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Biomedical subjects

C Gross

Publications and source records attributed to C Gross.

At least 19 recordsLinked to original sources
PubMed2001

Cloning and characterization of human WDR10, a novel gene located at 3q21 encoding a WD-repeat protein that is highly expressed in pituitary and testis.

Members of the steroid-thyroid-retinoid receptor superfamily regulate a spectrum of cellular functions, including metabolism and growth and differentiation. We sought to isolate novel members of this family by using degenerate oligonucleotide primers directed to sequences encoding the AF-2 domain of these molecules in a PCR-based approach. The AF-2 domain serves a critical function in recruiting coregulatory molecules and in transcriptional activation. We report the cloning and initial characterization of a novel gene, WDR10, which encodes a 140-kD protein that is highly expressed in pituitary and testis. This protein, WDR10p, contains an AF-2 domain as well as seven N-terminal WD repeats and is highly conserved through evolution. Chromosomal localization studies placed WDR10 at 3q21, near a locus for the Moebius syndrome, Hailey-Hailey disease, and rhodopsin, which is involved in several forms of retinitis pigmentosa. The expression pattern of WDR10 and its chromosomal location makes this novel gene a candidate gene for the hypogonadism associated with some forms of retinitis pigmentosa and the Moebius syndrome.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Altered fear circuits in 5-HT(1A) receptor KO mice.

The study of genetically altered mice has been used successfully to determine the influence of different neurotransmitter receptors on fear and anxiety. Mice with a genetic deletion of the serotonin 1A receptor (5-HT(1A)R knockout [KO]) have been shown to be more fearful in a number of behavioral conflict tests, confirming the important role of this receptor in modulating anxiety. Factor analysis of the behavior of WT and 5-HT(1A)R KO mice in the open field test shows that locomotion and anxiety measures segregate independently, supporting the idea that the anxious behavior of the KO mice is not the result of altered locomotion. KO mice also show increased anxiety in the novelty-suppressed feeding task, which differs from the other conflict tests in the motivational drive of the animals. In response to a discrete aversive stimulus, foot shock, the KO mice show increased freezing and increased tachycardia. However, activation of the hypothalamic-pituitary-adrenal axis in response to stress appears to be slightly blunted in the KO animals. Together, these data support the idea that the 5-HT(1A)R modulates an important fear circuit in the brain. The dual function of the 5-HT(1A)R as both a presynaptic autoreceptor, negatively regulating serotonin activity, and a postsynaptic heteroreceptor, inhibiting the activity of nonserotonergic neurons in forebrain structures, has complicated interpretation of the anxious phenotype of these KO mice. A more complete understanding of the function of the 5-HT(1A)R awaits further study of its role in behaving animals using tissue-specific antagonists and novel transgenic mice with tissue-specific expression of the receptor.

Animals↗
PubMed2000

Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays.

In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mac1 activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YFR055w, and YJL217w. Two of the last three newly identified Mac1 target genes have no known function; the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mac1, designated Mac1(up1), are not direct targets of Mac1. Induction or repression of these genes is likely a secondary effect of cells because of constitutive Mac1 activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5 and two genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1 expression arises from an indirect copper effect on cellular iron pools.

Carrier Proteins↗
PubMed2000

Functional independence of the two cysteine-rich activation domains in the yeast Mac1 transcription factor.

Mac1 is a transcriptional activator whose activity is inhibited by copper ions. Mutagenesis studies were carried out to map residues important in the copper inhibition of Mac1 activity. Seven new missense mutations were identified that resulted in copper-independent Mac1 transcriptional activation. All seven mutations were clustered in one of two C-terminal cysteine-rich motifs, designated the C1 motif. All but one of the constitutive Mac1 mutations occurred in one of the conserved six residues in the (264)CXC[(X)(4)]CXC[(X)(2)]C[(X)(2)][H(279)]C1 motif. The lone exception was a L260S substitution. Two additional MAC1 mutations exhibiting constitutive activity were in-frame deletions encompassing portions C1. Engineered mutations in the second cysteine-rich motif did not yield a constitutively active Mac1. These results are consistent with the C1 motif being the copper-regulatory switch. Both cysteine-rich motifs exhibited transactivation activity, although the C1 activator was weak relative to the C2 activator. Limited copper metalloregulation of Mac1 was observed with only the C1 activator fused to the N-terminal DNA binding domain. Thus, the two Cys-rich motifs appear to function independently. The C1 motif appears to be a functional copper-regulatory domain.

Amino Acid Sequence↗
PubMed2000

Fragment kinetic energies and modes of fragment formation

Kinetic energies of light fragments ( A</=10) from the decay of target spectators in 197Au+197Au collisions at 1000 MeV per nucleon have been measured with high-resolution telescopes at backward angles. Except for protons and apart from the observed evaporation components, the kinetic-energy spectra exhibit slope temperatures of about 17 MeV, independent of the particle species, but not corresponding to the thermal or chemical degrees of freedom at breakup. It is suggested that these slope temperatures may reflect the intrinsic Fermi motion and thus the bulk density of the spectator system at the instant of becoming unstable.

Journal Article↗
PubMed2000

Comparison of progression of macrovascular diseases after kidney or pancreas and kidney transplantation in diabetic patients with end-stage renal disease.

AIMS/HYPOTHESIS: The aim of the study was to examine the effect of pancreas-kidney transplantation on the progression of macrovascular diseases in Type I diabetic patients with end-stage renal disease. METHODS: The progression of cerebrovascular disease, coronary heart disease and peripheral vascular disease in uraemic patients with Type I (insulin-dependent) diabetes mellitus and who had had simultaneous pancreas-kidney transplantation was compared with that of recipients of a kidney transplant alone. Between 1986 and 1998 a total of 11 uraemic diabetic patients received a simultaneous pancreas-kidney transplantation and 10 diabetic patients a kidney transplant alone. All transplants functioned for at least 24 months, the mean observation period was 69 +/- 37 compared with 70 +/- 33 months in both patient groups. Macroangiopathic diseases were classified in four stages as described earlier. RESULTS: In the group with simultaneous pancreas-kidney transplantation progression of cerebrovascular and coronary heart disease was observed in four patients (36%) and progression of peripheral vascular disease in five subjects (45%). In the cohort with kidney transplant alone four patients (40%) showed progression of cerebrovascular and coronary heart disease and five progression of peripheral vascular disease (50%); the difference is not significant. Mean values of HbA1c (5.8 +/- 0.2 vs 7.5 +/- 0.6%, p < 0.001) and serum triglycerides (1.2 +/- 0.4 vs 2.0 +/- 1.0 mmol/l, p < 0.05) were significantly lower in the patients with pancreas-kidney transplantation than in the patient group with kidney transplant alone. Serum cholesterol concentrations and blood pressures were similar in both cohorts. CONCLUSION/INTERPRETATION: From our results we concluded that pancreas-kidney transplantation reduces risk factors for the development of macroangiopathy but fails to halt progression of macrovascular diseases similar to Type I diabetic patients with kidney transplant alone.

Adult↗
PubMed2000

Knockout mice reveal opposite roles for serotonin 1A and 1B receptors in prepulse inhibition.

The serotonergic system is involved in the modulation of prepulse inhibition (PPI) and habituation of startle, which are deficient in schizophrenia patients. PPI is the reduction in startle amplitude that occurs when a weak "prepulse" precedes a startling stimulus by 30-500 msec. The roles of 5-HT(1A) and 5-HT(1B) receptors in modulating PPI and habituation were examined using wild-type (WT), 5-HT(1A) knockout (1AKO), and 5-HT(1B) knockout (1BKO) mice. The 5-HT(1A/1B) agonist RU24969 reduced PPI and habituation in WT and 1AKO, but not 1BKO mice, whereas the 5-HT(1A) agonist 8-OH-DPAT increased PPI in WT and 1BKO, but not in 1AKO mice. Similarly, the selective 5-HT(1B) agonist anpirtoline reduced PPI in WT, but not in 1BKO mice. In experiments using intact 129Sv mice, the 5-HT(1A) agonist flesinoxan increased PPI while anpirtoline decreased PPI and habituation. Findings suggest that 5-HT(1B) receptor activation decreases PPI and habituation, and 5-HT(1A) receptor activation increases PPI in mice.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Regulation by homeoproteins: a comparison of deformed-responsive elements.

Homeotic genes of Drosophila melanogaster encode transcription factors that specify segment identity by activating the appropriate set of target genes required to produce segment-specific characteristics. Advances in understanding target gene selection have been hampered by the lack of genes known to be directly regulated by the HOM-C proteins. Here we present evidence that the gene 1.28 is likely to be a direct target of Deformed in the maxillary segment. We identified a 664-bp Deformed Response Element (1.28 DRE) that directs maxillary-specific expression of a reporter gene in transgenic embryos. The 1.28 DRE contains in vitro binding sites for Deformed and DEAF-1. The Deformed binding sites do not have the consensus sequence for cooperative binding with the cofactor Extradenticle, and we do not detect cooperative binding to these sites, though we cannot rule out an independent role for Extradenticle. Removing the four Deformed binding sites renders the 1.28 DRE inactive in vivo, demonstrating that these sites are necessary for activation of this enhancer element, and supporting the proposition that 1.28 is activated by Deformed. We show that the DEAF-1 binding region is not required for enhancer function. Comparisons of the 1.28 DRE with other known Deformed-responsive enhancers indicate that there are multiple ways to construct Deformed Response Elements.

Animals↗
PubMed2000

Factors associated with antiepileptic drug use among elderly nursing home residents.

UNLABELLED: BACKGROUND. Epilepsy, a chronic condition defined as two or more recurrent, unprovoked seizures, has the highest incidence at the end of life. Antiepileptic drugs (AEDs) are the primary therapeutic mode. Approximately 10%-11% of elderly nursing home residents receive one or more AEDs, a higher prevalence than would be expected in this age group. In the research literature, there is not a clear explanation of variations in AED use in nursing homes. The purpose of this study was to examine the prevalence and variations in use of AEDs by resident characteristics, AEDs used, drug dosage, and AED combinations in treatment regimens. METHODS: This was a retrospective, cross-sectional study of residents (N = 21,551) in a convenience sample of nursing homes in 24 states and the District of Columbia. The unit of analysis was the individual resident. The study period was a single day in 1995. Bivariate and multivariate analyses were used to test differences. RESULTS: The prevalence of AED use was 10.5% across all elderly residents. In a multivariate analysis, factors associated with AED treatment included seizure indication, age group, and geographic region. AED use by age group showed declining use as the residents aged, from 65-74 to 75-84 to > or =85 years. CONCLUSIONS: The inverse relationship between AED use and age group was unexpected because the incidence of epilepsy increases with advancing age. This finding raises important questions about the future use of these drugs in elderly nursing home residents.

Aged↗
PubMed2000

Changes in cardiac mechanics with heat acclimation: adrenergic signaling and SR-Ca regulatory proteins.

The involvement of adrenergic signaling and sarcoplasmic calcium regulatory proteins in the development of heat acclimation-induced adaptations in cardiac mechanics was studied in heat-acclimated (34 degrees C) rats for 2, 5, and 30 days (AC(2), AC(5), and AC(30), respectively). Control (C) rats were held at 24 +/- 1 degrees C. Systolic pressure (LVP) and velocities of contraction (dP/dt/P) and relaxation (-dP/dt/P) were measured using a Langendorff system. For adrenergic signaling, beta-adrenoreceptor (AR) density and affinity (Scatchard plots) and cardiac inotropic response to norepinephrine (10(-7) mM, +/- 10(-6) mM propranolol) were measured. For the regulatory proteins, steady-state levels of Ca(2+)-ATPase and phospholamban (PLB) mRNAs and the encoded proteins Ca(2+)-ATPase [sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] and PLB were measured using semiquantitative RT-PCR and Western immunoblotting, respectively. Both short (STHA; AC(2) and AC(5))- and long-term heat acclimation (LTHA; AC(30)) enhanced LVP. However, dP/dt. P and -dP/dt. P in STHA hearts resembled that of the controls, whereas on LTHA, both parameters decreased (P < 0.05), implying decreased velocity of contraction and relaxation. beta-AR density remained unchanged with their affinity markedly decreased (P < 0.05). AR responsiveness, however, diminished in AC(2) but was markedly enhanced on LTHA. During STHA, PLB and sarcoplasmic reticulum Ca(2+)-ATPase transcripts were upregulated with no change in the encoded proteins except for SERCA downregulation on AC(5), leading to an increased PLB/SERCA ratio (P < 0.05). This mismatched preacclimation lusitropic state on STHA and increased PLB/SERCA ratio was evident (P < 0.05) due to downregulation of SERCA and upregulation of PLB. Our data fit a biphasic acclimation model in which desensitized adrenergic signaling is dominant during STHA, whereas on LTHA, the contractile machinery is influenced by altered expression of the calcium regulatory proteins leading to both augmented adrenergic inotropic response (via PLB elevation) and decreased velocity of relaxation. The sustained low thyroxin measured on LTHA causally associates with this response.

Adaptation, Physiological↗
PubMed2000

Different modes of degeneration in autologous and heterologous heart valve prostheses.

BACKGROUND AND AIM OF THE STUDY: This study was performed to elucidate the mechanism of primary tissue failure of bioprosthetic heart valves, which were fabricated from autologous pericardium (Autogenics). Results were compared with the degeneration pattern of heterologous pericardial bioprostheses. METHODS: Between March 1994 and December 1996, 87 Autogenics heart valves were implanted in the aortic position. Since then, 15 valves had to be explanted due to structural deterioration. The average implant period was 33+/-8 months. All explants were examined by gross morphological evaluation and X-ray analysis to identify the failure mode of these devices. In eight explanted autologous tissue valves and six explanted heterologous pericardial bioprostheses, exact morphological evaluation was performed by scanning electron microscopy, microscopic and immunohistochemical techniques. RESULTS: All autologous tissue valves failed due to cuspal tears localized at the commissures. Nocalcification could be detected by X-ray analysis and microscopic methods. Endothelial cell coverage was evident at the outflow surface of all autologous bioprostheses. Histological examination showed severe disintegration of the collagen fibers by insudated plasma proteins and erythrocytes, and the absence of the original fibroblasts. Collagen fibers were vigorously altered between the inner and outer stent of the Autogenics valve. In contrast, heterologous pericardial valves failed due to severe calcification of the cusps. Histological evaluation displayed invasion of macrophages and calcific deposits. The collagenous texture of the pericardial tissue was significantly better preserved compared with autologous tissue. CONCLUSION: High biocompatibility of autologous tissue valves is indicated by the absence of calcium deposits, macrophages and foreign body giant cells, and the presence of endothelial cell ingrowth. Severe disintegration of autologous tissue suggests that brief immersion in glutaraldehyde generates inadequate mechanical stability of bioprosthetic heart valve material. Heterologous valves exhibit low biocompatibility but superior preservation of the collagenous biomaterial.

Aged↗
PubMed2000

[MRI].

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Bone Diseases↗
PubMed2000

[MRI].

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Diffusion of Innovation↗
PubMed2000

The incidence of thrombovenous and thromboembolic complications in kidney transplant patients with recurrent glomerulonephritis is dependent on the occurrence of severe proteinuria.

BACKGROUND: Patients with recurrent glomerulonephritis (RG) after kidney transplantation are at high risk for thromboembolic events but it is unclear when the risk begins to increase. PATIENTS AND METHODS: We evaluated the risk for thrombovenous and thromboembolic complications in relation to the occurrence of severe proteinuria (> or = 2 g protein in 24-hour urine) in 15 renal allograft recipients with biopsy-proven RG, who had received 20 allografts RG. The total period of observation was 53 (10-91) months. The post-transplant period before the occurrence of severe proteinuria lasted 18 (1-34) months and the subsequent proteinuric period until the end of the study, 35 (9-85) months. RESULTS: The monthly incidence of thrombovenous and thromboembolic complications was only 1/18 in the first period before and in contrast, 11/35 in the subsequent period after the occurrence of severe proteinuria. The mean urinary protein excretion increased from 0.4 +/- 0.1 g/day immediately after transplantation to 6.1 +/- 4.8 g/day at the end of the study (p < 0.001). During the same period there was a 1.2-fold increase of fibrinogen (from 366 +/- 88 to 442 +/- 120 mg/dl, p < 0.025) and a 1.2-fold decrease of antithrombin III (from 110 +/- 12 to 92 +/- 12%, p < 0.001). All thrombotic complications occurred in 6 patients with 9 grafts; at the end of the study this group showed higher fibrinogen concentrations (454 +/- 155 versus 433 +/- 89 mg/dl, NS) m and lower antithrombin III levels (88 +/- 11 versus 97 +/- 11%, p < 0.05) than the group without thrombotic complications. CONCLUSION: In kidney transplant patients with RG a high risk for thrombovenous and thromboembolic complications can be obs- served after the occurrence of severe proteinuria; this can mainly be explained by high fibrinogen and low antithrombin III levels. Anticoagulation therapy should be started in patients with RG immediately after the occurrence of severe proteinuria.

Adult↗
PubMed1999

Reorganization of area 5 neuron activity in trained deafferented monkeys.

A command function is attributable to certain area 5 neurons which clearly fire before movement in trained monkey. Statistical analysis allowed us to define two categories of spontaneous firing mode for these cells: type I which exhibits a random pattern of discharge (14%), and type II displaying markedly "bursty firing". After deafferentation, both categories were still observed in the same proportion. However, the discharge pattern and frequency in type II cells remained altered for 5 months. This paralleled rises in neural latency response (RS) and reaction time (RT). Beginning the 6th month, there was a progressive reorganization of the spontaneous activity along with normalization of RS and RT. Our results support the idea that an enhancement of the excitability of these area 5 neurons, initially depressed by the suppression of sensory inputs, occurs over time. This sensitivity gain could be due to neural network rearrangements induced by repetitive operant solicitation.

Afferent Pathways↗
PubMed1999

[Squamous cell carcinoma developing from epidermodysplasia verruciformis].

We report on a 50-year-old man who presented with squamous cell carcinoma of the forehead skin developing from epidermodysplasia verruciformis (EV). EV is an uncommon disease characterized by flat warts or scaling macules resembling pityriasis vericolor on sun-exposed skin. Histogenetic predisposition and human papilloma virus infection play a part. As shown in our case there is, depending on HPV subtype and additional exposure to ultraviolet light, a high risk of malignant transformation. These patients require close monitoring.

Carcinoma, Squamous Cell↗
PubMed1999

[Restrictive dermopathy].

Restrictive dermopathy is a rare, fatal, autosomal recessive, congenital skin disease. Rigidity of translucent thin skin, which is thus highly vulnerable and tears, spontaneously causes intra-uterine fetal akinesia or hypokinesia deformation sequence (FADS), characteristic dysmorphic facies with fixed open mouth in O position, and generalized joint contractures (arthrogryposis). Polyhydramnios and pulmonary hypoplasia are distinctive manifestations, leading to respiratory insufficiency and premature delivery at about 31 weeks of gestation. We report on a case of a prematurely born infant who presented with the typical morphological features and describe the light- and electron-microscopical findings as described in the literature.

Abnormalities, Multiple↗