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Biomedical subjects

R Gross

Publications and source records attributed to R Gross.

At least 127 records · Page 7Linked to original sources

The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides.

Resistance profiles of the two Bordetella species B. bronchiseptica and B. pertussis against various antimicrobial peptides were determined in liquid survival and agar diffusion assays. B. bronchiseptica exhibited significantly higher resistance against all tested peptides than B. pertussis. The most powerful agents acting on B. bronchiseptica were, in the order of their killing efficiencies, cecropin P > cecropin B > magainin-II-amide > protamine > melittin. Interestingly, for B. bronchiseptica, the resistance level was significantly affected by phase variation, as a bvgS deletion derivative showed an increased sensitivity to these peptides. Tn5-induced protamine-sensitive B. bronchiseptica mutants, which were found to be very susceptible to most of the cationic peptides, were isolated. In two of these mutants, the genetic loci inactivated by transposon insertion were identified as containing genes highly homologous to the wlbA and wlbL genes of B. pertussis that are involved in the biosynthesis of lipopolysaccharide (LPS). In agreement with this finding, the two peptide-sensitive mutants revealed structural changes in the LPS, resulting in the loss of the O-specific side chains and the prevalence of the LPS core structure. This demonstrates that LPS plays a major role in the resistance of B. bronchiseptica against the action of antimicrobial peptides and suggests that B. pertussis is much more susceptible to these peptides due to the lack of the highly charged O-specific sugar side chains.

Anti-Bacterial Agents↗

Which primary care physicians treat depression?

The study attempted to determine the proportion of primary care physicians who treat depression and their characteristics. Data were from 677 respondents to a national survey of primary care physicians in Israel. Twenty-two percent always treated depression, 36.6 percent usually did, 28.6 percent sometimes did, and 12.6 percent never did. Logistic regression found that, compared with physicians who sometimes or never treated depression, those who always or usually treated depression treated more medical conditions, regarded themselves as the medical system's first contact for patients with psychosocial problems, had more frequent contact with social workers, and were more likely to have specialized in family medicine.

Adult↗

Assessment of lead exposure in schoolchildren from Jakarta.

Children attending schools in urban areas with high traffic density are a high risk group for lead poisoning. We assessed the magnitude of lead exposure in schoolchildren from Jakarta by analyzing blood lead concentrations and biomarkers of heme biosynthesis. A total of 131 children from four public elementary schools in Jakarta (two in the southern district and two in the central district) were enrolled in the study. To evaluate lead pollution in each area, soil samples and tap water were collected. The mean blood lead concentration was higher in the central district than in the southern district (8.3 +/- 2.8 vs. 6.9 +/- 3.5 microg/100 ml; p<0.05); 26.7% of the children had lead levels greater than 10 microg/100 ml. In 24% of the children, zinc protoporphyrin concentrations were over 70 micromol/mol hemoglobin; in 17% of the samples, hemoglobin was less than 11 g/100 ml. All other values were within the physiological range. Blood lead concentration and hematological biomarkers were not correlated. Analyses of tap water revealed lead values under 0. 01 mg/l; lead contamination of soil ranged from 77 to 223 ppm. Our data indicate that Indonesian children living in urban areas are at increased risk for blood lead levels above the actual acceptable limit. Activities to reduce pollution (e.g., reduction of lead in gasoline) and continuous monitoring of lead exposure are strongly recommended.

Child↗

Health system reform and the elderly: the case of Israel.

Following the implementation of the National Health Insurance Law in January 1995, major changes have taken place in the provision of health services by Israel's sick funds and the way these services are funded. This article presents the principal changes that have occurred and assesses their impact on those aged 65 and older, using findings of a survey conducted one year after the law's enactment. While the findings show that the elderly's situation has improved in some areas, they also raise concerns that the elderly are having difficulty navigating the reformed health system and that they are not benefiting from the new competition among the sick funds.

Aged↗

4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.

We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.

Animals↗

Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide.

We took advantage of the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create a new experimental diabetic syndrome in adult rats that appears closer to NIDDM than other available animal models with regard to insulin responsiveness to glucose and sulfonylureas. Among the various dosages of nicotinamide tested in 3-month-old Wistar rats (100-350 mg/kg body wt), the dosage of 230 mg/kg, given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded a maximum of animals with moderate and stable nonfasting hyperglycemia (155 +/- 3 vs. 121 +/- 3 mg/dl in controls; P < 0.05) and 40% preservation of pancreatic insulin stores. We also evaluated beta-cell function both in vitro and in vivo 4-9 weeks after inducing diabetes. In the isolated perfused pancreas, insulin response to glucose elevation (5-11 mmol/l) was clearly present, although significantly reduced with respect to controls (P < 0.01). Moreover, the insulin response to tolbutamide (0.19 mmol/l) was similar to that observed in normal pancreases. Perfused pancreases from diabetic animals also exhibited a striking hypersensitivity to arginine infusion (7 mmol/l). In rats administered STZ plus nicotinamide, intravenous glucose tolerance tests revealed clear abnormalities in glucose tolerance and insulin responsiveness, which were interestingly reversed by tolbutamide administration (40 mg/kg i.v.). In conclusion, this novel NIDDM syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM in that it has a significant response to glucose (although abnormal in kinetics) and preserved sensitivity to tolbutamide, may provide a particularly advantageous tool for pharmacological investigations of new insulinotropic agents.

Animals↗

[Characteristics of Israeli primary health care physicians who treat depression].

Primary health care physicians have a pivotal role in treating mental health problems. We determined the proportion of primary care physicians in Israel who treat depression and their characteristics. The study was based on a stratified national random sample of primary care physicians (n677, response rate 78%). From these physicians' reports 22% always treat depression, 36.6% usually, 28.6% sometimes, and 12.6% never. Based on a logistic regression model the physicians who always or usually treated depression were distinguished from the other physicians by their treating more medical conditions on their own, seeing themselves as having more first contact for psychosocial problems, having frequent contact with social workers and specializing in family medicine. Primary health care physicians play a major role in treating depression on their own. This raises new questions about how they treat depression themselves, and under what circumstances they treat or refer to a specialist.

Depression↗

[Brain imaging and its clinical application in psychiatry].

The common structural and functional brain imaging techniques are described from a practical, clinical point of view. The clinical indications for brain imaging in psychiatry are reviewed in relation to the specific limitations and advantages of each technique. The clinical applications of computerized tomography (CT), magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) are discussed in relation to the differential diagnosis between organic and functional psychiatric disorders. In a 55-year-old man with late onset of behavioral changes but without neurological signs the application of structural brain imaging (CT and MRI) in case management was demonstrated. The imaging findings involved the differential diagnosis between depression and focal brain lesions. In a 38-year-old man with personality changes and depression following a traumatic brain injury, time interval repeated functional brain imaging (SPECT) was used. Brain imaging reflected improvement in clinical status following treatment and was able to differentiate between reversible and permanent traumatic brain injuries. The superior yield of time interval repeated functional imaging in diagnosis and management of postconcussion syndrome is discussed.

Adult↗

Structure and function of a second gene cluster encoding the formate dehydrogenase of Wolinella succinogenes.

Wolinella succinogenes contains a single formate dehydrogenase, but two gene loci (fdhI and fdhII) code for the subunits of the enzyme. The nucleotide sequence of fdhII is almost identical with that of fdhI in the region comprising fdhEABCD. The sequences of fdhI and fdhII differ in the promotor regions upstream of fdhE. Deletion mutants lacking either fdhI or fdhII synthesize functional formate dehydrogenases, as shown by growth with formate as electron donor and either fumarate or polysulfide as acceptor substrates, and by the presence of the FdhA subunit and of enzyme activity. In the wild-type strain, the fdhI genes appear to be expressed preferentially during growth with formate and fumarate. The six-times greater amount of the enzyme present upon growth with formate and polysulfide is due to the expression of both fdhI and fdhII. The transcription start sites were located 196-bp and 129-bp upstream of the fdhE start codons of fdhI and fdhII, respectively. An apparently single transcript (5.6 kbp) was detected in polysulfide-grown W. succinogenes by Northern-blot analysis, suggesting that the five open reading frames form operons.

Amino Acid Sequence↗

Decorin and suramin inhibit ocular fibroblast collagen production.

BACKGROUND: The process of ocular wound healing with respect to glaucomatous filtering procedures is of current interest. Delaying this response in patients could possibly lead to more favorable surgical results. So far, only highly toxic antimetabolites have come into frequent clinical use. The possible efficacy of other groups of substances such as growth factor inhibitors has not yet been examined in vitro. METHODS: We exposed Tenon's capsule fibroblasts in tissue culture to various concentrations of decorin and suramin. The dose responses of type I and type III collagen to these inhibitors were measured using an ELISA-type dot blot assay. Total cellular protein production was assayed by measuring the incorporation of tritiated leucine. RESULTS: At a concentration of 10 micrograms/ml, suramin reduced the collagen production by more than 80%. Decorin, at a concentration of 100 micrograms/ml, reduced type I collagen production by about 50% while type III collagen was reduced by 80%. At these concentrations, the total cellular protein production was not inhibited. CONCLUSIONS: Both suramin and decorin, which specifically inhibit the action of growth factors on target cells, reduce the production of collagen synthesis by Tenon's capsule fibroblasts. This is a specific effect, because total protein production is not influenced. This sets these substances apart from antimetabolites. Decorin and suramin may have clinical relevance in that they appear to interfere with ocular wound healing more specifically than the substances so far frequently used.

Antineoplastic Agents↗

A new type of Ca-channel modulation by a novel class of 1,4-dihydropyridines.

Both Ca-antagonistic as well as Ca-agonistic 1,4-dihydropyridines (DHPs) have become extremely important tools to investigate the role of Ca-channels under various physiological and pathophysiological conditions. While Ca-antagonists stabilize the inactivated state of the Ca-channel without influencing the voltage dependent open and closed times, Ca-agonists prolong the mean open time of the channel. We here report for the first time the effects of a novel DHP, BAY Y 5959, which modulates Ca-channel gating in a unique manner: It increases both the mean open time and the mean closed time of the Ca-channel by binding to the DHP receptor. This results in a reduced rate of Ca-current activation, an increased peak current, and a strongly prolonged tail current decay. All these effects are strongly voltage dependent. Therefore it depends on resting membrane potential and shape of the action potential whether and how the Ca-influx into the cell is influenced. This novel mode of action of BAY Y 5959 results in an interesting pharmacological profile: It has a strong positive inotropic effect in the heart without influencing vessel tone. Therefore the term Ca-promoter is suggested; it could become a new approach for the drug treatment of congestive heart failure.

Action Potentials↗

Does budget-holding have a long-term effect on expenditure, staff and patients?

Kupat Holim Clalit (KHC), Israel's largest sick fund, initiated a unique demonstration program to transform primary care clinics into autonomous budget-holding units. The program was accompanied by an evaluation study that examined the influence of the program on clinic staff, level of expenditure, quality of service and patient satisfaction. Few studies have empirically examined the influence of a budget-holding program in relation to such a wide range of expected outcomes. A longitudinal study was conducted from 1991 to 1994 employing two methodologies: (a) a controlled case study of one experimental and one control clinic and (b) monitoring of all nine budget-holding clinics over time, compared to other clinics in the district. Multiple research tools were used: staff surveys, patient surveys, in-depth interviews, and analysis of financial data. The findings indicate that the budget-holding program has the potential to achieve cost containment without injuring staff morale, the service to patients or patient satisfaction. However, the KHC program did not lead to the expected improvement in staff motivation and attitudes, clinic services and clinic responsiveness to patients' needs. Implications for the literature on organization and management and for organizations considering the implementation of budget-holding programs are discussed.

Attitude of Health Personnel↗

The effect of dietary iron deficiency on the fatty acid composition of plasma and erythrocyte membrane phospholipids in the rat.

Severe iron deficiency was introduced in rats by feeding outbred male Wistar rats a purified diet that was either adequate or deficient in iron. The rats were weighed regularly over 4 weeks to monitor body weight differences, after which blood was drawn from a subsample to determine the haemoglobin concentrations and fatty acid composition of plasma total phospholipids and to measure the erythrocyte membrane phosphatidylcholine and phosphatidylethanolamine levels. Comparisons between dietary iron adequate (control) and dietary iron deficient (experimental) rats showed that the experimental rats had lower body weight and plasma total phospholipid linoleic acid levels typical of the symptoms of essential fatty acid deficiency. Erythrocyte membrane phosphatidylethanolamine arachidonic acid levels were increased (P < 0.05) with concomitant decreases in oleic acid (P < 0.01). Correlations between fatty acids and growth suggest that the mechanism whereby iron deficiency affects growth is in some way related to abnormal fatty acid shifts that disturb the delicate balance of essential fatty acids in membranes. Additional omega 3 and omega 6 fatty acids may be necessary to counteract the effect of iron deficiency in rats.

Animals↗

Anaemia is associated with reduced productivity of women workers even in less-physically-strenuous tasks.

While many studies show reduced work output in heavy labour with poor nutritional status, data among less-physically-strenuous industrial occupations is scarce. In the present study the output of ninety-two women jute-factory workers over a 1-month period was measured together with haemoglobin, BMI, arm muscle and fat area, physical work capacity (maximum O2 consumption; VO2max), as well as socio-economic, health and activity variables. A significant correlation was found between haemoglobin and work output, which remained significant (P < 0.005) after a multiple-regression analysis with other potentially confounding factors. Anaemic workers and those with VO2max values less than 1.5 l/min were significantly less active at home than non-anaemic workers (P < 0.015). Anaemic women produced an average of 5.3% less in the factory and performed an average of 6.5 h less housework per week.

Adolescent↗

Mechanisms involved in the effect of nitric oxide synthase inhibition on L-arginine-induced insulin secretion.

1. A constitutive nitric oxide synthase (NOSc) pathway negatively controls L-arginine-stimulated insulin release by pancreatic beta cells. We investigated the effect of glucose on this mechanism and whether it could be accounted for by nitric oxide production. 2. NOSc was inhibited by N omega-nitro-L-arginine methyl ester (L-NAME), and sodium nitroprusside (SNP) was used as a palliative NO donor to test whether the effects of L-NAME resulted from decreased NO production. 3. In the rat isolated perfused pancreas, L-NAME (5 mM) strongly potentiated L-arginine (5 mM)-induced insulin secretion at 5 mM glucose, but L-arginine and L-NAME exerted only additive effects at 8.3 mM glucose. At 11 mM glucose, L-NAME significantly inhibited L-arginine-induced insulin secretion. Similar data were obtained in rat isolated islets. 4. At high concentrations (3 and 300 microM), SNP increased the potentiation of arginine-induced insulin output by L-NAME, but not at lower concentrations (3 or 30 nM). 5. L-Arginine (5 mM) and L-ornithine (5 mM) in the presence of 5 mM glucose induced monophasic beta cell responses which were both significantly reduced by SNP at 3 nM but not at 30 nM; in contrast, the L-ornithine effect was significantly increased by SNP at 3 microM. 6. Simultaneous treatment with L-ornithine and L-arginine provoked a biphasic insulin response. 7. At 5 mM glucose, L-NAME (5 mM) did not affect the L-ornithine secretory effect, but the amino acid strongly potentiated the alteration by L-NAME of L-arginine-induced insulin secretion. 8. L-Citrulline (5 mM) significantly reduced the second phase of the insulin response to L-NAME (5 mM) + L-arginine (5 mM) and to L-NAME + L-arginine + SNP 3 microM. 9. The intermediate in NO biosynthesis, NG-hydroxy-L-arginine (150-300 microM) strongly counteracted the potentiation by L-NAME of the secretory effect of L-arginine at 5 mM glucose. 10. We conclude that the potentiation of L-arginine-induced insulin secretion resulting from the blockade of NOSc activity in the presence of a basal glucose concentration (1) is strongly modulated by higher glucose concentrations, (2) is not due to decreased NO production but (3) is probably accounted for by decreased levels of NG-hydroxy-L-arginine or L-citrulline, resulting in the attenuation of an inhibitory effect on arginase activity.

Animals↗

Longitudinal observation of growth of Vietnamese children in Hanoi, Vietnam from birth to 10 years of age.

OBJECTIVE: To investigate the physical growth of Vietnamese children on a longitudinal basis and with regard to any secular trend. DESIGN: A longitudinal study with four birth cohorts: 1981, 1982, 1983 and 1984 followed up in their homes from birth to 10 y. SUBJECTS: Two-hundred twelve children (128 boys and 84 girls) from two (Hai Ba and Hoan Kiem) out of the four districts in Hanoi. MONITORING OF PHYSICAL GROWTH: Weight, height, feeding practices and diseases were recorded monthly from birth to 12 months, three monthly from 12-36 months, six monthly from 36-72 months, and annually thereafter until 10 y of age. RESULTS: Mean body weight and height of the children at birth was reduced and after the first 3-4 months were comparable to NCHS reference data. Thereafter weight and height fell progressively from the NCHS reference. The most intense period of growth retardation was 15-36 months. The highest proportion of stunting occurred at 21 months (59.4% of males and 58.3% of females). Anthropometric data of Vietnamese children living 1981-1995 in Hanoi were lower than from those living at the same time in Paris but higher than from those living in earlier decades in Vietnam. CONCLUSIONS: The longitudinally-followed children showed growth retardation at birth due to the poor nutritional and health status of their mothers. Children grew well during the first 3-4 months of age, then growth faltering was observed due to inadequate complementary feeding practices. There was a positive secular trend among Vietnamese children.

Anthropometry↗