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H Ashkenazi

Publications and source records attributed to H Ashkenazi.

7 recordsLinked to original sources

Resumption of oocyte meiosis in mammals: on models, meiosis activating sterols, steroids and EGF-like factors.

De novo synthesis of meiosis activating sterols (MAS) was stimulated by LH- and AY-9944 in rat cultured follicles and cumulus oocyte complexes (COCs), but could not be measured in denuded oocytes. Thus, MAS synthesized by the somatic compartment of the follicle could serve as a signal for the resumption of meiosis. Nevertheless, the delay in germinal vesicle breakdown (GVB) after MAS or AY-9944 stimulation as compared with gonadotropins, obtained by several groups, remains the strongest evidence against the suggested role of MAS as an essential mediator of LH in meiosis resumption. Recently several studies using mammalian COCs in culture have implied that steroids, like in fish and amphibians, serve as signals in mediating the LH/hCG stimulation of meiosis. However, in these studies there was no clear distinction between the requirement for steroids for the acquisition of meiotic competence, oocyte and follicle wellbeing or as a signal for meiotic resumption. Further, some of the authors overlooked earlier studies showing that blocking ovarian or follicular steroidogenesis does not affect GVB, the first step of meiosis resumption. Finally, in vivo and in vitro studies in the rat confirm and extend recent studies showing that locally produced and released EGF-like factors, such as epiregulin, seem to mediate at least part of the LH/hCG actions on oocyte maturation and release of ova at ovulation.

Animals↗

Epidermal growth factor family members: endogenous mediators of the ovulatory response.

Previous studies showed that epidermal growth factor (EGF) and TGFalpha mimic the action of LH on the resumption of oocyte maturation. We tested whether EGF-like agents, such as amphiregulin (AR), epiregulin (ER), and betacellulin (BTC), also mediate the LH stimulation of the ovulatory response in the rat. LH induced transient follicular expression of AR, ER, and BTC mRNA, reaching a maximum after 3-h incubation. Furthermore, the addition of ER, AR, and BTC to the culture medium could mimic some of LH actions. AR and ER fully simulated LH-induced resumption of meiosis in vitro, whereas BTC was less effective. To study the putative involvement of EGF-like factors in mediation of LH signal, the effect of the EGF receptor kinase inhibitor AG1478 was tested. When added with LH, AG1478, but not its inactive analog AG43, reduced EGF receptor phosphorylation and oocyte maturation compared with follicles treated with LH only. In addition to the inhibition of resumption of meiosis, AG1478 administration into the bursa (3 microg/bursa) resulted in 51% (P < 0.0005) inhibition of ovulation in the treated ovaries, compared with the untreated contralateral ones, as well as to the vehicle-treated ovaries (P < 0.02). LH, as well as ER, induced the expression of genes associated with the ovulatory response like rat hyaluronan synthase-2, cyclooxygenase-2, and TNFalpha-stimulated gene 6 mRNA, whereas AG1478 inhibited this effect of LH. Release of EGF-like factors from the membrane is dependent on activated metalloproteases. Indeed, Galardin, a broad-spectrum metalloprotease inhibitor, but not a specific matrix metalloprotease 2 and 9 inhibitor, suppressed meiotic maturation induced by LH. Conversely, meiotic maturation induced by ER was not affected by Galardin, thus, supporting the notion that LH releases follicular membrane-bound EGF-like agents. In summary, EGF-like factors such as ER, AR, and BTC seem to mediate, at least partially, the LH stimulation of oocyte maturation, ovulatory enzyme expression, and ovulation.

Amphiregulin↗

Photoinactivation of Acinetobacter baumannii and Escherichia coli B by a cationic hydrophilic porphyrin at various light wavelengths.

Photodynamic treatment by the cationic TMPyP photosensitizer was undertaken on the multiple antibiotic-resistant bacteria Acinetobacter baumannii and Escherichia coli. Total eradication of the bacterial cultures was determined immediately after initiation of illumination when these bacteria were treated with 5, 10, 15, 20-tetra (4-N methylpyridyl)porphine (TMPyP) at a concentration of 29.4 micromol/L and illuminated by blue, green, or red light. Total eradication of both bacteria was obtained also after treatment of bacterial cultures with 3.7 micromol/L TMPyP and illumination with blue light (400-450 nm). On the other hand, an 8- or 16- to 20-fold higher light intensity, respectively, was required for total eradication upon illumination with green (480-550 nm) or red light (600-700 nm). A 407-nm blue light only 7 and 9 joules/cm2, respectively, was needed for total eradication of both bacteria even at a concentration of 3.7 micromol/L TMPyP. X-ray-linked microanalysis demonstrated loss of potassium and a flood of sodium and chloride into the cells, indicating serious damage to the cytoplasmic membrane. Transmission electron microscopy (TEM) revealed structural changes and damage to the membrane of treated E. coli. In A. baumannii-treated cells, mesosomes and black dots that resemble aggregation of polyphosphate polymers could be seen. DNA breakage appeared only after a long period of illumination, when the bacterial cell was no longer viable. It can be concluded that cytoplasmic membrane damage and not DNA breakage is the major cause for bacterial death upon photosensitization.

Acinetobacter↗

Incidence of immunoglobulin G antibodies to Chlamydia pneumoniae in acute myocardial infarction patients.

BACKGROUND: Recent studies have suggested a possible association between Chlamydia pneumoniae infection and coronary heart disease. OBJECTIVES: To determine titers of antibodies to C. pneumoniae in patients with acute myocardial infarction compared with titers in several control groups. METHODS: This prospective case-control study investigated 209 individuals. We assessed the serum IgG antibody titers to C. pneumoniae in 57 consecutive patients admitted with AMI to our intensive coronary care unit during a 4 month period. A serum sample was drawn upon admission and after 6 weeks. Results were compared with those of four control groups: a) patients admitted with community-acquired pneumonia (n = 18), b) patients with community-acquired urinary tract infection (n = 42), c) patients with angiographically normal coronary artery disease (n = 44), and d) patients with stable coronary artery disease (n = 48). Serum immunoglobulin G antibody titers to C. pneumoniae were determined using standard micro-immunofluorescence technology. RESULTS: Of 57 patients with AMI, 32 (56%) had a high IgG titer to C. pneumoniae (> or = 1:256) on the initial test, which remained unchanged (62%) after 6 weeks. The percentage of patients with high titers was significantly lower in the control groups: 5 of 18 patients (28%) in the pneumonia group (P < 0.01), 11 of 42 (26%) in the urinary tract infection group (P < 0.01), 11 of 44 (25%) with normal coronary arteries (P < 0.01), and 17 of 48 (35%) with stable chronic ischemic heart disease (P < 0.05). CONCLUSION: The detection of high titers of IgG antibodies to C. pneumonia in many patients with AMI, compared to control groups, suggests that chronic Chlamydia pneumoniae infection plays a role in the pathogenesis of atherosclerosis and acute ischemic events.

Antibodies↗

Eradication of Acinetobacter baumannii by photosensitized agents in vitro.

The photodynamic effects of photosensitizers on Acinetobacter baumannii were studied. These Gram negative bacteria have recently been implicated in various infections, mainly acquired in hospitals. They have outstanding characteristics of multidrug high resistance to antimicrobial agents. The best photodynamic effect was obtained when A. baumannii cultures were treated with light activated deuteroporphyrin (Dp) at a concentration of 34 mumoles l-off and polymyxin nonapeptide (PMNP) at a concentration of 200 mumoles l-1. At these concentrations the culture in brain heart infusion (BHI) broth was found to be sterile after l h of treatment. Some inhibition was also obtained under the same conditions with Cd-texaphyrin (Cd-Tx) in the presence of PMNP. Treatment with various other photosensitizers in the presence of PMNP exhibited only marginal antibacterial activity. The cationic photosensitizer tetra-methylpyridyl porphine (TMPyP) did not exhibit any photodynamic effect on A. baumannii when illuminated during its growth in BHI broth. Bacteria grown in nutrient broth or suspended in saline and treated by TMPyP resulted in a significant photoinactivation by the sensitizer alone even in the absence of PMNP. It was found that a high concentration of the proteins present in BHI or in serum prevent TMPyP from acting as a photosensitizer against A. baumannii. Bovine serum albumin at the same high protein concentration prevents Dp (in the presence of PMNP) to act as a photosensitizer. The anionic photosensitizer tetra-sulfonatophenyl porphine (TPPS4) did not show any photodynamic effect in high or low protein media. In this study it was found that despite the high resistance of the Acinetobacter baumannii to antibiotics, these bacteria can be significantly photoinactivated by treatment with either Dp + PMNP or TMPyP in low protein content environments. When the protein concentration is high photoinactivation efficiency depends on the type of protein present in the medium.

Acinetobacter↗

Sebaceous cyst excision with minimal surgery.

Sebaceous cysts are common benign tumors found on the scalp, ears, retroauricular areas, scrotum, face and thorax. A technique involving minimal surgical trauma and good cosmetic results is described. In a series of 302 patients, the recurrence rate was extremely low (0.66 percent) during 18 months of follow-up. Experience with a minimal-incision technique suggests that this method is a satisfactory alternative to conventional, more invasive surgery.

Epidermal Cyst↗