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Y Katz

Publications and source records attributed to Y Katz.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis of complement proteins in the human chorion is differentially regulated by cytokines.

The aim of the current paper was to determine the chorion's contribution to complement synthesis in the placenta and its regulation by cytokines. Biosynthetic labeling followed by immunoprecipitation with polyclonal antibodies was performed in chorionic tissue and chorion-derived cells. Eight complement proteins, factor B, C3, C1r, C1s, C1 inhibitor, factor H, C4 and C2 were detected in chorionic tissue and were secreted extracellularly. In chorion-derived cells, IL-1beta stimulated factor B synthesis but had no effect on C1r, C1 inhibitor, C1s, factor H and C4. TNFalpha had no stimulative effect on any of the complement proteins tested. In contrast, both IL-1beta and TNFalpha highly induced IL-6 secretion in chorion-derived cells, demonstrating the overall responsiveness of these cells to these stimuli. Interestingly, IFN-gamma increased the synthesis of C1s, C1r, C1 inhibitor, C4 and factor H in chorion-derived cells. The fact that the latter two complement proteins have opposing effects on immune activation of the complement cascade demonstrates the complex balance required to both maintain an ability to ward off infections but simultaneously suppress the immune response to enable tolerance of the allograft fetus.

Cells, Cultured↗
PubMed2005

Retrosternal block use in the treatment for dyspnoea.

We present a technique of retrosternal block for symptomatic treatment for dyspnoea of various aetiologies. In our experience with 20 patients, a retrosternal block using lignocaine improved symptoms within minutes. The block was easy to perform and was helpful when the patients' symptoms were not relieved by conventional therapy. Prospective controlled studies are needed to further assess this simple and promising treatment.

Aged↗
PubMed2003

Cysteine-induced hypoglycemic brain damage: an alternative mechanism to excitotoxicity.

Central neural damage caused by L-cysteine (L-Cys) was first reported more than 30 years ago. Nevertheless, the exact mechanisms of L-Cys-mediated neurotoxicity are still unclear. Preliminary study in mice demonstrated that, following L-Cys injection, animals developed tachypnea, tremor, convulsions, and death in conjunction with documented hypoglycemia. The aim of the present study was to further investigate the mechanism of L-Cys-mediated hypoglycemic effect and neural damage. Neonatal ICR mice (n=6) were injected with L-Cys (0.5-1.5 mg/g body weight [BW]), and their blood glucose and insulin levels were determined up to 90 min following the injection. Experiments were repeated in chemically (streptozotocin [STZ]) pancreatectomized animals. Brain histology was assessed. Mice injected with L-Cys exhibited dose-dependent neurotoxicity and higher mortality as compared with controls. L-Cys (1.2-1.5 mg/g BW) caused severe hypoglycemia (glucose<42 mg/dl) ( P<0.001). In STZ-treated (diabetic) animals, L-Cys (1.5 mg/g BW) increased plasma insulin levels 2.3-fold and decreased serum glucose levels by 50% ( P<0.01). Brain histology revealed destruction of as much as 51% of hippocampal neurons in the L-Cys-treated mice but not in the glucose-resuscitated animals. These findings suggest that L-Cys injection can cause pronounced hypoglycemia and central neural damage which is glucose reversible. Since L-Cys is chemically different from the other excitatory amino acids (glutamate and aspartate), L-Cys-mediated neurotoxicity may be connected to its hypoglycemic effect.

Animals↗
PubMed2003

Solubility, adsorption, and the thermodynamics of the cutoff effect.

For many years, the expression "cutoff effect of anesthesia," has been used to denote the failure of the higher alcohols or paraffins to produce anesthesia. As such, it is used to assess the plausibility of specific models, proposed for anesthesia. However, the uses were shown, in many respects, to be problematic. This article augments the notion of the cutoff to fit for all cases in which only some of the molecules in a homologous series are anesthetics. We find that the location of the cutoff points is affected by three free energy quantities: that of the adsorption of the agent to the anesthetic "site" (f(sl,site)), that of the perturbation of the site (f(ll,site)), and that of the evaporation of the agent from its pure condensed phase (Deltamu degrees (evaporation)). This outcome indicates that the cutoff cannot be attributed to a single parameter. In addition, the analyses that attribute the cutoff to the failure of compounds to obey the much-used Meyer-Overton correlation will have to be amended. This article shows that cutoff results can be used to elucidate the structure of a site.

Adsorption↗
PubMed2003

Allergy to sesame in humans is associated primarily with IgE antibody to a 14 kDa 2S albumin precursor.

The goal of this study was to identify and characterise the major allergen(s) of sesame seed. Detection of specific IgE to sesame proteins was performed with Pharmacia CAP System and Western blotting, after separation of sesame proteins by SDS-PAGE, using sera from 28 subjects diagnosed as allergic to sesame. The major allergen was separated by gel filtration chromatography and identified by selective proteolysis followed by peptide sequence analyses, employing electrospray-ionization mass spectrometer. Twenty-four of the 28 subjects had sesame-specific IgE. A 14 kDa protein belonging to the 2S albumin family was recognised by 22 of the 24 sera used. Subjecting the 14 kDa after HPLC separation to proteolysis with Lys C yielded 3 peptides, but only one reacted positively in the dot blot test. This peptide, corresponds in the whole protein chain to residues 24-94. The reactivity of the 14 kDa protein with most of the sera indicates that this is the major sesame allergen, later identified as 2S albumin precursor; and its peptide which reacted positively in the dot blot test evidently contains an epitope(s). Some minor sesame allergens, of higher molecular weight, were also revealed.

Adolescent↗
PubMed2003

Intramuscular administration of lidocaine or bupivacaine alters the effect of midazolam from sedation to hypnosis in a dose-dependent manner.

We examined the sedative/hypnotic interaction between the administration of intravenous (i.v.) midazolam and intramuscular (i.m.) lidocaine or bupivacaine. Women undergoing gynecological surgery (n = 150) were randomly assigned to 15 dose groups of 10 patients each. Fifty patients received one of five predetermined doses of midazolam for the calculation of its median effective dose (ED50). The remaining patients (n = 100) received i.v. midazolam 0.1 mg/kg following an i.m. injection of either bupivacaine, lidocaine, or saline (control). Three minutes after the i.v. dose, the loss of response to verbal command was evaluated. The ED50 of midazolam was 0.226 mg/kg (95% confidence interval [CI] 18-027; p = 0.03). Both bupivacaine and lidocaine enhanced the effect of midazolam in a dose-dependent fashion. The hypnotic ED50 for bupivacaine and lidocaine was 0.7 mg/kg (95% CI 0.5-1.0) and 3.32 mg/kg (95% CI 2.2-11.7), respectively. The slopes of the dose-response curves were significantly different (p < 0.01). Local anesthetics that are well within the range of clinical use for regional blocks or local infiltration can bring the effect of midazolam from the sedative into the hypnotic range.

Adult↗
PubMed2003

Successful delivery despite conception with a maximal endometrial thickness of 4 mm.

PURPOSE: To evaluate the minimal endometrial thickness at the time of ovulation at which conception is possible. METHODS: Treatment with luteal phase progesterone support after oocyte release despite attainment of a maximal thickness of 4 mm. RESULTS: A pregnancy and successful delivery were achieved. CONCLUSIONS: Pregnancy is possible with only a 4 mm peak endometrial thickness, at least when follicle maturing drugs are not used.

Adult↗
PubMed2003

Slow rising serial chorionic gonadotropins predict poor pregnancy outcome despite sonographic viability.

PURPOSE: To determine the prognosis of women with slow rising beta-hCG levels when viability is detected by ultrasound. METHODS: Serum beta-hCG levels were obtained every two to three days in the early first trimester. Doubling-time (DT) of beta-hCG levels was defined as DT exceeding 3.2 days. Sonography was performed at eight weeks and then after 12 weeks. RESULTS: There were 158 consecutive pregnancies evaluated and 111 (70%) had normal rising beta-hCG levels, viable ultrasound at eight weeks, and viable pregnancies after 12 weeks. There were 22 pregnancies with slow rising beta-hCG levels (13.9%) with 16 (72.7%) showing viability at eight weeks but not after the first trimester. A sac-crown rump length discrepancy with a sac smaller than normal was found in 11 of these 16 (68.7%) women. CONCLUSIONS: Patients with slow rising beta-hCG levels should not be given an optimistic prognosis even if viability is demonstrated at eight weeks.

Adult↗
PubMed2002

Large subcutaneous hematoma complicating epidural block.

We present a case of a large subcutaneous hematoma in the lumbar region that occurred after epidural block was performed for the relief of labor pain. Epidural analgesia was begun in a young and healthy primigravida. Eight hours later, she needed an emergency cesarean section. Before anesthesia, blood was observed flowing freely around the site of the catheter insertion. General anesthesia was administered. Postoperative computed tomography showed a large subcutaneous hematoma in the lumbar region. Her postpartum course was complicated by an unexplained fever, which responded to antibiotic therapy and warranted prolonged hospitalization. Coagulation and bleeding studies were normal. We conclude subcutaneous hematoma after epidural block can cause significant morbidity and should be added to the list of neuroaxial block complications.

Adult↗
PubMed2001

Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins 1,6, and 8 in skin and synovial fibroblasts: a possible role as a "fine-tuning cytokine" in inflammation processes.

OBJECTIVE: To compare the singular and combined effects of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-17 on messenger RNA (mRNA) expression, translation, and secretion of IL-6, IL-8, and IL-1beta in fibroblasts. METHODS: Fibroblasts were stimulated with the relevant cytokine(s), pulse labeled with 35S-methionine, and the newly synthesized proteins were immunoprecipitated and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gene expression was determined by Northern blot analysis. Secreted proteins were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-17 alone was a weaker stimulator of the transcription, translation, and secretion of other interleukins than was TNFalpha or IL-1beta. IL-17 (10 ng/ml) stimulated the expression of IL-6 mRNA by 1.3-fold, while TNFalpha (1 ng/ml) increased it by 3.7-fold, and IL-1beta (0.1 ng/ml) increased it by >30-fold. Unlike TNFalpha and IL-1beta, IL-17 hardly affected the expression of IL-8 and IL-1beta mRNA. Translation of IL-6 was 6.2 times greater with IL-17, but TNFalpha and IL-1beta stimulated it 28.9- and 174-fold, respectively. ELISA-measured secretion of IL-6 and IL-8 increased by 6.7 and 5.8 times, respectively, with IL-17, compared with 52 and 269 times with TNFalpha stimulation and 1,356 and 1,084 times with IL-1beta stimulation. Yet, when IL-17 was combined with other cytokines, these activities were stimulated much beyond the sum of the individual effects. The combination of IL-17 and TNFalpha induced the expression of IL-6 or IL-1beta mRNA 7 times more than their additive stimulation, and that of IL-8 mRNA 3.8 times more. Likewise, the secretion of IL-6 and IL-8 was 20 times and 5 times higher, respectively, than expected. This synergism started after 4 hours of combined treatment, and decayed after 24-48 hours regardless of cytokine presence. It could be blocked with anti-IL-17 but not with anti-IL-1. CONCLUSION: Our findings suggest that the primary role of IL-17 is to synergize with TNFalpha and to fine-tune the inflammation process. Therefore, IL-17 may be a potential target for therapeutic intervention.

Adult↗
PubMed2001

Intravenous midazolam significantly enhances the lethal effect of thiopental but not that of ketamine in mice.

Intravenous (i.v.) drug combinations are used in clinical anaesthesia in order to combine the desired effects and minimize toxicity from large doses of single agents. This fundamental assumption has not been systematically evaluated. We examined its validity by testing the influence of midazolam on the lethal effect of i.v. thiopental and ketamine in mice. Dose-response curves were constructed for the lethal effect of i.v. thiopental and ketamine, and for the loss of righting reflex effect by midazolam, in sexually mature male ICR mice weighing 20-40 g. For each curve, six or seven groups of eight to 10 mice each were used. A quarter of the median effective dose (ED50) for loss of righting reflex by midazolam was combined with the two other drugs to deduce dose-response curves for the lethal effect of the combinations. The ED50 for loss of righting reflex by i.v. midazolam was 43.5 mg x kg(-1) (95% confidence interval [CI], 40.4-46.5). The median lethal dose (LD 50) of i.v. thiopental was 50.6 mg x kg(-1) (95% CI, 50.0-54.9) and that of ketamine 42.9 mg x kg(-1) (95% CI, 32.3-52). In the presence of 10 mg x kg(-1) midazolam, the LD50 of thiopental was reduced to 20 mg x kg(-1) (17.7-22.2), but that of ketamine remained 44.4 mg x kg(-1) (37.7-54.9). Midazolam increased the lethal effect of thiopental 2.5-fold, but did not affect that of ketamine. Interactions at the toxic level between commonly used anaesthetic agents may differ from those at the hypnotic or analgesic levels, which should prompt evaluation of such combinations before their introduction to routine clinical use.

Anesthetics, Dissociative↗
PubMed2001

Extrahepatic synthesis of complement proteins in inflammation.

The demonstration of local complement protein synthesis leads to speculation as to the biological significance of this phenomenon. A narrative review is provided to illuminate several queries. It is difficult to establish a causal role for the locally produced complement because participation of systemic complement cannot be excluded. It is also difficult to discern whether local complement synthesis is a beneficial response to an inflammatory event or whether it promotes tissue damage. Finally, it remains to be seen if the roles of local and systemic complement differ in these respects. Extrahepatic expression of complement components of the activation pathways may provide a rapid response to microbial invasion. Once produced and activated, these proteins evoke a phlogistic response composed of cells and soluble mediators of inflammation. Many cells, not only synthesize complement proteins, but can also be stimulated via their complement receptors. This positive feedback may enhance local immune defense, especially in organs isolated from plasma components. In addition, local environmental factors in different organs may differentially regulate complement synthesis. These factors may include pro-inflammatory molecules and non-immune effectors, such as tissue ischemia/reoxygenation and drugs. Local complement dysregulation due to inhibition of activity of a complement regulatory component was shown to cause disease and restoration of the capacity to regulate the complement pathway restored health. Extrahepatic complement synthesis may also modulate local cellular responses, as to decrease detrimental damage of the inflammatory reaction. The demonstration that complement proteins play a significant role in the clearance of apoptotic cells suggests that local synthesis and activation of complement may contribute not only to tissue damage but also to tissue repair.

Arthritis↗
PubMed2001

Prodrugs of butyric acid. Novel derivatives possessing increased aqueous solubility and potential for treating cancer and blood diseases.

The synthesis and biological activities of acidic, basic and neutral types of butyric acid (BA) prodrugs possessing increased aqueous solubility are described. The compounds are butyroyloxyalkyl derivatives of carboxylic acids, which possess functionalities suitable for aqueous solubilization. The anticancer activity of the prodrugs in vitro was evaluated by examining their effect on the growth of human colon, breast and pancreatic carcinoma cell lines, and their solubility in aqueous media was determined. The most promising compounds, with respect to activity and solubility, were found to be the butyroyloxymethyl esters of glutaric 2a and nicotinic acids 4a and phosphoric acid as its diethyl ester 10a, which displayed IC(50) values of 100 microM or lower. These prodrugs are expected to release formaldehyde upon metabolic hydrolysis. The corresponding butyroyloxyethyl esters (2b, 4b and 10b) that release acetaldehyde upon metabolism were significantly less potent. A similar correlation was observed for growth inhibition of the human prostate carcinoma cell lines PC-3 and LnCap and for induction of differentiation and apoptosis in the human myeloid leukemia cell line HL-60. The higher biological activity of the formaldehyde-releasing prodrugs 2a and 10a was further confirmed when induction of hemoglobin (Hb) synthesis in the human erythroleukemic cell line K562 was measured. Moreover, a therapeutic index (IC(50)/ED(50)) of ca. 5 was observed. The acute i.p. toxicity LD(50) in mice for 2a, 2b, 10a and 10b was similar and in the range of 400-600 mg kg(-1). The results obtained support the potential use of the butyric acid prodrugs for the treatment of neoplastic diseases and beta-globin disorders.

Animals↗
PubMed2001

A corpus luteum is not a prerequisite for the expression of progesterone induced blocking factor by T-lymphocytes a week after implantation.

PURPOSE: To determine if production of the immunomodulatory protein, progesterone induced blocking factor (PIBF), requires merely progesterone or whether other factors made by the corpus luteum are required. METHODS: The percentage of peripheral lymphocytes expressing PIBF was determined by obtaining a blood sample from women 9-12 days after embryo transfer. The embryos were either fresh ones following hyperstimulation and oocyte retrieval or were frozen-thawed embryos. Preparation for frozen embryo transfer required corpus luteum suppression with exogenous estrogen. The percentage of lymphocytes expressing PIBF was determined by an immunocytochemistry method. RESULTS: PIBF expression (>1%) was found in 20.5% of COH and 13.3% of frozen embryo transfer cycles. There either was a significant difference or a trend for higher pregnancy rates when PIBF expression was detected. CONCLUSIONS: These data corroborate previous conclusions that PIBF is detected in a minority of women in the late luteal phase. A corpus luteum is not required for its expression.

Corpus Luteum↗
PubMed2001

High insulin requirements and poor metabolic control do not modify the expression, regulation and PKC mediated activation of the p21ras pathway in PBMC from type II diabetic patients.

AIMS: To asses whether clinically severe insulin resistance and poor metabolic control in patients with type 11 diabetes are associated with aberrant expression or function of the p21ras pathway. METHODS: We examined the expression and function of the p21ras pathway in resting and activated PBMC from 10 insulin treated patients with type II diabetes characterized by high insulin requirements and poor metabolic control (IR group) and 10 age and sex matched well controlled patients treated by diet alone or oral hypoglycemic medications (WC group). RESULTS: Levels of p21ras and its regulatory elements: p21rasGAP and hSOS1, were comparable in the two groups. The induced activities of p21ras and its associated down-stream regulatory enzyme MAP-kinase following TPA stimulation were also comparable in the IR and WC patients. CONCLUSIONS: Taken together, these data indicate that clinically significant severe insulin resistance does not modify the expression, regulation and activation of p21ras pathway in PBMC of patients with type II diabetes.

Aged↗