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Biomedical subjects

R Gross

Publications and source records attributed to R Gross.

At least 73 records · Page 4Linked to original sources

The role of the primary care physician in the Israeli health care system as a 'gatekeeper'--the viewpoint of health care policy makers.

The aim of the study was to determine the attitudes of policy makers in the health care system in Israel to a change in the role of primary care physicians (PCP) and to ascertain the conditions under which they would be ready to adopt the model of PCP as gatekeeper. The study design was qualitative, with analyses of in-depth structured interviews of 20 policy makers from the Ministry of Health, the Sick Funds' central administrations and the Israel Medical Association (IMA) central office. The majority of the respondents claim that they want highly trained PCPs (family physicians, pediatricians and internals) to play a central role in the health care system. They should be co-ordinators, highly accessible and should be able to weigh cost considerations. However, only about half of the respondents support a full gatekeeper model and most of them think that the gatekeeper concept has a negative connotation. They also feel that it would be difficult to implement regulations regarding primary care. The barriers to implementation of the gatekeeper model, as cited by the respondents include loss of faith in PCPs by the general population, dearth of PCPs with adequate training, low stature, lack of availability on a 24-h basis, resistance by specialists, strong competition between the sick funds including promises of direct access to specialists, the medical care habits of the general population many of whom do not settle for only one opinion, and a declared anti-gatekeeper policy by one of the sick funds. Ways to overcome these obstacles include implementation of fundholding clinics, patient education on the importance of having a personal physician, appropriate marketing by family medicine and primary care advocates, and continued training in primary care. Israeli health care policy makers have an ambivalent attitude to strengthening the role of primary care. In theory, they profess support for placing primary care physicians in a central role in the health care system. However, in practice almost half oppose the full gatekeeper model. Therefore, introduction of a gatekeeper model into the Israeli health care system should be implemented gradually, based on incentives rather than regulations. Furthermore, the idea should be marketed by the primary care physicians' professional organizations, the Ministry of Health and the sick funds to physicians as well as to patients, in order to garner their support. In light of the broad consensus that competent primary care physicians are the basis for implementation of the gatekeeper model, board certification should be gradually required by employers of primary care physicians. The process of training physicians currently working in the system should be encouraged and supported by the Ministry of Health. Given the existing opposition of policy makers to giving primary care physicians exclusive referral rights to specialists, the current policy of direct access to a limited number of specialties should be continued but not extended to other specialties.

Administrative Personnel↗

New insights into symbiotic associations between ants and bacteria.

Many ants live in complex mutualistic or parasitic relationships with other insects or plants, some of which are classical examples of the mutual benefit of symbiosis. However, only in the past few years have new insights into the symbiosis of ants and microorganisms been reported. Examples are the symbiosis of ants of the genus Camponotus with intracellular bacteria present in their midgut, and the tripartite relationship of ants of the tribe Attini with an extracellular bacterium essential for the cultivation of their fungus gardens. The analysis of the parasitic and mutualistic interactions of these organisms will allow interesting insights into the evolution of symbiosis and possibly lead to novel strategies of pest control.

Animals↗

Structure-function relationships in the Bvg and Evg two-component phosphorelay systems.

The unorthodox two-component phosphorelay systems BvgAS and EvgAS of Bordetella pertussis and E. coli, respectively, are suitable model systems to investigate the molecular basis of signalling specificity, because, despite their high relatedness on the sequence level, they do not cross-talk to each other. We could show that the two systems belong to the obligate type of phosphorelay systems and that signalling specificity is mediated by the HPt modules of the histidine kinases and the receiver domains of the effector proteins. To gain more insight into signalling specificity on the molecular level, we started a detailed structural analysis of the respective proteins using a combination of genetic and biochemical methods including limited proteolysis and chemical modification of purified proteins and their mass spectrometrical analysis.

Amino Acid Sequence↗

Preproinsulin I and II mRNA expression in adult rat submandibular glands.

Mammalian salivary glands are known to produce a number of biologically active peptides. The aim of this study was to extend our previous results showing the presence of a biologically active insulin-like immunoreactive peptide in rat salivary glands. In rodents, where two nonallelic and functional insulin genes are expressed, the co-expression of both genes seems to be limited to beta-cells of pancreatic islets or to embryologic developmental processes. We have investigated the expression of insulin genes in rat submandibular glands and in a murine immortalized submandibular cell line, SCA-9. For this purpose, total RNAs were isolated and submitted to reverse transcription. The cDNAs obtained were amplified by a nested polymerase chain reaction using rat preproinsulin I and II primers. Our data show that both preproinsulin I and II mRNAs are expressed in adult rat submandibular glands as well as in the SCA-9 cell line. The identification of salivary gland rat preproinsulin I and II was confirmed by direct sequencing. These results provide, for the first time, evidence for the expression of both preproinsulin I and II mRNA in an extra-pancreatic tissue from adult rodents.

Animals↗

A NapC/NirT-type cytochrome c (NrfH) is the mediator between the quinone pool and the cytochrome c nitrite reductase of Wolinella succinogenes.

Wolinella succinogenes can grow by anaerobic respiration with nitrate or nitrite using formate as electron donor. Two forms of nitrite reductase were isolated from the membrane fraction of W. succinogenes. One form consisted of a 58 kDa polypeptide (NrfA) that was identical to the periplasmic nitrite reductase. The other form consisted of NrfA and a 22 kDa polypeptide (NrfH). Both forms catalysed nitrite reduction by reduced benzyl viologen, but only the dimeric form catalysed nitrite reduction by dimethylnaphthoquinol. Liposomes containing heterodimeric nitrite reductase, formate dehydrogenase and menaquinone catalysed the electron transport from formate to nitrite; this was coupled to the generation of an electrochemical proton potential (positive outside) across the liposomal membrane. It is concluded that the electron transfer from menaquinol to the catalytic subunit (NrfA) of W. succinogenes nitrite reductase is mediated by NrfH. The structural genes nrfA and nrfH were identified in an apparent operon (nrfHAIJ) with two additional genes. The gene nrfA encodes the precursor of NrfA carrying an N-terminal signal peptide (22 residues). NrfA (485 residues) is predicted to be a hydrophilic protein that is similar to the NrfA proteins of Sulfurospirillum deleyianum and of Escherichia coli. NrfH (177 residues) is predicted to be a membrane-bound tetrahaem cytochrome c belonging to the NapC/NirT family. The products of nrfI and nrfJ resemble proteins involved in cytochrome c biogenesis. The C-terminal third of NrfI (902 amino acid residues) is similar to CcsA proteins from Gram-positive bacteria, cyanobacteria and chloroplasts. The residual N-terminal part of NrfI resembles Ccs1 proteins. The deduced NrfJ protein resembles the thioredoxin-like proteins (ResA) of Helicobacter pylori and of Bacillus subtilis, but lacks the common motif CxxC of ResA. The properties of three deletion mutants of W. succinogenes (DeltanrfJ, DeltanrfIJ and DeltanrfAIJ) were studied. Mutants DeltanrfAIJ and DeltanrfIJ did not grow with nitrite as terminal electron acceptor or with nitrate in the absence of NH4+ and lacked nitrite reductase activity, whereas mutant DeltanrfJ showed wild-type properties. The NrfA protein formed by mutant DeltanrfIJ seemed to lack part of the haem C, suggesting that NrfI is involved in NrfA maturation.

Amino Acid Sequence↗

Insulinotropic effect of Citrullus colocynthis fruit extracts.

Infusions of Citrullus colocynthis Schrad. (Cucurbitaceae) fruits are traditionally used as antidiabetic medication in Mediterranean countries, but to our knowledge no studies have been undertaken so far to determine the possible mechanisms involved in the antidiabetic properties of the fruit. The present study was designed to investigate whether these fruits possess insulinotropic effects. For this purpose, different extracts of Citrullus colocynthis seed components were obtained: RN II (crude extract), RN VI (hydro-alcoholic extract), RN X (purified extract) and RN XVII (beta-pyrazol-1-ylalanine), the major free amino acid present in the seeds. The insulin secretory effects of these different extracts were evaluated in vitro in the isolated rat pancreas and isolated rat islets in the presence of 8.3 mM glucose. All tested extracts, when perfused for 20 min at 0.1 mg/ml, immediately and significantly stimulated insulin secretion. This effect was transient. In addition, the purified extract (RN X) provoked a clear dose-dependent increase in insulin release from isolated islets. Moreover, a significant and persistant increase in pancreatic flow rate appeared during RN VI, RN X and RN XVII perfusions. In conclusion, our results show that different Citrullus colocynthis seed extracts have an insulinotropic effect which could at least partially account for the antidiabetic activities of these fruits.

Amino Acids↗

Neural activity related to anger in cocaine-dependent men: a possible link to violence and relapse.

This study examined the neural correlates of cue-induced anger in cocaine-dependent men in an initial investigation of possible neurobiological explanations for the putative association between cocaine addiction and violence. We used positron emission tomography (PET) to localize alterations in regional cerebral blood flow (rCBF) during mental imagery of a personal anger-associated scene and of an emotionally neutral scene in ten cocaine-dependent men. Compared to the emotionally neutral imagery control condition, anger was associated with marked decreases in rCBF in multiple areas of the frontal cortex (particularly the right inferior frontal gyrus), left posterior insula, left fusiform gyrus, and midbrain. Conversely, this same inferior frontal area was activated by anger imagery in nicotine-dependent men. Anger was also associated with increases in rCBF in the right fusiform gyrus, right and left middle occipital gyri, left post-central gyrus, left medial frontal gyrus, left cuneus, and in the left anterior cingulate gyrus. The study showed that cue-induced anger in cocaine-dependent men was associated with decreased activity in frontal cortical areas involved in response monitoring and inhibition. The lack of this association in nicotine-dependent men suggests a possible deficit in anger regulation associated with cocaine dependence and a possible link between cocaine dependence, violence, and relapse.

Adult↗

Who needs a gatekeeper? Patients' views of the role of the primary care physician.

BACKGROUND: The primary care physician serving as a 'gatekeeper' can make judicious decisions about the appropriate use of medical services, and thereby contribute to containing costs while improving the quality of care. However, in Israel, sick funds competing for members have not adopted this model for fear of endangering their competitive stance. The purpose of this study was to examine, for the first time, the stated preferences and actual behaviour of a national sample of members of the four Israeli sick funds regarding self-referral to specialists, and to identify the characteristics of patients who prefer the gatekeeper model. METHODS: Data were derived from a national telephone survey carried out in 1997. A random representative sample of 1084 of all adult sick fund members were interviewed, with a response rate of 81%. Bivariate analysis was conducted using over all chi-square tests, and multivariate analysis was performed using logistic regression models. RESULTS: A third of all respondents prefer self-referral to a specialist, 40% prefer their family physician to act as gatekeeper and 19% prefer the physician to co-ordinate care but to refer themselves to a specialist. Independent variables predicting preference for the gatekeeper model are: living in the periphery, sick fund membership, low level of education, being male, fair or poor health status, having a permanent family physician and being satisfied with the professional level of the family physician. A significant correlation was found between practising self-referral and preference for self-referral. CONCLUSIONS.: The findings indicate the importance of surveying patients' attitudes as an input in policy formulation. The study identified specific population groups which prefer the gatekeeper model, and explored the advantages of a flexible model of gatekeeping.

Adult↗

Premature complementary feeding is associated with poorer growth of vietnamese children.

The objective of this longitudinal study was to investigate the association between the premature initiation of complementary feeding and physical growth of children. Four cohorts of newborn children were included, consisting of 90 infants born in 1981, 90 in 1982, 60 infants in 1983 and 60 in 1984. The weights and heights of children were measured monthly up to 1 y, then every 3 mo for y 2 and 3, and once every 6 mo in y 4. Information on feeding practices and diseases of the children was obtained by interviewing the mothers at each home visit. All but three children (98.6%) were breast-fed. Although 87.1% of the mothers breast-fed their children for at least 1 y, only 3.3% of the infants were breast-fed exclusively at the age of 4 mo. In the analyses of growth, care was taken to address the biases of reverse causality, regression to the mean and confounding. There was little association between feeding pattern at 15 d and growth in length in mo 1. However, partially breast-fed and weaned infants gained weight more slowly than those exclusively or predominantly breast-fed. From 1 to 3 mo, exclusively breast-fed infants grew more quickly in both weight and length, followed by predominantly breast-fed infants. From 3 to 6 mo, exclusively breast-fed infants gained more weight compared with the other groups, but there was a slight difference (P = 0.047) in length gain only between exclusively and partially breast-fed infants. In the older period (6-12 mo), exclusively and predominantly breast-fed infants grew in length more quickly than partially breast-fed and weaned groups. However, there was no difference in weight gain among groups. Morbidity from diarrhea and acute respiratory infections was significantly lower for the >/=3 mo exclusively breast-fed group (chi(2) and Fisher-Exact Test). Over nearly the whole age range from 1 mo to 4 y, Z-scores for all indices (weight-for-age, height-for-age and weight-for-height) of the children who received complementary food were significantly lower than those of children who were exclusively breast-fed for at least 3 mo (repeated measures ANOVA, adjusted for sex, family size, maternal education and family income). These results show a long-term deterioration of physical growth in infants who received premature complementary feeding and confirm the importance of exclusive breast-feeding for infants for at least 3 mo.

Body Height↗

Poor micronutrient status of active pulmonary tuberculosis patients in Indonesia.

Malnutrition is observed frequently in patients with pulmonary tuberculosis (TB), but their nutritional status, especially of micronutrients, is still poorly documented. The objective of this study was to investigate the nutritional status of patients with active TB compared with that of healthy controls in Jakarta, Indonesia. In a case-control study, 41 out-patients aged 15-55 y with untreated active pulmonary TB were compared with 41 healthy controls selected from neighbors of the patients and matched for age and sex. Cases had clinical and radiographic abnormalities consistent with pulmonary TB and at least two sputum specimens showing acid-fast bacilli. Anthropometric and micronutrient status data were collected. Compared with the controls, TB patients had significantly lower body mass index, skinfold thicknesses (triceps, biceps, subscapular, suprailiac), mid-upper arm circumference, proportion of fat, and concentrations of serum albumin, blood hemoglobin, plasma retinol and plasma zinc, whereas plasma zinc protoporphyrin concentration, as a measure of free erythrocyte protoporphyrin concentration, was greater. When patients and controls were subdivided on the basis of nutritional status, concentrations of serum albumin, blood hemoglobin, and zinc and retinol in plasma were lower in malnourished TB patients than in well-nourished healthy controls, well-nourished TB patients and malnourished healthy controls. In conclusion, the nutritional status of patients with active pulmonary TB was poor compared with healthy subjects, i.e., significantly more patients were anemic and more had low plasma concentrations of retinol and zinc. Low concentrations of hemoglobin, and of retinol and zinc in plasma were more pronounced in malnourished TB patients.

Adolescent↗

Systematic relationships and cospeciation of bacterial endosymbionts and their carpenter ant host species: proposal of the new taxon Candidatus Blochmannia gen. nov.

The systematic relationships of intracellular bacteria of 13 Camponotus species (carpenter ants) from America and Europe were compared to those of their hosts. Phylogenetic trees of the bacteria and the ants were based on 16S rDNA (rrs) gene sequences and mitochondrial cytochrome oxidase subunit I (COI) gene sequences, respectively. The bacterial endosymbionts of Camponotus spp. form a distinct lineage in the y-subclass of the Proteobacteria. The taxa most closely related to these bacteria are endosymbionts of aphids and the tsetse fly. The bacterial and host phylogenies deduced from the sequence data show a high degree of congruence, providing significant evidence for cospeciation of the bacteria and the ants and a maternal transmission route of the symbionts. The cloned rrs genes of the endosymbionts contain putative intervening sequences (IVSs) with a much lower G+C content than the mean of the respective rrs genes. By in situ hybridization specific 16S rDNA oligonucleotide probes verified the presence of the bacteria within tissues of three of the eukaryotic hosts. It is proposed that the endosymbionts of these three carpenter ants be assigned to a new taxon 'Candidatus Blochmannia gen. nov.' with the symbionts of the individual ants being species named according to their host, 'Candidatus Blochmannia floridanus sp. nov.', 'Candidatus Blochmannia herculeanus sp. nov.' and 'Candidatus Blochmannia rufipes sp. nov.'.

Animals↗

Phagosome acidification has opposite effects on intracellular survival of Bordetella pertussis and B. bronchiseptica.

Bordetella pertussis is readily killed after uptake by professional phagocytes, whereas its close relative Bordetella bronchiseptica is not and can persist intracellularly for days. Phagocytosis of members of either species by a mouse macrophage cell line results in transport of the bacteria to a phagosomal compartment positive for the lysosome-associated membrane protein 1, the protease cathepsin D, and the late endosomal vacuolar proton-pumping ATPase but negative for the early endosome antigen 1 and the early endosomal transferrin receptor. In addition, we demonstrate that Bordetella-containing phagosomes rapidly acidify to pH 4.5 to 5.0. Taken together, these data demonstrate that Bordetella-containing phagosomes rapidly mature to an acidic late endosomal/lysosomal compartment. Following up on this observation, we determined that B. pertussis does not survive in bacterial growth media adjusted to a pH of 4.5, whereas this pH has only minor effects on the growth of B. bronchiseptica. Raising the intracellular pH in infected macrophages by the addition of bafilomycin A(1), ammonium chloride, or monensin increases the survival of acid-sensitive B. pertussis but, surprisingly, decreases that of acid-tolerant B. bronchiseptica. In summary, we hypothesize that the differential survival of B. pertussis and B. bronchiseptica in macrophages is, at least in part, due to the differences in their acid tolerance.

Animals↗

Identification of immunodominant antigens from Helicobacter pylori and evaluation of their reactivities with sera from patients with different gastroduodenal pathologies.

Colonization of the gastric mucosa by Helicobacter pylori is the major cause of gastroduodenal pathologies in humans. Studying the outcome of the humoral immune response directed against this gastric pathogen may contribute substantially to vaccine development and to the improvement of diagnostic techniques based on serology. By using two-dimensional gel electrophoresis, 29 proteins from H. pylori G27 were identified which strongly react with sera derived from H. pylori-infected patients suffering from different gastroduodenal pathologies. These antigens were characterized by mass spectrometry and proved to correspond to products of open reading frames predicted by the H. pylori genome sequence. The comparison of the antigenic patterns recognized by these sera revealed no association of specific H. pylori antigens with antibodies in patients with particular gastroduodenal pathologies.

Antibodies, Bacterial↗

Characterization of a bordetella pertussis diaminopimelate (DAP) biosynthesis locus identifies dapC, a novel gene coding for an N-succinyl-L,L-DAP aminotransferase.

The functional complementation of two Escherichia coli strains defective in the succinylase pathway of meso-diaminopimelate (meso-DAP) biosynthesis with a Bordetella pertussis gene library resulted in the isolation of a putative dap operon containing three open reading frames (ORFs). In line with the successful complementation of the E. coli dapD and dapE mutants, the deduced amino acid sequences of two ORFs revealed significant sequence similarities with the DapD and DapE proteins of E. coli and many other bacteria which exhibit tetrahydrodipicolinate succinylase and N-succinyl-L,L-DAP desuccinylase activity, respectively. The first ORF within the operon showed significant sequence similarities with transaminases and contains the characteristic pyridoxal-5'-phosphate binding motif. Enzymatic studies revealed that this ORF encodes a protein with N-succinyl-L,L-DAP aminotransferase activity converting N-succinyl-2-amino-6-ketopimelate, the product of the succinylase DapD, to N-succinyl-L,L-DAP, the substrate of the desuccinylase DapE. Therefore, this gene appears to encode the DapC protein of B. pertussis. Apart from the pyridoxal-5'-phosphate binding motif, the DapC protein does not show further amino acid sequence similarities with the only other known enzyme with N-succinyl-L,L-DAP aminotransferase activity, ArgD of E. coli.

Acyltransferases↗

Transport of C(4)-dicarboxylates in Wolinella succinogenes.

C(4)-dicarboxylate transport is a prerequisite for anaerobic respiration with fumarate in Wolinella succinogenes, since the substrate site of fumarate reductase is oriented towards the cytoplasmic side of the membrane. W. succinogenes was found to transport C(4)-dicarboxylates (fumarate, succinate, malate, and aspartate) across the cytoplasmic membrane by antiport and uniport mechanisms. The electrogenic uniport resulted in dicarboxylate accumulation driven by anaerobic respiration. The molar ratio of internal to external dicarboxylate concentration was up to 10(3). The dicarboxylate antiport was either electrogenic or electroneutral. The electroneutral antiport required the presence of internal Na(+), whereas the electrogenic antiport also operated in the absence of Na(+). In the absence of Na(+), no electrochemical proton potential (delta p) was measured across the membrane of cells catalyzing fumarate respiration. This suggests that the proton potential generated by fumarate respiration is dissipated by the concomitant electrogenic dicarboxylate antiport. Three gene loci (dcuA, dcuB, and dctPQM) encoding putative C(4)-dicarboxylate transporters were identified on the genome of W. succinogenes. The predicted gene products of dcuA and dcuB are similar to the Dcu transporters that are involved in the fumarate respiration of Escherichia coli with external C(4)-dicarboxylates. The genes dctP, -Q, and -M probably encode a binding-protein-dependent secondary uptake transporter for dicarboxylates. A mutant (DcuA(-) DcuB(-)) of W. succinogenes lacking the intact dcuA and dcuB genes grew by nitrate respiration with succinate as the carbon source but did not grow by fumarate respiration with fumarate, malate, or aspartate as substrates. The DcuA(-), DcuB(-), and DctQM(-) mutants grew by fumarate respiration as well as by nitrate respiration with succinate as the carbon source. Cells of the DcuA(-) DcuB(-) mutant performed fumarate respiration without generating a proton potential even in the presence of Na(+). This explains why the DcuA(-) DcuB(-) mutant does not grow by fumarate respiration. Growth by fumarate respiration appears to depend on the function of the Na(+)-dependent, electroneutral dicarboxylate antiport which is catalyzed exclusively by the Dcu transporters. Dicarboxylate transport via the electrogenic uniport is probably catalyzed by the DctPQM transporter and by a fourth, unknown transporter that may also operate as an electrogenic antiporter.

Anaerobiosis↗

[What do primary care physicians think of Israel's health policy reform?].

Opinions of the National Health Insurance (NHI) Law held by primary care physicians were surveyed. A questionnaire was submitted (April-July 1997) to 930 primary care physicians employed by sick funds, including general practitioners, family physicians, pediatricians and internists. Response rate was 86%. They supported the main components of the NHI law. It was considered desirable "to a great" or "very great extent" to allocate funds to sick funds based on age and number of members (76%), to require them to accept all applicants (72%), to designate a uniform basket of services (65%), to allow members to transfer freely between funds (63%), and to allow sick funds to sell supplemental insurance (59%). However, only 41% were satisfied with the implementation of the law. Multivariate analysis showed that employment by Maccabi, Meuhedet, or Leumit sick funds had an independent effect on low satisfaction with the law as implemented, and on negative opinions about the uniform basket of services, the accepting of all applicants, and allocation of funding based on age and number of members. Those employed by the Maccabi and Meuhedet funds were in favor of allowing sick funds to sell supplemental insurance. The findings of the study have implications for policy-makers interested in increasing support for national health reform by physicians. It is important to examine possibilities of developing direct channels of communication between national policy-makers and physicians, as well as institutionalizing mechanisms that involve physicians directly in formulation of national policy.

Adult↗

Computerized reminders for five preventive screening tests: generation of patient-specific letters incorporating physician preferences.

Compliance with preventive screening tests is inadequate in the United States. We describe a computer based system for generating reminder letters to patients who may have missed their indicated screening tests because they do not visit a provider regularly or missed their tests despite the fact that they do visit a provider. We started with national recommendations and generated a local consensus for test indications. We then used this set of indications and our electronic record to determine test deficiencies in our pilot pool of 3073 patients. The computer generated customized reminder letters targeting several tests. Physicians chose any patients who should not receive letters. The response rate for fecal occult blood (FOB) testing was 33% compared with an 18% historical compliance rate within the same community. FOB reminders generated improved test compliance. Test execution must be considered when commencing a program of screening test reminders.

Computers↗