Spermatid-specific overexpression of the TATA-binding protein gene involves recruitment of two potent testis-specific promoters

The gene encoding the TATA-binding protein, TBP, is highly overexpressed during the haploid stages of spermatogenesis in rodents. RNase protection analyses for mRNAs containing the previously identified first, second, and eighth exons suggested that most TBP mRNAs in testis did not initiate at the first exon used in somatic cells (here designated exon 1C). Using a sensitive ligation-mediated cDNA amplification method, 5' end variants of TBP mRNA were identified, and the corresponding cDNAs were cloned from liver and testis. In liver, a single promoter/first exon is used to generate a steady-state level of roughly five molecules of TBP mRNA per diploid cell equivalent. In testis, we detect modest up-regulation of the somatic promoter and recruitment of at least five other promoters. Three of the alternative promoter/first exons, including 1C and two of the testis-specific promoter/first exons, 1D and 1E, contribute roughly equivalent amounts of mRNA which, in sum, account for greater than 90% of all TBP mRNA in testis. As a result, round spermatids contain an estimated 1000 TBP mRNA molecules per haploid cell. Testis TBP mRNA also exhibits several low abundance 5' end splicing variants; however, all detected TBP mRNA leader sequences splice onto the common exon 2 and are expected to initiate translation at the same site within exon 2. The precise locations of the three major initiation exons are mapped on the gene. The identification of the strong testis-specific promoter/first exons will be important for understanding spermatid-specific tbp gene regulation.     

Effect of ozone therapy on hemostatic changes in patients with vascular atherosclerosis

Hemostatic changed induced by ozone therapy were studied in 81 patients with atherosclerosis of different vessels in 81 patients. It was found that use of ozone-oxygen mixtures leads to hypocoagulatory changes (diminution of platelet aggregation, lowering of fibrinogen concentration, prolongation of activated partial thromboplastin time, enhanced fibrinolytic activity) which contribute to clinical response.     

Alternative strategies of categorization

Psychological studies of categorization often assume that all concepts are of the same general kind, and are operated on by the same kind of categorization process. In this paper, we argue against this unitary view, and for the existence of qualitatively different categorization processes. In particular, we focus on the distinction between categorizing an item by: (a) applying a category-defining rule to the item vs. (b) determining the similarity of that item to remembered exemplars of a category. We begin by characterizing rule application and similarity computations as strategies of categorization. Next, we review experimental studies that have used artificial categories and shown that differences in instructions or time pressure can lead to either rule-based categorization or similarity-based categorization. Then we consider studies that have used natural concepts and again demonstrated that categorization can be done by either rule application or similarity calculations. Lastly, we take up evidence from cognitive neuroscience relevant to the rule vs. similarity issue. There is some indirect evidence from brain-damaged patients for neurological differences between categorization based on rules vs. that based on similarity (with the former involving frontal regions, and the latter relying more on posterior areas). For more direct evidence, we present the results of a recent neuroimaging experiment, which indicates that different neural circuits are involved when people categorize items on the basis of a rule as compared with when they categorize the same items on the basis of similarity.     

Rhinosporodium: case report

This is the first reported case of rhinosporidiosis in Ibadan, Nigeria. A review of literature shows that the patient came from northern Nigeria where the first case was reported in the country. The organism is difficult to culture and the diagnosis was based on microscopy and histological examination of the polyp. We present the case of recurrent rhinosporidiosis in a 16 year old girl a year after polypectomy in Zaria, northern Nigeria.     

Synthesis, rotamer orientation, and calcium channel modulation activities of alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates

A group of racemic alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates (13a-q) was prepared using a modified Hantzsch reaction that involved the condensation of a 3- or 6-substituted-2-pyridinecarboxaldehyde (7a-j) with an alkyl or 2-phenethyl 3-aminocrotonate (11a-d) and nitroacetone (12). Nuclear Overhauser (NOE) studies indicated there is a significant rotamer fraction in solution where the pyridyl nitrogen is oriented above the 1,4-dihydropyridine ring, irrespective of whether a substituent is located at the 3- or 6-position. A potential H-bonding interaction between the pyridyl nitrogen free electron pair and the suitably positioned 1,4-dihydropyridine NH moiety may stablize this rotamer orientation. In vitro calcium channel antagonist and agonist activities were determined using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays, respectively. Compounds having an i-Pr ester substituent acted as dual cardioselective calcium channel agonists (GPLA)/smooth muscle-selective calcium channel antagonists (GPILSM), except for the C-4 3-nitro-2-pyridyl compound which exhibited an antagonist effect on both GPLA and GPILSM. In contrast, the compounds with a phenethyl ester group, which exhibited antagonist activity (IC50 = 10(-5)-10(-7) M range) on GPILSM, were devoid of cardiac agonist activity on GPLA. Structure-activity relationships showing the effect of a substituent (Me, CF3, Cl, NO2, Ph) at the 3- or 6-position of a C-4 2-pyridyl moiety and a variety of ester substituents (Me, Et, i-Pr, PhCH2CH2-) upon calcium channel modulation are described. Compounds possessing a 3- or 6-substituted-2-pyridyl moiety, in conjuction with an i-Pr ester substituent, are novel 1,4-dihydropyridine calcium channel modulators that offer a new drug design approach directed to the treatment of congestive heart failure and may also be useful as probes to study the structure-function relationships of calcium channels.     

Fused aminotetralins: novel antagonists with high selectivity for the dopamine D3 receptor

Starting from a series of 2-aminotetralins 1, a novel series of N-[4-(4-phenylbenzoylamino)butyl]-octahydrobenzoquinolines and hexahydrobenzoindoles with high potency and selectivity for the dopamine D3 receptor has been designed. The effect of ligand chirality on binding affinity has been established. Selected derivatives (e.g. 2o, 2p) show high functional selectivity and enhanced in vivo properties compared to 1.     

Antibody reactivity to conserved linear epitopes of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1)

High concentrations of diazepam-binding inhibitor (DBI) have been detected in brain areas containing dopaminergic cell bodies and nerve terminals. In the present study, we have investigated the effect of a proteolytic fragment of DBI, the octadecaneuropeptide ODN, on apomorphine-induced yawning in Sprague-Dawley rats. Injection of graded doses of ODN (12.5 to 100 ng i.c.v.) caused a dose-dependent inhibition of apomorphine-induced yawning and penile erections. At a dose of 100 ng, intracerebroventricularly administered ODN was able to inhibit, during more than 3 h, the apomorphine-evoked yawning. ODN also inhibited pilocarpine-induced yawning. Apomorphine induces a bell-shaped dose-dependent effect on yawning with a maximum response at the dose of 100 microg/kg and a much lower effect at a dose of 200 microg/kg. Injection (i.c.v.) of 100 ng ODN markedly attenuated the number of yawns induced by 100 microg/kg apomorphine but partially restored the yawning behavior in rats treated with a 200 microg/kg dose of apomorphine. At doses of 0.5 or 5 mg/kg s.c., diazepam did not modify the inhibitory effect of ODN on the apomorphine-induced yawning. Taken together, the present data suggest that ODN inhibits yawning downstream dopaminergic as well as cholinergic synapses involved in yawning. In addition, the effect of ODN cannot be ascribed to an inverse agonistic activity on central-type benzodiazepine receptors.     

Morphologic aspects of experimental esophageal lye strictures. II. Effect of steroid hormones, bougienage, and induced lathyrism on acute lye burns

Among 77 dogs surviving standardized transmural esophageal lye injury for at least 2 weeks and as long as 12 weeks, 24 were untreated, 26 received corticosteroids and bougienage (S&B), and 27 received only the lathyrogen beta-aminoproprionitrile (BAPN). Stricture frequency was reduced markedly and significantly in the S&B and BAPN groups when compared to the controls (p less than 0,01). Strictures resulted from inward circumferential remodeling of all mural layers, not proliferating bulky scar tissue, and persistent ulceration was apparently not an influential factor in any group. The S&B dogs invariably showed reduction of the internal or mucosal length of the injured segment as compared to the outer length; these relations were quite variable in the other two groups so that mean internal shortening was significantly greater (p less than 0.01) in the S&B group. Marked mural thinning in the injured zone was present in all three groups but was most frequent in the BAPN-treated animals. The major conclusion is that BAPN-induced changes in the physical properties of reparative tissue can increase the ultimate caliber of an injured hollow viscus without resort to mechanical bougienage. In addition, the data suggest that wound contraction may play a role in stricture formation in this model.     

Variation of technique of episcleral sponge placement: effect on scleral indentation for retinal detachment repair

Seventy-eight 5 mm silicone sponges were sutured to autopsy eyes using various techniques, and resulting scleral indentation was compared to a control series. Indentation was decreased by suture separation narrower or wider than 8 mm, short suture passage, loose sutures, high intraocular pressure, and partial thickness sponges. Increased indentation resulted from excessively tight sutures and low intraocular pressure. No change was produced by variation of sponge stretch or lengthening scleral suture passage. Lateral adjustability of sponge position was gained when wide suture separation was used.