The PLC-PKC cascade is required for IL-1beta-dependent Erk and Akt activation: their role in proliferation

We investigated the signaling mechanisms that lead to IL-1beta-induced cell proliferation. Treatment of Balb 3T3 cells with IL-1beta activated two signaling pathways, Erk and Akt. IL-1beta also increased tyrosine phosphorylation of PLC-gamma in Src kinase-dependent manner. Pharmacological inhibition of the PLC-PKC cascade by using specific inhibitor for PLC-gamma (U73122) and PKC (GFX) strongly inhibited IL-1beta-induced Erk and Akt activation. Inhibition of MEK1 by its specific inhibitor, PD98059 substantially inhibited Erk activation. Similarly, inhibition of PI3K activation by its specific inhibitor LY294002 suppressed Akt phosphorylation. Moreover, IL-1beta-induced association of PLC-gamma with SHPS-1. SHPS-1 mutants lacking the tyrosine phosphorylation sites failed to associate with PLC-gamma. Finally, IL-1beta-induced proliferation of Balb 3T3 cells and inhibition of Erk and Akt signalings or their upstream signaling molecules, Src kinase and PKC by their inhibitors strongly inhibited IL-1beta-dependent cell proliferation. Taken together, our results suggest that a SHPS-1-PLC-gamma complex activate the PLC-PKC cascade, which is required for the activation of IL-1beta-dependent Erk and Akt signalings and cell proliferation.     

Mitral stenosis in a girl of five years

Mitral stenosis(MS) detected below the age of 20 years is called juvenile mitral stenosis (JMS). JMS constitute 25-40 % of all cases of isolated mitral stenosis, though overall incidence of rheumatic fever and rheumatic heart disease (RHD) within mixed population is 7.5- 7.8 per thousand. The patient was 5 years old girl hailing from Modhupur, Tangail got herself admitted into CCU Mymensingh Medical College Hospital with the complaints of low grade fever, shortness of breath and also associated with failure to thrive. She was ill looking, mildly anaemic. Precordial examination revealed apex beat was in the left 5th intercostals space, tapping in nature, palpable P(2). There was left parasternal heave. 1st heart sound loud, pulmonary component of the 2nd heart sound was accentuated, opening snap with mid diastolic murmur with pre systolic accentuation. Routine blood examination reveals leucocytosis with raised ESR. C-reactive protein (CRP) and ASO titre were significantly raised. X-ray chest P/A view showing the features of mitral stenosis. Echocardiography showing MS (moderate) with pulmonary hypertension. She was treated with antibiotics and other relevant drugs and discharge with an advice for follow up and take preparation for cardiac intervention.     

Antidiarrhoeal activity of the methanol extract of the barks of Xylocarpus moluccensis in castor oil- and magnesium sulphate-induced diarrhoea models in mice

The methanol (MeOH) extract of the barks of Xylocarpus moluccensis, and different fractions of this extract were studied for antidiarrhoeal activity using castor oil- and magnesium sulphate-induced diarrhoea models in mice. At the doses of 250 and 500 mg/kg, the MeOH extract showed significant antidiarrhoeal activity in both models. The EtOAc fraction (EAF) and the residual MeOH fraction (RMF) exhibited similar activity using a dose of 250 mg/kg in both models. No antidiarrhoeal activity was observed with the chloroform fraction (CHF) at the test doses. When tested for antibacterial effect, the MeOH extract displayed moderate inhibitory activity against Escherichia coli, Vibrio cholera, Staphylococcus aureus, Staphylococcus epidermis, Shigella dysentery, Staphylococcus pyogenes, Salmonella typhi, Pseudomonas aeruginosa and Enterobacter aerogenes. While the CHF inhibited the growth of Escherichia coli, Vibrio cholerae, Shigella dysenteriae, Shigella sonnei, Staphylococcus epidermis, Staphylococcus pyogenes and Pseudomonas aeruginosa, the EAF was active against all test organisms except Vibrio cholera and Staphylococcus epidermis. The RMF inhibited the growth of all the test organisms with moderate zone of inhibition. On the basis of these findings, it can be assumed that Xylocarpus moluccensis could be a potential source for novel 'lead' discovery for antidiarrhoeal drug development.     

Attention shift not memory averaging reduces foveal bias

Two experiments examined which of two mechanisms, attention shift or memory averaging, reduces foveal bias. The target stimulus was a black dot presented for 80 ms while observers maintained fixation. The two main conditions were 'with' and 'without' vertical and horizontal bars as landmarks, which were placed on more eccentric positions than the target stimulus. To induce attention, the landmark was flashed on for 80 ms (Experiment 1) or disappeared (Experiment 2) with a stimulus onset asynchrony of 0, 106.4, or 212.8 ms in both experiments. As a control, non-flashed and non-disappeared landmark conditions were employed. The observers' task was to point to the remembered location of the target with a mouse cursor. The results showed that the magnitudes of foveal bias were significantly lower in the flashed and disappeared landmark conditions than in the without landmark condition. Furthermore, the magnitudes in the flashed and disappeared landmark conditions did not differ from their respective control conditions. The latter finding in the disappeared landmark conditions provides evidence for 'attention shift' against 'memory averaging' as the mechanism reducing foveal bias.     

Haterumaimides F-I, four new cytotoxic diterpene alkaloids from an ascidian Lissoclinum species

Four new monochlorinated diterpene alkaloids, haterumaimides F-I (1-4), and two known ones, dichlorolissoclimide and chlorolissoclimide, were isolated from an ascidian Lissoclinum sp. Their structures with absolute stereochemistries were elucidated by chemical and spectral analyses. Haterumaimides F-I (1-4) inhibited the first cleavage of fertilized sea urchin eggs and exhibited potent to weak cytotoxicities against P388 cells.     

The role of chlamydospores of Paracoccidioides brasiliensis.

The role of chlamydospores in the conversion process from a mycelial-to-yeast form using the slide culture method was studied. Three clinical isolates and two other isolates from armadillo, belonging to the fungal species Paracoccidioides brasiliensis, were cultured on Sabouraud dextrose agar (SDA), potato dextrose agar (PDA) and brain heart infusion dextrose agar (BHIDA). Initially, the mycelial forms of each isolate were grown at 25 degrees C for 7, 14, 30 or 60 days on slide cultures and then the temperature was shifted to 35 degrees C. Interestingly, the slide cultures of all the isolates at 25 degrees C formed chlamydospores on either SDA or BHIDA, whereas, on PDA medium, aleurioconidia were formed. If the slide cultures on BHIDA were incubated at 35 degrees C for 7 to 14 days, multiple budding forms could be observed. This phenomenon was not evident in the slide cultures of SDA or PDA. The results of this morphological study indicate that in P. brasiliensis, chlamydospores may play an important role in the conversion process from a mycelial-to-yeast form.     

Interruption of shigellosis by hand washing

High attack rates, increasing resistance to antibiotics and high mortality make shigellosis a serious problem. As Shigella is associated with poor hygiene we examined the effectiveness of a simple intervention, washing hands with soap and water, in checking the spread of the disease.The study population was comprised of confirmed cases of shigellosis. These and matched controls were followed up for 10 days. Several pieces of soap and earthenware pitchers for storing water were provided to the study families and they were advised to wash their hands with soap and water after defaecation and before meals. Compliance was monitored daily by observing the size of the soap and residual water. Rectal swabs of contacts of both the groups were obtained daily for culture.The secondary infection rate was 10.1% in the study group and 32.4% in the control group. The secondary case (symptomatic) rate was 2.2% in the study eroun and 14.2% in the control eroun. These resuhs suggest that hand-washing has a positive interrupting effect, even in insanitary environments.