Search PubMed⌕ Search

Biomedical subjects

C Schweitzer

Publications and source records attributed to C Schweitzer.

35 records · Page 2Linked to original sources
PubMed1997

Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen.

Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB-related proteins, p130 and p107, in oncogenic transformation is unclear. The LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB, p107, and p130. We have previously shown that the N terminus and the LXCXE domain of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we demonstrate that TAg promotes the degradation of p130 and that the N terminus of TAg is required for this activity. The N terminus of TAg has homology to the J domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations in the J-domain homology region of TAg are defective for altering p130 and p107 phosphorylation and for p130 degradation. A heterologous J-domain from a human DnaJ protein can functionally substitute for the N terminus of TAg in the effect on p107 and p130 phosphorylation and p130 stability. We further demonstrate that the J-domain homology region of TAg confers a growth advantage to wild-type mouse embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both p130 and p107. This indicates that p107 and p130 have overlapping growth-suppressing activities whose inactivation is mediated by the J domain of TAg.

Amino Acid Sequence↗
PubMed1997

Effect of mitomycin C on the optic nerve in rabbits.

AIM: To prevent scarring after surgical optic nerve sheath decompression, it has been suggested that treating the area of fenestration with mitomycin C (MMC) might be effective. An animal model was used to test whether this toxic substance may cause optic neuropathy. METHODS: The optic nerves of 15 rabbits were exposed to balanced salt solution (BSS) or mitomycin C (MMC) in a concentration of 0.2 or 0.5 mg/ml. The unoperated fellow eyes and the eyes that received BSS served as controls. Steady state visual evoked potentials (VEPs) at 40, 50, and 60 Hz were recorded before and 4 weeks after surgery. The nerves were examined by light and electron microscopy after 5 weeks. RESULTS: VEPs in all non-operated eyes and eyes treated with BSS before and 4 weeks after surgery demonstrated responses at all three stimulus frequencies tested. Eyes operated with MMC had extinguished responses for one, two, or all the different temporal frequencies after 4 weeks with marked reduction in VEP amplitude. Eyes operated with MMC at a concentration of 0.5 mg/ml had significantly more reduced VEP responses than those where MMC 0.2 mg/ml was used. On histopathological examination, special stains for myelin and axons showed normal axons and myelin. On electron microscopy, no distinct abnormalities were seen among nerves operated with MMC and controls. CONCLUSION: The data from this study suggest that in rabbits, the application of MMC to the optic nerve has a dose dependent toxic effect in the short term postsurgical follow up period. While a functional alteration could be demonstrated reproducibly by steady state VEPs, the extent was not obvious on histopathological examination of the nerves.

Animals↗
PubMed1995

Sensory recovery in noninnervated flaps used for oral cavity and oropharyngeal reconstruction.

OBJECTIVES: To assess the clinical recovery of sensation in noninnervated flaps used for oral cavity and oropharyngeal reconstruction. To correlate the return of flap sensation to articulation and swallowing. DESIGN: Prospective nonrandomized study. Six months minimum follow-up. SETTING: Tertiary care center. PATIENTS: From April 1, 1991, to May 31, 1993, 12 patients underwent resection of stage III or greater squamous cell carcinoma of the oral cavity or oropharynx. Ten patients were previously untreated; two had failed previous full-course radiation therapy. Reconstruction was performed with either a pedicled musculocutaneous flap (four patients) or a fasciocutaneous free flap (eight patients). Flap sensation to touch, sharp vs dull, two-point discrimination, and warm vs cold was evaluated in each of these patients at monthly intervals by two independent observers. In addition, an extensive evaluation of articulation and swallowing was performed on all 12 patients a minimum of 6 months after surgery. 10 patients (83%) (eight of eight with fasciocutaneous free flaps and two of four with musculocutaneous flaps), with a strong trend for sensory recovery with the fasciocutaneous free flaps over the musculocutaneous flaps (P = .09). Sensory recovery correlated statistically with articulation (P = .045) and oral intake (P = .045). Patients who underwent reconstruction of base of tongue defects had significantly worse articulation and swallowing than those who underwent reconstruction of other sites (P = .04). No statistically significant correlation was found between patient age, flap size, history of irradiation, or length of follow-up (> 6 months) and flap sensation, articulation, or swallowing. CONCLUSIONS: Spontaneous return of flap sensation was documented by clinical testing in the majority (83%) of patients who underwent reconstruction of oral cavity or oropharyngeal defects with noninnervated flaps. Sensory recovery occurred more often in patients with fasciocutaneous free flaps (100%) than in those with musculocutaneous flaps (50%). Articulation and swallowing correlated statistically with the return of flap sensation.

Aged↗
PubMed1994

Allelic loss at chromosomes 3p, 8p, 13q, and 17p associated with poor prognosis in head and neck cancer.

BACKGROUND: Little is known about the molecular genetic events that contribute to the pathogenesis of squamous cell carcinoma of the upper aerodigestive tract. Previous molecular genetic studies have been limited to the identification of mutations of the p53 (also known as TP53) tumor suppressor gene, activation of a limited set of oncogenes, allelic loss at 3p and other locations, and occasional association with human papillomavirus infection. PURPOSE: Our purpose was to screen tumor tissue and blood from patients with squamous cell carcinoma of the upper aerodigestive tract for loss of heterozygosity at polymorphic loci corresponding to each of the autosomal chromosomes and to identify the locations of additional putative tumor suppressor genes, other than RB (also known as RB1) and p53, that may contribute to the pathogenesis of this disease. METHODS: Tumor tissue and blood were obtained from 68 consecutive patients with squamous cell carcinoma of the upper aerodigestive tract. In all cases, tumor tissue was obtained from the center of the surgical specimen. The relative absence of non-neoplastic tissue was confirmed by frozen-section histologic examination of immediately adjacent tissue. Initially, 30 paired tissue and blood samples were tested for loss of heterozygosity by polymerase chain reaction (PCR) to amplify 43 different highly polymorphic sequences containing small oligonucleotide repeats. After PCR amplification, with unique oligonucleotides flanking the repeat, visualization and sizing of the alleles on DNA sequencing gels were performed. Specific loss of heterozygosity was distinguished from random genetic loss due to generalized chromosomal instability if it occurred in more than 20% of specimens tested for a particular marker. RESULTS: Significant loss of heterozygosity (> 20%) occurred at alleles at chromosome bands 3p21 (32%), 3p25-26 (56%), 8pter-21.1 (31%), 13q14 (27%), and 17p12 (45%). Loss of heterozygosity at more than two loci was significant with a poor prognosis (P = .039). CONCLUSIONS: These findings demonstrate that squamous cell carcinoma of the upper aerodigestive tract exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis (the likelihood of the patient dying of disease). IMPLICATIONS: While tumor suppressor genes at 3p (VHL), 13q (RB), and 17p (p53) have been identified, altered genes at other loci on 3p and on 8p have not yet been characterized. Furthermore, the genotype at these loci for squamous cell carcinoma of the upper aerodigestive tract has prognostic importance and may identify the patients who should receive the most aggressive treatment.

Adult↗
PubMed1994

Isolation and identification of two CD34+ cell subpopulations from normal human peripheral blood.

Circulating CD34+ progenitors were separated from normal human peripheral blood on the basis of size and density by counterflow centrifugal elutriation (CCE). The CD34+ cells, 0.15% of peripheral blood mononuclear cells, were heterogeneous with respect to their elutriation characteristics, mainly size and density. The least mature CD34+ cells, characterized by lack of CD38 antigen, were predominantly found in the small lymphoid cell fraction. In fractions containing larger and denser cells (large lymphocytes, monocytes, and granulocytes), CD38 was increasingly expressed on the CD34+ cells, as were lineage commitment markers CD10 (B lymphoid), CD33 (myeloid), CD13 (myelomonocytic) and CD71 (erythroid) antigens. The smaller and less dense CD34+ cells expressed CD34 antigen brightly while the larger and denser CD34+ cells expressed it dimly. The smaller and less dense CD34+ high cells failed to establish colony growth in short-term culture while the larger and denser CD34+low cells gave rise to high counts of colony forming units-granulocyte macrophage (CFU-GM). Physical separation on the basis of size and density by CCE differentiates between two main classes of steady-state CD34+ cells from normal human peripheral blood. The smaller and less dense CD34+high cells correspond to the earliest progenitors that express differentiation markers poorly but CD34 antigen brightly, do not give rise to short-term colony growth in vitro, and thus represent indirect evidence for pluripotent hematopoietic stem cells (PHSC). The larger and denser CD34+low cells are the more mature progenitor cells, already committed to myeloid, lymphoid or erythroid differentiation but only dimly expressing CD34 antigen, and these cells were responsible for short-term colony growth in vitro.

Adult↗
PubMed1992

Primary cultures of endothelial cells from the human liver sinusoid are permissive for human immunodeficiency virus type 1.

Human endothelial cells isolated from hepatic sinusoids were infected in vitro with human immunodeficiency virus type 1 (HIV-1). An early sign of infection occurring in the culture was the formation of multinucleated cells. By double-labeling immunofluorescence, 5-15% of the cells recognized as endothelial cells owing to the presence of von Willebrand factor were found to contain HIV p24 and gp120 antigens after 2 weeks. Reverse transcriptase activity was released into the medium, and different steps in the process of viral budding were observed by electron microscopy. The virus produced by the endothelial cells was found to be infectious for CEM cells, a human T-cell line. CD4 molecules are present at the surface of the endothelial cells, as demonstrated by immunogold-silver staining and backscattered electron imaging. Treatment with an anti-CD4 antibody abolished productive infection of the sinusoidal endothelial cells. The possibility that endothelial cells of the liver sinusoid are infected in vivo with HIV remains to be clearly shown.

CD4 Antigens↗
PubMed1990

Permissivity of primary cultures of human Kupffer cells for HIV-1.

Kupffer cells (liver macrophages) represent the largest reservoir of fixed macrophages in the body. Accordingly, we have undertaken a study to evaluate their susceptibility to human immunodeficiency virus type 1 (HIV-1). Five-day-old primary cultures of Kupffer cells (KC) were infected with HIV-1, and as the infection progressed, syncytia appeared. Within the cells, viral proteins were detected by immunofluorescence using monoclonal antibodies directed against gp120 and p24. Electron microscopic examinations revealed the presence of typical Lentivirinae particles. The particles released from KC in the extracellular medium showed reverse transcriptase activity and p24 antigen; they could infect lymphocytic cells and were neutralized by a HIV+ patient's serum or an anti-gp120 monoclonal antibody. Our results thus demonstrate that the interaction of HIV-1 with KC in vitro leads to a productive infection. They suggest that the KC may be involved in the pathogenesis of HIV-1 infection and may (i) participate in the transmission of the infection to the peripheral blood cells, (ii) play a role in the depletion of uninfected CD4+ cells.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Enzymes for liberation of pantothenic acid in blood: use of plasma pantetheinase.

Reported normal concentrations for human whole-blood total pantothenic acid vary from 1.1 to 12 mumol/L. This wide range may partly arise from the various enzymes used for liberation of pantothenic acid from coenzyme A, particularly the source of pantetheinase. A purified pantetheinase from pig kidney had greater than 100 times the specific activity and less than 0.01 times the pantothenate content of other commonly used extracts. Endogenous pantetheinase activity in human plasma was identified (11.2 +/- 2.0 mumol pantothenate .min-1.L-1, n = 29) and found comparable to the activity usually added from exogenous sources for liberation of pantothenate from whole blood (1-13 mumol.min-1.L-1). Alkaline phosphatase alone liberated as much pantothenate from hemolyzed whole blood as did alkaline phosphatase with pantetheinase. Previous reports of total blood pantothenate may be elevated by pantothenate in the pantetheinase extracts, an unnecessary source of error. Whole-blood total pantothenate concentrations less than 4.6 mumol/L are normal and do not indicate deficiency, as is often currently quoted.

Alkaline Phosphatase↗
PubMed1989

The influence of electrical variables on analgesia produced by low current transcranial electrostimulation of rats.

Pulsed low current transcranial electrostimulation (TE) has been shown to induce analgesia in rats as measured by the wet tail flick test. This study investigates the effect of varying stimulus frequency, pulse width, charge balance and polarity, as well as the influence of electrode placement and time of day at which stimulus occurred. A biphasic, charge balanced waveform with a first phase duration of 2 msec, current 10 microA and repetition rate 10 Hz was found to induce maximum tail flick latency changes. The effects of morning or nighttime stimulation were statistically indistinguishable, as were the differences between monophasic and biphasic stimulation. Analgesia was maximized when a positive first phase was delivered into the right ears of the rats, but monolateral stimulation with both electrodes on either the left or the right ear produced no measurable effect. Examination of TE responses in sham and stimulated populations reveals normal response distributions with the stimulated group skewed toward a positive effect.

Analgesia↗
PubMed1986

The physical, psychological, educational and professional conditions of young adults given growth hormone for childhood growth hormone deficit.

Twenty five of the 75 patients having been given human growth hormone in the Pediatric Nancy Endocrinological Division have reach final adult height. All have been treated the same way, 10 boys and 4 girls were diagnosed as isolated deficit, 7 boys and 4 girls as combined deficit. The physical, sexual, radiological, intellectual, professional and psychological characteristics have been defined either during the treatment follow-up or at a final interview. All results have been compared to the familial conditions if possible. Final adult statures are in the low range of the normal (-2 DS). The sexual development, normal for patients with isolated deficit, has not been achieved completely by regular protocol for patients with combined deficit. The intellectual and professional achievements are rather low but this has to be matched with below the normal familial conditions. Psychological determination is quite satisfactory but the personality is dominated by shyness and lack of responsibility. It is likely that an earlier onset of treatment and a better psychological guidance may lead to a better final results judged both on physical grounds but also on psychological and professional conditions.

Adolescent↗
PubMed1984

Decreased filtration fraction during active proliferative lupus nephritis: relation to disease activity and reversibility of renal function.

Nine consecutive patients with systemic lupus erythematosus (SLE) were studied longitudinally for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during ten exacerbations of severe proliferative glomerulonephritis. At the onset of exacerbation, GFR decreased significantly whereas ERPF did not fall; the latter even increased in some patients. As a consequence mean filtration fraction (FF), the ratio of GFR and ERPF, fell from 0.20 to 0.10. At maximum exacerbation, both GFR and ERPF had decreased without change in FF. During remission FF rose to pre-exacerbation values as a result of increase in GFR without change in ERPF. We conclude that changes in FF reflect changes in renal haemodynamics in patients with SLE and active proliferative glomerulonephritis. Determination of FF may be of some value in assessing renal disease activity and the degree of reversibility of renal function in those patients.

Adult↗
PubMedDate not supplied

Computer registration of uveitis patients.

An analysis was made of 1309 patients with uveitis seen at University Hospitals participating in the Uveitis Centre of the Netherlands Ophthalmic Research Institute. In this series B27-associated anterior uveitis was the most frequent entity (18%) followed by Toxoplasma chorioretinitis (7%). Sarcoid uveitis, pars planitis and Fuchs' heterochromic cyclitis each accounted for approximately 4-5% of cases. In 44% of the patients no specific diagnosis could be made. Central diagnosis registration is of great importance when conducting clinical uveitis research.

Computers↗
PubMedDate not supplied

Multiplication of human immunodeficiency virus in primary cultures of human Kupffer cells--possible role of liver macrophage infection in the physiopathology of AIDS.

In primary cultures of Kupffer cells obtained from surgical biopsies of human liver by collagenase perfusion followed by centrifugal elutriation and infected with HIV, the virus multiplied abundantly, as attested by the appearance of a reverse transcriptase activity in the medium. Examined by electron microscopy, the cells were found to contain viral particles with typical features of Lentivirinae. Furthermore, the virus could be revealed by immunofluorescence using an HIV+ patient serum. HIV antibodies also neutralized the infectivity of the Kupffer cell-produced virus. Our results demonstrate that the cells constituting the largest fraction of fixed macrophages in the body may be infected by HIV, thereby suggesting that the Kupffer cells may play a role in the physiopathology of the disease, namely as a reservoir for the virus.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Morphine stimulates HIV replication in primary cultures of human Kupffer cells.

Intravenous drug abusers represent a high risk group for HIV infection in Europe and North America. Although the use of blood-contaminated needles undoubtedly constitutes the main factor of transmission of the virus, an effect of the drug itself either on the immune system or on virus replication, thus favouring the initiation of the infection, may not be excluded. We have formerly established that primary cultures of human Kupffer cells (KC) are permissive for HIV1. In this paper, we describe the effect of morphine hydrochloride on the multiplication of different isolates of HIV1 in cultured human KC. KC were obtained by dissociation of human liver fragments with collagenase and purified by centrifugal elutriation. Five-day-old KC were infected with HIV1; at different intervals, the production of virus was quantitated by the reverse transcriptase activity associated with the particles present in the culture medium. In primary cultures of KC preincubated for 48 h and maintained in the presence of morphine, the production of viral particles was increased. This enhancing effect was found with 3 different HIV1 isolates. Treatment of KC with morphine prior to infection was not required for the stimulation to take place, which indicated that the enhancing effect was not related to a more efficient adsorption of the virus to the KC plasma membrane. Stimulation of HIV1 production was observed for all the concentrations of morphine used (0.05 to 0.5 mg/ml). These results, if confirmed in vivo, may shed new light on the risk factors related to the intravenous administration of heroin.

Cells, Cultured↗