bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen, Progesterone, and Pregnancy Termination Alter Neural Activity in Brain Regions That Control Maternal Behavior in Rats
Authors: Sheehan Teige , Numan Michael
Published: April 2003

Estrogen stimulates maternal behavior in rats, but does so most potently when its administration is temporally coupled with the termination of pregnancy. In contrast, this effect of estrogen is blocked when subjects are administered a large dose of progesterone concurrent with estrogen. The current study was performed to examine the neural circuitry influenced by these treatments and pup presentation during the hormonally-mediated onset and inhibition of maternal behavior. In experiment I, estrogen induced c-Fos immunoreactivity (Fos-IR) in the medial preoptic area (MPOA) in virgin rats, but was much more effective when administered to pregnancy-terminated rats, suggesting that pregnancy termination increases MPOA’s susceptibility to the physiological effects of estrogen. In experiment II, administering progesterone concurrently with estrogen in pregnancy-terminated rats strongly inhibited estrogen-stimulated Fos-IR in the MPOA, indicating that the physiological effects of estrogen on the MPOA are blocked if high progesterone levels are maintained. In experiment III, pregnancy-terminated subjects were administered estrogen, progesterone, or both hormones and presented with pups for 2 h. Approximately half of the subjects administered estrogen alone showed maternal behavior, but subjects receiving the other treatments were not maternal. In the MPOA, ventral bed nucleus of the stria terminalis (BSTv), and dorsal and intermediate lateral septum (LSd,i), maternal subjects showed the highest levels of Fos-IR, whereas subjects treated with progesterone alone or progesterone in combination with estrogen showed low levels of Fos-IR. These experiments suggest that estrogen could promote maternal behavior by enhancing pup-stimulated activity in the MPOA, BSTv, and LSd,i, regions believed to constitute the neural circuit that promotes maternal behavior, whereas progesterone could inhibit maternal behavior by inhibiting neural activity in some of these regions.
Timing of Initiation of the Preovulatory Luteinizing Hormone Surge and Its Relationship with the Circadian Cortisol Rhythm in the Human
Authors: Kerdelhué Bernar d , Brown Samuel , Lenoir Véronique , Queenan Jr. John T. , Jones Georgeanna Seegar , Scholler Robert , Jones Jr. Howard W.
Published: April 2003

The relationship between the hypothalamo-pituitary-gonadal (HPG) axis and the hypothalamo-pituitary-adrenal (HPA) axis has been well documented in the rat. In most cases, a negative coupling was observed and an inhibitory effect of the HPA axis upon the HPG was shown. In the female rat, a marked circadian rhythm of corticosterone plasma values is observed during each day of the estrous cycle, with maximal values around 08:00 p.m. The preovulatory luteinizing hormone (LH) surge also occurs at 08:00 p.m. on the day of proestrus. Here we measured circadian variations of plasma cortisol in humans in relation with the time of initiation of the preovulatory LH surge. Blood samples were taken at 08:00 a.m., 12:00 a.m., 04:00 p.m., 08:00 p.m., 12:00 p.m., and 04:00 a.m. from 19 subjects for 4 consecutive days, once 17β-estradiol (E2) values reached 125 pg/ml (days 7–10 of the menstrual cycle). Serum E2 and LH determinations were performed by microparticle enzyme immunoassays. Serum progesterone and plasma cortisol determinations were made using RIA methods. For plasma cortisol values, a marked circadian rhythm, with 2- to 3-fold higher values during the morning than during the afternoon, was almost identical before, during and after the LH surge. However, values were generally higher during the follicular phase than during the luteal phase. Maximum cortisol values occurred between 04:00 and 08:00 a.m. and minimal cortisol values between 04:00 and 08:00 p.m. Initiation of the LH surge (50% over the mean of previous values) occurred at 04:00 a.m. (20% of the cases) or at 08:00 a.m. (80% of the cases). There was a strong coupling between the onset of the surge and the acrophase of the cortisol circadian rhythm: maximal cortisol plasma values were seen at 04:00 a.m. when the LH preovulatory surge started at 04:00 a.m. and 08:00 a.m. when it started at 08:00 a.m. The present results show that the positive coupling documented in the female rat between the HPA and the HPG axis at the time of preovulatory LH surge is also present during the menstrual cycle in the human.
Pituitary Adenylate Cyclase Activating Polypeptide and Neuropeptide Y Regulation of Gonadotropin Subunit Gene Expression in Tilapia: Role of PKC, PKA and ERK
Authors: Gur Gal , Bonfil David , Safarian Helena , Naor Zvi , Yaron Zvi
Published: April 2003

There is ample information on the hypophysiotropic function of pituitary adenylate cyclase-activating polypeptide (PACAP) and neuropeptide Y (NPY) in fish as in mammals, although evidence as to their direct effects on gonadotropic cells is scarce. We have previously reported that NPY and PACAP38 augment gonadotropin-releasing hormone (GnRH)-induced expression of glycoprotein α (α) subunit gene in the teleost fish, tilapia. The aim of the present study was to elucidate possible direct effects of these peptides on gonadotropin subunit gene expression in culture of tilapia pituitary cells, as well as the transduction pathways involved. Both NPY and PACAP38 (0.001–10 nM) increased the level of phosphorylated extracellular signal-regulated kinase (pERK) dose-dependently, reaching a peak at 0.1 and 0.01 nM, respectively. Inhibition of protein kinase C (PKC) by GF109203X (GF; 0.01–10 nM) suppressed NPY-stimulated pERK levels and its effect on α and luteinizing hormone (LH) β subunit mRNA levels. However, NPY had no effect on follicle stimulating hormone (FSH) β mRNA levels. NPY-elevated α, LHβ mRNA and pERK levels were also attenuated by inhibition of protein kinase A (PKA) with H89 (0.01–10 nM). Exposure of the cells to the MAPK kinase (MEK) inhibitor (PD98059; PD 10, 25 and 50 µM) completely blocked NPY-induced ERK activity. In addition, this inhibitor abated the α and LHβ mRNA responses to NPY. Similar experiments conducted to elucidate PACAP38 signaling revealed that PACAP38 (0.01 nM) elevated all three-gonadotropin subunit gene expression via both PKC-ERK and PKA-ERK cascades. It is suggested that both NPY and PACAP38 act directly on gonadotropes to elevate gonadotropin subunit gene expression. Whereas the expression of α and LHβ subunit genes is regulated by both NPY and PACAP, the effect on the FSHβ transcript is elicited only by PACAP38. NPY and PACAP38 stimulatory actions are mediated via protein kinase C (PKC) and protein kinase A (PKA), converging at the MEK-ERK cascade. These findings represent one of the fine tuning levels that differentially regulates gonadotropin subunit gene expression.
Correlation of Vascular Endothelial Growth Factor-C Expression with Tumor-Infiltrating Dendritic Cells in Gastric Cancer
Authors: Takahashi Akihiro , Kono Koji , Itakura Jun , Amemiya Hideki , Feng Tang Rui , Iizuka Hidehiko , Fujii Hideki , Matsumoto Yoshiro
Published: April 2003

It has been reported that dendritic cells (DCs) play a crucial role in the host’s immune defense against tumors, and there is an inverse correlation between the density of DCs and the expression of vascular endothelial growth factor (VEGF). However, the relationship between the expression of VEGF-C and DC infiltration remained unclear. In the present study, we investigated whether the expression of VEGF-C correlated with the number of DCs in vivo. We immunohistochemically analyzed gastric carcinoma tissue in this study. The survival curves show that the prognosis for patients with a low density of DCs was significantly poorer than that for patients with high DC density (p < 0.01). Further, the survival curves according to the VEGF-C status showed that the survival rate in patients with low VEGF-C expression was higher than that in patients with higher expression (p < 0.01). There was a significant negative correlation between the density of DCs and the expression of VEGF-C (r = –0.26, p < 0.05). We suggest that VEGF-C produced by cancer causes DCs to become dysfunctional. This may be one of the ways that cancers evade immunosurveillance.
Effects of Isopropyl Unoprostone, Latanoprost, and Prostaglandin E2 on Acute Rise of Aqueous Flare in Pigmented Rabbits
Authors: Zhang Xue-Yun , Hayasaka Seiji , Hayasaka Yoriko , Yanagisawa Shuichiro , Nagaki Yasunori
Published: April 2003

Purpose: To evaluate the effect of isopropyl unoprostone, latanoprost, and prostaglandin E2 (PGE2) on aqueous flare elevation. Methods: Isopropyl unoprostone (0.12%) or latanoprost (0.005%) was topically instilled. Transcorneal diffusion of PGE2, 25 µg/ml, using a glass cylinder, was achieved in pigmented rabbits. Aqueous flare was measured with a laser flare cell meter. Results: Topical instillation of isopropyl unoprostone induced aqueous flare elevation in rabbit eyes. Also, topical isopropyl unoprostone additionally induced aqueous flare elevation in eyes with transcorneal diffusion of PGE2. Latanoprost did not induce flare elevation. Conclusion: Isopropyl unoprostone induced aqueous flare elevation in rabbits, and latanoprost did not produce aqueous flare elevation.
Robot-Assisted Endoscopic Intrauterine Myelomeningocele Repair: A Feasibility Study
Authors: Aaronson Oran S. , Tulipan Noel B. , Cywes Robert , Sundell Håkan W. , Davis Georges H. , Bruner Joseph P. , Richards William O.
Published: April 2003

Background: Animal experiments have suggested that the intrauterine environment causes secondary injury to the congenitally dysplastic spinal cord. This in turn suggests that early closure of the myelomeningocele sac might prevent secondary injury and therefore improve neurologic outcome. This study was designed to examine the technical feasibility of performing intrauterine myelomeningocele repair using a robot-assisted endoscopic system in an animal model. Methods: Six fetal sheep underwent creation and repair of a full-thickness skin lesion using the da VinciTM system. Results: With the device’s advanced articulated instruments and three-dimensional optics, it was possible to endoscopically repair the induced skin defects. Conclusion: We conclude that, with the recent evolution in robotics and minimally invasive techniques, intrauterine endoscopic surgery has become a realistic goal that promises to reduce the associated risks of fetal surgery and extend the indications for its use.
Occurrence of Split Cord Malformation in Meningomyelocele: Complex Spina bifida
Authors: Kumar Raj , Bansal Krishan Kumar , Chhabra Devendra Kumar
Published: April 2003

Objective: To describe the clinical features and surgical outcome of a combined anomaly, i.e. split cord malformation (SCM) with meningomyelocele (MMC), and to propose an addition to Pang’s classification of SCM to accommodate a combined form of anomaly. Methods: We retrospectively analyzed 16 cases of such a combination, out of a total of 106 cases of spinal dysraphism treated and studied prospectively for outcome at our center. The clinical profile and outcome of these cases are described. Results: All cases had SCM and MMC. Nine patients were males, and the mean age of presentation was 3.9 years. Twelve patients had Pang’s type I SCM and the other 4 were of type II. The MMC sac was lumbar in 11 cases. In all the patients, SCM was present either at the same level as the MMC or one to two segments above it. Nine patients had motor weakness, 6 had hypoesthesia, 4 had urinary incontinence and 3 had trophic ulcers. Nine patients had neuroorthopedic syndrome. All cases, except 3 (who were operated on at birth, at which time ‘superficial surgery’ was performed without relevant imaging), underwent repair of the MMC and excision of the spur/septum at the same sitting. The 3 cases who had undergone superficial surgery, however, were operated on for SCM following investigation at our center, obviously at a second sitting. After an average follow-up of 7.2 months, 4 patients showed improvement in motor weakness, 5 in hypoesthesia and 3 in urinary symptoms, whereas trophic ulcers had healed in all cases. Conclusion: With respect to the occurrence of SCM at or above the level of an MMC, we feel it is apt to screen the entire spinal/neuraxis by MRI in children with MMC. We labeled this combined pathology ‘complex spina bifida’, and feel it is necessary to make a minor modification to Pang’s classification to accommodate the pure/combined anomalies together.
Comparative Study between Direct Mild Acid Extraction and Immunobead Purification Technique for Isolation of HLA Class I-Associated Peptides
Authors: Torabi-Pour N. , Nouri A.M.E. , Saffie R. , Oliver R.T.D.
Published: April 2003

Identification of tumour-specific peptide(s) hidden within the groove of human leucocyte antigens is a crucial prerequisite for peptide vaccine therapy. Conventionally, the peptide(s) are isolated by mild acid extraction (MA) technique followed by sequential ultra-filtrations. Here we describe a new approach for peptide isolation using the immunobead purification (IB-P) technique in conjunction with reverse-phase high-performance liquid chromatography. The obtained data were validated by SDS-PAGE followed by the silver staining technique. The results can be summarised as follows: (1) Comparison of class I-associated peptides isolated from a bladder cell line before and after the correction of class I antigens by gene transfection followed by IB-P technique showed the presence of peptides only from the class I-corrected cells. The data were confirmed using the silver staining technique as a way of detecting individual peptide bands. (2) Whilst peptides could be isolated by both techniques, the MA method led to the isolation of peptides from both class I-negative and class I-positive Fen cell lysates. (3) The IB-P approach could be used for isolation of class I-associated peptides from a normal kidney tissue. The data showed the high efficiency of the IB-P approach for isolation of class I-associated peptides. Unlike the MA technique, where the presence of non- class I-associated peptides was a problem, the IB-P approach isolated only peptides associated with the class I antigens. In addition, the data showed the feasibility of extracting peptides from tissue fragments by the IB-P method. The approach presented here may assist the future development of peptide vaccine therapy in urological cancers.
Biopsies of the Transitional Zone of the Prostate
Authors: Deliveliotis C. , Varkarakis J. , Albanis S. , Argyropoulos V. , Skolarikos A.
Published: April 2003

Purpose: In this prospective study we try to evaluate the necessity of performing additional transitional zone biopsies as part of the standard sextant biopsies procedure in order to detect prostate cancer. Materials and Methods: During a 12-month period we performed biopsies in 420 patients. All patients had two additional biopsies of the transitional zone biopsies. 289 of them were biopsies for the first time because they had an elevated PSA and/or a suspicious DRE. One hundred and thirty-one had a repeat biopsy because of the remaining elevated PSA after the previous negative one. Results: Of the 420 patients 143 (34%) had cancer, with 11 (7%) having cancer in the transitional zone only. Patients initially evaluated because of high PSA and or a positive DRE had only 2 (2.1%) cancers exclusively in the transitional zone. We found that this percentage rises (18.7%) when the patients had already at least one previous negative biopsy of the peripheral zone, and during the repeat biopsy the transitional zone is samples. Conclusions: The low yield of transitional zone biopsies (2.1%) during first time sampling of the prostate does not warrant their systematic use for the early detection of prostate cancer. Instead the effectiveness of biopsies in that area is higher when the biopsy is repeated after an initial previous negative biopsy of the peripheral zone.
Rare Secondary Carcinoma from Bladder to Testis
Authors: Beardo P. , Manasia P. , Corral J.M. , Truan D. , Alcover J.B. , Micali F.
Published: April 2003

Metastatic carcinoma to the testis is very unusual in daily urologic practice. We report a case of metastatic cancer to the testis detected as incidental findings in a squamous bladder tumor.
Comparison of 5-Day and 10-Day Cefixime in the Treatment of Acute Exacerbation of Chronic Bronchitis
Authors: Lorenz Joachim
Published: April 2003

The focus of a multicenter trial conducted in Germany was to investigate whether a 5-day short course of cefixime 400 mg was equivalent to a 10-day standard therapy of cefixime 400 mg in the treatment of acute exacerbation of chronic bronchitis (AECB). In the 167 patients who were evaluated, on day 11 following treatment with once-daily oral cefixime resulted in clinical success in 91 and 89% of cases in the 5-day and 10-day treatment groups, respectively. At days 6, 11 and 30 after treatment there was no statistically significant difference between the 2 dose groups (p < 0.01). Bacteriological equivalence was also demonstrated. Gastrointestinal adverse events showed a tendency to occur less frequently in the 5-day group, but the difference was not significant. The results indicate that a short course therapy is equivalent in efficacy to the standard 10-day therapy in patients with AECB, and may thus offer cost advantages.
Renal Sparing by Amphotericin B Colloidal Dispersion: Clinical Experience in 572 Patients
Authors: Gurwith M. , Mamelok R. , Pietrelli L. , Du Mond C.
Published: April 2003

Data from five clinical trials of amphotericin B colloidal dispersion (ABCD) in the treatment of invasive mycoses were pooled to analyze the renal sparing effects of ABCD. Serum creatinine levels at baseline and either during or at end of treatment were available for 499 of 572 patients (87.2%). The median cumulative dose of ABCD administered to the 499 evaluable patients was 4,050 (range: 30–74,250) mg, and the median duration of treatment was 18 (range: 1–407) days. For the entire group of evaluable patients, the median change in serum creatinine during treatment with ABCD was –0.1 mg/dl; for the subgroups of patients enrolled in the trials because of amphotericin B toxicity or preexisting renal impairment, the median changes in serum creatinine were –0.3 and –0.2 mg/dl, respectively. There was no trend of increasing serum creatinine with increasing cumulative dose of ABCD (correlation coefficient = –0.016). ABCD was prematurely discontinued in 19 of 572 patients (3.3%) because of elevated serum creatinine levels. Unlike conventional amphotericin B, ABCD is not associated with dose-dependent nephrotoxicity.
The Population Pharmacokinetics of Amphotericin B Colloidal Dispersion in Patients Receiving Bone Marrow Transplants
Authors: Amantea Michael A. , Bowden Raleigh A. , Forrest Alan , Working Peter K. , Newman Mary S. , Mamelok Richard D.
Published: April 2003

The purpose of this study was to identify the pharmacokinetics of Amphotericin B Colloidal Dispersion in patients undergoing bone marrow transplantations with systemic fungal infections and to assess the influence of ABCD on renal function. Seventy-five patients (42 females, 33 males) with a median age of 34.5 years and median weight of 70.0 kg were enrolled in the study. The plasma concentration data was available in 51/75 patients and was best described by a two-compartment model; both plasma clearance and volume of distribution increased with escalating doses; the overall average terminal elimination half-life was 29 h. Serum creatinine values over the duration of therapy were available in 59/75 patients. Overall, there was no net change in renal function over the duration of therapy.
Treatment of Lower Respiratory Tract Infections in Italy: The Role of Outpatient Parenteral Antibiotic Therapy
Authors: Esposito Silvano
Published: April 2003

The use of outpatient parenteral antibiotic therapy (OPAT) has enjoyed substantial success in Italy, where patients generally believe that treatment at home is better than in the hospital. Intramuscular administration, which is commonplace in Italy, facilitates OPAT, requiring minimal training and circumventing intravenous access problems. The Italian OPAT model is a general practice-based model, but a team approach is used in the presence of severe disease, such as HIV. Seven centers in Italy are participating in the International OPAT Outcomes Registry, and have enrolled about 200 patients over 8 months. Eighty patients (40%) were treated for lower respiratory tract infections (60 pneumonia, 20 bronchitis). Most pneumonia patients had concomitant disease, including chronic heart disease, HIV and cancer. The most frequently used therapy was ceftriaxone, which permits once-daily convenience due to its prolonged half-life. Antibiotics were administered intramuscularly in more than 50% of cases. Clinical outcome was excellent, and patient and physician satisfaction was high.
Penetration of Ravuconazole, a New Triazole Antifungal, into Rat Tissues
Authors: Mikamo Hiroshige , Yin Xiang Hua , Hayasaki Yoh , Shimamura Yoshiko , Uesugi Keizo , Fukayama Nobuyuki , Satoh Masaru , Tamaya Teruhiko
Published: April 2003

Ravuconazole (BMS 207147, ER-30346) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. The penetration of ravuconazole into rat tissues was examined. Fifty-five 7-week-old specific pathogen free female rats were used in this study. Plasma, lung and uterus tissue of rats were taken at 1, 2, 4, 8, 12, 16, 24, 32, 48, 60, and 72 h (n = 5) after oral administration of 10 mg/kg of ravuconazole. The quantitative assays of ravuconazole by HPLC after the extraction with diethylether were conducted for each tissue sample homogenate. tmax, t 1/2, and Cmax of ravuconazole is 8 h, 16.9 h and 1.68 µg/ml, respectively. The concentrations of ravuconazole in rat uterus and lung tissues were 2–to 6 times higher than the corresponding blood concentrations. The ratio of plasma to lung levels of ravuconazole was superior to the published data of other azoles. Considering its antifungal spectrum, ravuconazole would thus be a good candidate for treatment of deep-seated fungal infections caused by Candida, Aspergillus and Cryptococcus.
The Relevance of Stroboscopy in Functional Dysphonias1
Authors: Schneider B. , Wendler J. , Seidner W.
Published: April 2003

Objectives: Functional dysphonias are disorders of the voice characterized by sound and efficiency disturbances of the voice without any organic changes of structures being detectable. At present, functional dysphonias are generally subclassified into hyper- and hypofunctional dysphonias in clinical practice. Study Design: The study was designed for a critical evaluation of the relevance of stroboscopy to the diagnostics and classification of functional dysphonias. Methods: 45 patients were examined (27 hyperfunctional, 15 hypofunctional and 3 mixed type) using videostroboscopy. Several stroboscopic parameters were taken into consideration. Three geometrical and three time-dependent parameters were first analyzed in a uni- and multidimensional way, then cluster analyses were performed. Results: We could not confirm the clinical subdivision into hyper- and hypofunctional dysphonias as based on anamnestic data, perceptual evaluation of voice sound, voice profile measurements and videostroboscopy. Quantitative measurements of selected parameters did not correlate with qualitative subjective stroboscopic assessment. In addition to this, it was not possible to identify separate clusters of stroboscopic findings. Conclusions: The results do not deny the clinical relevance of stroboscopy to the diagnostics of functional dysphonias as a very useful tool to exclude organic lesions. However, a reliable subclassification into different types of functional dysphonias was not possible.
Frequency Distribution and Haplotypic Heterogeneity of βE-Globin Gene among Eight Minority Groups of Northeast Thailand
Authors: Fucharoen Goonnapa , Fucharoen Supan , Sanchaisuriya Kanokwan , Sae-ung Nattaya , Suyasunanond Urasri , Sriwilai Prayuk , Chinorak Phannee
Published: April 2003

The frequencies of hemoglobin E and βE-globin gene haplotypes were determined in eight minority groups living in the northeastern part of Thailand. A total of 478 samples of eight minority groups, namely Soui, Thai Khmer, So, Yor, Phuthai, Thai Puan, Thai Loei and Thai Dam, were examined. High prevalences of hemoglobin E (>50%) were observed in Soui, Thai Khmer, So, Yor and Phuthai inhabiting the region near Cambodia and Laos. Thai Puan, Thai Loei, Thai Dam and native Thai living in the same geographical area had prevalences of 42.6, 35.9, 21.4 and 27.9%, respectively. A prevalence of 9.5% was found among the Thai with Chinese background living in the same area. β-Globin gene haplotypes analysis demonstrated that most of the βE-globin genes in these Thai populations were associated with two haplotypes: (– + – + + + –) and (+ – – – – + –) on chromosomes with framework 2 variety. Some βE-globin genes in Soui and Thai Khmer groups were associated with the framework 3 chromosome. Genetic distances based on the β-globin gene haplotypes between minority groups revealed that Soui and Thai Khmer were closely related to each other. This finding has a valuable implication for study of the origin and spread of hemoglobin E in the region.
Clinical Diagnosis of Ischemic versus Hemorrhagic Stroke: Applicability of Existing Scores in the Emergency Situation and Proposal of a New Score
Authors: Stürmer Til , Schlindwein Gregor , Kleiser Bernhard , Roempp Achim , Brenner Hermann
Published: April 2003

Several scores exist to clinically differentiate between ischemic and hemorrhagic stroke, but none has been developed in the emergency situation in which transient ischemic attack (TIA) and cerebral infarction might not yet be clearly distinguished. Information on 540 patients with ischemia (including TIA) or hemorrhage was abstracted from medical charts. Of 540 patients hospitalized with stroke, 98 had a hemorrhage. Age, obesity, anamnestic stroke/TIA, peripheral arterial disease, onset during physical activity, headache, impaired consciousness, hemisyndrome, meningismus and systolic blood pressure contributed to the differential diagnosis and were included in our proposed score. The score performed well in comparison with existing scores. The inclusion of TIA and the explicit incorporation of incomplete information may enhance the applicability of differential diagnostic scores in the prehospital emergency situation.
Prevalence of Dementia and Apolipoprotein E Genotype Distribution in the Elderly of Buttapietra, Verona Province, Italy
Authors: Benedetti M.D. , Salviati A. , Filipponi S. , Manfredi M. , De Togni L. , Gomez Lira M. , Stenta G. , Fincati E. , Pampanin M. , Rizzuto N. , Danti G.
Published: April 2003

We investigated the prevalence of dementia and the apolipoprotein E (APOE) genotype distribution in the elderly of Buttapietra, a village near Verona, Italy. All residents over the age of 74 (n = 238), including those who were institutionalized, were studied using a direct-contact, single-phase design. The overall prevalence of dementia, clinically defined by DSM-III-R criteria, was 15.8 cases per 100 population, with age-specific figures increasing steeply with advancing age in both sexes. Alzheimer’s disease (AD) was the most frequent dementing disorder (43%). APOE genotyping was determined after DNA amplification by restriction isotyping. We found that the Ε4 allele and the Ε3/Ε4 genotype were associated with all types of dementia, although only the association of Ε3/Ε4 with AD reached statistical significance (odds ratio 4.5, 95% confidence interval 1.3–16.1). However, as reported in other Mediterranean countries, the frequency of the Ε4 allele in our population was low (8.9%), suggesting that the population-attributable risk for AD, at least for elderly individuals (≧75 years), could be small.
Event-Related Evoked Potential P300 in Frontotemporal Dementia
Authors: Jiménez-Escrig A. , Fernandez-Lorente J. , Herrero A. , Baron M. , Lousa M. , de Blas G. , Gobernado J.
Published: April 2003

There are no studies on event-related cognitive potentials in frontotemporal dementia (FTD). In order to evaluate the aptitude and usefulness of the event-related P300 potential in this disease, we prospectively examined 60 cases: 11 patients with FTD diagnosed according to the Lund and Manchester criteria and Neary consensus criteria, 33 patients with a probable Alzheimer’s disease diagnosis following NINCDS-ADRDA criteria, and 16 normal controls. P300 latency, amplitude and reaction time were recorded using an auditory oddball paradigm. In this sample, P300 potential could be reliably performed by 10/11 FTD patients, notwithstanding their language or executive function deficiencies. The FTD group P300 mean latency was midway between the normal controls and the Alzheimer’s disease group (ANOVA F2, 74199 = 16.5; p = 0.00003). The latency range of the FTD patients were within normal values (average plus 1.96 standard deviation of the values of the control group), except for one case with a latency of 448 ms. Post hoc Newman-Keuls analysis showed that the P300 latencies of the control and FTD groups did not differ significantly (p = 0.15) and that the Alzheimer’s disease group had a delayed P300 latency that differed significantly from that of the FTD (p = 0.002) and control group (p = 0.0002). However, there was overlapping in P300 latency values of the three groups. Despite these differences in latencies, the reaction time was significantly increased in the FTD and the Alzheimer’s disease groups. These findings indicate that the P300 potential is less affected in patients with FTD than those with Alzheimer’s disease. This fact could aid in FTD diagnosis, differential diagnosis with Alzheimer’s disease and possibly its clinical management.
The Domain-Specific, Stage-Limited Impact of the Apolipoprotein E Epsilon-4 Allele on Cognitive Functions in Alzheimer’s Disease
Authors: Kim K.W. , Jhoo J.H. , Lee J.H. , Lee D.Y. , Lee K.U. , Youn J.C. , Youn J.Y. , Woo J.I.
Published: April 2003

To examine the impact of the APOE Ε4 allele on the cognitive functions of Alzheimer’s disease (AD) patients, we administered the eight neuropsychological tests from the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery to 118 Korean AD patients. The impact of the APOE Ε4 allele was significant in the Word List Recall Test (WLRT) and the Word List Recognition Test (WLRcT) only, and its impact was confined to the very mild AD (VMAD) patients (F = 7.65, d.f. = 2, p < 0.01 for WLRT; F = 3.27, d.f. = 2, p = 0.04 for WLRcT). In the VMAD group, the performance on the two tests of the APOE-Ε4-positive patients was poorer than that of the APOE-Ε4-negative patients. Our findings suggest that the impact of the APOE Ε4 allele on cognitive functions in AD may be domain specific and confined to the early stage of AD.
Comparison of the Amplitude/Intensity Function of the Auditory Evoked N1m and N1 Components
Authors: Neukirch M. , Hegerl U. , Kötitz R. , Dorn H. , Gallinat U. , Herrmann W.M.
Published: April 2003

This study compared the intensity dependence of the auditory evoked N1 and N1m components in 10 healthy subjects. The evoked responses were recorded simultaneously at 33 channels for the auditory evoked potentials (AEP) and with a 37-channel magnetometer for the auditory evoked fields (AEF). They were satisfactorily modeled by a tangential and a radial dipole per hemisphere for the N1 component and a tangential dipole in the left hemisphere for the N1m component. The tangential dipoles showed different dipole characteristics. The amplitude of the AEP rose significantly with increasing stimulus intensity whereas the amplitudes of the AEF tended to plateau between the highest intensities. The magnetic dipole shifted to the surface of the skull with higher stimulus intensity whereas the electric tangential dipole moved to the center of the skull. The latencies decreased with increasing stimulus intensity.
A Study on Gender and Age Differences in Sleep Spindles
Authors: Huupponen Eero , Himanen Sari-Leena , Värri Alpo , Hasan Joel , Lehtokangas Mikko , Saarinen Jukka
Published: April 2003

In the present work, gender differences in sleep spindle topography were examined in 40 subjects. Their median age was 32 years (range 22–49 years). Spindles were detected from 3,306,060 s of visually scored stage 2 sleep EEG by a previously validated automatic fuzzy detector at 1-second intervals. A total of 271,168 spindles were found from the six EEG channels analyzed. Females showed a significantly higher percentage of spindles in the left frontal channel than males (Fp1-A2; p = 0.026). To confirm that this difference was gender and not age related, the subjects were divided into two age groups. No significant differences in spindle activity of the frontal channels were found between the groups. However, the interindividual spindle variability seemed to be at least as large as that stemming from gender.
Expression of Group I and II Metabotropic Glutamate Receptors in Trigeminal Neurons during Postnatal Development
Authors: Turman Jr. Jack E. , Hiyama Lauren , Castillo Marvin , Chandler Scott H.
Published: April 2003

Trigeminal motoneurons (Mo5), mesencephalic trigeminal neurons (Me5), supratrigeminal neurons (Su5), and intertrigeminal neurons (I5) are important constituents of the neural circuitry responsible for jaw movements. Glutamate neurotransmission, mediated by ionotropic and metabotropic glutamate receptors (mGluRs), is critical for the production of jaw movements. To better understand the role of mGluR-mediated modulation of these neurons during early postnatal development, we conducted a series of experiments to illustrate the ontogeny of mGluRs 1, 5 (group I) and mGluRs 2, 3 (group II) in Mo5, Me5, Su5, and I5 neurons using receptor immunohistochemistry. Results demonstrate that the temporal expression of mGluRs is differentially regulated between, and within these trigeminal nuclei. The localization of group I and II mGluRs in these nuclei suggests a role for these receptors in mediating glutamatergic neurotransmission in brainstem circuits responsible for oral-motor behaviors.
Serotonergic Heterotypic Sprouting in the Unilaterally Dopamine-Depleted Mouse Neostriatum
Authors: Yamazoe Ichiro , Takeuchi Yoshihiro , Matsushita Hiroko , Kawano Hisashi , Sawada Tadashi
Published: April 2003

The effects of unilateral 6-hydroxydopamine (6-OHDA) treatment on striatal serotonin neurons in 12-day-old mice were studied using immunohistochemistry. The unilateral 6-OHDA lesions were evaluated with tyrosine hydroxylase (TH) immunohistochemistry. The majority of the TH-immunoreactive structures disappeared from the substantia nigra and neostriatum on the 6-OHDA lesioned side. However, the density of serotonin fibers was markedly increased throughout the 6-OHDA-depleted neostriatum 1 year later. These results suggest that serotonergic heterotypic sprouting may be permanent.
Effect of Prenatal Exposure to Diazepam on Brain GABAA Receptor mRNA Levels in Rats Examined at Late Fetal or Adult Ages
Authors: Roberts Alice A. , Pleger Gloria L. , Kellogg Carol K.
Published: April 2003

This study tested the hypotheses that in utero exposure to diazepam (DZ): (1) exerts long-lasting effects on GABAA receptor function by altering GABAA receptor subunit mRNA levels in specific brain regions of adult animals and/or (2) alters GABAA subunit mRNA expression in exposed fetuses. We assayed levels of mRNAs encoding several of the most predominant GABAA receptor subunits as well as cyclophilin mRNA. Analysis of mRNA levels in the cortex in adults showed that only γ2S mRNA levels varied significantly with prenatal drug exposure, an effect unrelated to DZ action to the GABAA receptor. Analysis in fetuses indicated that mRNA levels varied as a function of both fetal sex and fetal drug environment. Irrespective of sex, DZ exposure increased both α1 and cyclophilin mRNAs in fetal brainstem whereas the mRNA levels of γ2S were increased and decreased, respectively, in the telencephalon and hypothalamus of DZ-exposed fetuses.
Sexually Dimorphic Effect of Glutamate Treatment on Cell Cycle Arrestment of Astrocytes from the Preoptic Area of Neonatal Rats
Authors: Hsu Chin , Hsieh Ya-Lun , Ho Mei-Ling , Hsu Hseng-Kuang , Yu John Yuh-Lin
Published: April 2003

Neurotoxicological studies have indicated that L-glutamate exhibits more pronounced effects on the preoptic area (POA) neurons of male rats than on those of females in the neonatal period. However, no information has previously been available as to whether or not such sexual dimorphism also exists for the effects of glutamate on astrocytes from POA. The present paper reports the differential effects of L-glutamate on astrocytes isolated from POA of neonatal male and female rats. The proliferation of astrocytes was measured by methods of cell count and cell cycle analysis. In addition, the activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) was assayed to understand its role in the glutamate-induced disturbance of the cell cycle progression of astrocytes. The results revealed that L-glutamate, at doses of 0.5 and 1.0 mM, inhibited the proliferation of astrocytes derived from male rats more severely than those derived from females. The L-glutamate treatment blocked the cell cycle progression and caused an accumulation of cells in the S phase. The activity of CaM kinase II declined more markedly in astrocytes derived from male rats than in those from females after glutamate treatment. These findings suggest that the proliferation of astrocytes derived from POA of neonatal rats can be inhibited in a sexually dimorphic manner by L-glutamate, possibly through blocking the cell cycle progression and partially related to the inactivation of the CaM kinase II.
Differential Response of Immature and Mature Neurons to Hypoxia in Rat Mesencephalic Cultures
Authors: Andreeva Nadejda , Heldt Julia , Leclere Norbert , Gross Johann
Published: April 2003

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 pO2 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.
Doppler Sonography of Vertebral Arteries in Adult Patients with Vertigo
Authors: Bakr Mohamed S. , Abd Elrazek Mohamed A. , Saleh Ezzat M. , Mostafa Mostafa M. , Ali Hassan M.
Published: April 2003

Objectives: The present study was designed to determine the value of the blood flow velocity and hemodynamic changes in the extracranial vertebral arteries in adults with vertigo by using color flow Doppler ultrasonography. Material and Methods: Ninety-six adult patients with vertigo without definite otogenic causes (clinically and audiologically normal) were investigated by color flow Doppler ultrasonography. Electronystagmography was done to correlate its findings with those of vertebral arteries Doppler blood flow (VABF). Results: A significantly slow VABF was reported in the vertigo group when compared with the control group. Velocity of vertebral artery in 54.2% cases showed abnormal findings: a laterality in 29.2% and a low circulatory velocity in 25%. In 66.6% of cases the findings of Doppler and Electronystagmography are in agreement. Conclusion: Doppler ultrasonography is a recent valuable tool which gives useful information on VABF in the diagnosis of dizzy patients especially those who are clinically and audiologically normal.
Promoter Methylation Status of the DNA Repair Genes hMLH1 and MGMT in Gastric Carcinoma and Metaplastic Mucosa
Authors: Oue Naohide , Sentani Kazuhiro , Yokozaki Hiroshi , Kitadai Yasuhiko , Ito Reiko , Yasui Wataru
Published: April 2003

Hypermethylation of CpG islands in the promoter region is associated with the silencing of a variety of tumor suppressor genes. DNA repair genes human Mut L homologue 1 (hMLH1) and O6-methylguanine-DNA methyltransferase (MGMT) have been shown to be hypermethylated in certain carcinomas. We studied DNA methylation of CpG islands in hMLH1 and MGMT in 50 gastric carcinomas and 10 intestinal metaplastic mucosa samples. We analyzed the methylation status of hMLH1 and MGMT using methylation-specific polymerase chain reaction and DNA sequencing analysis. We measured protein levels of hMLH1 using Western blot and immunohistochemical analysis. CpG island hypermethylation of hMLH1 and MGMT was detected in 11 (22%) and 8 (16%) of the 50 gastric tumors, respectively. Hypermethylation of the promoter was more common in intestinal-type gastric carcinomas than in poorly diffuse-type gastric carcinomas (p = 0.016 and 0.021, respectively; Fisher’s exact test). However, hMLH1 promoter hypermethylation did not coincide with MGMT promoter hypermethylation except in 1 patient. Hypermethylation of the hMLH1 promoter but not the MGMT promoter occurred in intestinal metaplastic mucosae. Immunohistochemical analysis revealed a corresponding reduction in hMLH1 protein expression in some of the intestinal metaplastic mucosae. Our results suggest that at least two types of promoter methylation participate in the development of gastric carcinoma. Tumor-specific promoter hypermethylation of hMLH1 may be an early event in carcinogenesis in the stomach.
Frequent mitotic errors in tumor cells of genetically micro-heterogeneous glioblastomas
Authors: Loeper S. , Romeike B.F.M. , Heckmann N. , Jung V. , Henn W. , Feiden W. , Zang K.D. , Urbschat S.
Published: April 2003

Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity as to both histomorphology and genetic changes, displaying a wide variety of numerical chromosome aberrations the most common of which are monosomy 10 and trisomy 7. Moreover, GBM in vitro are known to have variable karyotypes within a given tumor cell culture leading to rapid karyotype evolution through a high incidence of secondary numerical chromosome aberrations. The aim of our study was to investigate to what extent this mitotic instability of glioblastoma cells is also present in vivo. We assessed the spatial distribution patterns of numerical chromosome aberrations in vivo in a series of 24 GBM using two-color in situ hybridization for chromosomes 7/10, 8/17, and 12/18 on consecutive 6-µm paraffin-embedded tissue slides. The chromosome aberration patterns were compared with the histomorphology of the investigated tumor assessed from a consecutive HE-stained section, and with the in vitro karyotype of cell cultures established from the tumors. All investigated chromosomes showed mitotic instability, i.e., numerical aberrations within significant amounts of tumor cells in a scattered distribution through the tumor tissue. As to chromosomes 10 and 17, only monosomy occurred, as to chromosome 7 only trisomy/polysomy, apparently as a result of selection in favor of the respective aberration. Conversely, chromosomes 8, 12, and 18 displayed scattered patterns of monosomy as well as trisomy within a given tumor reflecting a high mitotic error rate without selective effects. The karyotypes of the tumor cell cultures showed less variability of numerical aberrations apparently due to clonal adaptation to in vitro conditions. We conclude that glioblastoma cells in vivo are characterized by an extensive tendency to mitotic errors. The resulting clonal diversity of chromosomally aberrant cells may be an important biological constituent of the well-known ability of glioblastomas to preserve viable tumor cell clones under adaptive stress in vivo, in clinical terms to rapidly recur after antitumoral therapy including radio- or chemotherapy.
PHF3 expression is frequently reduced in glioma
Authors: Fischer U. , Struss A.-K. , Hemmer D. , Michel A. , Henn W. , Steudel W.-I. , Meese E.
Published: April 2003

Glioblastoma is the most frequent brain tumor and accounts for approximately 50–60% of all astrocytic tumors. Many chromosome alterations have been described in glioblastoma, but only for a few alterations were the genes identified and linked to genetic pathways in glioblastoma development. To contribute to the identification of novel genes involved in glioblastoma development we used a combined immunological and molecular screening approach. Here we report the identification and expression analysis of a novel gene from human chromosome 6q12 that is considered to be the third member of a family of PHD finger containing genes and is termed PHF3. PHF3 is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastoma, glioblastoma cell lines, anaplastic astrocytomas and astrocytomas. The PHF3 protein sequence contains several protein motifs frequently found in transcription factors. One of those motifs is a PHD finger, also termed LAP motif and known to bind large portions of DNA. Another region of the protein revealed a high homology to the transcription factor TFIIS, especially to a region that is necessary for the Polymerase II binding properties of TFIIS. Combining these results, PHF3 is a novel member of a large class of regulatory proteins containing a LAP motif, and loss of its expression in glioblastoma may contribute to glioma development.
Diabetes mellitus and Outcome after Successful Percutaneous Coronary Revascularization: The Mayo Clinic Experience 1979–1998
Authors: Hasdai David , Rizza Robert A. , Grill Diane E. , Scott Christopher G. , Garratt Kirk N. , Holmes Jr. David R.
Published: April 2003

Objective: To examine whether the outcome of patients after successful percutaneous coronary revascularization is influenced by diabetic status. Design: Retrospective analysis of the Mayo Clinic PTCA Registry. Materials and Methods: We analyzed the occurrence of all-cause death and death/myocardial infarction among diabetic (n = 2,155) and nondiabetic patients (n = 9,354) after successful percutaneous coronary revascularization at Mayo Clinic from October 1979 through December 1998. Results: Of the 11,509 patients who underwent percutaneous coronary revascularization during the study period, 2,155 were diabetic at the time of their index percutaneous coronary revascularization. The clinical success rate was similar for the two groups (≈87%). Among the patients with clinically successful interventions, the median (25th, 75th interquartiles) time of follow-up was 3.1 (1.1, 6.1) years for diabetic patients and 4.3 (2.0, 8.2) years for nondiabetic patients (p < 0.001). Diabetes mellitus was associated with increased adjusted risk (95% confidence interval) of death (1.73 [1.54, 1.94]) and death/infarction (1.62 [1.46, 1.79]). Conclusions: Although diabetic and nondiabetic patients had similar clinical success rates for percutaneous coronary revascularization, diabetic patients had significantly worse long-term outcomes.