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Biomedical subjects

L Israel

Publications and source records attributed to L Israel.

At least 19 recordsLinked to original sources
PubMed2005

Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination.

BACKGROUND: Aspergillus fumigatus is a pathogenic mould causing allergic and invasive respiratory diseases. Allergic bronchopulmonary Aspergillosis (ABPA) is a severe pulmonary complication resulting from hypersensitivity to A. fumigatus proteins. Aspergillus allergen Asp f6 is recognized by IgE from ABPA patients, but not from sensitized individuals, a fact that can be used to differentiate between these two groups of allergic patients. METHODS: Proteins from hyphae, resting and germinating conidia of A. fumigatus were compared by SDS-PAGE. Protein identification was performed using MALDI-TOF mass spectrometry. Recombinant A. fumigatus allergens were used to isolate specific monoclonal antibodies (mab) from a hybridoma bank generated against Aspergillus proteins. RESULTS: A hyphae-specific 23 kDa A. fumigatus protein was identified as the allergen Asp f6/manganese-dependent superoxide dismutase (MnSOD). Differential expression of MnSOD was confirmed by immunoblot using a specific mab. In contrast, Asp f8 another intracellular, but not ABPA-specific allergen, was detected in hyphae and conidia. CONCLUSIONS: Aspergillus fumigatus is able to colonize its environment by the formation of hyphae. Hyphae are found in the lung of ABPA patients, but not in patients suffering from atopic asthma. Our finding that Asp f6 is specifically expressed in hyphae might explain why an IgE response to Asp f6 is specific for ABPA patients.

Allergens↗
PubMed2002

Long-term effects of the mammary carcinogen 7,12-dimethylbenz(a) anthracene on hypothalamic gonadotropin-releasing hormone and its pituitary receptor gene expression, during the promotion stage, in female Sprague-Dawley rats.

A single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA) has been shown to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of these tumors is preceded by a series of neuroendocrine disturbances, including attenuation of the preovulatory luteinizing hormone (LH) surge and amplification of the preovulatory 17beta-estradiol surge, and gonadotropin-releasing hormone (GnRH) released in vitro. In this study, we examined the hypothesis that DMBA administration decreases levels of GnRH mRNA in the preoptic area-anterior hypothalamus (POA-AH) and GnRH receptor (GnRH Rc) mRNA and protein in the anterior pituitary gland. Sprague-Dawley rats, 55-60 days of age with regular estrous cycles, received a single dose of 15 mg DMBA in 1 ml sesame oil delivered by intragastric intubation. A first series of experiments was performed for the measurement of hypothalamic GnRH mRNA and pituitary GnRH Rc mRNA levels. A second series of experiments was performed for the measurement of pituitary GnRH receptor. In both experiments, animals were sacrificed by decapitation at 11.00, 16.00, 18.00 and 20.00 h on each day of the 7th or 8th estrous cycle (28-32 days) after treatment. GnRH and GnRH receptor mRNAs were quantified using solution hybridization-RNase protection assay. The GnRH Rc was quantified using the 125I-D-Ala6-N-Met-Leu6-des-Gly10-ethylamide GnRH. DMBA-treatment produced no significant effect on the overall mean values of GnRH mRNA. GnRH mRNA levels in control rats rose significantly between 16.00 and 20.00 h on proestrus and between 18.00 and 20.00 h on diestrus I. DMBA-treated rats had a surge in GnRH mRNA levels at 18.00 h on proestrus, and showed additional surges at 18.00h on diestrus II and estrus. GnRH receptor mRNA content in the anterior pituitary gland surged at 16.00h on certain days of the cycle in both groups of rats. In control rats, only the surge on diestrus II proved significant, whereas DMBA-treated rats exhibited significant surges on diestrus I, diestrus II and proestrus. GnRH receptor mRNA values were significantly lower on both days of diestrus in DMBA-treated rats compared with controls. GnRH Rc peptide content, like GnRH receptor in RNA surged at 16.00h in both groups with the exception of a marked fall on proestrus day for DMBA treated rats. A reduction in the amplitude of the surge was also seen on the day of estrous and to a lesser extend on the day of diestrus DII in DMBA treated animal. Overall, there was a disruption of the GnRH Rc pattern which culminate on the day of proestrus in DMBA-treated animals. Interestingly, the daily rise between 11.00 and 16.00h which is the more pronounced on the day of proestrus in control animals, was completely blunted in DMBA-treated rats. Overall, the results are consistent with the hypothesis that the carcinogen attenuates, directly or indirectly, preovulatory biosynthesis of the GnRH receptor and LH release. Obviously, the changes in GnRH might occur simultaneously, independently from mammary tumorigenesis, but may play a role, in association with others DMBA-induced neuroendocrine disorders, in the promotion stage of mammary tumors in the Sprague-Dawley female rat.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

The work impact of asthma and rhinitis: findings from a population-based survey.

Asthma and rhinitis are common chronic conditions that affect adults of working age. Little is known about their relative impacts on work loss and decreased productivity. Using random digit telephone dialing, we carried out a population-survey of adults in Northern California aged 18-50 years. We interviewed 125 persons with asthma (with or without concomitant rhinitis) and 175 persons with rhinitis alone. Study eligibility was based on subject report of a physician's diagnosis of asthma and/or a rhinitis-related condition. Any adult labor force participation since condition onset was lower among those with asthma (88%) than among those with rhinitis alone (97%) (P = 0.002). In contrast, among those still employed, decreased job effectiveness was more frequently reported in the rhinitis group (43 of 121; 36%) compared to those with asthma (14 of 72; 19%) (P = 0.02). Condition-attributed lost work was common in both groups, with more than 20% reporting one or more complete or partial work days lost in the 4 weeks previous to interview. Taking into account age, gender, race, and smoking status, those with asthma were more likely to have no labor force participation after diagnosis (OR = 3.0; 95% CI 1.1-7.7) and less likely to report decreased job effectiveness among those remaining employed (OR = 0.4; 95% CI 0.2-0.9). Excluding subjects from the rhinitis group most likely to have unreported asthma based on past medication use had little impact on these associations. Both asthma and rhinitis negatively affect work productivity. Those with asthma are less likely to be employed at all, while among those remaining on the job, rhinitis is a more potent cause of decreased work effectiveness. The economic impact of asthma and rhinitis and related conditions may be under-appreciated.

Absenteeism↗
PubMed2001

Why barium enemas fail to identify colorectal cancers.

BACKGROUND: The aim of the present study was to determine the cause and clinicopathological factors associated with the failure of barium enemas to detect colorectal cancers. METHODS: A histopathological database was used to identify all patients with a diagnosis of colorectal cancer between 1991 and 1995. These records were matched with the records from patients who underwent barium enema examinations between 1990 and 1995. Those patients who had a colorectal cancer histologically diagnosed within 24 months of a barium enema in which no carcinoma was seen, were identified. Where possible the radiology was reviewed. Failure to identify a carcinoma was then attributed to either simple failure, technical, interpretive or perceptive difficulties. RESULTS: There were 967 patients with colorectal cancers treated in Christchurch Hospital during the study period 1991-1995. Matching of these patient details with all barium enema records revealed 313 patients who had barium enemas and histologically proven colorectal cancer. There were 21 (6.7%) patients in whom a carcinoma was missed. Of these, 18 had a barium enema within 8 months of surgery, and three were performed outside this timespan (15, 18 and 28 months, respectively). On review, 11 carcinomas could not be identified (nine due to technical error: poor coating (n = 1), overlapping loops (n = 3), single-contrast enema (n = 4), faecal residue (n = 1)); and seven could be seen on review of the films (two interpretation errors, one technical and perceptive error, and four perceptive errors). In three cases films could not be found for review. In 16 of the 21 missed lesions the patient had a double-contrast barium enema (DCBE) while five patients had single-contrast barium enema (SCBE). The site and stage of missed tumours is presented. CONCLUSIONS: The most common reason for missed tumours was technical. The percentage of missed tumours in each region of the bowel correlates with the known incidence of tumours in each region and with a normal Dukes stage distribution, except in the caecum where the number of missed lesions was higher than expected.

Aged↗
PubMed2000

[Legislating the precautionary principle and physician patient relations in the area of severe diseases with uncertain outcomes. Some proposals].

The application to medicine of the caution principle goes with increasing legal problems between patients and doctors. In the field of severe diseases with uncertain outcome are analyzed below some possible ways of remedying a situation which could induce from doctors a reluctance to take some necessary risks. These ways could consist on one part to include a special training and perhaps selection of the practitioners involved, in order to insure that all the needs of their patients, psychologic, spirituals, culturals, ethicals will be met with. On another part it is proposed that decision theory should be fully studied in medical school in order to allow physicians to explicitly include in medical records the evaluation of risks and the rationale for choosing a given strategy, with regards to what is known objectively and subjectively about different probabilities, which were the utilities and preferences and scientific as well as ethic criteria considered in a given situation of uncertainty.

Culture↗
PubMed1999

The association between occupation and asthma in general medical practice.

BACKGROUND: In general practice settings, the proportion of adult asthma attributable to occupational factors is not known. OBJECTIVE: The goal of this study was to estimate the proportion of adult asthma cases that can be attributed to occupational factors initiating new disease onset and exacerbating preexisting disease. METHODS: We performed a cross-sectional analysis of interview data for 150 adults with asthma recruited from a random sample of family practice specialists. We ascertained the asthma and work histories of the subjects and estimated the proportion with likely work-initiated asthma and work-related asthma recrudescence. RESULTS: Seventy-four subjects (49%) reported adult-onset asthma while employed; an additional 25 (17%) reported recrudescence of previously quiescent childhood-onset asthma during employment. Of those with new-onset asthma while employed, 15 (10% of the study group; 95% confidence interval, 5 to 15%) were employed in occupations at increased risk of occupational asthma initiation on the basis of an independent job scoring matrix. Of those with asthma recrudescence in adulthood, seven (5% of the study group; 95% confidence interval, 2 to 8%) were employed in occupations at increased risk of exposures aggravating asthma. CONCLUSIONS: Among adults with asthma treated in general practice settings, > 1 in 10 patients has a work history strongly suggestive of a potential relationship between exposure and disease.

Adolescent↗
PubMed1998

Human sperm NADH and NADPH diaphorase cytochemistry: correlation with sperm motility.

OBJECTIVES: We have examined the correlation between the retention of residual sperm cytoplasm and sperm motility in semen from men presenting for infertility evaluation. METHODS: Semen samples (n = 12) were obtained from nonazoospermic men presenting for infertility evaluation at our institution. Samples were fractionated into high-, intermediate-, and low-density subpopulations by Percoll gradients in order to examine the correlation between the retention of residual sperm cytoplasm and sperm motility. Residual sperm cytoplasm retention was detected by cytochemical staining of sperm for nicotinamide adenine dinucleotide (NADH)- or nicotinamide adenine dinucleotide phosphate (NADPH)-dependent diaphorase activity. RESULTS: The different sperm subpopulations (low, intermediate, and high density) had significantly different percentages of sperm with droplet retention (analysis of variance, P < 0.05). Using either NADH or NADPH diaphorase staining as a marker of the cytoplasmic space, a significant negative correlation was observed between the percentage of sperm with residual cytoplasmic droplets and the percentage of motile sperm (r = -0.58 and -0.61, respectively, P < 0.05). CONCLUSIONS: Assessment of residual sperm cytoplasm retention is a simple diagnostic test. Although this test is of unproven value in the management of infertile men, this and other studies suggest that it may provide useful data on sperm function.

Dihydrolipoamide Dehydrogenase↗
PubMed1997

[A critical review of available tools for evaluating memory enhancers in Alzheimer's disease].

The study reviews critically the neuropsychological measurement tools available to assess the efficacy of potential memory enhancers in patients with Alzheimer's disease (AD). A review of some concepts concerning the characteristics of memory impairment in AD patients and of problems related to the selection of a study population provides a framework for this analysis. The tools available for efficacy evaluations are then classified according to their conceptual and formal characteristics: psychometric tests, rating scales and clinician global assessment tools. In each category the instruments were assessed according to several criteria: construct and ecological validity; sensitivity to changes in symptomatology; inter-rater reliability and the reliability of equivalent forms; feasibility for use with AD patients, especially brevity, to encourage their cooperation. Examining advantages, drawbacks and limitations of instruments in each category yields two conclusions: no single instrument scale or test battery fills all the criteria for a clinical trial, but these imperfect instruments are complementary. Accordingly, a battery including the three categories of instruments and allowing for investigation of the different memory systems has been proposed.

Alzheimer Disease↗
PubMed1996

Tumour progression: random mutations or an integrated survival response to cellular stress conserved from unicellular organisms?

The current paradigm states that cancer progression is caused by random independent mutations, each selected for its survival advantages. The accelerated rates of phenotypic changes, the pleiotropic effect of several genes involved in progression--which need not be necessarily mutated for inducing the observed changes in cancer cell behaviour--lead us to propose an alternative hypothesis. Malignant progression might be a result of the unveiling of a cell-survival program, induced by various aggressions in the same way as the SOS system is induced and regulated in bacteria. This hypothesis depends on the homology between several genes involved in cancer progression (such as bcl2, mdm2, the mismatch repair genes, the heat shock protein genes, the pleiotropic resistance genes, the telomerase gene ...) and several genes involved in the survival of prokaryotes and eukaryotes under stress. The development of multicellular organisms could not take place without the building of a control program, exemplified by the so-called anti-oncogenes. However, this control program had to integrate some weaknesses, in order to allow for embryogenesis, growth, and wound healing. These weaknesses, neutral from an evolutionary point of view--since most cancers are sporadic and kill their hosts long after the birth of the offspring--are exploited by the survival program of individual cells, inherited from the genome of prokaryotes and unicellular eukaryotes, and repressed but not suppressed in animals. If this theory is true, it is probable that (i) no anti-oncogenes will be found in unicellular organisms, (ii) the sensitivity to mutations will be higher in genes involved in proliferation and in anti-oncogenes such as p53 and Rb, than in genes not involved in the cancer process, (iii) a process of transfer of genetic information exists in cancer cells as it exists in bacteria. The identification of the genes governing the survival program could lead to new therapeutic approaches.

Animals↗
PubMed1995

Candida epiglottitis in an adult with acquired immunodeficiency syndrome treated with oral fluconazole.

Candida epiglottitis has been reported in immunocompromised patients, but in only one paediatric patient with human immunodeficiency virus. We present possibly the first reported case of Candida infection of the epiglottis in an adult with human immunodeficiency virus treated with oral fluconazole. We review the symptoms, diagnosis, and management of the published cases of Candida epiglottitis in patients without the human immunodeficiency virus. Laryngoscopy and culture are diagnostic.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Selective interactions between mammary epithelial cells and fibroblasts in co-culture.

Paracrine interactions between breast-cancer cells (MCF7) and stromal fibroblasts were studied in relation to the presence of steroid hormones, using co-cultures in which the 2 populations were separated by a microporous membrane. Densities and DNA-synthesis rates of the co-existing populations were interrelated. Proliferation was, therefore, viewed as the cumulative result of several factors, some of which are non-specific, e.g., are density-dependent, and some are specifically related to the feeders' origin and/or to culture conditions. Specific effects were measured and evaluated by stepwise analysis of covariance. MCF7 stimulated proliferation of fibroblasts differentially. Malignant-tumour fibroblasts were stimulated more than non-pathological ones. The magnitude of these effects was dependent on the presence of steroids. A similar analytical method was used for evaluating differential stromal influences on 4 epithelial phenotypic characters commonly used as prognostic markers. The estrogen-receptor, progesterone-receptor, pS2 and cathepsine-D phenotypes of MCF7, as well as their interrelations, were dependent on the origin of the fibroblasts, i.e., embryonic or adult, normal or tumoral.

Adenocarcinoma↗
PubMed1994

Fibroblast-mediated differentiation in human breast carcinoma cells (MCF-7) grown as nodules in vitro.

The growth of cells in 3-dimensional form as nodules in vitro facilitates studies of in vivo cellular interactions. Taking advantage of this technique, human breast carcinoma cells (MCF-7) were co-cultured with stromal fibroblasts isolated from either normal or tumorous breast tissue to study the influence of such fibroblasts on tumor-cell growth and differentiation. Ten days after co-culture of carcinoma cells with fibroblasts from normal tissue at a 1:10 ratio, the size of nodules began to increase and stabilize by day 30 while the fibroblast number decreased and finally disappeared. Concurrently, the carcinoma cells underwent a progressive redifferentiation process which histologically resulted in the appearance of highly developed papillar and tubular structures after 2 months in culture. The production of mucins was further evidence that these cells had undergone differentiation. By contrast, when MCF-7 cells were grown alone or with fibroblasts isolated from a breast carcinoma, the nodules continued to exhibit their characteristic histodedifferentiation properties and did not grow. The re-establishment of a normal epithelial state of differentiation in MCF-7 carcinoma nodules indicates that the phenotypic characteristics of tumor cells are reversible and are influenced or controlled by the stromal environment by which these tumor cells are surrounded or in contact with. Overall, our results open the possibility of exploiting the effects that connective tissue cells have on tumor-cell differentiation for use in prevention and treatment of cancer.

Breast Neoplasms↗
PubMed1994

Proliferative responses of epithelial cells to 8-bromo-cyclic AMP and to a phorbol ester change during breast pathogenesis.

We have explored the relationship of changes in proliferative responses of human mammary epithelial cells to a phorbol ester (TPA) and to 8-Br-cAMP, which modulate the activities of protein kinases A and C (PKA and PKC), with breast tumour progression. Treatment with TPA had no effect on nontumorigenic cell lines established from human fibrocystic biopsies and apparently normal tissue around a tumour. In contrast, TPA strongly inhibited the proliferation of numerous human tumorigenic breast cell lines. Treatment with 8-Br-cAMP decreased the proliferation of all studied nontumorigenic and tumorigenic cell lines. We have also studied the effect of TPA and 8-Br-cAMP on growth of epithelial cells in short-term culture obtained from surgical human mammary biopsies with different states of breast disease. Both drugs enhanced growth of normal breast cells but had no significant effects on cells from biopsies with benign breast disease. In contrast, all examined cultures from breast cancer biopsies were strongly inhibited by 8-Br-cAMP. Otherwise, TPA had an inhibitory effect only in the case of invasive ductal carcinoma of grade III. Malignant Ha-ras-transformation of nontumorigenic TPA-insensitive breast HBL-100 cells induced an inhibitory effect of TPA. In addition, a TPA-insensitive MCF7 clone was much less tumorigenic in athymic mice than the parental strain shown to be inhibited by TPA. These data suggest that the two intracellular transduction pathways change at different stages of breast pathogenesis. Alterations in the PKA pathway are early events and are probably important to cell immortalization but do not necessarily lead to malignant development. In contrast, changes in PKC pathway are rather later events associated with advanced malignant transformation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Cisplatin-5-fluorouracil in small cell lung cancer. A phase II study in 109 patients.

One hundred nine previously untreated patients with small cell lung cancer were treated for five consecutive days with 20 mg/m2/day of cisplatin and 600 mg/m2/day of 5-fluorouracil. One cycle of chemotherapy was administered every three weeks. The patients received a median number of three cycles. Then they were transferred to CAE chemotherapy. A 77% overall response rate (95% confidence interval of 0.70-0.85) was observed after initial cisplatin-5FU treatment. Twenty-three complete responses (21%) and 62 partial responses (56%) were obtained. In cerebral metastases the response rate was high at 91% (21 out of 23), with 43% complete responses. In the limited forms, statistical survival at 1 year was 25%. A Grade 3-4 thrombocytopaenia was observed in 10 patients (9%) and a Grade 2-3 leukopaenia in four patients. Three patients suffered from a Grade 2 cardiac toxicity. The cisplatin-5-fluorouracil combination demonstrates promising initial response rate in small cell lung cancers. Its main interest is in its important action on cerebral metastases and its moderate haematological toxicity.

Adult↗
PubMed1994

Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment.

A double-blind randomized trial was performed involving 162 patients with age-associated memory impairment (AAMI) selected and followed by their general practitioners. Two intervention methods--a drug and a cognitive therapy--were assessed in combination. Three randomized parallel groups of 54 patients each, aged 55 years and over, were followed and treated for 3 months. After a placebo wash-out period of 10 days, one group received 2.4 g of piracetam, another group, 4.8g, and the third, a placebo. A total of 135 patients, 45 in each group, completed the study. Combined therapy was most effective in patients whose baseline performance on memory tests was lowest. The best results were observed with 4.8 g of piracetam, especially when training sessions began after 6 weeks of drug treatment. This result was confirmed by the global impression of the principal investigator.

Aged↗