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Biomedical subjects

W Lenz

Publications and source records attributed to W Lenz.

At least 37 records · Page 2Linked to original sources

Agonist-induced down-regulation of the m4 muscarinic acetylcholine receptor occurs without changes in receptor mRNA steady-state levels.

The regulation of m4 muscarinic acetylcholine receptor mRNA expression by receptor activation was studied in N1E-115 neuroblastoma and AtT-20 pituitary cells that endogeneously express the m4 muscarinic receptor. Receptor concentration was measured by binding of the muscarinic receptor radioligand [3H]quinuclidinyl benzilate, and RNA-RNA solution hybridization/RNase protection assay with a m4 receptor-specific [32P]-cRNA probe was used to evaluate the levels of receptor mRNA. Treatment of both cell lines with a receptor-saturating concentration of the agonist carbachol decreased receptor number. However, there was no change in steady-state levels of m4 mAChR mRNA in both cell lines. Determination of mRNA stability in the presence of the transcription blocker actinomycin D revealed that carbachol treatment increased half-life of receptor mRNA in N1E-115 cells, but not in AtT-20 cells, suggesting that receptor activation can regulate m4 receptor mRNA stability dependently on cell type. Analysis of receptor degradation kinetics in the presence of the protein synthesis inhibitor cycloheximide showed that receptor down-regulation in N1E-115 and AtT-20 cells is sufficiently accounted for by increased receptor degradation. These results indicate than m4 muscarinic receptor down-regulation is substantially different from that of the muscarinic receptor subtypes m2 and m3 which is reported to be associated with agonist-induced reduction in receptor mRNA.

Animals↗

Isolation, sequence and functional expression of the mouse m4 muscarinic acetylcholine receptor gene.

Molecular cloning studies have demonstrated the existence in mammals of five genes encoding distinct muscarinic acetylcholine receptors which are heterogeneously expressed in the central nervous system and the target organs of the autonomic nervous system. In order to determine the factors responsible for regulation of receptor expression, we isolated a genomic clone encoding the mouse m4 muscarinic acetylcholine receptor. The gene contains no introns in the coding sequence, and encodes a polypeptide of 479 amino acids that is able to bind various muscarinic ligands with affinities typical for mAChRs and to couple efficiently to inhibition of adenylyl cyclase.

Amino Acid Sequence↗

Study of isolated apparent amniogenic limb deficiency in Hungary, 1975-1984.

A population-based and validated data set of 206 cases with apparent amniogenic limb deficiency was ascertained in Hungary between 1975 and 1984. Such limb defects frequently (36%) associated with nonlimb abnormalities. In 134 cases with isolated defects typically more limbs are affected, upper and lower limbs, right and left sides, and both sexes are equally affected. Case-control analysis of such isolated cases indicates a lower socioeconomic status of parents, a higher parity, more frequent unwanted pregnancies, preterm birth, and a higher rate of threatened abortion. Familial occurrence was not found in 415 first-degree relatives.

Abnormalities, Drug-Induced↗

Causal study of isolated ulnar-fibular deficiency in Hungary, 1975-1984.

A population-based and validated data set of 114 cases with isolated ulnar-fibular deficiency was evaluated in Hungary, 1975-1984. Ulnar-fibular type had the third most common birth prevalence (0.07 per 1000) among isolated congenital limb deficiency types. This type is relatively rarely associated with nonlimb defects, a single limb is affected in two-thirds of cases, nearly all other cases had femur-fibula-ulna (FFU) dysostosis. Upper and lower limbs, right and left sides, are equally affected, however, there is an obvious male excess (71%). Case-control analysis indicated a lower birth weight due to intrauterine growth retardation, higher birth order, lower socioeconomic status of parents, and a more frequent reported subfertility. The family study identified one familial cluster (one siboccurrence) among 331 first-degree relatives.

Abnormalities, Drug-Induced↗

A morphological and family study on isolated terminal transverse type of congenital limb deficiency in Hungary, 1975-1984.

A population-based and validated data set of 195 cases with isolated terminal transverse-type congenital limb deficiency was evaluated in Hungary, 1975-1984. Terminal transverse types of congenital limb deficiency are not usually associated with non-limb defects, and typically only one limb is affected. Upper limb is more frequently affected than lower (9:1) in monomelic cases. The left side and females are affected more often in upper limbs while lower limb defects are evenly distributed between right and left sides and both sexes. Familial occurrence was not found.

Congenital Abnormalities↗

FFU complex: an analysis of 491 cases.

A study of 491 patients with femur-fibula-ulna (FFU) complex is presented. The term FFU complex has been proposed for cases in which the femur, fibula and/or ulna show defects, which tend to be associated. These cases are usually sporadic. Some rare anomalies of the arms which are present are particularly frequent in FFU complex. These are amelia, peromelia of humerus, humero-radial synostosis and defect of ulna. In our study, 491 patients were investigated for involvement of limb malformations. Our results, showing nearly equal proportions of the most common malformations in four analysed groups (with one, two, three and four limbs affected) supports the hypothesis that even if one arm or one leg only is affected, the cases may still be classifiable as FFU complex. There is a striking asymmetry in presence and in degree. All malformations are more often unilateral than bilateral. Upper limbs are affected more often than lower limbs. The right side and the male sex are preferentially affected. The limb malformations present in the FFU complex are different from those seen in most other types of limb defects, so there is virtually no overlap between FFU and other limb malformations. Some arguments in favour of early somatic mutation as a cause are discussed.

Child↗

A family study on isolated congenital radial and tibial deficiencies in Hungary, 1975-1984.

Radial and tibial deficiencies are frequently (70%) associated with non-limb abnormalities. Isolated radial and tibial deficiencies may have a different etiology: in this study radial deficiencies were more frequent, there were milder subtypes and one-limb involvement was found in 70% of cases, tibial deficiencies were rare, mild subtypes did not occur and in general more limbs were involved. Among multimelic cases, one case had hypoplasia of the tibia with polydactyly and two cases had tibial aplasia with split hand +/- foot of autosomal dominant inheritance. Of 40 cases, four were familial. Findings of a case-control study on this population-based and validated 10-year cohort showed a lower mean birth weight and a higher rate of low birth weight in cases with isolated radial and tibial deficiency.

Bone Diseases, Developmental↗

Phenotypical and genotypical characterization of epidemic clumping factor-negative, oxacillin-resistant Staphylococcus aureus.

A total of 50 oxacillin-resistant Staphylococcus aureus (ORSA) strains that were clumping factor negative (CFN) and protein A negative by latex agglutination were collected from patients in six different hospitals at different locations in Germany during 1991 and 1992. Antibiograms, bacteriophage typing, and plasmid analysis were performed. The antibiograms showed that, besides oxacillin, all CFN ORSA strains were resistant to gentamicin, clindamycin, erythromycin, ciprofloxacin, and fosfomycin. All these isolates were nontypeable with an international set of phages, and an additional experimental phage set indicated that the strains were phage type 16, 192. Moreover, all isolates possessed a single plasmid of 30 kb, and restriction analysis of those plasmids revealed identical patterns. For genotyping, these 50 isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) and polymerase chain reaction (PCR) of the coagulase and protein A genes and then by restriction enzyme digestion and analysis of restriction fragment length polymorphisms (RFLPs). With 49 strains, electrophoresis of SmaI-digested chromosomal DNA revealed identical PFGE patterns regarding the number and size of the DNA fragments, which could be differentiated from those of clumping factor-positive ORSA strains. Typing for the coagulase gene by PCR revealed PCR products of identical sizes. The AluI restriction digestion patterns of the PCR products were identical. PCR with primers derived from the region of that part of the protein A gene that encodes the immunoglobulin G-binding domains showed a PCR product that was about 170 bp smaller than that of the protein A gene from strains that were positive in the protein A latex agglutination test. Since it is precisely this size that is required in order to encode one immunoglobulin G-binding region, we assume that this is not present in the CFN ORSA strains. The phenotypical and genotypical features identify these very unusual CFN ORSA stains as being of clonal origin.

Base Sequence↗

An epidemiological study of isolated split hand/foot in Hungary, 1975-1984.

A population based and validated 10 year cohort of 94 cases with split hand/foot born in Hungary, 1975-1984 was evaluated. This type of congenital limb deficiency was relatively frequently (43%) associated with non-limb defects. Fifty-four cases with isolated split hand/foot are evaluated in this paper. A single limb was affected in 78% of cases. The upper limbs were 21 times more frequently affected in unimelic cases with a right sided predominance and male excess. Case-control analysis indicated intrauterine growth retardation and lower socioeconomic status of parents of cases. Family study showed six familial cases with autosomal dominant inheritance among 152 first and 452 second degree relatives. All familial cases were males.

Case-Control Studies↗

[Incidence, frequency and resistance characteristics of methicillin-oxacillin resistant Staphylococcus aureus strains in Germany].

In a multicentre study, the methicillin-resistant Staphylococcus aureus (MRSA) isolates in 19 large clinics in Germany were recorded, and the resistance characteristics of these strains were studied. Oxacillin-mannitol-salt agar plates were distributed to all participants to ensure uniformity of screening, and each laboratory used these plates to investigate 200 consecutive Staphylococcus aureus isolates for oxacillin-methicillin resistance. Of the 3,794 evaluable Staphylococcus aureus isolates, 71.5% were penicillin and 3.7% (142) oxacillin resistant; four study centres reported methicillin-oxacillin resistance rates of more than 5%. Of the MRSA isolates, 75% were also resistant to ciprofloxacin, 61% to fosfomycin, 52% to imipenem, 50% to trimethoprim/sulfamethoxazole and 36% to clindamycin. All isolates were sensitive to vancomycin and teicoplanin. Of the Staphylococcus aureus strains isolated from patients in intensive therapy units, 10.4% were methicillin-oxacillin resistant. Drains and catheter tips (9.8% and 5.2% respectively) were the materials with the highest proportions of MRSA. Of the MRSA isolates in this study, 58.2% belonged to lysis group II.

Ciprofloxacin↗

Craniofacial dysostosis, hypertrichosis, genital hypoplasia, ocular, dental, and digital defects: confirmation of the Gorlin-Chaudhry-Moss syndrome.

We report clinical, orofacial and radiological manifestations in a 4-year-old girl and a 33-year-old female with the Gorlin-Chaudhry-Moss (GCM) syndrome. Typical findings in the GCM syndrome are short stature, stocky body build, midface hypoplasia, small eyes, downslanting palpebral fissures, conductive hearing loss, highly arched and narrow palate, malocclusion, abnormally shaped teeth, oligodontia, microdontia, low scalp hairline, hypertrichosis of scalp, face, trunk and limbs and genital hypoplasia. Radiological features include premature synostosis of the coronal suture, brachycephaly, and maxillary under-development. Hypoplasia of the distal phalanges of fingers and toes (also present in the 2 original cases) represents a further manifestation of the GCM syndrome.

Abnormalities, Multiple↗

Distal limb deficiency following chorionic villus sampling?

We have reviewed the follow-up of almost 3000 completed pregnancies in the Münster CVS Program and identified 4 children with distal limb deficiencies. Two cases involved only minor anomalies of distal digital phalanges. One child had a Hanhart anomaly (hypoglossia hypodactylia). We also reviewed 24 cases of limb defects following CVS reported previously. With the exception of a single series, neither the overall incidence of affected children nor cases reported from larger series provide unambiguous evidence of an increased risk of distal limb deficiency caused by CVS.

Child, Preschool↗

Primary melanoma of urinary bladder.

The fourth case of primary melanoma of the bladder is presented together with a review of the previously reported cases and the relevant literature on malignant melanoma in urology. The criteria for classification of the bladder lesion as the primary site are discussed. The eighty-one-year-old female patient was felt not to be suitable for extensive surgery and was successfully treated with a combination of radiation and immunotherapy with recombinant alpha 2 interferon. After previous monthly recurrences of the tumor the patient is in complete remission fifteen months after initiation of therapy. It appears that this form of treatment might be a valuable alternative to radical surgery in elderly patients.

Aged↗

Phage susceptibility, enterotoxigenicity and antibiograms of Staphylococcus aureus strains isolated from human wounds and diarrhoea.

The phage types, enterotoxigenicity and antibiograms of Staphylococcus aureus strains isolated from human diarrhoea and skin wounds in Nigeria were determined. Of 194 strains tested, 140 (72.2%) were typable using a combination of phages in the International Phage Set (IPS) for human strains of S. aureus and the bovine phage set. IPS phages lysed 118 (60.8%) strains while 96 (49.5%) were susceptible to bovine phages. S. aureus strains from adult diarrhoea were significantly (P less than or equal to 0.01; x2) more sensitive to bovine phages (52.8%) than to IPS human phages (16.7%). Strains isolated from wounds were however significantly (P less than or equal to 0.001; x2) more susceptible to IPS human phages (72.9%) than to bovine phages (41.5%). Phage group III strains were predominant amongst diarrhoeal isolates while wound strains were most susceptible to group II phages. Phage 119, a bovine phage, lysed all 19 strains of diarrhoeal origin sensitive to group M phages but all wound strains were resistant. Overall, 132 (68.0%) strains were enterotoxigenic producing staphylococcal enterotoxins A (SEA), B (SEB), C (SEC) or a combination of these. A majority of diarrhoeal strains elaborated SEC while SEB production was predominant amongst wound strains. Of the eight antimicrobial agents used, S. aureus strains were most resistant to penicillin (71.6%) and least to sulfamethoxazole/trimethoprim (1.0%). Occurrence of resistance to one or more antibiotics was higher amongst wound strains (97.5%) than amongst strains isolated from diarrhoea (52.6%). It was concluded that bovine phage 119 may be a useful epidemiologic marker for S. aureus strains of bovine origin associated with human diarrhoea in Nigeria. It is however difficult to ascribe any aetiological significance to these strains because other enteropathogens not assayed for may have been present.

Adult↗

Staphylococcal skin colonization in children with atopic dermatitis: prevalence, persistence, and transmission of toxigenic and nontoxigenic strains.

Staphylococcal skin colonization is a common feature of atopic dermatitis (AD) in adults. Little is known about prevalence and persistence of staphylococci in children. Forty-one AD children (mean age, 70 months) and 41 age-matched controls were studied. S. aureus was isolated from 38 AD patients (93%; 32% of controls, P less than .001) and 37% of AD patients (5% of controls, P less than .001) harbored toxigenic (enterotoxins, toxic shock syndrome toxin) S. aureus strains. No individual biotype prevailed. On follow-up (mean interval, 9 months), 70% of S. aureus strains were reisolated. Nasal and cutaneous S. aureus strains were identical in 73% of AD patients (7% of controls, P less than .001), reflecting increased self-contamination. Identical staphylococcal strains in AD children and their mothers were observed in 38% (S. aureus) and 16% (coagulase-negative strains; P less than .001). The prevalence of staphylococcal colonization in AD children is comparable to that in adults. High rates of self-contamination, transmission to contacts, and prevalence of toxigenic strains in AD children may have clinical and epidemiologic implications.

Adolescent↗