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Biomedical subjects

J Gross

Publications and source records attributed to J Gross.

At least 55 records · Page 3Linked to original sources

Mutational analysis of the neuronal cadherin gene CELSR1 and exclusion as a candidate for catatonic schizophrenia in a large family.

The cadherin gene CELSR1 is specifically expressed in the brain and located on chromosome 22q13.33, a region that has recently been shown to be involved in the etiopathogenesis of familial catatonic schizophrenia. The gene is a strong positional candidate and was considered for mutational analysis. A total of 17 allelic variants of CELSR1 was found by sequencing all 35 exons, intron-exon junctions, and the putative promoter region by screening two patients from a large family mainly supporting this locus, and three control subjects in a first step. No variant exclusively co-segregates with the disease in the large pedigree, providing evidence that CELSR1 is not causative for the pathogenesis of catatonic schizophrenia in this family.

Alleles↗

Differential response of immature and mature neurons to hypoxia in rat mesencephalic cultures.

The effect of hypoxia on immature and mature mesencephalic neurons was studied in in vitro rat cerebral cell cultures on different days. In immature cultures (6-8 days in vitro), exposure to 24 h of hypoxia (10-20 mm Hg pO(2) in the culture medium) did not change the number of neuron-specific enolase (NSE)-immunoreactive (IR) (NSE-IR) neurons but increased the number of tyrosine hydroxylase (TH)-IR (TH-IR) cells, which might be attributed to transient induction of TH. In mature cultures (13-15 days in vitro), 16 h of hypoxia induced a considerable loss of both NSE- and TH-IR cells. A decrease in the number of TH-IR cells 6 and 24 h after hypoxia was more pronounced than that of NSE-IR cells; however, their numbers equalized 48 h after hypoxia, suggesting similar hypoxic vulnerability of dopaminergic and nondopaminergic neurons in mature mesencephalic cultures. In immature cultures, hypoxia slightly stimulated both apoptosis and necrosis, while in mature cultures, it dramatically increased the number of solely necrotic cells.

Aging↗

Paget-Schroetter syndrome in sports activities--case study and literature review.

The authors report 7 patients with thromboses in the upper extremity resembling Paget-Schroetter syndrome. According to their case histories, all patients had a temporal and causal relationship between partially unusual sports activities and the genesis of the thrombosis. The cause of this condition is a strain on the subclavian and axillary veins by retroversion or hyperabduction of the arm. This can entail microtraumatizations of the venous intima, consequently leading to a consecutive local activation of coagulation and to a possible thrombosis of the vessel. A mechanical compression of the vein by adjoining bone, ligament, and muscle structures can intensify the effects. Further primary diseases and risk factors as secondary causes for thromboses where taken into consideration when examining the patients. The Paget-Schroetter syndrome should be considered as a possible cause for unspecified trouble in the upper extremity reported by athletes. If such prolapses occur, they can be categorized as accidents by private and statutory insurance companies that cover accidents.

Axillary Vein↗

The chemical and physical stability of a 1:1 mixture of propofol and methohexital.

Anesthetic drugs are frequently mixed or coadministered to optimize anesthetic effects while minimizing adverse effects. Methohexital advantages include its low cost and rapid onset, while propofol provides improved airway anesthesia and extremely rapid clearance from the plasma. Therefore, a mixture of these agents might well be superior to either drug given alone. We wished to determine whether a mixture of methohexital and propofol is chemically and physically stable. A 1:1 mixture of propofol 10 mg/ml and methohexital was prepared. At times varying from 0 to 48 hours, mixtures with an internal standard of thymol kept at room temperature were thrice extracted with a 2:1 v/v mixture of diethyl ether:pentane, dried under nitrogen, and treated overnight with bis-trimethylsilyl-trifluoroacetamide. The resultant derivatives were transferred to microsample vials and analyzed by GC-MS. Drug stability was quantified by electronic integration of peak areas representing characteristic ions for each drug. For each sample, the peak area of the methohexital ion (m/z 239) or propofol ion (m/z 235) relative to the corresponding thymol ion (m/z 207) served as an index of the concentration of the drug in the sample. At times varying from 0 to 48 hours, mixtures without thymol were used to determine mean droplet size of the particles. This was accomplished using both an Accusizer and a Nicomp 370 Particle Sizer. One way ANOVA tested for significant changes in drug concentrations and mean particle size as a function of time. There was no significant breakdown of propofol or methohexital when combined in a 1:1 mixture and allowed to stand for 48 hours, nor was there an increase in particle size suggestive of emulsion instability. We concluded that a 1:1 mixture of propofol and methohexital was stable up to 48 hours after mixing.

Analysis of Variance↗

Differential effects of hypoxia on untreated and NGF treated PC12 cells.

Perinatal hypoxia is known to induce long-lasting changes in the central dopaminergic system. In order to understand the cellular mechanism of these changes, we studied the effects of hypoxia on the levels of dopamine (DA) and tyrosine hydroxylase (TH) mRNA in untreated and NGF treated PC12 cells. On the second day after plating (DAP), cells were exposed to a hypoxic episode (pO2 = 10-20 mm Hg, 24 h), and the levels of DA and TH mRNA were examined on DAP 4 and DAP 8. In untreated cells, hypoxia induced a two fold increase both in DA and TH mRNA levels on DAP 4 which normalized up to DAP 8. This increase correlated with an activation of the hypoxia inducible factor (HIF-1alpha), measured with a reporter gene. In contrast, NGF treated cells responded to hypoxia with an increase of DA level on DAP 8. In these cells neither an increase of the HIF-1alpha activity measured immediately after hypoxia nor a significant increase of the TH mRNA level on DAP 8 were found. The findings indicate that NGF shifts the hypoxia induced changes of DA levels from a short-term to a long-term mode. The long-term increase of dopamine levels is the most likely result of changes connected with cell growth and differentiation and not the result of a long-term TH mRNA level increase.

Animals↗

Cortico-muscular synchronization during isometric muscle contraction in humans as revealed by magnetoencephalography.

Magnetoencephalographic (MEG) and electromyographic (EMG) signals were recorded from six subjects during isometric contraction of four different muscles. Cortical sources were located from the MEG signal which was averaged time-locked to the onset of motor unit potentials. A spatial filtering algorithm was used to estimate the source activity. Sources were found in the primary motor cortex (M1) contralateral to the contracted muscle. Significant coherence between rectified EMG and M1 activity was seen in the 20 Hz frequency range in all subjects. Interactions between the motor cortex and spinal motoneuron pool were investigated by separately studying the non-stationary phase and amplitude dynamics of M1 and EMG signals. Delays between M1 and EMG signals, computed from their phase difference, were found to be in agreement with conduction times from the primary motor cortex to the respective muscle. The time-dependent cortico-muscular phase synchronization was found to be correlated with the time course of both M1 and EMG signals. The findings demonstrate that the coupling between the primary motor cortex and motoneuron pool is at least partly due to phase synchronization of 20 Hz oscillations which varies over time. Furthermore, the consistent phase lag between M1 and EMG signals, compatible with conduction time between M1 and the respective muscle with the M1 activity preceding EMG activity, supports the conjecture that the motor cortex drives the motoneuron pool.

Adult↗

Perinatal asphyxia induces region-specific long-term changes in mRNA levels of tyrosine hydroxylase and dopamine D(1) and D(2) receptors in rat brain.

To study the effects of neonatal asphyxia on gene expression of the dopaminergic systems, we determined quantitatively the mRNA levels of tyrosine hydroxylase, dopamine transporter, dopamine D(1) and D(2) receptors in substantia nigra/ventral tegmental area, striatum and limbic area. The mRNA levels were determined at one and 4 weeks after asphyxia by a quantitative reverse transcription polymerase chain reaction method. Spontaneously and Caesarean section born rats showed similar mRNA levels with the exception of an increase of tyrosine hydroxylase mRNA levels in the limbic area of 4-week-old animals. Five min of asphyxia did not change the mRNA levels in any region compared to that in the spontaneously born rats. Fifteen and twenty min of asphyxia induced region-specific alterations in mRNA levels. In SN/VTA an increase of tyrosine hydroxylase mRNA levels in the 1-week-old rats and in striatum an increase of D(1) and D(2) dopamine receptor mRNA levels in the 4-week-old rats were observed. Fifteen min of asphyxia induced a selective increase of D(1) and D(2) dopamine receptor mRNA levels in the limbic area of 4-week-old rats. These observations indicate that neonatal asphyxia triggers a cascade of gene expressions for tyrosine hydroxylase and D(1) and D(2) dopamine receptors. In 1-week-old rats, the gene expression of tyrosine hydroxylase increased in the cell body region substantia nigra/ventral tegmental area. This change may increase the D(1) and D(2) dopamine receptor expression in the target regions striatum and limbic area during further development.

Aging↗

A temperature-sensitive adenylyl cyclase mutant of Dictyostelium.

Dictyostelium development starts with the chemotactic aggregation of up to 10(6) amoebae in response to propagating cAMP waves. cAMP is produced by the aggregation stage adenylyl cyclase (ACA) and cells lacking ACA (aca null) cannot aggregate. Temperature-sensitive mutants of ACA were selected from a population of aca null cells transformed with a library of ACA genes, a major segment of which had been amplified by error-prone PCR. One mutant (tsaca2) that can complement the aggregation null phenotype of aca null cells at 22 degrees C but not at 28 degrees C was characterized in detail. The basal catalytic activity of the enzyme in this mutant was rapidly and reversibly inactivated at 28 degrees C. Using this mutant strain we show that cell movement in aggregates and mounds is organized by propagating waves of cAMP. Synergy experiments between wild-type and tsaca2 cells, shifted to the restrictive temperature at various stages of development, showed that ACA plays an important role in the control of cell sorting and tip formation.

Adenylyl Cyclases↗

The incidence of positive margins with breast conserving therapy following mammotome biopsy for microcalcification.

BACKGROUND AND OBJECTIVES: The ability to achieve clean margins with breast conserving therapy varies greatly even when the diagnosis of carcinoma is known beforehand. Although several reports reveal that the incidence of positive margins decreases after stereotaxic core biopsy of nonpalpable lesions and fine-needle aspiration biopsy of palpable lesions, the data on the results following mammotome biopsy (mmbx) is scanty. METHODS: Two hundred and ninety-eight biopsy specimens for mammographically indeterminate microcalcification from 1/97 through 3/30/98 were reviewed. Biopsies were performed using the biopsys method utilizing an 11-gauge multidirectional, vacuum-directed device. RESULTS: Ten percent (n = 31) of the mammotome biopsies were atypical and 9% (n = 27) were malignant. These 58 cases (19%) were recommended for surgical excision. The incidence of positive margins in this subset was determined. Of patients who underwent lumpectomy as their initial surgical procedure 69% had negative surgical margins. Seventy-seven percent of patients with carcinoma diagnosed by mammotome biopsy had definitive initial surgery with a single surgical procedure. CONCLUSIONS: Mmbx facilitates fewer surgical procedures to achieve negative margins, and thus provides a better cosmetic result.

Adult↗

The role of phonology in a letter detection task.

In two experiments, we investigated whether onsets and rimes have a role in the processing of written English. In both experiments, participants detected letter targets (e.g., t) in nonwords like vult faster than in nonwords like vust. This finding is consistent with Selkirk's (1982) view that sonorants (e.g., the /l/ of vult) cohere with preceding short vowels and are part of the vowel nucleus. In contrast, the /t/ of vust is part of the syllable's coda st and so is harder to isolate. Experiment 2 demonstrated that the time required for one to detect single-member codas following vowel digraphs (e.g., the t in veet) was similar to the time to detect the same target letter following a postvocalic sonorant (e.g., the t in vult). No evidence was found for onsets. The results provide support for a phonological organization among letters of printed rimes.

Adult↗

Synchronised oscillations of the human sensorimotor cortex.

Oscillations are a prominent feature of macroscopic human sensorimotor cortical activity as recorded non-invasively with electroencephalography (EEG) and magnetoencephalography (MEG). The advent of whole-scalp MEG systems allowing rapid non-invasive recording from the entire cortex and accurate localisation of neural sources, and the development of refined signal analysis methods are important factors that led to an increasing interest in studies of sensorimotor oscillations during the last 10 years. Investigations on healthy subjects revealed frequency-specific localisation and modality-specific reactivity of 10 Hz and 20 Hz sensorimotor oscillations. Task-specific coherence between motor cortical and electromyographic oscillations, reflecting cortico-motoneuronal coupling, point towards a functional role of precentral oscillations in the cortical control of voluntary movements. Furthermore, abnormal cortico-motoneuronal coupling may underlie clinical symptoms of motor disorders, such as tremor. Thus, investigation of oscillatory sensorimotor activity proceeds from phenomenology to function and provides an interesting approach to address questions in human motor physiology and pathophysiology.

Cortical Synchronization↗

Psoriasis risk factors: role of lifestyle practices.

Psoriasis is a complex, multifactorial chronic skin disease. As in other chronic disorders, various lifestyle factors have been associated with its morbidity. We have pointed to the significance of the patient's lifestyle practices as they relate to psoriasis outcome. Several reports in the literature suggest that exogenous and endogenous factors, including emotional stress, alcohol use, smoking, and obesity, may have deleterious effects on the increased morbidity of psoriasis. In this study, we carried out a comprehensive evaluation to assess the effects of stress, alcohol use, smoking, obesity, and exercise on the natural history of psoriasis.

Alcohol Drinking↗

Early hypoxia modulates the phenotype of dopaminergic cells in rat di- and mesencephalic cell cultures and induces a higher vulnerability of non-dopaminergic neurons to a second hypoxic exposure.

To investigate long-term effects of hypoxia on a cellular level, di- and mesencephalic cell cultures were exposed to hypoxia on in vitro day 2 (incubation in culture medium, pO2 = 10-20 mmHg, 24 h) and on in vitro day 13 (incubation in an electrolyte solution, pO2 = 10-20 mmHg, 8 h). The numbers of neuron-specific enolase immuno-reactive (NSE-IR) and tyrosine hydroxylase immuno-reactive (TH-IR) neurons and the levels of dopamine, its main metabolites and the spontaneous and potassium-stimulated DA release were determined on DIV 15. Hypoxia on DIV 2 did not affect the numbers of NSE-IR and TH-IR neurons, but increased the dopamine content and dopamine release by about 100% in both di-and mesencephalic cultures. In addition, this hypoxia increased the vulnerability of non-TH-IR neurons to the second hypoxic episode applied during more advanced stages of the culture development on DIV 13. On the contrary, hypoxia exposure did not affect the vulnerability of TH-IR cells.

Animals↗

A prospective comparison of stereotaxic fine-needle aspiration versus stereotaxic core needle biopsy for the diagnosis of mammographic abnormalities.

BACKGROUND: Confidence in a negative stereotaxic breast biopsy result allows for safe clinical and mammographic follow-up, whereas a positive or equivocal diagnosis leads to excision. Direct comparison of stereotaxic core needle biopsy (SCBX) and fine-needle aspiration (SFNA) is needed, and should be based on the use of appropriate current methods of practice, and address the indication of each for different types of mammographic lesions. METHODS: The diagnostic accuracy of SFNA, SCBX, and combined SFNA with SCBX performed at a community radiology practice were assessed for different mammographic lesions and levels of radiologic suspicion. Negative predictive values (NPVs) measured the confidence that a negative diagnosis (failure to identify atypia or malignancy) was benign and therefore suitable for follow-up. A benign outcome was accepted only after surgical excision or > or =24 months' follow-up of the lesion. Positive predictive values (PPVs) [final diagnoses at least atypical (A) or carcinoma (CA)] also were calculated. RESULTS: SFNA was performed for 495 lesions and was combined with SCBX for 252 of these. Nondiagnostic (SFNA, 2%; SCBX, 8%) and atypical (SFNA, 7%; SCBX, 3%) rates were low. The authors obtained 94% follow-up (81% > or = 24 months). NPVs were all SFNAs, 99%; SCBXs, 95% (corresponding SFNAs, 98%); and SFNA with SCBX, 99%. NPVs were 100% for masses, ill-defined densities, and architectural distortions. NPVs for microcalcifications (for low, moderate, and high suspicion) were all SFNAs, 97% (100, 95, and 75); SCBXs, 93% (94, 93, and 67), corresponding SFNAs, 96% (100, 94, 75); and SFNA with SCBX, 98% (100, 97, 75). All false-negative lesions were microcalcifications. Calcium was recognized in 98% of SFNA specimens and in 89% of SCBX specimens from microcalcifications. No calcium was identified in the histologic sections in 63% (5 of 8) SCBX false-negative specimens. PPVs(A) were atypical (SFNA, 46%; SCBX, 88%) and suspicious (SFNA, 93%). PPVs(CA) were SFNA carcinoma, 100%; SCBX in situ, 89%; and SCBX invasive, 100%. CONCLUSIONS: SFNA identified benign lesions more reliably for follow-up, particularly microcalcifications. Based on these results, the authors suggest 1) added SCBX if on-site SFNA assessment is nondiagnostic, atypical, or positive (and needs preoperative confirmation of invasion); 2) either SCBX or SFNA for masses, architectural distortions, and ill-defined densities; 3) SFNA for microcalcifications, with SCBX added for moderately and highly suspicious lesions; and 4) surgical excision for all highly suspicious microcalcifications.

Biopsy, Needle↗

[Assessment of the attention-deficit hyperactivity disorder in adults].

The attention-deficit hyperactivity disorder (ADHD) is one of the most common disorders in childhood and adolescence with a prevalence of app. 5%. The importance of ADHD in childhood as a factor of vulnerability for psychiatric disorders in adults is becoming a focus of discussion. It was shown that there is a comorbidity in adults with substance abuse, delinquency and personality disorders. There is a growing evidence that ADHD will persist in a significant number of patients during adulthood. This is the first german study to evaluate this interdependence. We examined 164 adult inpatients and 48 healthy volunteers with the Wender Utah Rating Scale (WURS), a retrospective self-evaluation scale for the diagnosis of ADHD in childhood, and the Eysenck impulsiveness questionnaire I7. It could be shown that the WURS and the I7 are suitable instruments for the evaluation of the ADHD in adults especially concerning the aspects of attention deficits and impulsiveness.

Adult↗

Hypoxia induces differential changes of dopamine metabolism in mature and immature mesencephalic and diencephalic cell cultures.

Perinatal hypoxia is known as a high risk factor for the development of long-lasting abnormalities in dopaminergic system. The early developmental alterations of dopamine (DA) metabolism induced by hypoxia could contribute to these abnormalities. To understand the hypoxia-induced changes of intra- and extracellular dopamine levels and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in immature dopaminergic neurons, we compared these changes in rat mesencephalic and diencephalic cell cultures on day in vitro (DIV) 2 (immature cells), DIV 8 and DIV 13 (mature cells). Cell cultures were exposed to an oxygen-free gas mixture in a Billups chamber for 2-4 hours. Mature cell cultures responded to hypoxia with an increase of DA levels in the cells and in the medium during the first 45 min (by an average of 57 and 114% respectively). Thereafter, DA levels decreased, and returned to the baseline within the next 30 min. The cellular DA levels continued to decrease up to 15% of the baseline during 255 min hypoxia whereas the extracellular DA content stabilized at the prehypoxic levels. Immature cell cultures (DIV 2) in contrast to mature ones, were unable to maintain normal extracellular DA levels during hypoxia and showed a decrease of the cellular and extracellular levels to 50% of the prehypoxic levels. DOPAC and HVA changes mimick, however, at a lower level, the pattern of DA changes during the exposure to hypoxia. In principle, in the diencephalic cell culture similar effects of hypoxia exposure on the investigated parameters were found (studied during 0-120 min). The present study demonstrates that mature and immature dopaminergic cells differ in the regulation of the extra- and intracellular DA levels during hypoxia. In immature cells the low synthetic capacity of tyrosine hydroxylase and the deficient capacities of the transport and storage processes result in decreased extracellular DA levels. This could be an important factor for the long-term modulation of the expression of tyrosine hydroxylase and subsequent long-term behavioral and/or neurological abnormalities induced by perinatal hypoxia.

3,4-Dihydroxyphenylacetic Acid↗

Neuronal soma-dendritic and prejunctional M1-M4 receptors in gastrointestinal and genitourinary smooth muscle.

A variety of neurons in gastrointestinal and genitourinary smooth muscle express muscarinic auto- as well as heteroreceptors. These receptors are found on the soma and dendrites of many cholinergic, sympathetic and NANC neurons and on axon terminals. A given neuron may contain both excitatory and inhibitory presynaptic muscarinic receptors. The subtypes involved are species- and tissue-dependent, and neuronal M1 to M4 receptors have been shown to be expressed in smooth muscle tissues. In this study, the ability of several selective muscarinic receptor antagonists to inhibit the effect of arecaidine propargyl ester (APE) on prejunctional muscarinic receptors on sympathetic nerve endings in the rabbit anococcygeus muscle (RAM) was investigated to characterise the receptor subtype involved. Electrical field stimulation (EFS) resulted in a release of noradrenaline (NA) eliciting monophasic contractions due to stimulation of postjunctional alpha1-adrenoceptors. The selective muscarinic agonist APE did not reduce contractions to exogenous NA, but caused a concentration-related and N-methylatropine-sensitive inhibition of neurogenic responses. All muscarinic antagonists investigated failed to affect the EFS-induced contractions, but shifted the concentration-response curve of APE to the right in a parallel and surmountable fashion. Schild analysis yielded regression lines of unit slope, indicating competitive antagonism. The following rank order of antagonist potencies (pA2 values) was found: tripitramine (9.10) > AQ-RA 741 (8.26) > or = himbacine (8.04) > or = (S)-dimethindene (7.69) > pirenzepine (6.46) > or = p-F-HHSiD (6.27). A comparison of the pA2 values determined in the present study with literature binding and functional affinities obtained at native or recombinant M1 to M5 receptors strongly suggests that NA release from sympathetic nerve endings in RAM is inhibited by activation of prejunctional muscarinic M2 receptors.

Adrenergic alpha-Antagonists↗

Hypoxia during early developmental period induces long-term changes in the dopamine content and release in a mesencephalic cell culture.

The present study was conducted to elucidate the long-term effects of exposure to hypoxia of dopaminergic neurons during the early developmental period. Primary mesencephalic cell cultures prepared from fetal rats and containing 0.5-2% of dopaminergic neurons were exposed to hypoxia between in vitro days 1 and 6, the putative critical developmental period. Changes in the content, release and uptake of dopamine were found to depend on the degree of hypoxia and on the duration of exposure. Following moderate hypoxia (7 h, 5% O2) on two consecutive days between in vitro days 1 and 3, the cultures showed a small increase in the dopamine levels, by 16%. After severe hypoxia (0% O2/95% N2 for 24 h), during the same time window, the cellular dopamine content was elevated by 100%. Moreover, severe hypoxia produced long-lasting modulations of the dopaminergic system. On in vitro day 14, cells exhibited increased levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid (by 34% and 55%, respectively), and elevations of both the spontaneous and potassium-stimulated dopamine release by 70%. The dopamine transport and metabolism of cells exposed to hypoxia between in vitro days 4 and 6 remained unchanged with regard to long-term effects. The present study provides strong evidence for the induction of long-term changes in dopaminergic cells due to hypoxia during the critical developmental period in mesencephalic culture. The developmental period capable of inducing long-lasting changes in dopamine metabolism is restricted to in vitro days 1-3.

Animals↗