical complement pathway. Agents which are potential activators of the pathway include beta-amyloid protein (A beta) and amyloid P (AP), since these in vitro activators have been reported to be associated with both senile plaques (SPs) and eNFTs. To investigate the apparent order in which these proteins are deposited, we studied by immunohistochemistry the relative association of AP, A beta, and the classical complement protein C4d with eNFTs in Alzheimer's disease (AD), parkinsonism-dementia complex of Guam (lytico-bodig, LB), and elderly non-demented cases. In normal elderly cases with mild tangle development, most but not all eNFTs were AP positive. Substantially fewer eNFTs were C4d positive, and in two of the three cases no eNFTs were A beta positive. In AD and mild LB cases with more extensive tangle development, a high portion of eNFTs were AP positive, and most of them were C4d positive. Only a few were A beta positive. In severe LB cases, with dense tangle development, almost all eNFTs were AP and C4d positive, and a significant number were also A beta positive. AP seems to be deposited early in eNFT exposure and could therefore be a potential activator of the complement pathway, while A beta deposition occurs relatively late in the process, and is therefore unlikely to be responsible.

Aged↗
PubMed1997

Dystrophic neurites are associated with early stage extracellular neurofibrillary tangles in the parkinsonism-dementia complex of Guam.

We found tangle-associated neuritic clusters (TANCs), previously reported as being present in Alzheimer's disease (AD), to be common in early and mild cases of the parkinsonism-dementia complex of Guam (PDC, bodig disease). These entities were observed around extracellular neurofibrillary tangles (eNFTs), apparently as a transient phenomenon. They were not observed around normal neurons, or neurons with intracellular neurofibrillary tangles (iNFTs). They were also not observed around late stage eNFTs. The TANCs contained both type 1 (elongated) and type 2 (globular) dystrophic neurites, as well as small, granular structures. The type 1 dystrophic neurites in TANCs were immunostained by antibodies to neuroskeletal proteins, while type 2 dystrophic neurites were immunostained by antibodies to amyloid precursor protein (APP). The eNFTs surrounded by TANCs were almost all immunopositive for amyloid P, while only some were immunopositive for C4d, and only a minority had beta-amyloid protein (A beta) associated with them. We hypothesize that the eNFTs are a source of complement activation which results in destruction of surrounding neurites. We further hypothesize that the degenerating neurites are a source of A beta which forms long-term deposits around eNFTs.

Aged↗
PubMed1997

Familial nature and continuing morbidity of the amyotrophic lateral sclerosis-parkinsonism dementia complex of Guam.

Chamorros suffer from two neurologic syndromes known as ALS and the parkinsonism-dementia complex (PDC) of Guam. We report mortality figures for these syndromes during 1991 to 1995 and compare them with those at 5-year intervals dating back to 1951. In contrast to predictions of disease disappearance, both syndromes remain prevalent. However, age of onset and age at death have increased for both syndromes, suggesting that shifting environmental factors are causing disease postponement. We also report the clinical, familial, neuropathologic, and immunohistochemical findings on a consecutive autopsy series of Guamanian Chamorro cases. Twelve cases were diagnosed as PDC, known locally as "bodig," and three as ALS, known locally as "lytico." All but three of these fifteen patients had a pronounced family history of similar illness. Eight of twelve boding patients had siblings who were also affected with bodig; two of three lytico cases had siblings afflicted with lytico. The family histories are compatible with genetic transmission of each syndrome. The neuropathology of bodig is characterized by severe and widespread neurofibrillary tangle (NFT) development. NFTs are surrounded by reactive microglia and reactive astrocytes, and complement proteins and other molecules connected with inflammation are associated with them. Similar inflammatory responses also occur in Alzheimer's disease (AD) but have been largely attributed to the presence of senile plaques. These data indicate that tangles, as well as plaques, generate inflammatory reactions that such reactions may exacerbate the fundamental pathology in bodig as well as in AD.

Aged↗
PubMed1997

Intrapulpar temperature during continuous CO2 laser irradiation in human molars: an in vitro study.

To establish safety parameters, we in vitro studied the increase in intrapulpal temperature caused by the use of a cw CO2 laser. A thermistor was implanted in the inner part of the pulpal chamber of 25 human lower third molars to measure the intrapulpal temperature produced by laser powers between 2-10 W and exposure times of 0.5-25.0 s. The Pearson linear correlation factor applied to the measured values showed there is a direct relationship between the independent variable and the applied power. A variance analysis produced the linear regression equation: T = 1.10 + (0.127)E where T is the temperature and E the energy. The results showed that, with a power of 4 W and maximum exposure time of 2:5 s (10 J) and a power density of 12,738.85 W cm-2, there will be no damaging reactions affecting the pulpal tissues.

Analysis of Variance↗
PubMed1997

LMA obstruction.

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Airway Obstruction↗
PubMed1996

Granules in glial cells of patients with Alzheimer's disease are immunopositive for C-terminal sequences of beta-amyloid protein.

Granular structures that are recognized by antibodies specific for the C-terminal but not the N-terminal sequences of the beta-amyloid protein (A beta) fragments are present in a subset of microglia and astrocytes in Alzheimer brain tissue. The immunohistochemical profile indicates that the A beta in these granules is truncated between the residues 17 and 31 and terminates at the residue 42 or 43. Such granule-containing glia occur only in brain areas with the heavy A beta deposits. Whether the intraglial A beta fragments accumulate as a result of phagocytosis of extracellular A beta or are formed intracellularly by glial cells from amyloid precursor protein (APP) remains unknown.

Aged↗
PubMed1996

Midkine-like immunoreactivity in extracellular neurofibrillary tangles in brains of patients with parkinsonism-dementia complex of Guam.

Midkine (MK) has been shown to be present in amyloid deposits in Alzheimer's disease (AD). In the present study, expression of midkine was examined immunohistochemically in brains of patients with the parkinsonism-dementia complex of Guam, lytico bodig disease (LB), using an affinity purified antibody to midkine. Positive staining was identified on some extracellular neurofibrillary tangles. The relative prevalence was somewhat less than for beta-amyloid protein (Abeta)-positive extracellular tangles. The results demonstrate that expression of MK and Abeta is not an exclusive feature of amyloid deposits in Alzheimer brain, but is also found in LB brain.

Antibody Specificity↗
PubMed1996

Neurofibrillary tangles of Guam parkinson-dementia are associated with reactive microglia and complement proteins.

Guamanian parkinsonism-dementia, locally described as bodig, is characterized by the widespread appearance of neurofibrillary tangles in cortical and subcortical areas. These tangles have similar regional distribution and immunohistochemical profile to those found in Alzheimer disease (AD). We studied the immunohistochemical staining of these tangles, as well as those of AD, using antibodies to complement proteins and related molecules. In bodig, as in AD, extracellular tangles were intensely decorated with antibodies to C1q, C4d and C3d, but not fraction Bb of factor B, properidin or immunoglobulins. This is evidence that the classical, but not the alternative complement pathway is activated on extracellular tangles and that the activation is independent of antibodies. Immunohistochemical staining for amyloid P, an in vitro activator of complement, was remarkably similar to that for the C1q, C4d and C3d in both bodig and AD. This was not the case for beta-amyloid protein (BAP), another in vitro complement activator. Positive staining was observed in only a minority of extracellular tangles in bodig and was only rarely observed in those of AD. BAP would therefore not appear to be a candidate for activating complement on extracellular neurofibrillary tangles. Reactive microglia and reactive astrocytes were closely associated with complement positive extracellular neurofibrillary tangles, indicating an inflammatory response similar to that seen in AD.

Adult↗