bluuebunny/crossref_metadata_2025 huggingface dataset:
PPARs in Alzheimer′s Disease
Authors: Kummer Markus P. , Heneka Michael T.
Published: July 2008

Peroxisome proliferator‐activated receptors (PPARs) are well studied for their peripheral physiological and pathological impact, but they also play an important role for the pathogenesis of various disorders of the central nervous system (CNS) like multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer′s, and Parkinson′s disease. The observation that PPARs are able to suppress the inflammatory response in peripheral macrophages and in several models of human autoimmune diseases lead to the idea that PPARs might be beneficial for CNS disorders possessing an inflammatory component. The neuroinflammatory response during the course of Alzheimer′s disease (AD) is triggered by the neurodegeneration and the deposition of the β‐amyloid peptide in extracellular plaques. Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been considered to delay the onset and reduce the risk to develop Alzheimer′s disease, while they also directly activate PPARγ. This led to the hypothesis that NSAID protection in AD may be partly mediated by PPARγ. Several lines of evidence have supported this hypothesis, using AD‐related transgenic cellular and animal models. Stimulation of PPARγ receptors by synthetic agonist (thiazolidinediones) inducing anti‐inflammatory, anti‐amyloidogenic, and insulin sensitising effects may account for the observed effects. Several clinical trials already revealed promising results using PPAR agonists, therefore PPARs represent an attractive therapeutic target for the treatment of AD.
PPAR Alpha Regulation of the Immune Response and Autoimmune Encephalomyelitis
Authors: Yang Yuhong , Gocke Anne R. , Lovett-Racke Amy , Drew Paul D. , Racke Michael K.
Published: July 2008

PPARs are members of the steroid hormone nuclear receptor superfamily and play an important role in the regulation of lipid metabolism, energy balance, artherosclerosis and glucose control. Recent studies suggest that they play an important role in regulating inflammation. This review will focus on PPAR‐α regulation of the immune response. We describe how PPAR‐α regulates differentiation of T cells by transactivation and/or interaction with other transcription factors. Moreover, PPAR‐α agonists have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in mice, suggesting that they could provide a therapy for human autoimmune diseases such as multiple sclerosis.
Human Aflatoxin Albumin Adducts Quantitatively Compared by ELISA, HPLC with Fluorescence Detection, and HPLC with Isotope Dilution Mass Spectrometry
Authors: McCoy Leslie F. , Scholl Peter F. , Sutcliffe Anne E. , Kieszak Stephanie M. , Powers Carissa D. , Rogers Helen S. , Gong Yun Yun , Groopman John D. , Wild Christopher P. , Schleicher Rosemary L.
Published: July 2008

Essential to the conduct of epidemiologic studies examining aflatoxin exposure and the risk of heptocellular carcinoma, impaired growth, and acute toxicity has been the development of quantitative biomarkers of exposure to aflatoxins, particularly aflatoxin B1. In this study, identical serum sample sets were analyzed for aflatoxin-albumin adducts by ELISA, high-performance liquid chromatography (HPLC) with fluorescence detection (HPLC-f), and HPLC with isotope dilution mass spectrometry (IDMS). The human samples analyzed were from an acute aflatoxicosis outbreak in Kenya in 2004 (n = 102) and the measured values ranged from 0.018 to 67.0, nondetectable to 13.6, and 0.002 to 17.7 ng/mg albumin for the respective methods. The Deming regression slopes for the HPLC-f and ELISA concentrations as a function of the IDMS concentrations were 0.71 (r2 = 0.95) and 3.3 (r2 = 0.96), respectively. When the samples were classified as cases or controls, based on clinical diagnosis, all methods were predictive of outcome (P < 0.01). Further, to evaluate assay precision, duplicate samples were prepared at three levels by dilution of an exposed human sample and were analyzed on three separate days. Excluding one assay value by ELISA and one assay by HPLC-f, the overall relative SD were 8.7%, 10.5%, and 9.4% for IDMS, HPLC-f, and ELISA, respectively. IDMS was the most sensitive technique and HPLC-f was the least sensitive method. Overall, this study shows an excellent correlation between three independent methodologies conducted in different laboratories and supports the validation of these technologies for assessment of human exposure to this environmental toxin and carcinogen. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1653–7)
Mathematical Modeling of Folate Metabolism: Predicted Effects of Genetic Polymorphisms on Mechanisms and Biomarkers Relevant to Carcinogenesis
Authors: Ulrich Cornelia M. , Neuhouser Marian , Liu Amy Y. , Boynton Alanna , Gregory Jesse F. , Shane Barry , James S. Jill , Reed Michael C. , Nijhout H. Frederik
Published: July 2008

Low-folate status and genetic polymorphisms in folate metabolism have been linked to several cancers. Possible biological mechanisms for this association include effects on purine and thymidine synthesis, DNA methylation, or homocysteine concentrations. The influence of genetic variation in folate metabolism on these putative mechanisms or biomarkers of cancer risk has been largely unexplored. We used a mathematical model that simulates folate metabolism biochemistry to predict (a) the effects of polymorphisms with defined effects on enzyme function (MTHFR and TS) and (b) the effects of potential, as-of-yet-unidentified polymorphisms in a comprehensive set of folate-metabolizing enzymes on biomarkers and mechanisms related to cancer risk. The model suggests that there is substantial robustness in the pathway. Our predictions were consistent with measured effects of known polymorphisms in MTHFR and TS on biomarkers. Polymorphisms that alter enzyme function of FTD, FTS, and MTCH are expected to affect purine synthesis, FTS more so under a low-folate status. In addition, MTCH polymorphisms are predicted to influence thymidine synthesis. Polymorphisms in methyltransferases should affect both methylation rates and thymidylate synthesis. Combinations of polymorphisms in MTHFR, TS, and SHMT are expected to affect nucleotide synthesis in a nonlinear fashion. These investigations provide information on effects of genetic polymorphisms on biomarkers, including those that cannot be measured well, and highlight robustness and sensitivity in this complex biological system with regard to genetic variability. Although the proportional changes in biomarkers of risk with individual polymorphisms are frequently small, they may be quite relevant if present over an individual's lifetime. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1822–31)
The hOGG1 Ser326Cys Polymorphism and Lung Cancer Risk: A Meta-analysis
Authors: Li Haixin , Hao Xishan , Zhang Wei , Wei Qingyi , Chen Kexin
Published: July 2008

The potentially functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase (hOGG1) gene has been implicated in lung cancer risk, but published studies have mixed findings. To summarize published data, we did a comprehensive meta-analysis. Two investigators extracted data independently from 17 case control studies published in the PubMed using the search phrases “hOGG1/OGG1/OGG and polymorphism/genetic variation and lung cancer.” The meta-analysis included 6,375 cancer cases and 6,406 control subjects. The results showed that individuals carrying the hOGG1 Cys/Cys genotype did not have significantly increased risk of lung cancer [odds ratios (OR), 1.15; 95% (confidence interval) CI, 0.94-1.41] compared with those with the Ser/Ser genotype; similarly, no significant association with lung cancer risk was found either in the recessive (OR, 1.09; 95% CI, 0.90-1.32 for Cys/Cys versus Ser/Cys+Ser/Ser) or dominant model of the Ser326 allele (OR, 1.06; 95% CI, 0.93-1.21 for Cys/Cys+Ser/Cys versus Ser/Ser). However, significantly increased risks were found among Asian subjects (OR, 1.18; 95% CI, 1.01-1.38 for Cys/Cys+Ser/Cys versus Ser/Ser) in a dominant model. In stratified analyses by control source, compared with the Ser/Ser genotype, lung cancer risk associated with the hOGG1 Cys/Cys genotype was significantly increased in population-based studies (OR, 1.32; 95% CI, 1.04-1.67) but not in hospital-based studies (OR, 1.18; 95% CI, 0.98-1.42); in stratified analyses by the smoking status, however, the increased risk was observed only among nonsmokers in a dominant model (OR, 1.32; 95% CI, 1.04-1.67). The meta-analysis suggested that a careful matching should be considered in future larger genetic association studies including multiple ethnic groups. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1739–45)
Breast Density Assessment in Adolescent Girls Using Dual-Energy X-ray Absorptiometry: A Feasibility Study
Authors: Shepherd John A. , Malkov Serghei , Fan Bo , Laidevant Aurelie , Novotny Rachel , Maskarinec Gertraud
Published: July 2008

Breast density, the radiographically opaque fraction of the breast in a mammogram, is one of the strongest biomarkers of breast cancer risk. However, younger populations do not typically have mammograms due to radiation concerns. This study explored a commercially available dual-energy X-ray absorptiometer (DXA) system as a low-dose method to measure breast fibroglandular density in adolescent girls. Eighteen girls (13-14 years old) indicated their breast development according to Tanner and underwent three dedicated DXA scans, two of their left and one of their right breasts. Total projected breast area was manually delineated on each image and percent fibroglandular volume density (%FGV), absolute fibroglandular volume (FGV), total breast area, and volume were computed. It was possible to image breasts representing all five Tanner stages; %FGV ranged from 31.9% to 92.2% with a mean of 71.1 ± 14.8%, whereas FGV ranged from 80 to 270 cm3 with a mean of 168 ± 54 cm3. Left and right breast %FGV were highly correlated (rp = 0.97, P < 0.0001) and of the same magnitude (P = 0.18). However, left total volume and FGV were larger than the right by 38 cm3 (P = 0.04) and 19 cm3 (P = 0.02), respectively. Total volume and FGV increased by Tanner stage, whereas %FGV did not. Our method had excellent precision for %FGV and moderate precision for FGV (root mean square SDs of 2.4% and 16.6 cm3). These pilot data indicate that dedicated DXA breast scans may be useful in studies exploring breast density in girls. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1709–13)
A Phase I and Pharmacokinetic Study of Lapatinib in Combination with Letrozole in Patients with Advanced Cancer
Authors: Chu Quincy S.C. , Cianfrocca Mary E. , Goldstein Lori J. , Gale Meg , Murray Nicholas , Loftiss Jill , Arya Nikita , Koch Kevin M. , Pandite Lini , Fleming Ronald A. , Paul Elaine , Rowinsky Eric K.
Published: July 2008

Purpose: The main objectives of this phase I and pharmacokinetic, open-label study were to determine the optimally tolerated regimen (OTR), safety, pharmacokinetics, and clinical activity of lapatinib in combination with letrozole in patients with advanced solid malignancies.

Experimental Design: Patients with advanced breast cancer with immunohistochemically detectable estrogen or progesterone receptors or other cancers were eligible. Doses of lapatinib were escalated in cohorts of three subjects from 1,250 to a maximum of 1,500 mg/d based on dose-limiting toxicities in the first treatment cycle. The letrozole dose was fixed at 2.5 mg/d. Additional patients were enrolled at the OTR dose level to further evaluate safety and for pharmacokinetic analyses.

Results: Thirty-nine patients were enrolled in the study: 12 in the dose-escalation group, 7 in the OTR safety group, and 20 in the pharmacokinetic group. The OTR dose level was identified as 1,500 mg/d lapatinib and 2.5 mg/d letrozole. The most common (>25% of patients) drug-related adverse events were diarrhea (77%), rash (62%), nausea (46%), and fatigue (26%). No significant differences were observed in the pharmacokinetic variables (Cmax and AUC) of lapatinib and letrozole when coadministered compared with single-agent administration. One patient with endometrial cancer had a confirmed partial response.

Conclusions: Clinically relevant doses of lapatinib in combination with letrozole were well tolerated and did not result in a pharmacokinetic interaction, and clinical antitumor activity was observed.
Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel
Authors: Galmarini Carlos M. , Treilleux Isabelle , Cardoso Fatima , Bernard-Marty Chantal , Durbecq Virginie , Gancberg David , Bissery Marie-Christine , Paesmans Marianne , Larsimont Denis , Piccart Martine J. , Di Leo Angelo , Dumontet Charles
Published: July 2008

Purpose: To evaluate the role of microtubule-associated variables as potential predictors of response and clinical outcome in patients with advanced breast cancer receiving single-agent docetaxel or doxorubicin chemotherapy.

Experimental Design: The analysis was done on 173 tumor samples from patients with locally advanced or metastatic breast cancer who have participated in the TAX-303 phase III trial in which patients were randomly assigned to receive docetaxel or doxorubicin. Expression of total α- and β-tubulin, classes II to IV β-tubulin isotypes, and τ protein was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded tumors from the primary breast cancer.

Results: We observed that patients with “high” expression of class III β-tubulin isotype had a higher probability of response to docetaxel than to doxorubicin treatment (odds ratio, 1.9; 95% confidence interval, 1.01-3.7; P = 0.05). No difference was observed in terms of time to progression or in terms of overall survival.

Conclusions: This study suggests that the superiority of docetaxel over doxorubicin seems to be confined to the subgroup of patients with “high” expression of class III β-tubulin isotype.
Dual Tyrosine Kinase Inhibitor for Focal Adhesion Kinase and Insulin-like Growth Factor-I Receptor Exhibits Anticancer Effect in Esophageal Adenocarcinoma In vitro and In vivo
Authors: Watanabe Nobuyuki , Takaoka Munenori , Sakurama Kazufumi , Tomono Yasuko , Hatakeyama Shinji , Ohmori Osamu , Motoki Takayuki , Shirakawa Yasuhiro , Yamatsuji Tomoki , Haisa Minoru , Matsuoka Junji , Beer David G. , Nagatsuka Hitoshi , Tanaka Noriaki , Naomoto Yoshio
Published: July 2008

Purpose: Focal adhesion kinase (FAK) regulates integrin and growth factor–mediated signaling pathways to enhance cell migration, proliferation, and survival, and its up-regulation correlates malignant grade and poor outcome in several types of cancer. In this study, we aimed to raise a potential therapeutic strategy using a FAK inhibitor for Barrett's esophageal adenocarcinoma.

Experimental Design: The expression status of FAK in clinical Barrett's esophageal adenocarcinoma tissues was determined by immunohistochemistry. Cultured esophageal adenocarcinoma cells were treated with TAE226, a specific FAK inhibitor with an additional effect of inhibiting insulin-like growth factor-I receptor (IGF-IR), to assess its anticancer effect in vitro. Western blot was carried out to explore a participating signaling pathway for TAE226-induced cell death. Furthermore, TAE226 was orally administered to s.c. xenograft animals to investigate its anticancer effect in vivo.

Results: Strong expression of FAK was found in 94.0% of Barrett's esophageal adenocarcinoma compared with 17.9% of Barrett's epithelia, suggesting that FAK might play a critical role in the progression of Barrett's esophageal adenocarcinoma. When esophageal adenocarcinoma cells were treated with TAE226, cell proliferation and migration were greatly inhibited with an apparent structural change of actin fiber and a loss of cell adhesion. The activities of FAK, IGF-IR, and AKT were suppressed by TAE226 and subsequent dephosphorylation of BAD at Ser136 occurred, resulting in caspase-mediated apoptosis. In vivo tumor volume was significantly reduced by oral administration of TAE226.

Conclusions: These results suggest that TAE226, a dual tyrosine kinase inhibitor for FAK and IGF-IR, could become a new remedy for Barrett's esophageal adenocarcinoma.
Analysis of Overall Survival in Patients with Nonmetastatic Castration-Resistant Prostate Cancer Treated with Vaccine, Nilutamide, and Combination Therapy
Authors: Madan Ravi A. , Gulley James L. , Schlom Jeffrey , Steinberg Seth M. , Liewehr David J. , Dahut William L. , Arlen Philip M.
Published: July 2008

Purpose: We reported previously the first randomized study of any kind in patients with nonmetastatic, castrate-resistant prostate cancer. The study employed vaccine, the hormone nilutamide, and the combined therapy (crossover for each arm) with an endpoint of time to progression. We now report survival analyses at 6.5 years from the initiation of therapy with a median potential follow-up of 4.4 years.

Experimental Design: Forty-two patients were randomized to receive either a poxvirus-based prostate-specific antigen (PSA) vaccine or nilutamide. Patients in either arm who developed increasing PSA without radiographic evidence of metastasis could cross over to receive the combined therapies.

Results: Median survival among all patients was 4.4 years from date of enrollment. Median survival exhibited a trend toward improvement for patients initially randomized to the vaccine arm (median, 5.1 versus 3.4 years; P = 0.13). Starting from the on-study date, the retrospectively determined subset of 12 patients who initially received vaccine and then later received nilutamide suggested improved survival compared with the 8 patients who began with nilutamide and subsequently were treated with vaccine (median, 6.2 versus 3.7 years; P = 0.045). A subgroup analysis of patients randomized to the vaccine arm versus the nilutamide arm showed substantial improvements in survival if at baseline patients had a Gleason score <7 (P = 0.033) and PSA <20 ng/dL (P = 0.013) or who had prior radiation therapy (P = 0.018).

Conclusions: These data indicate that patients with nonmetastatic castration-resistant prostate cancer (D0.5) who receive vaccine before second-line hormone therapy may potentially result in improved survival compared with patients who received hormone therapy and then vaccine. These data also suggest that patients with more indolent disease may derive greater clinical benefit from vaccine alone or vaccine before second-line hormone therapy compared with hormone therapy alone or hormone therapy followed by vaccine. These findings have potential implications for both the design and endpoint analysis of larger vaccine combination therapy trials.
Ixabepilone in Combination with Capecitabine and as Monotherapy for Treatment of Advanced Breast Cancer Refractory to Previous Chemotherapies
Authors: Lechleider Robert J. , Kaminskas Edvardas , Jiang Xiaoping , Aziz Robeena , Bullock Julie , Kasliwal Ravindra , Harapanhalli Ravi , Pope Sarah , Sridhara Rajeshwari , Leighton John , Booth Brian , Dagher Ramzi , Justice Robert , Pazdur Richard
Published: July 2008

Purpose: To describe the considerations leading to marketing approval of ixabepilone in combination with capecitabine and as monotherapy for the treatment of advanced breast cancer that is refractory to other chemotherapies.

Experimental Design: Data from one randomized multicenter trial comparing combination therapy with ixabepilone and capecitabine to capecitabine alone were analyzed for support of the combination therapy indication. For monotherapy, a single-arm trial of ixabepilone was analyzed. Supporting data came from an additional single-arm combination therapy study and two single-arm monotherapy studies.

Results: In patients with metastatic or locally advanced breast cancer who had disease progression on or following an anthracycline and a taxane, ixabepilone plus capecitabine showed an improvement in progression-free survival compared with capecitabine alone {median progression-free survival, 5.7 [95% confidence interval (95% CI), 4.8-6.7] versus 4.1 (95% CI, 3.1-4.3) months, stratified log-rank P < 0.0001; hazard ratio, 0.69 (95% CI, 0.58-0.83)}. As monotherapy for patients who had disease progression on or following an anthracycline, a taxane, and capecitabine, ixabepilone as monotherapy showed a 12% objective response rate by independent blinded review and 18% by investigator assessment. The major toxicities from ixabepilone therapy were peripheral neuropathy and myelosuppression, particularly neutropenia.

Conclusions: On October 16, 2007, the Food and Drug Administration approved ixabepilone for injection in combination with capecitabine or as monotherapy for the treatment of patients with advanced breast cancer who have experienced disease progression on previous chemotherapies.
Therapeutic Options Against BCR-ABL1 T315I-Positive Chronic Myelogenous Leukemia
Authors: Quintás-Cardama Alfonso , Cortes Jorge
Published: July 2008

Despite the efficacy of imatinib therapy in chronic myelogenous leukemia, the development of resistance continues to challenge the treatment of this disease. Mutations within the kinase domain of BCR-ABL1 constitute the most frequent mechanism of resistance in patients with chronic myelogenous leukemia treated with imatinib or the second generation tyrosine kinase inhibitors nilotinib and dasatinib. Of particular concern is the substitution of the threonine residue at the highly conserved gatekeeper residue 315 with a bulkier hydrophobic isoleucine amino acid. This mutation causes steric hindrance precluding the access ATP-competitive inhibitors to the ATP-binding pocket. To expedite the identification of strategies to override the resistance imposed by the T315I mutation, several strategies have been pursued, including the exploitation of BCR-ABL1 kinase sites distant from the ATP-binding pocket to cripple the kinase activity of the enzyme and inhibiting signaling pathways downstream from BCR-ABL1. Recent insights gained regarding the structural biology of T315I have led to the development of a variety of compounds against this mutant. We herein summarize the most clinically promising anti-T315I therapies.
RLIP76 and Cancer
Authors: Awasthi Sanjay , Singhal Sharad S. , Awasthi Yogesh C. , Martin Bryan , Woo Jung-Hee , Cunningham C. Casey , Frankel Arthur E.
Published: July 2008

RLIP76 is a multifunctional membrane protein that transports glutathione conjugates of electrophilic compounds and other xenobiotics including chemotherapy agents out of cells. The protein is overexpressed in lung carcinomas, ovarian carcinomas, and melanomas. The protein also binds Ral and participates in mitotic spindle function, clathrin-dependent endocytosis, and triggers GTPase-activating protein activity. It is found throughout the cell, in membrane, cytosol, and the nucleus, and is known to shift between these compartments in response to stress. Loss of RLIP76 by antibody or antisense therapy is associated with increased sensitivity to radiation and chemotherapy. Conversely, liposomally delivered RLIP may treat poisoning and wounds.
Effect of Proteinase Inhibitors on Rabbit Uterine Ultrastructure
Authors: Lescoat D.
Published: July 2008

Rabbit uterine epithelium was examined by electron microscopy after treatment with two proteinase inhibitors, aprotinin and antipain, administered as a single injection. Both compounds had similar effects, those of antipain being slighter. After treatment, uterine epithelium showed an increased number of very enlarged cells. Lateral cell membranes were often brocken off; basal cell membrane and basement membrane integrities are impaired. The possible interference of the system proteinase-proteinase inhibitors with the implantation process was discussed.
Development and Morphology of Rat Synovial Membrane
Authors: Stofft E. , Effendy W.
Published: July 2008

The development of the knee joint and synovial membrane in Wistar rats was studied from the 13th fetal day until adulthood by means of light microscopy, transmission electron microscopy and scanning electron microscopy. Using acid phosphatase and peroxidase methods, the different cell types of synovial membrane could be identified.
Modification of Bone Formation Rate by Growth Hormone, Melanocyte-Stimulating Hormone, and Cortisone in the Normal Rat
Authors: Aspenberg Per , Hansson Lars Ingvar , Thorngren Karl-Göran
Published: July 2008

Bone growth and remodelling was studied in rats after injection of growth hormone, melanocyte-stimulating hormone (α-MSH), and cortisone daily for 20 days with tetracycline as intravital marker. An increase of both longitudinal and periosteal growth with growth hormone was found. A decrease of both was found after a high cortisone dose. Lower cortisone doses seem to have stimulated periosteal growth. No effect of α-MSH was found.
Long-Term Effect of Somatostatin 14 on Mouse Stomach, Antrum, Intestine and Exocrine Pancreas
Authors: Senegas-Balas F. , Balas D. , Pradayrol L. , Laval J. , Bertrand C. , Ribet A.
Published: July 2008

Mice were injected 3 times a day for 12 days with 8 µg/kg of somatostatin 14 which caused ahypoplasia of parietal and goblet cells, a hypotrophy and hypofunctionality of pancreatic acinar cells with a decrease in lipase and chymotrypsin activities, a decrease in the secretory function of the Brunner gland and in the number of dark granules of G cells. Neither villous and microvillous areas nor brush border hydrolase activities were affected. The number of peptic cells and Paneth cells increase as the level of pepsin and lysozyme. Mice were injected 4 times per hour with 2 µg/kg of somatostatin. 2 h after the first injection of somatostatin and 90 min after a single injection of tritiated thymidine, fundic, antral, jejunal and ileal labelling indexes strongly decrease (maximal effect in ileum). The inhibitory effect of somatostatin on the digestive epithelial cell proliferation compared to its long-term action only directed on specific cell types evokes probable compensatory mechanisms induced to maintain the equilibrium of the digestive epithelia.
Sur l’artère cérébelleuse inférieure postérieure
Authors: Jeličić N. , Draganić V. , Jovanović S.
Published: July 2008

The posterior inferior cerebellar artery has a curved course in the region of the medulla oblongata. Besides its frequent individual variations, this vessel exhibits three morphological types: in type 1 (the commonest type, i.e. more than 50% of the cases) it curves with its vertex turned upwards; in type 2, the posterior inferior cerebellar artery turns in a gentle arch on to the posterior surface of the medulla oblongata, so there is no real curve; in type 3, the posterior inferior cerebellar artery curves but its vertex turns downwards. In all of these cases, the artery is in close relationship with the last four cranial nerves. This relationship is most characteristic in the 1st and 3rd types. The morphological types could be recognised on the angiograms
Growth-Depressing Effects of Alcohol and Nicotine in Two Strains of Rats
Authors: Riesenfeld Alphonse
Published: July 2008

Inbred Buffalo and Fisher rats were submitted to daily treatment with alcohol and nicotine for a period of 6 months. Alcohol treatment was pre- and postnatal, nicotine treatment postnatal only. All parameters of bone length and weight were depressed in both experiments in spite of the continuous growth of the rats. Although the level of depression was greater in some areas than in others, a clear target area applicable to both sexes and strains could not be found. Fisher and Buffalo females tolerated nicotine better than males. Buffalo rats showed a greater tolerance to alcohol than Fisher rats, and males tolerated alcohol better than females. This was particularly evident in pregnant rats: whereas all alcohol-treated Fisher embryos were stillborn, some of their Buffalo counterparts survived. This is most likely due to the lesser bone robusticity of Fisher over Buffalo rats and resorption of the fetal bones in Fisher embryos resulting from the decalcifying effect of alcohol.
Regression of the Corpus luteum of Pregnancy following Parturition in the Ewe
Authors: O’Shea J.D. , Wright P.J.
Published: July 2008

Corpora lutea (CL) of pregnancy from single-lambing ewes were examined by light and electron microscopy within 24 h and at 8, 15, 23, 31 and 41 days after parturition (2 ewes per stage). Within 24 h of parturition the structure of the CL was well preserved and both large and small luteal cells, characteristic of this species, were present in substantial numbers. However, both types of luteal cell contained numerous cytoplasmic lipid droplets, and smooth endoplasmic reticulum and secretory granules in large luteal cells were less prominent than in normal functional CL of cyclic ewes. Leucocytic infiltration, and death of some luteal and endothelial cells, were also observed at this stage. Further regression of the CL progressed slowly, and lipid-rich large luteal cells were still readily recognisable 15 days after parturition. The size of the CL declined progressively, and the proportion of tissue occupied by intercellular substances increased. Corpora albicantia = 3–4 mm in diameter were still recognisable 41 days after parturition. It was concluded that luteal regression post partum progresses much less rapidly than at the end of the oestrous cycle.
A Peculiar Arteriovenous Leptomeningeal Complex in the Guinea Pig
Authors: Azzarelli Biagio , Muller Jans , Maguire Nancy , Goheen Michael
Published: July 2008

In most areas of the body, arteries and veins run close together, often sharing a common connective tissue sheath. One exception to this is observed in the brain, where arteries come in from the base and veins collect over the convexity. Classically the larger blood vessels are formed by three coats: intima, media, and adventitia. Leptomeningeal vessels are further reinforced by a monolayer of pial cells. In the guinea pig, however, above the corpus callosum we found a group of blood vessels (an artery and several veins) enclosed in a common leptomeningeal sheath. The artery arises at the confluence of the anterior cerebral arteries; the veins drain into the straight sinus. The epithelial nature of the sheath is evident by the close apposition of cell membranes, the presence of junctional devices, and the existence of a basal lamina. The ultrastructural features of this epithelium are similar to those of the arachnoid-dural membrane. Whether this peculiar vascular complex has any specific function needs to be investigated further.The presence of these vessels apparently ‘isolated’ within a leptomeningeal subcompartment may provide a suitable model to study vascular-extravascular-cerebrospinal fluid substance exchange.
Terminals of Intralaminar Thalamic Neurons in the Pallidum externum of Saimiri sciureus
Authors: Lee B.H. , Hassler R.G. , Chung Y.W. , Hasegawa Y. , Nitsch F.M.
Published: July 2008

Stereotactic coagulations of intralaminar thalamic nuclei in 6 squirrel monkeys Saimiri sciureus produced dark degenerations only of type IV synapses in pallidum externum, according to the classification of Hassler and Chung often preserving the slightly asymmetric contact and subsynaptic densities. Other type IV boutons underwent semidark degeneration, whereas others showed crystalloid degeneration. Some of type IV boutons show the deposition of many dense core vesicles and mitochondria with loss of most synaptic vesicles. Enlarged type IV boutons are sometimes overcrowded with irregularly shaped lysosomes. Thus, a monosynaptic connections of intralaminar thalamic nuclei to pallidum externum could be demonstrated.
Variations in the Method of the Division of the Hypoglossal Canal in Sienese Skulls of Known Age and Sex
Authors: Bastianini A. , Guidotti A. , Hauser G. , De Stefano G.F.
Published: July 2008

In 300 Sienese skulls of known age and sex (146 male and 154 female) 6 modes of expression of bipartition of the hypoglossal canal were studied on the basis of a new scheme of notation that takes into account gradually increasing intensity. The analysis of data, including also the traditional method of notation confirms the criticisms expressed by various authors on the loss of information when the variability of this trait is neglected, especially with reference to age-dependent changes (hyperostotic effects).
Functional Aspects of Ano-Rectal Vascularity
Authors: Foster Michael E. , Lancaster John F. , Leaper David J.
Published: July 2008

The blood supply of the ano-rectum has been studied in cadaveric specimens by angiographic methods. The vascular anastomosis between the middle rectal and superior rectal vessels was found to be demonstrable on one side only. There appears to be a midline paucity of vessels in both the posterior and anterior rectal walls, and this may be important in the aetiology of anastomotic dehiscence in low anterior resection.
Cell Types of the Pars distalis of the Hedgehog (Erinaceus europaeus L.) Adenohypophysis: Cytological, Immunocytochemical and Ultrastructural Studies
Authors: Girod C. , Lhéritier M. , Trouillas J. , Dubois M.P.
Published: July 2008

Staining and histochemical methods, immunofluorescence and electron microscopy were used to individualize the opiocorticomelanotropic cells in the adenohypophysis of the non-hibernating hedgehog. One cell type was differentiated; its characteristics at the electron-microscopic level were presented. Immunofluorescence has confirmed the functional significance of this cell type and the validity of the denomination ‘opiocorticomelanotropic cells’.
Embryonal Hypermobility and Articular Development
Authors: Ruano-Gil D. , Nardi-Vilardaga J. , Teixidor-Johé A.
Published: July 2008

This investigation was devised to correlate development of the articular system of the embryo with variations of motility by introducing reserpine to chick embryos at a Hamburger-Hamilton stage 25–26. Administration of reserpine was followed by hypermotihty or paralysis in a dose-dependent fashion. Size of joint cavities varies with motility of the limbs. Larger than normal cavities are due to excess movements, while lack of these impedes differentiation. These data are consistent with the primary role of motility in articular development.
Architecture of the Human Gastrocnemius Muscle and Some Functional Consequences
Authors: Huijing P.A.
Published: July 2008

Measurements were performed on the m. gastrocnemius of eight human cadavers in order to describe, in some detail, the architecture of the muscle and its heads. The fibres of the lateral head contain more sarcomeres than those of the medial head. The effect of this difference on the length-force curve of the muscle, calculated with a planimetric muscle model, is diminished by the effect of the difference of fibre angle with respect to the line of pull of the muscle. Within the heads some variation of the number of sarcomeres of the proximal and distal fibres occurs in all muscles. In the lateral head the distal fibres contain fewer sarcomeres than the proximal fibres. In the medial head this is also found in some heads, while others show the reverse. In the lateral head the longer fibres have smaller angles of attachement to the tendon plate and vice versa, while in the medial heads this relationship is only found occasionally. Some variation in the number of sarcomeres is found in the fibres of one bundle. The effects of variations in the number of sarcomeres on the length-force curve are probably insignificant at greater muscle lengths, but may have some importance for the individual with relatively small muscle lengths.
Comparison of the Effects of Barbiturate and Ethanol Given to Neonates on the Cerebellar Morphology
Authors: Yanai Joseph , Waknin Sion
Published: July 2008

Previous studies from different laboratories have suggested that neonatal exposure to barbiturate and ethanol induces long-term changes in cerebellar morphology. The present study was designed to compare in similar conditions the effect of neonatal exposure to maximal doses of barbiturate or ethanol on cerebellar morphology. Phenobarbital was administered via daily injections of 50 mg/kg on neonatal days 2–21 (B group). Ethanol was similarly administered in doses of 3 g/kg (E3g) and the submaximal dose of 2 g/kg (E2g). At age 50 days, the cerebella of treated and control offspring were subjected to histological analysis. The sagittal areas of the cerebellar layers were similarly reduced compared to controls in both B and E3g groups. In addition, B and E3g groups exhibited a similar deficit in the number of the cerebellar Purkinje and granule neurons. As barbiturate and E3g, a submaximal dose of ethanol (B2g) induced a deficit in the number of cerebellar Purkinje cells. However, it did not affect the granule cells and the area of the cerebellar layers. The results suggest that under standardized conditions, barbiturate and ethanol have a similar potent neurotoxic effect on the cerebellum. That is, they both impair the development of the cerebellar layers to a similar extent and destroy neurons even after they have already formed.
Morphometry of Monocytes of Human Blood
Authors: Sokol R.J. , James N.T. , Wales J. , Hudson G.
Published: July 2008

Morphometric methods have been used to analyse the ultrastructural characteristics of human blood monocytes in 20 normal adults. Data were obtained relating to whole cell, nucleus and mitochondria and, using a method not previously applied to blood cells, for the distribution of heterochromatin and euchromatin. The results provide a normal baseline against which monocyte changes in disease can be assessed.
Effects of Pilocarpine Treatment and of Electrical Stimulation of the Vagus Nerve on the Rat Parathyroid Gland, with Special Reference to the Alteration of Storage Granules
Authors: Setoguti Takao , Inoue Yasuhisa , Shin Masashi , Matsumura Hidekatsu
Published: July 2008

Effects of pilocarpine treatment and of electrical vagal stimulation on the rat parathyroid were studied ultrastructurally. The number of type I storage granules with a narrow halo (NSG-I) and hat of type II storage granules having a wide halo (NSG-II) were calculated. After pilocarpine treatment, NSG-I gradually decreased and reached a minimum at 30 min; in contrast, NSG-II gradually increased and reached a maximum at 20 min, but thereafter it slightly decreased and instead vacuolar bodies increased. Excluding these alterations, the ultrastructure of parenchymal cells showed no remarkable changes. Electrical vagal stimulation furthermore confirmed these results. Acid phosphatase activity was occasionally found in storage granules of both types in control and experimental rats. It was concluded that storage granules normally may be transformed from type I into type II and finally into vacuolar bodies as a result of hydrolysis, and that these processes may be accelerated by parasympathetic stimulation.
Constant Number of Immunogloblin G Positive Plasma Cells around the Penicilli in Murine Spleen with Increasing Age
Authors: Shimizu Kiyoshi , Honda Kyoko , Hokano Masami
Published: July 2008

The splenic lymphoid tissue of mice reared in a conventional environment regressed with increasing age. Immunogloblin G positive plasma cells gathered along the peniciUi in the senile spleen as well as in the adult control spleen. The number of plasma cells around the peniciUi showed no difference in the senile spleen as compared to the adult spleen. Since mature plasma cells remain in the lymph node for a short time only and seldom divide there, our results indicate that the transformation from B lymphocyte to plasma cell is not affected by age.
Radioautographic Study of Glycoprotein Synthesis and Migration in the Major Sublingual Gland of the Mongolian Gerbil (Meriones unguiculatus)
Authors: Klenk Eckhard , Korfsmeier Karl-Hermann
Published: July 2008

Intracellular glycoprotein synthesis and migration in the major sublingual gland of the Mongolian gerbil were studied with light-microscopic radioautography, using L-4, 5-[¾]-leucine, Z)-l-[3H]-glucose and N-[3H]-acetyl-D-mannosamine as precursors. The time elapsed from the beginning of the synthesis of the secretion products to their release was longer in the mucous acinar cells than in any other exocrine cell investigated until now. A slow addition of the terminal sugars (especially sialic acid) to the glycoprotein molecule and a prolonged storage of the glycoproteins in the apical granules were assumed to be the reasons for this delay in schedule. The secretion in the serous demilune cells was much faster than in the mucous acinar cells. The lack of uptake of labelled mannosamine showed that the demilunes are likely to produce substances different from those of the mucous acinar cells, presumably a protein-rich material with a high turnover.
Relationship between Characteristics of Immunoreactive LH/FSH Cells and the Levels of Gonadotropin in the Female Rat
Authors: Nakamura Fumio , Taya Kazuyoshi , Sasamoto Shuji , Yoshimura Fujio
Published: July 2008

Morphological and functional changes of pituitary LH/FSH cells in the female rat were investigated using the parameters on the radioimmunoassay, immunohistochemistry and ultrastructure. Changes in immuno-stainability, populations of intensely immunostained LH and FSH cells and total volume of secretory granules were correlated with the changes in pituitary LH and FSH contents during the estrous cycle. The immunohistochemical feature of gonadotropin release is the transformation of intensely immunostained gonadotrophs into the weakly stained ones. Secretory granules of small diameter (less than 150 nm) were numerous just before LH and FSH surges then sharply declined along with LH and FSH surges. The number of secretory granules of large diameter (larger than 150 nm) also decreased when LH and FSH surges took place. Then the number increased progressively until 17.00 h on the day of diestrus, corresponding to the increase in pituitary LH and FSH contents. It is suggested that small secretory granules are a release pool while large ones are a reserve pool.
Histological Markers of Solid Cell Nests of the Thyroid
Authors: Harach H. Rubén
Published: July 2008

It was recently demonstrated that C cells, mucosubstances, and the intermediate filament epidermal keratin are present in solid cell nests (SCN) of the thyroid. The reliability and usefulness of these markers in detecting these ultimobranchial nests have, so far, not been comparatively investigated. In the light of this, a study for the presence of these tracers in SCN at different stages of postnatal life was undertaken. The existence of carcinoembryonic antigen (CEA) in this gut-derived tissue was also searched for. Epidermal keratin was present in the epidermoid-like cells from all SCN studied; calcitonin-immunoreactive C cells and mucosubstances did not always occur. These findings reveal that this cytokeratin would remain as a potential marker to detect and trace back the ultimobranchial tissue component of the thyroid in earlier stages of development. The presence of CEA in practically all SCN surveyed would further support the view that they originate in the gut. This antigen would also be of great value for histological identification of these nests. The usefulness of these markers for the interpretation of the histogenesis of some ultimobranchial-related thyroid neoplastic growths, specifically the medullary and mucoepidermoid carcinomas, is briefly discussed.
Ultrastructure of Bovine Embryos Frozen and Thawed by a Two-Step Freezing Method
Authors: Hyttel P. , Lehn-Jensen H. , Greve T.
Published: July 2008

An ultrastructural evaluation of a rapid tow-step freezing method, by which 6–7-day-old bovine embryos equilibrated in 1.4 M glycerol in Dulbecco’s phosphate-buffered saline were frozen and thawed, was undertaken. In all non-frozen control embryos trophoblastic and embryonic cells formed a spherical structure enclosed by an intact zona pellucida. The spacial arrangement of the cells of the frozen embryos was less regular and the surrounding zona pellucida was damaged in approximately half of the cases. Some embryonic cells had increased electron density and lysosomal content showing reaction sites for acid phosphatase. In all frozen embryos, cytoplasmic defects appearing as non-membrane-bound ‘empty spaces’ were observed more frequently in the trophoblastic cells than in the embryonic cells. Culture of frozen embryos for 24 h revealed that cells appearing non-defective after culture may have the capability of organizing a viable embryonic structure. It was found that the most commonly used freezing method is associated with certain morphological changes. However, no additional cryoinjuries were observed in comparisons with the more complicated freezing procedures using dimethylsulfoxide as cryoprotectant.
Changes in the Innervation and Catecholamine Concentrations in the Myometrium of Pregnant and Non-Pregnant Sheep
Authors: Sigger J.N. , Harding R. , Summers R.J.
Published: July 2008

The innervation of the myometrium in virgin, pregnant and post-partum ewes was examined using the SPG histofluorescence method and a high-performance liquid chromatographic catecholamine assay. In non-pregnant ewes, fluorescent axons were visible in all regions of the uterus. At 50 days of pregnancy the innervation was unchanged, but at 100 days axons were scarce over the whole uterus with the exception of the tubal extremities of the uterine horns. Noradrenaline concentrations were also significantly lower in late pregnancy, and significant variations occurred in different regions of the uterus, with the greatest concentrations present in the tubal extremities. At 13–16 weeks post partum, the density of innervation was variable, although the noradrenaline concentration was only slightly less than in virgin animals. Dopamine was also present in substantial quantities, but the mean concentrations remained unchanged during pregnancy.
Labelling of Amoeboid Microglial Cells in Rats of Various Ages following an Intravenous Injection of Horseradish Peroxidase
Authors: Kaur C. , Ling E.A. , Wong W.C.
Published: July 2008

The macrophagic amoeboid microglial cells in the corpus callosum of postnatal rats were labelled following an intravenous injection of horseradish peroxidase (HRP). The earliest time when these cells were labelled was 3 h after the injection of HRP in postnatal (1–10 days) rats. Similar cells around the mesencephalic aqueduct and the fourth ventricle were also labelled. These cells, however, were weakly labelled in developing (11–20 days) and unlabelled in weaning (21–30 days) rats. The results suggest that in the postnatal rats, the HRP passed through the endothehal lining of the blood vessels and was then ingested by the amoeboid microglial cells. In the developing and older rats, the wall of blood vessels had developed fully thereby preventing the free passage of HRP into the brain tissues.
Response of the Mandibular Joint to Loss of Incisal Function in the Rat
Authors: Hinton Robert J. , Carlson David S.
Published: July 2008

In a study of the rat mandibular joint (MJ), Simon [Acta anat. 97: 351–360 (1977)] suggested that reduction in condylar cartilage thickness noted in animals subjected to removal or trimming of incisors resulted from the lessening of joint reaction forces produced during incision. In order to explore this question further, the microanatomy of the MJ in 47-day-old rats whose incisors had been trimmed every other day was compared to that in control animals and in a third group fed a soft diet as a control for reduced joint reaction forces. Both the incisor-clipped and soft-diet groups exhibited reduced size and density of bony trabeculae underlying the condylar cartilage and diminished staining for alcian blue. The thickness of the prechondroblastic layer of the condylar cartilage was significantly (p ≦ 0.01) reduced relative to controls in both experimental groups on the superior aspect of the cartilage, but was reduced in the more posterior parts of the cartilage only in the incisor-clipped group. While not denying that joint reaction forces may affect MJ response, the reduced prohferative response noted in the posterior region of the condylar cartilage in incisor-clipped animals is perhaps best explained by a decrease in the frequency and extent of protrusion of the lower jaw due to a lack of incisal preparation of food items.