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Loss of olfactory receptor genes coincides with the acquisition of full trichromatic vision in primates.

Olfactory receptor (OR) genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian). Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates.

Alouatta↗

Pleural effusion in an asymptomatic patient. Spectrum and frequency of causes and management considerations.

We conducted retrospective chart and literature reviews to analyze the frequency and spectrum of causes of asymptomatic pleural effusion (APE). In our series, 16 percent of patients undergoing thoracentesis for PE were asymptomatic and the spectrum of causes was similar to that for symptomatic patients. Asymptomatic PEs were evenly distributed among transudates, exudates and indeterminate effusions. More symptomatic (S) PE were exudates, although the difference was not statistically significant (p greater than 0.1). In comparison to SPE, APE were more often free flowing and small. In both groups, the four most common diagnoses were malignancy, CHF, parapneumonic and postoperative effusions accounting for greater than 70 percent of each group. Review of the literature demonstrated the following associations with APE: recent childbirth or abdominal surgery, benign asbestos effusion, uremia, malignancy, and tuberculosis. In the uncomplicated postpartum or postoperative setting or in patients with typical findings of left ventricular failure, observation without diagnostic studies is appropriate. In all other situations, APE should be evaluated in traditional fashion. If thoracentesis is non-diagnostic and the effusion is an exudate, closed pleural biopsy and less often, fiberoptic bronchoscopy, should follow. Once malignant or granulomatous pleuritis has been excluded, it may be appropriate to observe for a period of time before proceeding to more invasive procedures.

Humans↗

Prophylactic effect of aqueous propolis extract against acute experimental hepatotoxicity in vivo.

Propolis has been extensively used in folk medicine for the management of a wide spectrum of disorders. In a previous study, we demonstrated the protective effect of the aqueous propolis extract (APE) against the injurious effects of carbon tetrachloride (CCl4) on hepatocytes in vitro. The present investigation was carried out to show whether the hepatoprotective effect of the extract could also be manifested in vivo. Rats were given APE orally for 14 consecutive days, before being subjected to a single intraperitoneal injection of CCl4. One day after the CCl4 injection, the animals were sacrificed, hepatocytes were isolated and liver homogenates were prepared for the assessment of liver injury. In isolated hepatocytes, APE afforded protection against CCl4-induced injury as manifested by a decrease in the leakage of the cytosolic enzyme lactate dehydrogenase (LDH), decreased generation of lipid peroxide and maintenance of cellular reduced glutathione (GSH) content. In principle, similar findings were observed in liver homogenates. The present findings show that APE has in vivo hepatoprotective potential which could be attributed at least in part to the maintenance of cellular GSH content. The latter effect seems to play an important role in conserving the integrity of biomembranes as it was associated with a decrease in lipid peroxidation and reduced leakage of cytosolic LDH.

Administration, Oral↗

Nucleotide diversity in gorillas.

Comparison of the levels of nucleotide diversity in humans and apes may provide valuable information for inferring the demographic history of these species, the effect of social structure on genetic diversity, patterns of past migration, and signatures of past selection events. Previous DNA sequence data from both the mitochondrial and the nuclear genomes suggested a much higher level of nucleotide diversity in the African apes than in humans. Noting that the nuclear DNA data from the apes were very limited, we previously conducted a DNA polymorphism study in humans and another in chimpanzees and bonobos, using 50 DNA segments randomly chosen from the noncoding, nonrepetitive parts of the human genome. The data revealed that the nucleotide diversity (pi) in bonobos (0.077%) is actually lower than that in humans (0.087%) and that pi in chimpanzees (0.134%) is only 50% higher than that in humans. In the present study we sequenced the same 50 segments in 15 western lowland gorillas and estimated pi to be 0.158%. This is the highest value among the African apes but is only about two times higher than that in humans. Interestingly, available mtDNA sequence data also suggest a twofold higher nucleotide diversity in gorillas than in humans, but suggest a threefold higher nucleotide diversity in chimpanzees than in humans. The higher mtDNA diversity in chimpanzees might be due to the unique pattern in the evolution of chimpanzee mtDNA. From the nuclear DNA pi values, we estimated that the long-term effective population sizes of humans, bonobos, chimpanzees, and gorillas are, respectively, 10,400, 12,300, 21,300, and 25,200.

Animals↗

Comparative studies of the growth promoting effects of ascitic or pleural effusion from patients with malignant tumors, human serum and fetal calf serum on human cells cultured in vitro.

Twelve specimens of ascitic and pleural effusion (APE) from patients with malignant diseases were examined quantitatively for growth promoting effect on three human cell lines and one human cell strain, by four different assay procedures. Simultaneously, healthy human serum (HS) and fetal calf serum (FCS) were also examined for comparison. When the activity per mg protein of the test specimen was evaluated, the value of APE on an average was somewhat greater than that of HS in three out of four different assays, although FCS gave a higher average value than either APE or HS did in two of the three assays. However, a portion of APE specimens were found to have a unique promoting activity responsible for increase in number of cell colonies.

Animals↗

Effects of exercise at different ages on bone density and mechanical properties of femoral bone of aged mice.

We determined the bone density and mechanical properties of bone specimens from 5 groups of aged mice, which had been subjected to voluntary exercise at different ages. ICR 10-week-old female mice were divided into control (C), and exercise-trained during age periods of 10-70 weeks (EE), 10-30 weeks (GPE), 30-50 weeks (MPE) and 50-70 weeks (APE). It was found that in the exercise-trained groups body weight gain was suppressed during the exercise-training period, and that de-training accelerated weight gain. Bone density was significantly higher in all the exercise-trained groups than in the C group and cortical thickness index (CTI) was higher in the exercise-trained groups, except for the APE group. Maximum breaking force, ultimate stress and elasticity in the exercise-trained groups were higher than in the C group except for the APE group, whereas deformation in the APE group had a tendency to be higher than in the other groups. Blood C-terminal parathyroid hormone, calcitonin and calcium concentrations were similar among every group, but phosphorus concentrations tended to be higher in the exercise-trained groups than in the C group. These observations suggest that exercise-training at every age suppresses age-associated bone loss, and that the effect of exercise during youth is greater than that during old age. The results of this study suggest that the effect of exercise on bone at an older age is different from that at other ages.

Aging↗

A phylogenetic study of the structural and functional characteristics of corticosteroid binding globulin in primates.

A monospecific antiserum against human corticosteroid binding globulin (hCBG) has been used to identify structural similarities between hCBG and CBG in the blood of other primates and representative species of different vertebrate classes. Double immunodiffusion analysis indicated that only CBG in Old World monkeys and apes cross-react with the hCBG antiserum. This was confirmed by a solid-phase radioimmunoassay for hCBG which also demonstrated that CBG in apes is immunologically identical to hCBG and that Old World monkey CBG comprises most, but not all, of the hCBG epitopes. The electrophoretic mobilities of human, gorilla and gibbon CBG were similar (RF 0.50-0.51), but differed from Old World monkey CBG (RF 0.44-0.49) and chimpanzee CBG (RF 0.47). Although serum/plasma cortisol binding capacities were similar in Old World primates, the dissociation half-times (t 1/2) of cortisol were higher from human and ape CBG (18-25 min) than from Old World monkey CBG (14-18 min). The steroid binding specificities of human and ape (CBG corticosterone greater than cortisol greater than progesterone greater than or equal to testosterone) were also different from those of Old World monkey CBG (corticosterone much greater than cortisol approximately equal to progesterone greater than testosterone). Lemur plasma cortisol binding capacity and CBG dissociation t 1/2 of cortisol were similar to hCBG, but its steroid binding specificity was different (cortisol greater than corticosterone greater than progesterone greater than or equal to testosterone) and it did not cross-react with the hCBG antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The relationship of anti-endothelial cell antibodies to anti-phospholipid antibodies in patients with giant cell arteritis and/or polymyalgia rheumatica.

Sera from patients with giant cell arteritis and/or polymyalgia rheumatica were tested for the presence of IgG, IgM and IgA antibody to endothelial cells (AEC), cardiolipin (ACL) and phosphatidylethanolamine (APE) using enzyme-linked immunosorbent assays. There were strong correlations between ACL and APE, but also between AEC and ACL IgM (p < 0.02) and between AEC and APE IgA (p < 0.003). Inhibition of AEC binding was achieved by absorption onto EC, but ACL and APE binding was also significantly reduced. In contrast, the binding of AEC antibody could not be inhibited by incubation with CL. Our data suggest that AEC constitute a heterogeneous population of autoantibodies.

Aged↗

[Immunohistochemical studies of putative neurotransmitters in the lower urinary tract].

Putative neurotransmitters of the lower urinary tract were investigated in apes, rabbits and cats using immunohistochemical techniques of PAP (Peroxidase antiperoxidase) staining and IGSS (Immunogold silver staining) methods for Neuron specific enolase (NSE), Acetylcholine (Ach), Noradrenaline (NA), Vasoactive intestinal polypeptide (VIP), Substance P (SP) and Calcitonin gene related peptide (CGRP). 1) The localization of pelvic ganglions exhibited more striking evidence of species difference. Huge pelvic ganglions were found particularly in the dorsolateral area of the prostate in apes. On the other hand, in cats and rabbits, many ganglion cells were found around the uretero-vesical junctions. 2) In the pelvic ganglions of the apes, Ach immunoreactives were detected in nearly 70 percent of the cell bodies. 10-15 percent were NA immunoreactive cells. In addition, 15-20 percent VIP and a smaller percentage of SP immunoreactive cells were detected in the same ganglions. Axons extending from the ganglion cells showed the intense neurotransmitters immunoreactivity. 3) In the apes, varicose fibers containing SP were widely distributed in the epithelium, submucosa, muscle layer, and around the vessels of the bladder. SP immunoreactive cell bodies were found in the dorsal root ganglion at levels of L7, S1 and at the same levels in the posterior horn. On the other hand, the bulbourethral gland and the seminal vesicle contained SP immunoreactive cell bodies. 4) CGRP containing fibers were distributed in similar locations as SP containing fibers in the bladder. 5) VIP immunoreactive fibers were also widely distributed, being most dense at the base of the bladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evolution of exon 1 of the dopamine D4 receptor (DRD4) gene in primates.

The dopamine D4 receptor (DRD4) gene exhibits a large amount of expressed polymorphism in humans. To understand the evolutionary history of the first exon of DRD4-which in humans contains a polymorphic 12bp tandem duplication, a polymorphic 13bp deletion, and other rare variants-we examined the homologous exon in thirteen other primate species. The great apes possess a variable number of tandem repeats in the same region as humans, both within and among species. In this sense, the 12bp tandem repeat of exon 1 is similar to the 48bp VNTR of exon 3 of DRD4, previously shown to be polymorphic in all primate species examined. The Old World monkeys show no variation in length, and a much higher conservation of amino acid sequence than great apes and humans. The New World monkeys show interspecific differences in length in the region of the 12bp polymorphism, but otherwise show the higher conservation seen in Old World monkeys. The different patterns of variation in monkeys compared to apes suggest strong purifying selective pressure on the exon in these monkeys, and somewhat different selection, possibly relaxed selection, in the apes.

Animals↗

Incomplete recovery of lung perfusion after 3 months in patients with acute pulmonary embolism treated with antithrombotic agents. THESEE Study Group. Tinzaparin ou Heparin Standard: Evaluation dans l'Embolie Pulmonaire Study.

UNLABELLED: We assessed the time course of lung perfusion after 3 mo of anticoagulant therapy for acute pulmonary embolism (APE) on the basis of perfusion lung scan (PLS) findings for 157 patients included in the Tinzaparin ou Heparin Standard: Evaluation dans l'Embolie Pulmonaire Study (THESEE), a multicenter, randomized, nonmasked trial comparing standard, continuous, adjusted-dose intravenous heparin with once-daily, subcutaneous, low-molecular-weight heparin in patients with APE. METHODS: We calculated the percentage-of-vascular-obstruction score (PVOs) on PLSs on the day of diagnosis of APE (PVOsD1), on day 8 (PVOsD8), and after 3 mo (PVOsM3) and the mean relative changes in PVOs on day 8 versus the day of diagnosis and after 3 mo versus the day of diagnosis. RESULTS: Mean PVOsD1 +/- SD was 49% +/- 20%, PVOsD8 was 29% +/- 18%, and PVOsM3 was 19% +/- 18%. PVOsD1 was at least 50% in 49% of patients. Reperfusion did not correlate with age, importance of initial obstruction, or clinical severity of disease at inclusion in THESEE. Relative change after 3 mo versus at diagnosis was lower in the 87 patients with associated prior cardiopulmonary disease than in those without. In the 43 patients with a history of thromboembolic disease, neither mean PVOsD1 nor the time course of PVOs was different from those in patients without a history of thromboembolic disease. Residual defects after 3 mo were observed in 104 patients (66%), including 13 with a PVOs of at least 50%. CONCLUSION: These results emphasize the need for a control PLS at completion of anticoagulant therapy for APE, even in patients with full resolution of symptoms.

Acute Disease↗

Prevalence of various antiphospholipid antibodies in pregnant women.

Antiphospholipid antibodies (APAs) are characterized as a heterogeneous population of autoantibodies directed against different target antigens, predominantly anionic phospholipids or phospholipid-containing structures. The presence of APAs has been strongly associated with a variety of clinical disorders including adverse pregnancy complications such as spontaneous abortions, pregnancy-induced hypertension, preeclampsia and intrauterine growth retardation. The purpose of this study was to compare the prevalence of anticardiolipin antibodies (ACAs), which are routinely examined, with APAs directed against phosphatidylserine (APS), phosphatidylinositol (API), phosphatidylethanolamine (APE) and phosphatidylcholine (APC) in the sera of pregnant women. We examined 410 serum samples of pregnant women hospitalized in the department for pathological pregnancies. They underwent prenatal biochemical screening of fetal congenital abnormalities in the first and the second trimester of gravidity. Anticardiolipin IgG and IgM were measured using commercial ELISA kits (ImmuLisa Anti-Cardiolipin Antibody), whereas APS, APE, API and APC were determined by our modified ELISA kit. Among 410 pregnant women we found 21 patients (5.1%) positive for ACA IgG (>20 GPL) and 30 patients (7.3%) positive for ACA IgM (>10 MPL). It was found that 7.8% of pregnant women had at least one high-titer APA IgG and 9.8% high-titer APA IgM. One third of ACA IgG or IgM positive sera contained polyspecific autoantibodies reactive to at least two various phospholipids. In the group of IgG ACA positive women, 28.6% patients were positive for APS, 28.6% were positive or moderately positive for API, 23.8% for APC and 19% for APE. In the group of IgM ACA positive women, 33.3% were also positive for APS, 26.7% for APE, 26.7% for API and 23.3% for APC were present. IgG and IgM ACA negative patients exhibited a significantly lower incidence of other APA than the group of ACA positive pregnant women. It still remains to clarify if the routine examination of APA reacting with other anionic and zwitterionic antigens other than cardiolipin would improve the probability of identifying women liable to adverse pregnancy complications.

Adult↗

Ventilation/perfusion scan and dead space in pulmonary embolism: are they useful for the diagnosis?

The diagnostic strategy for pulmonary embolism, based on the mismatch of the ventilation/perfusion scan, was developed some 30 years ago on the following assumption: since the disorder involves the pulmonary vessels, it was surmised that in the embolized regions lung alveoli are unperfused or poorly perfused but well ventilated. Hence, it was inferred that this disorder was characterized, unlike parenchymal disease, by ventilation/perfusion mismatch in the affected lung zones and by an obvious increase of wasted ventilation, i.e., dead space. As matter of fact, experimental evidence on the redistribution of ventilation away from the vascular occluded lung had been already obtained in the early 60s of the last century. More recently, the behavior of regional pulmonary ventilation (V(A)) and blood flow (Q) in patients with acute pulmonary embolism (APE) has been studied by applying the multiple inert gas elimination technique (MIGET). It has been shown that the development of lung units with high V(A)/Q ratio (those with relative prevalence of perfusion obstruction) is accompanied by substantial redistribution of ventilation away from these units. Furthermore, radioisotopic techniques, used to visualize the topographic distributions of V(A) and Q in the same patients studied by MIGET, have shown reduced or absent V(A) in the embolized regions. This may occur by different mechanisms in the various stages of APE: bronchoconstriction mediated by local hypocapnia, atelectasis (occasionally hemorrhagic) related to alteration of surfactant production, bronchiolar obstruction and pulmonary infarction ascribed to degenerative and/or necrotic changes secondary to insufficient blood flow. In dogs and humans alike, the dead space measured by MIGET does not increase and that obtained from CO2 increases far less than the amount of unperfused lung in APE thus confirming a substantial redistribution of ventilation away from the embolized lung zones. Taken together, all these observations provide the pathophysiological explanation of the unacceptedly low level of sensitivity for the diagnostic strategy of APE based on the mismatch of the ventilation/perfusion scan.

Acute Disease↗

Review of findings of the Andhra Pradesh Eye Disease Study: policy implications for eye-care services.

The Andhra Pradesh Eye Disease Study (APEDS) was conducted in order to design long-term strategies to reduce blindness in the background of non-availability of recent population-based data on various aspects of blindness. The objectives of APEDS were to determine the prevalence and causes of blindness and visual impairment, prevalence of and risk factors for major eye diseases, barriers to eye-care services, and quality of life among the visually impaired. Multistage sampling was used to select 11,786 subjects of all ages from 24 urban clusters and 70 rural clusters in one urban and three rural areas belonging to different parts of Andhra Pradesh, with the aim of obtaining a study sample representative of the urban-rural and socioeconomic distribution of the population of this state. A total of 10,293 subjects underwent a detailed interview and dilated eye examination by trained professionals. The adjusted prevalence of blindness (presenting visual acuity <6/60 or central visual field <20 degrees in the better eye) was 1.84%, and moderate visual impairment (presenting visual acuity <6/18-6/60 or equivalent visual field loss in the better eye) was 8.1%. Cataract and refractive error were responsible for 60.3% of blindness and 85.7% of moderate visual impairment. Increasing age, decreasing socioeconomic status, female gender, and rural area of residence were associated with higher risk of blindness. Projections from APEDS suggest that there were 18.7 million blind people in 2000 in India, and that this number is likely to increase to 24.1 million and 31.6 million in 2010 and 2020 respectively, if the current trend continues. This review summarizes the findings of APEDS and discusses the implications of these data on the policy and planning of eye-care services.

Blindness↗

Pharmacokinetics of mycophenolic acid in kidney transplant recipients treated with a low dose (1 gram/day) of mycophenolate mofetil.

Pharmacokinetic studies of mycophenolic acid (MPA) were performed in 16 stable Thai kidney transplant recipients treated with 1 g/d of mycophenolate mofetil (MMF). The complete area under the blood concentration-time curve (AUC) of MPA was determined using the linear trapezoidal rule from 8 concentrations at, 0, 1, 2, 3, 4, 6, 8, and 12 h after MMF administration. The mean values of AUC(0-12) were 37.54 + 0.80 microg x h/ml. MPA concentrations at 8 h after dosing, not the trough or maximum levels, showed the best correlation with AUC(0-12) (r2 = 0.72). The equation model of abbreviated AUC of MPA, derived by multiple linear regression analysis, that had the highest correlation (r2) and lowest absolute prediction error (APE) was: AUC = 0.6 C1 + 1.9 C3 + 8.68 C8 + 4.65 (r2 = 0.92, APE = 2.05 +/- 0.32%). The best abbreviated AUC equations obtained by linear trapezoidal rule were: AUC = 4.5 C0 + C1 + 1.5 C2 + 5 C4 (r2 = 0.78, APE = 5.78 +/- 1.14%) and AUC = 5 C0 + C1 + C2 + 5 C3 (r2 = 0.76, APE = 6.21 +/- 1.46%).

Adult↗

[Acute pulmonary embolism after cesarean section; report of a case].

We present a case of acute pulmonary embolism (APE) after cesarean section. A cesarean section was performed on a 27-year old woman with normal course. However, one day after operation, she suddenly developed syncope and dyspnea. Soon after the symptom, she developed hypotension 60 mmHg. As a result of various examinations, her illness was diagnosed as APE with right ventricular dysfunction after cesarean section. She was consulted to our hospital for treatment. Soon after her arrival, we treated her for both APE and cardiogenic shock. The combined with antithrombotic therapy using heparin sodium, was successfully treated the patient from cardiogenic shock due to APE with right ventricular dysfunction after cesarean section.

Acute Disease↗

[Electrocardiography and prediction of myocardial damage in patients with acute pulmonary embolism].

UNLABELLED: Acute pulmonary embolism (APE) may lead to myocardial necrosis detected by elevation of cardiac troponin levels. We tried to assess, if electrocardiographic abnormalities may help to define APE patients with myocardial damage and at high risk of complicated clinical course. Therefore we analyzed 50 patients (34F) aged 64.6 +/- 16.9 with confirmed APE. On admission 12-lead standard ECG was recorded and cardiac troponin T (cTnT) was determined quantitatively (Roche). Serum cTnT levels > 0.01 ng/ml, regarded to indicate myocardial injury, were detected in 29 (58%) patients. ST segment depression in ECG was found in 24% of all patients and was more frequent in cTnT + then in group without myocardial injury (41.4% vs 0%, p=0.004). Complicated clinical course and death in acute pulmonary embolism were also more frequently observed in group with ST segment depression (47.1% vs 12.1%, p = 0.03 and 75.0% vs 14.3%, p = 0.02 respectively). Although negative T waves were slightly more frequent in patients with elevated serum troponin T level (65.5% vs 42.9%) and in patients, who died of pulmonary embolism (62.5% vs 54.8%), the difference did not reach statistical significance. CONCLUSION: ST segment depression detected in standard ECG in patients with APE suggests myocardial injury and may indicate unfavourable clinical course.

Acute Disease↗

"You can't make a monkey out of us": Galen and genetics versus Darwin.

The views on the biological relationship between human and ape are polarized. One end is summarized by the axiom that "man is the third chimpanzee", a thesis put forward in an indirect way initially by Charles Darwin in the 19th century. The other is a very modern concept that although similar, the human and ape genomes are distinctly different. We have compared these two views on the subject with the stance of the ancient medical writer Galen. There is a striking resemblance between current and ancient opinion on three key issues. Firstly, on the fact that man and apes are similar but not identical. Secondly, on the influence of such debates on fields much wider than biology. And finally, on the comparative usefulness of apes as a substitute for human anatomy and physiology studies.

Animal Experimentation↗