Biomedical subjects
P Frommelt
Publications and source records attributed to P Frommelt.
Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.
BACKGROUND: Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early-onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving. METHODS: The entire open reading frame of the PS1 gene was sequenced in a series of 414 consecutive patients referred for diagnostic testing, including 372 patients with AD and 42 asymptomatic persons with a strong family history of AD. RESULTS: Forty-eight independent patients screened had a PS1 mutation including 21 novel mutations. In addition, 3% of subjects (11/413) had a known polymorphism, the Glu318Gly substitution. The majority of the mutations were missense substitutions but there were three insertions and Delta exon 10 mutation. With six exceptions (codons 35, 178, 352, 354, 358, and 365) most of the mutations occurred at residues conserved in the homologous PS2 gene or in PS1 of other species. CONCLUSIONS: Eleven percent of a referral-based series of patients with AD can be explained by coding sequence mutations in the PS1 gene. The high frequency of PS1 mutations in this study indicates that screening for PS1 mutations in AD is likely to be successful, especially when directed at patients with a positive family history with onset before 60 years (90% of those with PS1 mutations were affected by age 60 years). This will also have significance for the secondary identification of at-risk relatives who might be candidates for future prophylactic therapies for AD.
[References for evaluation scales in quality assurance in rehabilitation--1. II. Measuring functional independence in rehabilitation with the Functional Independence Index].
Presented is an instrument assessing functional independence in rehabilitation. This instrument, the Functional Independence Measure (FIM), was developed in the USA and translated into German. Considerable experience and research has accumulated concerning its application, formal properties and function in interdisciplinary rehabilitation. Application and evaluation of the FIM is demonstrated in a case study. The FIM is shown to be a reliable and highly informative instrument measuring disability according to ICIDH criteria in clinical practice. It reflects reliably the amount of help and assistance required by the individual patient.
Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.
The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T-->C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.
Familial Alzheimer disease: a large, multigeneration German kindred.
A German family with 21 members affected by Alzheimer disease (AD) was studied clinically and genetically. The diagnosis was histologically verified in three affected family members. Ancestors were traced through seven generations to a couple residing in East-Westfalia during the middle of the 19th century. Dementia was often accompanied by extrapyramidal features and myoclonus. No cases of Down syndrome or hematologic malignancy occurred in this family. Clinical manifestations, temporal progression, neurological testing, and neuropathological features do not differ from the more common sporadic form of AD. The inheritance pattern is most consistent with autosomal-dominant transmission.
Hippocampal lesions in dominantly inherited Alzheimer's disease.
We compared hippocampal lesions in three pedigrees of Familial Alzheimer's Disease (FAD). In these pedigrees, the disease is inherited as an autosomal dominant disorder and has been linked to DNA markers on chromosome 21. In eight cases of FAD (four from one pedigree and two each from two others) we quantified neurofibrillary tangles (NFT) and senile plaques (SP) in hippocampal subdivision CA1-4, subiculum, presubiculum, and dentate gyrus. We observed consistent patterns of the distribution of lesions: The highest density of NFT and SP was present in CA1-2; virtually no SP or NFT were present in presubiculum; SP diameter was consistently greatest in CA4. We found no overall differences among pedigrees in total densities of NFT and SP, but statistical analyses disclosed that an uncommon type of SP was disproportionately present in two pedigrees. This type of SP was usually restricted to CA4, had a marked amyloid core devoid of argyrophilic neurites. These studies also disclosed inter- and intrafamilial heterogeneity of lesion distribution (including congophilic angiopathy and cerebellar plaques) in these three pedigrees.
Successful medical treatment of Candida parapsilosis endocarditis in a premature infant.
Endocarditis is an uncommon complication of disseminated candidiasis among premature infants, but has been recently reported to be almost uniformly fatal. The lone previously documented survivor required extensive surgical resection as well as prolonged systemic antifungal therapy. The present report details a premature infant who recovered from Candida endocarditis with medical therapy alone.
Effect of increased pressure on ventricular growth in stage 21 chick embryos.
We studied the effect of increased ventricular pressure on heart growth in the stage 21 (3.5-day) chick embryo. Ventricular pressure was increased by constricting the conotruncus with a loop of 10-0 nylon tied in an overhand knot. The embryos were reincubated, and physiology and cellular morphology were evaluated at successive stages of development, stages 21, 24, 27, and 29. Ventricular pressure was measured with a servo-null pressure system, and cardiac output was measured with a 20-MHz pulsed Doppler velocity meter. Ventricular and embryo dry weights were measured on an electronic microbalance, myocyte organelle composition was measured by a point counting technique, and cell growth response was measured by DNA and protein assay. The conotruncal loop increased ventricular pressure in experimental compared with control embryos, i.e., at stage 24, 2.88 +/- 0.13 vs. 1.96 +/- 0.05 (SE) mmHg (P less than 0.05), respectively, without affecting cardiac output. Ventricular dry weight increased in experimental vs. control embryos, i.e., at stage 24, 114 +/- 7 vs. 85 +/- 4 micrograms (P less than 0.05), respectively, whereas embryo weights were similar between the two groups. The difference in ventricular weights was due to myocyte hyperplasia, since organelle proportion of myofibrils and mitochondria, DNA-to-protein ratio, and myocyte area were similar in experimental voice control embryos. Thus the adjustment of myocardial mass to ventricular work occurs even during the earliest stages of embryonic development. Cardiac growth and morphogenesis are parallel but separable processes.
[A psychophysiologic time series study with 20 students over 8 weeks].
A longitudinal (time series) study was performed (N = 20 students; T = 16 points of observation during 8 weeks) on a considerable number of psychological and physiological variables to investigate the suitability of these parameters for general and individual state change description. Some problems of correlational analysis and the generality-individuality-dilemma of this kind of research are discussed.
[Time serial study of orthostatic cardiovascular regulations].
In a repeated measurement design (16 times during 8 weeks) active orthostasis was investigated in a sample of twenty male students, utilizing a tilt table. Additional data included cardiovascular and pulmonary tests, psychological scales, items from a diary and meterorological data. Analysis of orthostatic time-series was carried out with hierarchical grouping analysis for heart rate and blood pressure. Results indicated three intraindividual patterns of orthostatic reaction called normo-, hyper- and hyporeactive. These patterns are independent of the known interindividual orthostatic reaction types. Analysis of variance of the described patterns revealed differences for physiological and meteorological data and some items of the diary. These results have been crossvalidated.
[The post-polio syndrome].
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