Ovarian small cell tumors: an electron microscopic review

Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms.     

Fcgamma receptor IIA H/R131 polymorphism in patients with antiphospholipid antibodies

A role for Fcgamma receptor in the pathophysiology of thrombosis in APS has been hypothesized. The polymorphism of this receptor, FcgammaRIIA H/R131, is associated with the binding affinity for human IgG2 (i.e. FcgammaRIIA-H131 isoform has a higher affinity than FcgammaRIIA-R131). Since anti-beta2 glycoprotein I antibodies (anti beta2GPI), which play a major pathogenic role in APS, show IgG2 dominant distribution, we investigated the prevalence of receptor isoforms in patients with antiphospholipid antibodies (aPL) by a PCR-RFLP method. We studied 100 Caucasian patients with aPL (57 primary APS, 32 secondary APS to SLE and 11 other diseases with aPL) and 41 healthy controls. H131/H131, H131/R131 and R131/R131 genotypes were found in 21 (21%), 50 (50%) and 29 (29%) in the patient group, and 9 (22%), 23 (56%) and 9 (22%) in control group, respectively. Thus there was no statistically significant difference in the prevalence of each genotype in these groups. None of the clinical manifestations of primary APS (arterial/venous thrombosis, recurrent pregnancy loss and thrombocytopenia) was significantly correlated with any FcgammaRIIA genotype. In conclusion, FcgammaRIIA polymorphism did not correlate with the manifestations of APS, and FcgammaRIIA genotype is not a genetic marker of APS.     

Optimization of exopolysaccharide production by Lactobacillus delbrueckii subsp. bulgaricus RR grown in a semidefined medium

The role of K+ channels in the nitric oxide-independent renal vasodilator effect of acetylcholine (Ach) was examined to address the hypothesis that the mechanism underlying this response was different from that of bradykinin, because an earlier study indicated the possibility of different mediators. We used the rat isolated, perfused kidney that was constricted with phenylephrine and treated with nitroarginine and indomethacin to inhibit nitric oxide synthase and cyclooxygenase, respectively. The nonspecific K+ channel inhibitors, procaine and tetraethylammonium (TEA), reduced vasodilator responses to Ach and cromakalim, but not those to nitroprusside. Glibenclamide, an inhibitor of ATP-sensitive K+ channels, reduced vasodilator responses to cromakalim but did not affect those to Ach or nitroprusside. Charybdotoxin, an inhibitor of Ca(++)-activated K+ channels, reduced vasodilator responses to Ach without affecting those to cromakalim or nitroprusside. Iberiotoxin and apamin, inhibitors of large- and small-conductance Ca(++)-activated K+ channels, respectively, did not reduce vasodilation induced by Ach, cromakalim or nitroprusside. The inhibitor of cytochrome P450, clotrimazole, reduced the renal vasodilator effects of Ach and bradykinin but not those of nitroprusside or SCA 40, an agonist for Ca(++)-activated K+ channels. These results suggest that in the rat kidney, Ach, like bradykinin, utilizes a charybdotoxin-sensitive Ca(++)-activated K+ channel of intermediate conductance to elicit vasodilation and that this effect may be dependent on cytochrome P450 activity.     

Long-term effect of alkaline, organic acid, or hot water washes on the microbial profile of refrigerated beef contaminated with bacterial pathogens after washing

One hundred consecutive patients (81 male and 19 female) with unstable angina pectoris undergoing coronary angiography were divided according to Braunwald's clinical classification. Seventeen (17%) patients had new onset angina (class I), 68 (68%) sub-acute angina (class II) and 15 (15%) had acute rest angina (class III). Twenty-seven (27%) patients had secondary unstable angina pectoris (class A), 49 (49%) primary unstable angina (class B) and 24 (24%) had post-infarction unstable angina (class C). ST-T wave changes on ECG were present in 54 (54%) while absent in 46 (46%) patients. On coronary angiography, 26 (26%) patients had single vessel disease, 30 (30%) double vessel disease and 39 (39%) patients had triple vessel disease. Five (5%) patients were found to have normal coronaries. Classification of patients according to Braunwald's clinical classification showed single vessel disease to be higher in class I as compared to class II (47% vs 22%; p = 0.04) and classes III (47% vs 20%; p<0.01). Single vessel disease was found to be higher in class C as compared to class B (41.7% vs 16.4; p = 0.01). Double vessel disease was higher in class B as compared to class A (40.8% vs 18.5%, p = 0.04). Triple vessel disease incidence was not found to be significantly different among different clinical classes. Morphology of coronary artery lesions was classified according to Ambrose's classification. Out of the total of 248 lesions in the whole study group, there were 68 (27.42%) concentric lesions, 55 (22.18%) eccentric type I lesions, 23 (9.27%) eccentric type II lesions, 42 (16.94%) multiple irregularity lesions and 60 (24.19%) totally occluded lesions. Concentric lesions were found to be higher in class C as compared to class B (40% vs 19.8%; p = 0.014). Statistically significant difference was not present in the distribution of other morphological type of lesions among different clinical classes. In the whole study group, intra-luminal thrombus was found to be present in 17 (17%) of patients. Distribution of intra-luminal thrombus according to Braunwald's classification showed that none of the patients in class I had intra-luminal thrombus, while 13 (19.1%) patients in class II and 4(26.7%) in class III had intra-luminal thrombus. The difference in the occurrence of intra-luminal thrombus between class I and class II (p = 0.004) and class I and class III (p = 0 .03 was found to be significant. Thus, majority of patients undergoing coronary angiography had primary sub-acute rest angina. Single vessel disease was higher in new onset angina. Patients with unstable angina pectoris and ST-T changes on ECG had higher number of lesions per patient and higher eccentric type I lesions. Intra-luminal thrombus was more frequently encountered with acute rest angina. However, the distribution of different morphological type of lesions on coronary angiography did not differ significantly in different clinical classes of unstable angina pectoris divided according to Braunwald's classification.     

Modulation of excitatory synaptic transmission in locus coeruleus by multiple presynaptic metabotropic glutamate receptors

Metabotropic glutamate receptors have been implicated in modulation of synaptic transmission in many different systems. This study reports the effects of selective activation of metabotropic glutamate receptors on synaptic transmission in intracellularly recorded locus coeruleus neurons in brain slice preparations. Perfusion of either L-2-amino-4-phosphonobutyric acid (L-AP4; 0.1-500 microM) or (+/-)-1-aminocyclopentane-trans-1,3,dicarboxylic acid (t-ACPD; 0.1-500 microM) caused a depression of excitatory postsynaptic potentials in a dose-dependent fashion to about 70% inhibition. Both agonists exerted their effects at relatively low concentrations with estimated EC50s of 2.6 microM and 11.5 microM for L-AP4 and t-ACPD, respectively. This inhibition was not observed with the potent group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG; 100 microM). Conversely, (R)-4-carboxy-3-hydroxyphenyl-glycine (4C-3H-PG), a group I antagonist/group II agonist, and 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a novel and specific group II agonist, also caused an inhibition of excitatory postsynaptic potentials. Both t-ACPD and L-AP4 produced an increase in paired-pulse facilitation, and failed to change the locus coeruleus response to focally applied glutamate, indicating a presynaptic locus of action. The L-AP4 inhibition was antagonized by (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP4: group III antagonist) but not by (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG; mixed antagonist], suggesting that this agonist acts through a type 4 metabotropic glutamate receptor. Conversely, t-ACPD was antagonized by MCPG and by ethyl glutamate (group II antagonist), but not by aminoindan dicarboxylic acid (AIDA; group I antagonist) or MAP4, suggesting that this agonist acts on a type 2 or 3 metabotropic glutamate receptor. Taken together, these results suggest that two pharmacologically distinct presynaptic metabotropic glutamate receptors function in an additive fashion to inhibit excitatory synaptic transmission in locus coeruleus neurons. These receptors may be involved in a feedback mechanism and as such may function as autoreceptors for excitatory amino acids.     

Delaying transfer to the third day post-insemination, to select non-arrested embryos, increases development to the fetal heart stage

Voluntary food intake, digestibility and water turnover were determined in adult Malaysian lesser mouse-deer (Tragulus javanicus) given unlimited access to lundai foliage (Sapium baccatum). Daily dry matter (DM) intake was 42.4 g/kg metabolic live mass (M0.73) or 3.7% M. Digestible energy intake was 853 kJ/day (571 kJ metabolisable energy per M0.73), calculated to be used with 79% efficiency. Apparent digestibility (%) of organic matter was 83.8, crude fibre 63.7, acid detergent fibre 60.5, neutral detergent fibre 72.1 and crude protein 65.0. Urinary excretion of the purine derivative, allantoin, was 0.05 mg/g digestible DM intake suggesting rumen microbial yield efficiency may be lower than in other ruminant species. Total water intake was 182 ml/M0.82. The body-water content of the fed mouse-deer, from tritiated water dilution, was 77% M, consistent with a very lean carcass. Turnover of body water was 17% per day. The mouse-deer produced relatively dry, well-defined faecal pellets.