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Biomedical subjects

B Berger

Publications and source records attributed to B Berger.

At least 55 records · Page 3Linked to original sources

Bacterial vaginosis is not associated with circumcision status of the current male partner.

OBJECTIVE: Bacterial vaginosis (BV) is common in sexually active women, and in a large proportion the underlying aetiology is unknown. We evaluated partner circumcision status as a potential risk and hypothesised that women with uncircumcised partners were at increased risk for BV. METHODS: Retrospective audit of a partner study (272 heterosexual couples) conducted in Baltimore between 1990 and 1992. BV defined by clinical criteria and circumcision status of males was determined by physical examination. RESULTS: BV was diagnosed in 83 (30%) female partners; 75 (27%) males were uncircumcised. In males and females respectively, gonorrhoea was diagnosed in 20% and 16%, and chlamydia in 7% and 11%. In women with circumcised partners, 58/197 (29%) had BV compared with 25/75 (33%) with uncircumcised partners (p = 0.53). CONCLUSION: Women with uncircumcised current partners are not at increased risk for BV.

Adult↗

Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry.

OBJECTIVE: Our objective was to analyze the prevalence, incidence, and mortality of diabetes in a population of 280,539 inhabitants. RESEARCH DESIGN AND METHODS: The incidence, prevalence, and deaths from diabetes at all ages of a population have been prospectively followed in the county of Skaraborg, Sweden, since 1991. RESULTS: The annual incidence of diabetes per 100,000 inhabitants in 1991-1995 was (mean +/- 95% CI) 14.7 +/- 3.2 for type 1 diabetes (diagnosed at 24.1 +/- 2.2 years of age) and 265.6 +/- 16.1 for type 2 diabetes (diagnosed at 66.6 +/- 0.6 years of age). The incidence of type 2 diabetes was significantly (P < 0.001) higher among men. There was no significant change in the age at diagnosis of diabetes. Although the incidence rate and the age at diagnosis were constant, the prevalence of diabetes increased by 6% each year. The relative mortality risk for diabetic patients was almost four times higher than expected. The median age at death, however, increased significantly, from 77.2 to 80.2 years (P < 0.05), during the study. CONCLUSIONS: The prevalence but not the incidence rate of diabetes increased during the years 1991-1995. Although diabetic patients showed a high relative mortality, increased survival apparently explains the increase in prevalence of diabetes in the country of Skaraborg.

Adolescent↗

Deprivation and abstinence in psychoanalytic psychotherapy.

Freud used the concept of "abstinence" in relation to the patient-therapist relationship, and saw "deprivation" as a motivating force in the treatment. Later authors related to "deprivation" and "abstinence" in different terms. Kleinians tend to emphasize the non-gratifying approach, designed to produce transference of all kinds; Bion suggests that an atmosphere of deprivation and abstinence in the psychoanalytic treatment allows for an "intuitive" approach to mental events and phenomena; Kohut points at abstinence as a structuring aspect in the patient's personality; but he also speaks about optimal frustration. Winnicott recommends, in the treatment of people who suffered severe "holding" deprivation, maximum adjustment of the therapeutic setting to the patient's needs. Deprivation and abstinence, in this respect, apply to the therapist; but, on the other hand, a state of "holding" in the treatment allows the patient to experience severe deprivations and anxieties. This paper also discusses the extent to which wishes and needs are satisfied in the treatment as well as the causes for unnecessary abstinence and deprivation which are due to the therapist's mistakes or failures. Inspired mainly by Winnicott's spirit, this paper also deals with the paradoxes all therapists must face in their work.

Adult↗

Computational learning reveals coiled coil-like motifs in histidine kinase linker domains.

The recent rapid growth of protein sequence databases is outpacing the capacity of researchers to biochemically and structurally characterize new proteins. Accordingly, new methods for recognition of motifs and homologies in protein primary sequences may be useful in determining how these proteins might function. We have applied such a method, an iterative learning algorithm, to analyze possible coiled coil domains in histidine kinase receptors. The potential coiled coils have not yet been structurally characterized in any histidine kinase, and they appear outside previously noted kinase homology regions. The learning algorithm uses a combination of established sequence patterns in known coiled coil proteins and histidine kinase sequence data to learn to recognize efficiently this coiled coil-like motif in the histidine kinases. The common appearance of the structural motif in a functionally important part of the receptors suggests hypotheses for kinase regulation and signal transduction.

Algorithms↗

Hippocampal developmental changes in patients with partial epilepsy: magnetic resonance imaging and clinical aspects.

Developmental disorders of the hippocampal formation (HF) have been described in epileptic syndromes associated with lissencephaly, but HF malformations can be found without widespread cortical changes. We report 19 patients with partial epilepsy and abnormal HF patterns on magnetic resonance imaging (MRI). The changes consisted of incomplete folding with abnormal medial location along the choroid fissure, globular shape and/or verticalization, and were observed in the following three contexts: (1) diffuse disorder of neuronal migration (n=1); (2) temporal lobe malformation (n=5), including heterotopia, abnormal gyration, and, in 2 cases, reduced HF volume; and (3) apparently isolated HF changes (n=13, bilateral in 3 cases). The clinical features were heterogeneous in terms of severity of epilepsy and, when the focus could be determined, in localization (temporal or extratemporal). In 4 patients with apparently isolated HF changes, MRI was suggestive of both abnormal development and hippocampal sclerosis. In these patients, presurgical investigation and postoperative results suggested multiple epileptogenic foci, involving the frontal lobes in 2 cases. One HF specimen was large enough for the observation of developmental abnormalities corresponding to the changes seen on MRI. HF changes in shape and/or position should be included among the structural abnormalities associated with partial epilepsies. They may represent the visible part of a more extensive or more distant disorder of brain development.

Adolescent↗

On the Structure of the Scaffolding Core of Bacteriophage T4 and Its Role in Head Length Determination.

The scaffolding core in bacteriophages is a temporary structure that plays a major role in determining the shape of the protein shell that encapsulates the viral DNA. In the currently accepted structure for the scaffolding core in bacteriophage T4, there is a symmetry mismatch between the protein shell, which has fivefold symmetry, and the scaffolding core, which is believed to consist of six helical chains. Alternate structures for the scaffolding core in T4 are investigated. Starting with the hypothesis that the shell and a 10-helix core would have matching symmetry, a Vernier mechanism is proposed that explains the previously unexplained behavior of the length determination process in giant head mutants of T4. Other possible Vernier mechanisms for core structures containing six and eight helices are also explored. Copyright 1998 Academic Press.

Journal Article↗

Mitochondrial phylogeny of the genus Regulus and implications on the evolution of breeding behavior in sylvioid songbirds.

We tested four hypotheses about the relationships of the kinglets (genus Regulus)to seven closely related genera of the songbird superfamily Sylvioidea using mitochondrial DNA sequences. The kinglets were suggested to be closely related to the tits (Parus) or to the Old World Warblers (Phylloscopus) and were also suggested to constitute the, or at least one of the, most ancestral splits among the sylvioids. Our phylogenetic analysis grouped the kinglets as the sister group of a clade comprising Parus and Phylloscopus and including the genera Sylvia, Aegithalos, and Leptopoecile. Two of the taxa were placed more ancestral to the kinglets: Sitta and Certhia. We also identified the endemic kinglet species from the Canary Islands s the sister group of R. regulus. The superimposition of breeding behavior on the phylogeny suggests that hole nesting is ancestral and various other patterns of nest construction have evolved from it. The placement of Parus implies that hole nesting in the Paridae is likely to have originated secondarily. Further, Leptopoecile and Aegithalos, two genera for which a helper system of elder offspring in breeding was described, were resolved as a clade.

Animals↗

Local rules simulation of the kinetics of virus capsid self-assembly.

A computer model is described for studying the kinetics of the self-assembly of icosahedral viral capsids. Solution of this problem is crucial to an understanding of the viral life cycle, which currently cannot be adequately addressed through laboratory techniques. The abstract simulation model employed to address this is based on the local rules theory of. Proc. Natl. Acad. Sci. USA. 91:7732-7736). It is shown that the principle of local rules, generalized with a model of kinetics and other extensions, can be used to simulate complicated problems in self-assembly. This approach allows for a computationally tractable molecular dynamics-like simulation of coat protein interactions while retaining many relevant features of capsid self-assembly. Three simple simulation experiments are presented to illustrate the use of this model. These show the dependence of growth and malformation rates on the energetics of binding interactions, the tolerance of errors in binding positions, and the concentration of subunits in the examples. These experiments demonstrate a tradeoff within the model between growth rate and fidelity of assembly for the three parameters. A detailed discussion of the computational model is also provided.

Biophysical Phenomena↗

Protein folding in the hydrophobic-hydrophilic (HP) model is NP-complete.

One of the simplest and most popular biophysical models of protein folding is the hydrophobic-hydrophilic (HP) model. The HP model abstracts the hydrophobic interaction in protein folding by labeling the amino acids as hydrophobic (H for nonpolar) or hydrophilic (P for polar). Chains of amino acids are configured as self-avoiding walks on the 3D cubic lattice, where an optimal conformation maximizes the number of adjacencies between H's. In this paper, the protein folding problem under the HP model on the cubic lattice is shown to be NP-complete. This means that the protein folding problem belongs to a large set of problems that are believed to be computationally intractable.

Algorithms↗

The prevalence of diabetes in a Swedish population of 280,411 inhabitants. A report from the Skaraborg Diabetes Registry.

OBJECTIVE: To estimate the prevalence of known diabetes in a Swedish county (Skaraborg) and to evaluate capture-recapture methods for validation of the diabetes prevalence. RESEARCH DESIGN AND METHODS: Four sources were used to find known diabetic patients: 1) the Skaraborg Diabetes Registry (SDR), a case-finding inventory, 2) an administrative hospital registry, 3) a registry for the retinopathy screening program, and 4) a pharmacy prescription inventory. The capture-recapture method was applied to various combinations of sources to determine the prevalence of diabetes. RESULTS: The completeness of the SDR was 88.4 +/- 1.3%, indicating a diabetes prevalence of 3.20 +/- 0.08%. When the SDR was not used as one of the sources, the estimated prevalence varied between 2.2 and 4.5%. CONCLUSIONS: A case-finding registry is important in reliably estimating the prevalence of diabetes.

Body Mass Index↗

Clinical judgement as a basis for choice of recall interval in child dental care?

OBJECTIVE: Extending recall intervals can be an important strategy for making children's dental care more efficient. The purpose of this study was to describe the recall intervals that the clinicians decided were appropriate for children and adolescents when they were instructed to extend and individualise the routines based on clinical judgement. In addition, the effect on recall interval of the profession of the clinician (dentist or dental hygienist), the child's age and the need for fillings were studied. DESIGN: In a four week period in 1995, all dentists and dental hygienists in one county in Norway reported recall intervals for 2,513 children aged 3 to 18 years. RESULTS: The mean current interval since the previous examination was 17.1 months (SD = 4.7 months) and the mean proposed interval until the next examination was 16.4 months (SD = 4.4 months). Approximately 50% of children were evaluated by the clinicians to be suitable for recall intervals of 20 months or more and 10% were assessed as requiring a new examination within 12 months. The length of the current recall interval, the age of the child, whether or not the child received fillings, and whether the decision-maker was a dentist or a dental hygienist were statistically significantly associated with the length of the proposed recall interval. CONCLUSIONS: Basing recall intervals on clinical judgement resulted in intervals longer than 12 months for the majority of the children.

Adolescent↗

Primary structure of a copper-binding metallothionein from mantle tissue of the terrestrial gastropod Helix pomatia L.

A novel copper-binding metallothionein (MT) has been purified from mantle tissue of the terrestrial snail Helix pomatia using gel-permeation chromatography, ion-exchange chromatography and reverse-phase HPLC. Copper was removed from the thionein by addition of ammonium tetrathiomolybdate. The resulting apothionein (molecular mass 6247 Da) was S-methylated and digested with trypsin, endoproteinase Arg-C and endoproteinase Lys-C. Amino acid sequences of the resulting peptides were determined by collision-induced dissociation tandem MS. The protein is acetylated at its N-terminus, and consists of 64 amino acids, 18 of which are cysteine residues. A comparison with the cadmium-binding MT isolated from the midgut gland of the same species shows an identical arrangement of the cysteines, but an unexpectedly high variability in the other amino acids. The two MT isoforms differ in total length and at 26 positions of their peptide chains. We suggest that the copper-binding MT isoform from the mantle of H. pomatia is responsible for regulatory functions in favour of copper, probably in connection with the metabolism of the copper-bearing protein, haemocyanin.

Amino Acid Sequence↗

Retrosplenial/presubicular continuum in primates: a developmental approach in fetal macaques using neurotensin and parvalbumin as markers.

In spite of numerous hodological and neuropsychological studies emphasizing the multimodal connections and integrative functions of the retrosplenial cortex in primates, the precise fate of its caudoventral extent and the composition of the merging area with the hippocampal formation remain a matter of debate. We reported previously how the anlage of the retrosplenial cortex merges with the immature presubicular zone in the fetal rhesus monkey at the end of the first trimester of gestation. In the present study, this caudal area was further defined on a chemoarchitectonic basis, particularly during the late prenatal and perinatal stages, which correspond to the development of the cingulate sulcus and temporal gyri, and the differentiation of the retrosplenial/subicular complex. Neurotensin (NT), a pyramidal cell marker in the limbic cortex, and parvalbumin (PV), a marker of a subset of inhibitory local circuit neurons in the hippocampal formation, were used as immunocytochemical markers. According to distinct chemoarchitectural patterns, (1) areas 29 l and 29 m of the retrosplenial cortex formed a triangle-shaped ventral expansion which merged with a similar but dorsal expansion of the pre/parasubicular fields. A temporal extension of area 29 m down to area TH could not be detected. The pre/parasubiculum contributed with area 29 m to the lateral bank of the calcarine sulcus as far as the most caudal extent of the hippocampal formation. (2) The lamina principalis interna of the presubiculum was well individualized and did not appear as a simple horizontal shift of adjoining fields. (3) NT and PV displayed a distinct temporal profile of development. NT was already expressed in the pyramidal cells of the prospective retrosplenial cortex and ventral hippocampal formation at E47 (term 165 days). Major pathways of the hippocampal formation and retrosplenial cortex (fimbria, fornix, angular and cingulum bundles) were progressively labeled indicating early developing projections. A large set of NT-positive afferents reached the retrosplenial cortex between E114 and E120. Their laminar distribution was compatible with a thalamic or a subicular origin. (4) The development of PV expression was delayed until the last quarter of gestation, supporting its proposal as a signal of functional onset. The developmental fate and the particular connections of the presubiculum suggest that its functional importance should be further investigated during infancy and adulthood.

Animals↗

MultiCoil: a program for predicting two- and three-stranded coiled coils.

A new multidimensional scoring approach for identifying and distinguishing trimeric and dimeric coiled coils is implemented in the MultiCoil program. The program extends the two-stranded coiled-coil prediction program PairCoil to the identification of three-stranded coiled coils. The computations are based upon data gathered from a three-stranded coiled-coil database comprising 6,319 amino acid residues, as well as from the previously constructed two-stranded coiled-coil database. In addition to identifying coiled coils not predicted by the two-stranded database programs, MultiCoil accurately classifies the oligomerization states of known dimeric and trimeric coiled coils. Analysis of the MultiCoil scores provides insight into structural features of coiled coils, and yields estimates that 0.9% of all protein residues form three-stranded coiled coils and that 1.5% form two-stranded coiled coils. The MultiCoil program is available at http:/(/)theory.lcs.mit.edu/multicoil.

Algorithms↗

An iterative method for improved protein structural motif recognition.

We present an iterative algorithm that uses randomness and statistical techniques to improve existing methods for recognizing protein structural motifs. Our algorithm is particularly effective in situations where large numbers of sufficiently diverse examples of the motif are not known. These are precisely the situations that pose significant difficulties for previously known methods. We have implemented our algorithm and we demonstrate its performance on the coiled coil motif. We test our program LearnCoil on the domain of 3-stranded coiled coils and subclasses of 2-stranded coiled coils. We show empirically that for these motifs, our method overcomes the problem of limited data.

Algorithms↗

Pharmacological and toxicological aspects of new imidazoacridinone antitumor agents.

Imidazoacridinones represent a new group of antitumor compounds developed by J. Konopa and coworkers in Gdansk, Poland (W.M. Cholody, J. Med. Chem., 33: 49-52, 1990). The compounds exert activity against a broad spectrum of human tumors in the National Cancer Institute in vitro screening scheme. In this work, the in vitro cytotoxicity, cellular pharmacology, and genotoxic/transforming potential of five selected imidazoacridinones were studied. The compounds were highly cytotoxic (0.01-0.40 microM) to dividing cells, such as Friend erythroleukemia cells (line F4-6), V79 Chinese hamster cells, and exponentially growing C3H/M2 mouse fibroblasts. In contrast, nondividing primary rat hepatocytes and C3H/M2 cells in confluency were less sensitive to the toxicity of the imidazoacridinones. Multidrug-resistant-overexpressing F4-6 cells, 200-fold resistant to doxorubicin, showed only partial resistance (4-10 fold) to the imidazoacridinones. The cellular transport of the fluorescent imidazoacridinones occurred rapidly, and most of the drug fluorescence was localized in the nucleus. Cellular accumulation and retention of two selected imidazoacridinones (C-1310 and C-1311) in sensitive as well as in resistant F4-6 cells were determined with laser-excited flow cytometry. After an incubation with C-1311 and C-1310 for 60 min at 37 degrees C, the cellular accumulation of the less cytotoxic compound C-1310 was greater than that of C-1311, and for both compounds, the fluorescence in the resistant F4-6 cells was one-half of that in the sensitive F4-6 cells. Lowered temperature (4 degrees C) reduced the cellular accumulation for both compounds in the sensitive and in the resistant F4-6 cells and was comparable to the uptake in resistant F4-6 cells. The treatment of the resistant F4-6 cells with the multidrug-resistant modulator verapamil led to an enhanced accumulation of C-1310 and C-1311 by the cells. All five compounds produced a dose-dependent inhibition of [3H]uridine and [14C]thymidine incorporation and, except for C-1336, preferentially inhibited DNA synthesis. The affinity of the imidazoacridinones to DNA is also indicated by an increase of the DNA melting point by 9-11 degrees C. The mutagenic potential of the imidazoacridinones was investigated in the hypoxanthine guanine phosphoribosyl transferase test; the compounds C-1310 and C-1311 were additionally tested in the Salmonella typhimurium-microsome assay. Limited mutagenicity was detected in the hypoxanthine guanine phosphoribosyl transferase test, and in Salmonella typhimurium, mutagenicity was observed only in the strain TA1537. Furthermore, no induction of DNA repair synthesis was observed after treatment of primary hepatocytes with the five imidazoacridinones. The compounds did not transform C3H/M2 fibroblasts. One derivative, C-1336, led to a significant induction of cell differentiation in Friend erythroleukemia cells. The results of this study show that the imidazoacridinones display a strong cytotoxic effect in rapidly dividing cells and only a partial resistance toward multidrug resistant cells; in addition, they showed a limited mutagenic potential in V79 fibroblasts and Salmonella typhimurium and no transforming potential in C3H/M2 cells. The imidazoacridinones are, therefore, an interesting group of new antitumor agents, and further in vivo studies are warranted to explore the usefulness of these compounds for the treatment of human cancer.

Acridines↗

Neurochemical development of the hippocampal region in the fetal rhesus monkey, III: calbindin-D28K, calretinin and parvalbumin with special mention of cajal-retzius cells and the retrosplenial cortex.

In spite of continuing controversy on the precise function of the calcium-binding proteins expressed in the hippocampal formation, nothing is known about their prenatal development in primates. In this study, calbindin-D28K, calretinin, and parvalbumin were localized in the hippocampal formation of seven rhesus monkey fetuses aged E47 to E90 (term 165 days). All of the three markers were expressed during the first half of gestation in distinct subsets of nonpyramidal neurons: calretinin-containing cells were the most numerous and relatively differentiated contrasting with a more restricted, less mature, parvalbumin-labeled population and a poor calbindin-positive nonpyramidal contingent. The granule cells and pyramidal neurons were calbindin-positive, including the pyramids of CA3 and the subicular complex, in contrast to the situation found in the adult monkey. The presubiculum and retrosplenial cortex, whose merging formed the caudal pole of the hippocampal formation, also expressed precociously the three calcium-binding proteins. A heterogeneous population of Cajal-Retzius-like cells was demonstrated in the marginal zone of the ventral hippocampal formation. The majority co-expressed calbindin-D28K and calretinin and displayed acetylcholinesterase activity but no GABA-like immunoreactivity. Major intrinsic and extrinsic pathways of the hippocampal system (mossy fiber system, alveus, fimbria, angular, and cingular bundles) were immunoreactive for calretinin and/or calbindin. The distinct developmental time course and regional pattern of distribution of calbindin-D28K, calretinin, and parvalbumin in the nonprincipal neurons suggests a precocious but asynchronous prenatal development of different inhibitory circuits in the hippocampal formation of primates. The labeling of several fiber systems in keeping with comparable early events in the entorhinal cortex (Berger et al.: Hippocampus 3:279-305, 1993), suggests the possibility of earlier functional circuits than hitherto inferred from the observations available in rodents, a hypothesis that deserves further investigation.

Animals↗