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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 253 records · Page 14Linked to original sources
PubMed1997

A strategy for rational design of fully synthetic glycopeptide conjugate vaccines.

The present study describes a strategy to rationally design fully synthetic glycopeptide conjugate vaccines. Glycopeptide immunogens were constructed by coupling synthetic oligosaccharides comprising repeating units of synthetic 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate (sPRP) to synthetic peptides containing potent T-helper cell determinants and B-cell epitopes of the Haemophilus influenzae type b (Hib) outer membrane proteins (OMPs) P1, P2, and P6. Rabbit immunogenicity studies revealed that some of these fully synthetic glycoconjugates were capable of eliciting high titers of both anti-PRP and anti-OMP immunoglobulin G antibodies. In addition, we systematically investigated the factors which could influence their immunogenicity. We observed that the magnitude of the anti-PRP antibody response markedly depended on the relative spatial orientation of sPRP and T-cell epitopes, the anti-PRP antibody response was enhanced when a multiple antigenic peptide was used as a carrier, the anti-PRP antibody response was optimal for three PRP repeating units, and lipidation of peptide-PRP conjugates had a minimal effect on the magnitude of the anti-PRP antibody response. The results of this study clearly demonstrate that coupling a carbohydrate hapten to a peptide can provide T-cell help and convert it into a T-cell-dependent antigen. The antisera raised against these conjugates were also found to be protective against Hib infection in the infant rat model of bacteremia.

Amino Acid Sequence↗
PubMed1997

Rapid development of synaptic connections and plasticity between sensory neurons and motor neurons of Aplysia in cell culture: implications for learning and regulation of synaptic strength.

We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron-motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.

Animals↗
PubMed1997

Clinical consequences of activating germline mutations of TSH receptor, the concept of toxic hyperplasia.

Activating mutations of TSH-R have been described in toxic nodules and more recently in familial nonautoimmune thyrotoxicosis. This last entity is still confused with familial Graves' disease and the aim of this study is to define its phenotype. Based on 49 patients coming from our first family and on the 4 other kindreds secondarily described in the literature, the phenotypic expression is: a high incidence of hyperthyroidism, an early onset of disease, a higher men/women ratio (17/32) than in Graves, disease, the absence of ophthalmopathy and of circulating and intrathyroid signs of immunity, a pathology similar to toxic nodule, the need for a total destruction of thyroid tissue to cure the patients. The total analogy with toxic nodule leads us to name this new entity "toxic hyperplasia'. Among 92 successive diffuse nonfamilial thyrotoxicosis cases (initially considered as Graves) we isolated 5 cases without extra- and intrathyroidal autoimmunity, raising the question of the existence of an apparent "sporadic' form of toxic hyperplasia (neomutation?).

Animals↗
PubMed1997

Annular pancreas.

Explore the source record for details and available documents.

Anastomosis, Surgical↗
PubMed1997

[Improving the facial profile by implant supported dentures].

Forty toothless patients were examined over a period of 3 years for the purpose of improving the face profile after integration of implant-supported, removable full dentures. The data before the treatment were related to the corresponding normal values. The same parameters were measured 3 months after the prosthetic treatment was finished and were compared to the preoperative data. In all parameters we saw an significant increase in the normal value rate.

Adult↗
PubMed1997

[Determination of body feat in treatment of anorexia nervosa].

Bioimpedance analysis was used for weekly assessments of body fat content in 20 adolescents with anorexia nervosa (mean BMI 15.6 kg/m2; mean age, 14 years 5 months) until the desired weight had been achieved, but for a minimum of 12 weeks. As expected, body fat content increased with BMI. Total body fat increased faster than fat-free body mass, the relative increase being 66%, vs 11% for fat-free body mass. However, an expected association between an increase in the percentage of body fat and resumption of menstruation did not occur. As a noninvasive, repeatable procedure including the assessment intraabdominal fatty tissue, determination of total body fat by bioimpedance analysis is suitable for use in longitudinal studies of anorexia nervosa.

Adipose Tissue↗
PubMed1997

[Selection criteria for conservative therapy of splenic trauma in adults].

The safety and effectiveness of nonoperative management of selected adults have been confirmed in those patients who meet selection criterias of isolated splenic injury and hemodynamic stability. The CT scan is a very precise and the most specific diagnostic procedure in splenic trauma. Nonoperative treatment is successful in 80% of adults in such selected group of patients.

Adolescent↗
PubMed1996

[Classification and epidemiology of thyroid tumors].

Thyroid diseases are the most prevalent endocrine diseases. Faced with a thyroid enlargement or nodule, it is a challenge for the physician to determine with the best sensibility and specificity and the least cost which one are benign tumours and which are malignant neoplasms that need to be removed. The prevalence of solitary nodules is 1 to 5%. Only 2 to 12% of these nodules are cancers. Papillary and follicular carcinomas, two carcinomas derived from follicular cells, are the most common types and occur more frequently in women. Both have a good prognosis. Medullary carcinoma derives from C-cells. Familial forms have to be searched. Anaplastic carcinoma and other malignant tumours are less frequent but have poor prognosis.

Carcinoma, Medullary↗
PubMed1996

Different energization mechanisms drive the vacuolar uptake of a flavonoid glucoside and a herbicide glucoside.

Glycosylation of endogenous secondary plant products and abiotic substances such as herbicides increases their water solubility and enables vacuolar deposition of these potentially toxic substances. We characterized and compared the transport mechanisms of two glucosides, isovitexin, a native barley flavonoid C-glucoside and hydroxyprimisulfuron-glucoside, a herbicide glucoside, into barley vacuoles. Uptake of isovitexin is saturable (Km = 82 microM) and stimulated by MgATP 1.3-1.5-fold. ATP-dependent uptake was inhibited by bafilomycin A1, a specific inhibitor of vacuolar H+-ATPase, but not by vanadate. Transport of isovitexin is strongly inhibited after dissipation of the DeltapH or the DeltaPsi across the vacuolar membrane. Uptake experiments with the heterologue flavonoid orientin and competition experiments with other phenolic compounds suggest that transport of flavonoid glucosides into barley vacuoles is specific for apigenin derivatives. In contrast, transport of hydroxyprimisulfuron-glucoside is strongly stimulated by MgATP (2.5-3 fold), not sensitive toward bafilomycin, and much less sensitive to dissipation of the DeltapH, but strongly inhibited by vanadate. Uptake of hydroxyprimisulfuron-glucoside is also stimulated by MgGTP or MgUTP by about 2-fold. Transport of both substrates is not stimulated by ATP or Mg2+ alone, ADP, or the nonhydrolyzable ATP analogue 5'-adenylyl-beta,gamma-imidodiphosphate. Our results suggest that different uptake mechanisms exist in the vacuolar membrane, a DeltapH-dependent uptake mechanism for specific endogenous flavonoid-glucosides, and a directly energized mechanism for abiotic glucosides, which appears to be the main transport system for these substrates. The herbicide glucoside may therefore be transported by an additional member of the ABC transporters.

Adenosine Diphosphate↗
PubMed1996

An H3 coding region regulatory element is common to all four nucleosomal classes of mouse histone-encoding genes.

We have previously identified the alpha element within the mouse H2A and H3 histone gene coding region activating sequences (CRAS). This common element is required for normal in vivo expression of these two replication-dependent genes and interacts with nuclear factor(s). Here we report that the CRAS alpha element is present in the coding region sequences of two other replication-dependent mouse H genes, H2B and H4. The DNA-protein interactions were examined by DNase I footprinting and methylation-interference assays, and are very similar, if not identical, for these replication-dependent genes, confirming that the alpha element is the binding site for common nuclear protein(s) in H genes of all four nucleosomal classes. Moreover, we show that the same nuclear factor is involved in these DNA-protein interactions. Our findings, together with the fact that a replication-independent H gene, H3.3, has a mutated alpha element that fails to interact with nuclear proteins, suggest that this regulatory element is involved in the coordinate expression of the replication-dependent core H genes in the eukaryotic cell cycle.

Animals↗
PubMed1996

Indication of an involvement of interleukin-1 beta converting enzyme-like protease in intramedullary apoptotic cell death in the bone marrow of patients with myelodysplastic syndromes.

Our previous studies using in situ end labeling (ISEL) of fragmented DNA revealed extensive apoptotic cell death in the bone marrows (BM) of patients with myelodysplastic syndromes (MDS) involving both stromal and hematopoietic cells. In the present report we show greater synthesis of interleukin-1 beta (IL-1 beta) in 4 hour cultures of density separated BM aspirate mononuclear (BMAM) cells from MDS patients as compared to the cultures of normal BM from healthy donors or lymphoma patients (1.7 +/- 0.37 pg/10(5) cells, n = 29 v 0.42 +/- 0.24 pg/10(5) cells, n = 11, respectively, P = .049). Further, these amounts of IL-1 beta in MDS showed a significant correlation with the extent of apoptosis detected by ISEL in corresponding plastic embedded BM biopsies (r = .480, n = 30, P = .007). In contrast normal BMs did not show any correlation between the two (r = .091, n = 12, P = .779). No significant correlation was found between the amounts of IL-1 beta and % S-phase cells (labeling index; LI%) in MDS determined in BM biopsies using immunohistochemistry following in vivo infusions of iodo- and/or bromodeoxyuridine. Neither anti-IL-1 beta antibody nor IL-1 receptor antagonist blocked the apoptotic death of BMAM cells in 4 hour cultures (n = 5) determined by ISEL (apoptotic index; AI%), although the latter led to a dose-dependent accumulation of active IL-1 beta in the culture supernatants. On the other hand, a specific tetrapetide-aldehyde inhibitor of ICE significantly retarded the apoptotic death of BMAM cells at 1 mumol/L in 5/6 MDS cases studied (AI% = 2.99 +/- 0.30 in controls v 1.58 +/- 0.40 with ICE-inhibitor, P = .05) and also reduced the levels of active IL-1 beta synthesized (5.59 +/- 2.63 v 2.24 +/- 0.93 pg/10(6) cells, respectively). In normal cells, neither IL-1 blockers nor the ICE inhibitor showed any effect on the marginal increase in apoptosis observed in 4 hour cultures. Our data thus suggest a possible involvement of an ICE-like protease in the intramedullary apoptotic cell death in the BMs of MDS patients.

Antibodies, Monoclonal↗
PubMed1996

4-O-phosphoryl-L-threonine, a substrate of the pdxC(serC) gene product involved in vitamin B6 biosynthesis.

The Escherichia coli pdxC(serC) gene codes for a transaminase (EC 2.6.1.52). The gene is involved in both pyridoxine (vitamin B6) and serine biosynthesis and was overexpressed as a MalE/PdxC(SerC) fusion protein. The fusion protein was purified by affinity chromatography on an amylose resin and hydrolyzed in the presence of protease factor Xa. Both the fusion protein and the PdxC(SerC) protein were characterized (K(M) value, turnover number, optimum pH). Both enzymes used 4-O-phosphoryl-L-threonine rather than 4-hydroxy-L-threonine as a substrate indicating that the phosphorylated rather than the non-phosphorylated amino acid is involved in pyridoxine biosynthesis. Pyridoxal phosphate was shown to be the cofactor for both enzymes and therefore seems to be involved in its own biosynthesis.

Base Sequence↗
PubMed1996

[Cardiosurgical therapy of coronary heart disease in terminal kidney insufficiency].

OBJECTIVE: To determine retrospectively the complications and long-term results of aortocoronary bypass grafting in patients with end-stage renal disease. PATIENTS AND METHODS: 65 patients with coronary heart disease (CHD) and on dialysis (54 men, 11 women; average age 56.9 +/- 8.1 years) underwent aortocoronary bypass grafting between 1982 and 1992. Mean duration of dialysis (haemo- or peritoneal) was 41.1 +/- 45.0 (1-215) months. All patients had had haemofiltration treatment in conjunction with the bypass operation. RESULTS: Coronary angiography demonstrated triple-vessel disease in 40 patients (62%). Average number of bypasses was 2.8 per patient. Perioperative death rate was 4.6%. 95% of survivors were free of symptoms 6 months postoperatively. Long-term survival rate was 71% after 3 years and 55% after 5 years. CONCLUSION: Aortocoronary bypass grafting for CHD in patients with end-stage renal disease can be performed with a low perioperative mortality rate and significantly improves symptoms.

Adult↗
PubMed1996

Fibrocartilaginous dysplasia.

We present the case of a 53-year-old patient with fibrocartilagenous dysplasia. The area involved was in the proximal femur and presented a lytic lesion with extensive calcifications which radiologically mimicked chondrosarcoma. The radiopathological pattern of this rare entity is discussed in detail and the literature reviewed.

Biopsy↗