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Biomedical subjects

B Bloch

Publications and source records attributed to B Bloch.

At least 19 recordsLinked to original sources
PubMed2005

Correlations of work, leisure, and sports physical activities and health status with socioeconomic factors: a national study in Israel.

OBJECTIVE: To evaluate levels of physical activities at work, leisure, and sports and to correlate them with socioeconomic and health factors. METHODS: Validated questionnaire administered to a random sample of 406 adults. Items covered demographic data, health status, smoking, and duration, frequency, intensity of physical activities. Indices of physical activity at work, leisure, and sports were analysed. RESULTS: Adults (both sexes) with poor self perceived health status and less than 13 years of education, regardless of their body mass index, perform no or few physical activities during their leisure time. CONCLUSIONS: The correlations of physical activity with socioeconomic and health factors differ significantly for work, leisure, and sports. Physicians should differentiate physical activities by type and intensity during anamneses.

Adult↗
PubMed2002

Peripheral neuropathy associated with mitochondrial disorders: 8 cases and review of the literature.

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.

Adolescent↗
PubMed2002

Prevalence of pre-cancerous lesions and cervical cancer in South Africa--a multicentre study.

OBJECTIVES: To describe the age-specific prevalence rates of cancer of the cervix in South African women presenting for screening. DESIGN: A multicentre prevalence survey in 10 geographically defined areas following a common core protocol. Services were located in existing service sites, with the exception of KwaZulu-Natal which used a mobile service. Women aged 20 years and above were eligible for inclusion. OUTCOME MEASURES: Age-specific cervical cytologically diagnosed abnormality rates according to the Bethesda classification. RESULTS: During the study 20,603 women participated. Eighty per cent of the sample had never had a Pap smear before and just over 91% had not had a Pap smear in the last 5 years. In this study population 468 women screened (2.42%) were found to have low-grade squamous intra-epithelial lesions (LSIL) and the average age of these women was 33.1 years; 366 (1.8%) had high-grade SIL (HSIL) and these women were statistically significantly older at 37.97 years of age; and 92 women (0.47%) were found to have cytologically diagnosed invasive cancer. These women were significantly older, with an average age of 51.3 years. A clear relationship was found between age and LSIL, with younger women having a high rate of LSIL which decreases with increasing age. A similar but inverse relationship between age and invasive cancer is described, with the rate being low in young women and increasing with increasing age. A clear relationship between HSIL and age is not described in these data. The adequacy rate (satisfactory and satisfactory but limited) of the slides was 95%, and just under 92% of the study sample received their results. Not all women were appropriately referred and it was not possible to assess if women referred for treatment received it. CONCLUSIONS: These data indicate that cancer of the cervix is a common disease and that, similar to other countries, it is a disease of older women. These data give some positive indicators for future screening--older women will present for screening and the majority of women received their results. However, improvements in health system functioning are needed. A uniform national cytology reporting system is required as well as clear guidelines for providers on what action to take based on cytology reports. Linkage between the site of screening and treatment centre is inadequate and requires urgent attention in order to decrease cervical cancer mortality.

Adult↗
PubMed2001

In vivo internalization of the somatostatin sst2A receptor in rat brain: evidence for translocation of cell-surface receptors into the endosomal recycling pathway.

To determine whether cellular compartmentalization of somatostatin receptors can be regulated in vivo, we examined the immunocytochemical distribution of the sst2A receptor (sst2AR) after stereotaxical injections of somatostatin analogs into the rat parietal cortex. Whereas CH-275, a sst1R agonist, failed to induce changes in the diffuse sst2AR immunostaining pattern characteristic of control animals, somatodendritic profiles displaying intracytoplasmic immunoreactive granules became apparent short-term after injection of either somatostatin or the sst2R agonist octreotide. Confocal microscopy revealed that 90% of sst2AR-immunoreactive endosome-like organelles displayed transferrin receptor immunoreactivity. At the electron microscopic level, the percentage of sst2AR immunoparticles dramatically decreased at the plasmalemma of perikarya and dendrites after octreotide injection. Conversely, it significantly increased in endosomes-like organelles. These results demonstrate that sst2ARs undergo, in vivo, rapid and massive internalization into the endocytic recycling compartment in response to acute agonist stimulation and provide important clues toward elucidating somatostatin receptor signaling in the mammalian brain.

Animals↗
PubMed2001

ACTH silent adenoma shrinking under cabergoline.

OBJECTIVES: The authors present a case report that proposes the use of cabergoline treatment in silent ACTH adenoma, an unusual member of the heterogeneous group of the so-called clinically non-functioning pituitary adenomas. DESIGN: Following the clinical and radiological improvement of a recurrent silent ACTH adenoma in a 77-year-old patient treated with cabergoline (0.5 mg every 2 days for 2 years), in vitro studies of the original tumor were performed. METHODS: The original tumor from the patient was studied by in situ hybridization and dopamine D2 receptor autoradiography. It was compared with four macroprolactinomas and two macroadenomas from patients with Cushing's disease. RESULTS: The D2 receptor mRNA signal of the reported case was intense and of the same order of magnitude as that observed in control prolactinomas. Dopamine D2 receptor autoradiography was twice that of control corticotroph adenomas and was close to that observed in prolactinomas. CONCLUSIONS: This is the first description of an in vivo shrinkage of an ACTH silent adenoma under cabergoline. We demonstrate in vitro, the presence of D2 receptors in the primitive tumor in concentrations similar to those found in control prolactinomas. These results suggest that therapeutic trials with cabergoline might be undertaken in recurring cases of ACTH silent tumors and more generally, non-functioning pituitary adenomas.

Adenoma↗
PubMed2001

Histologic findings in a series of 1,540 corneal allografts.

We present a series of 1,540 corneal allografts studied since 1982. Corneal edema was the major lesion in 439 corneal specimens (28.4%). Keratitis was the largest group with 378 cases (24.5%), including 134 cases of corneal scarring (8.7%). There were 113 cases of herpes simplex virus keratitis (7.3%), mostly of the disciform stromal type, and 60 cases of non herpetic interstitial keratitis (3.9%), 44 of superficial keratitis (2.8%) and 10 of ulcerative keratitis (0.6%). Among the 17 other cases (1.1%), there were 3 of fungal keratitis, 2 syphilitic keratitis and one case of acanthamoebic keratitis. The third group was formed by corneal dystrophies with 376 cases (24.4%). There were 192 keratoconus (12.5%), 121 Fuchs' dystrophies (7.9%), 28 calcific band keratopathies (1.8%), 18 had corneal dystrophies with amyloid deposits and 16 did not. There were 169 regrafts (11%) and 135 traumatic lesions (8,8%). Among the 43 miscellaneous cases (2,8%), there were 22 cases with previous refractive eye surgery, one corneal myxoma, 5 cases of dysplasia, 5 pterigia, 3 sclerocornea, one fish-eye disease, one floppy eyelid syndrome and 5 unclassifiable cases. The mechanisms of these lesions are mainly related to an autoimmune disease in most cases of herpes keratitis. Some rare forms of corneal dystrophies contain amyloid deposits produced by an abnormal kerato-epithelin. Cases of graft failure are not particulary frequent, due to the avascularity of the cornea and its particular immune status.

Acanthamoeba Keratitis↗
PubMed2000

Mapping, characterization, and expression analysis of the SM-20 human homologue, c1orf12, and identification of a novel related gene, SCAND2.

Major psychosis was shown to segregate with a balanced translocation (1q42.1; 11q14.3) in a multigenerational family. This study describes the identification of a human SM-20 homologue gene that lies at about 400 kb on the centromeric side of the 1q42.1 breakpoint. The full-length cDNA sequence and gene structure were determined. Expression analysis was performed, showing high expression levels in skeletal and cardiac muscles; in the central nervous system, expression was restricted to dopaminergic neurons and spinal motoneurons. A second gene displaying high sequence similarity with SM-20 was also identified by BLAST. This gene, located on chromosome 15, is likely to have evolved by retroposition of SM-20 mRNA and an exon-shuffling mechanism. It encodes a 306-amino-acid protein harboring strong homology with an N-terminal motif found in some zinc-finger proteins. This gene was named SCAND2 (SCAN domain-containing 2).

Adult↗
PubMed2000

Phenotypical characterization of the neurons expressing the D1 and D2 dopamine receptors in the monkey striatum.

The striatum is regulated by dopaminergic inputs from the substantia nigra. Several anatomical studies using in situ hybridization have demonstrated that in rodents, dopamine D1 and D2 receptors are segregated into distinct striatal efferent populations: dopamine D1 receptor into gamma-aminobutyric acid (GABA)/substance P striatonigral neurons, and dopamine D2 receptor into GABA/enkephalin striatopallidal neurons. The existence of such a segregation has not been investigated in primates. Therefore, to quantify the efferent striatal GABAergic neurons in the adult Cynomolgus monkey, we detected GAD67 mRNA expression while considering that only a minority of the GABAergic population is composed of interneurons. To characterize the peptidergic phenotype of the neurons expressing dopamine D1 or D2 receptors, we examined the mRNA coding for these receptors in the striatum at the cellular level using single- and double in situ hybridization with digoxigenin and 35S ribonucleotide probes. Double in situ hybridization demonstrated a high coexpression of dopamine D1 receptor and substance P mRNAs (91-99%) as well as dopamine D2 receptor and preproenkephalin A mRNAs (96-99%) in medium-sized neurons throughout the nucleus caudatus, putamen, and nucleus accumbens. Only a small subpopulation (2-5%) of the neurons that contained dopamine D1 receptor mRNA also expressed dopamine D2 receptor mRNA in all regions. Large-sized neurons known to be cholinergic expressed D2R mRNA. However, within the nucleus basalis of Meynert, the large cholinergic neurons expressed D2R mRNA, but the neurons producing enkephalin expressed neither D1R nor D2R mRNA. These results demonstrate that the striatal organizational pattern of D1 and D2 receptor segregation in distinct neuronal populations described in rodent also exists in primate.

Animals↗
PubMed2000

Dopamine tone regulates D1 receptor trafficking and delivery in striatal neurons in dopamine transporter-deficient mice.

In vivo, G protein-coupled receptors (GPCR) for neurotransmitters undergo complex intracellular trafficking that contribute to regulate their abundance at the cell surface. Here, we report a previously undescribed alteration in the subcellular localization of D1 dopamine receptor (D1R) that occurs in vivo in striatal dopaminoceptive neurons in response to chronic and constitutive hyperdopaminergia. Indeed, in mice lacking the dopamine transporter, D1R is in abnormally low abundance at the plasma membrane of cell bodies and dendrites and is largely accumulated in rough endoplasmic reticulum and Golgi apparatus. Decrease of striatal extracellular dopamine concentration with 6-hydroxydopamine (6- OHDA) in heterozygous mice restores delivery of the receptor from the cytoplasm to the plasma membrane in cell bodies. These results demonstrate that, in vivo, in the central nervous system, the storage in cytoplasmic compartments involved in synthesis and the membrane delivery contribute to regulate GPCR availability and abundance at the surface of the neurons under control of the neurotransmitter tone. Such regulation may contribute to modulate receptivity of neurons to their endogenous ligands and related exogenous drugs.

Animals↗
PubMed2000

Co-stimulation of D(1)/D(5) and D(2) dopamine receptors leads to an increase in c-fos messenger RNA in cholinergic interneurons and a redistribution of c-fos messenger RNA in striatal projection neurons.

The anatomical subdivision of striatum in patch and matrix compartments plays an important role for the processing of neurotransmission through the basal ganglia in primates and rodents. Here we report that co-administration of D(1)/D(5) and D(2) receptor agonists, which induces a heterogenous and patchy pattern of c-fos messenger RNA expression in striatum, stimulates c-fos messenger RNA expression in cholinergic interneurons. Moreover, this treatment induces c-fos messenger RNA in projection neurons containing D(1)-, rather than D(2)-receptor messenger RNA. The preferential induction of c-fos messenger RNA in patches does not depend upon a higher degree of co-localization between D(1) and D(2) receptors in this area, since double in situ hybridization experiments showed a large segregation of D(1) and D(2) receptor messenger RNAs in the patch as well as the matrix compartments. By contrast, treatment with a full D(1)/D(5) receptor agonist up-regulates striatal c-fos messenger RNA homogenously and in similar proportions of D(1) and D(2) receptor messenger RNA-containing projection neurons in both medial and lateral striatum, but has only minor effects on c-fos messenger RNA expression in cholinergic interneurons. These results provide a neuroanatomical/neurochemical correlate to the well-known behavioral interaction between dopamine D(1)/D(5) agonists and dopamine D(2) agonists. They also suggest that there may be a relation between a heterogenous, patch-enriched c-fos messenger RNA expression and an increased expression of this immediate early gene in cholinergic interneurons.

Animals↗
PubMed2000

Agonist stimulation provokes dendritic and axonal dopamine D(1) receptor redistribution in primary cultures of striatal neurons.

To investigate the influence of neurotransmitter on G-protein-coupled receptor trafficking and compartimentalization in neurons, we have developed a model of primary neuronal cultures from fetal rat striatum on which we have studied the cellular and subcellular distribution and trafficking of the D(1) dopaminergic receptor. This receptor is known to be somatodendritic and axonal targeted in vivo, mostly to extrasynaptic locations. Immunohistochemical studies at the light and electron microscopic levels showed that, in cultures, the D(1) dopaminergic receptor is expressed in the absence of dopamine stimulation. The pattern of D(1) dopaminergic receptor immunostaining after stimulation by the D(1) dopaminergic receptor agonist SKF 82958 (1 microM) is dramatically modified with a decrease of the number of labeled D(1) dopaminergic receptor puncta (-40%) and an increase of their size in both dendrites (+120%) and axons (+240%). Seven hours after removal of the agonist, return to normal pattern was observed. The D(1) dopaminergic receptor antagonist SCH 23390 (2 microM) abolishes the effect of SKF 82958. Electron microscopy demonstrated, in dendrites, a translocation of the labeling from the plasma membrane to endosomes. Axonal D(1) dopaminergic receptor redistribution after acute stimulation indicates that the D(1) dopaminergic receptor is membrane targeted and responsive to stimulation. These results validate primary culture of striatal neurons to study subcellular localization and intraneuronal trafficking of G-protein-coupled receptors. This preparation will be useful to address various questions concerning the behavior and the trafficking of these receptors in neurons in relation to the neurotransmitter environment.

Animals↗
PubMed2000

Adaptive changes in the nigrostriatal pathway in response to increased 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration in the mouse.

Although several adaptive mechanisms have been identified that mask the existence of Parkinson's disease and delay the onset and aggravation of motor symptoms, the timescale and implications of this compensatory process remain an enigma. In order to examine: (i) the nature of the dopaminergic adaptive mechanisms that come into action; (ii) their sequential activation in relation to the severity of degeneration; and (iii) their efficacy with regard to the maintenance of a normal level of basal ganglia activity, we analysed the brains of mice treated daily with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP, 4 mg/kg, i.p.) and killed at 5-day intervals from day 0 (D0) to D20. Our results demonstrate the sequential activation of two compensatory mechanisms: (i) an increase in striatal tyrosine hydroxylase (TH) protein content attested by the persistence of TH immunolabelling up to D15, contrasting with the decrease observed in both the number of nigral TH-immunoreactive neurons (-70.2%) and striatal dopamine content (-38.4%); (ii) a downregulation of DA uptake in surviving terminals at D20 (73.4% of nigral degeneration). At this point, the failure of adaptive mechanisms to maintain striatal dopaminergic homeostasis is also illustrated by an increase in the cytochrome oxidase activity of substantia nigra pars reticulata, a marker of neuronal function. It has been postulated that an increase in dopamine release per pulse could constitute an adaptive mechanism. The data we present from our MPTP mice model infirm this hypothesis. This study explores the link between the degree of nigral degeneration and the sequential activation of dopaminergic compensatory mechanisms in the nigrostriatal pathway and, in so doing, proposes a rethink of the paradigm applied to these mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Dopamine control of striatal gene expression during development: relevance to knockout mice for the dopamine transporter.

The aim of this study was to determine at which developmental stage and how dopamine regulates the expression of striatal dopamine receptor and neuropeptide mRNAs. For this, we studied the expression of these mRNAs, in relation to dopamine innervation, in normal mice from gestational day 13 (G13) to adult. Particularly, we investigated the adaptive changes in the expression of these markers in mice lacking the dopamine transporter during development. We detected tyrosine hydroxylase, by immunohistochemistry, in the ventral mesencephalon and the striatal anlage in both genotypes at G13, whereas the dopamine transporter appeared in the striatum of normal mice at G14. By in situ hybridization, we detected striatal dopamine D1, D2, D3 receptor, and substance P mRNAs at G13, preproenkephalin A mRNA at G14 and dynorphin mRNA at G17 in normal mice. Although the time of initial detection and the distribution were not affected in mutant mice, quantitative changes were observed. Indeed, D1 and D2 receptor as well as preproenkephalin A mRNA levels were decreased from G14 on, and dynorphin mRNA level was increased from G17 on. In contrast, substance P mRNA level was unaffected. Our data demonstrate that the influence of dopamine on striatal neurons occurs early during the development of the mesostriatal system as quantitative changes appeared in mutant mice as soon as G14. These findings bring new insights to the critical influence of dopamine on the expression of striatal dopamine receptor and neuropeptide mRNAs during development, and suggest that mesostriatal dopamine transmission functions from G14 on.

Animals↗
PubMed2000

Differential regulation of the dopamine D1, D2 and D3 receptor gene expression and changes in the phenotype of the striatal neurons in mice lacking the dopamine transporter.

Mice with a genetic disruption of the dopamine transporter (DAT-/-) exhibit locomotor hyperactivity and profound alterations in the homeostasis of the nigrostriatal system, e.g. a dramatic increase in the extracellular dopamine level. Here, we investigated the adaptive changes in dopamine D1, D2 and D3 receptor gene expression in the caudate putamen and nucleus accumbens of DAT-/- mice. We used quantitative in situ hybridization and found that the constitutive hyperdopaminergia results in opposite regulations in the gene expression for the dopamine receptors. In DAT-/- mice, we observed increased mRNA levels encoding the D3 receptor (caudate putamen, +60-85%; nucleus accumbens, +40-107%), and decreased mRNA levels for both D1 (caudate putamen, -34%; nucleus accumbens, -45%) and D2 receptors (caudate putamen, -36%; nucleus accumbens, -33%). Furthermore, we assessed the phenotypical organization of the striatal efferent neurons by using double in situ hybridization. Our results show that in DAT+/+ mice, D1 and D2 receptor mRNAs are segregated in two different main populations corresponding to substance P and preproenkephalin A mRNA-containing neurons, respectively. The phenotype of D1 or D2 mRNA-containing neurons was unchanged in both the caudate putamen and nucleus accumbens of DAT-/- mice. Interestingly, we found an increased density of preproenkephalin A-negative neurons that express the D3 receptor mRNA in the nucleus accumbens (core, +35%; shell, +46%) of DAT-/- mice. Our data further support the critical role for the D3 receptor in the regulation of D1-D2 interactions, an action being restricted to neurons coexpressing D1 and D3 receptors in the nucleus accumbens.

Animals↗
PubMed1999

Regulation of the subcellular distribution of m4 muscarinic acetylcholine receptors in striatal neurons in vivo by the cholinergic environment: evidence for regulation of cell surface receptors by endogenous and exogenous stimulation.

Our aim was to determine how the cholinergic environment influences, in vivo, the membrane abundance and the intracellular trafficking of the muscarinic receptor m4 (m4R). Immunohistochemistry at light and electron microscopic level was used to detect the subcellular localization of m4R in several populations of striatal cholinoceptive neurons, including cholinergic neurons and medium spiny neurons. (1) In control rats, in cholinergic neurons, m4R is mostly restricted to intracytoplasmic sites involved in its synthesis, especially endoplasmic reticulum. In contrast, m4R is preferentially located at the plasma membrane in cell bodies and dendritic shafts and spines of medium spiny neurons. The density of m4R was greater at the membrane of perikarya in patches (striatal areas with low acetylcholine activity) than in matrix (striatal areas with high acetylcholine activity). (2) Stimulation of muscarinic receptor with oxotremorine provokes translocation of m4R from the membrane to endosomes in perikarya and dendrites of medium spiny neurons but has no influence on the localization of m4R in the cytoplasm of cholinergic cell bodies. Our results suggest that the intraneuronal trafficking and the abundance of membrane-bound m4R in vivo is under regulation of the cholinergic environment. The m4R subcellular compartmentalization depends on the phenotype of the cholinoceptive neuron and on its neurochemical environment. Such regulation, by modulating availability of receptor for endogenous and exogenous ligands, may play key roles in the response of target neurons.

Acetylcholine↗