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Biomedical subjects

A Furst

Publications and source records attributed to A Furst.

At least 55 records · Page 3Linked to original sources

Cell division cycle of cultured neural precursor cells from Drosophila.

In Drosophila neuroblast cells, which give rise to the embryonic nervous system, undergo a limited number of asymmetric cell divisions. These cell lineages result in the formation of clusters of neurons when neuroblasts are isolated and cultured. A significant proportion of these neural cell clusters (NCC) arise from individual precursor cells. The formation of NCC containing more than two neurons is repressed when DNA synthesis is inhibited. Cell division during NCC development was examined by [3H]thymidine autoradiography. The pattern of DNA synthesis by neural cells was that expected based on observations in situ. The pattern in individual NCC was consistent with single precursor origins for more than 80% of NCC, under our conditions of culture. Based on this, we show that the largest neural precursors at gastrulation undergo the most cell divisions in culture. The neuroblast cell division cycle averages approximately 1.5 hr, and is similar to that of blastoderm cells.

Animals↗

Conformationally restricted C-terminal peptides of substance P. Synthesis, mass spectral analysis and pharmacological properties.

Four cyclic analogues of the C-terminal hepta- or hexapeptide of substance P were prepared by the solution method. The cyclizations were obtained by substituting with cysteine the residues normally present in positions 5 or 6 or 11 of substance P and by subsequent disulfide bond formation. The final products were identified by ordinary analytical procedures and advanced mass spectroscopy. The biological activities were determined on three bioassays: the guinea pig ileum, the guinea pig trachea and the rabbit mesenteric vein. Results obtained with these assays indicate that all peptides with a disulfide bridgehead in position 11 are inactive and that a cycle between positions 5 and 6 already strongly reduces the biological activity. The acyclic precursors containing thiol protection groups display weak biological activities. These results further underline the importance of the side chain in position 11 of substance P and suggest that optimal biological activities may require a linear peptide sequence.

Animals↗

Rapid immunofluorescent screening procedure using primary cell cultures or tissue sections.

We describe a rapid procedure for immunofluorescent screening of hybridoma supernatants. Use of primary cell cultures as substrates allows immediate detection and partial characterization of antibodies binding selectively to specific cell types. Sulfonated tissue culture cluster lids are used as a single substrate upon which cells are cultured and all stages of the antibody binding assay are performed, including microscopic observation. They may also be used for mounting cryostat sections of tissues. Condensation rings on the lids isolate individual groups of cells for each assay. Cells may be live or fixed, as desired. Very small volumes of culture supernatant are required for each assay, and nearly all steps are performed in bulk.

Animals↗

Mechanism of action of nickel as a carcinogen: needed information.

It is generally accepted that cancer induction by organic compounds is a multistage process. Attempts to explain the carcinogenic action of nickel have been limited in scope, and centre around its interaction with nucleic acids, so that only one phase of the initiation process is emphasized. Other possible modes of action of nickel as a carcinogen have not received adequate attention. Classical initiation-promotion experiments employing nickel compounds as either the initiator or the promoter appear to be lacking. Also, little attention has been given to the possible indirect role of nickel as a stabilizer of free radicals formed by the oxidation of various unsaturated molecules including the dienes, cholesterol, and the well-known aromatic carcinogenic hydrocarbons. Other problems to be investigated include the role of nickel, if any, in the enhancement of the kinetics of the formation of ultimate carcinogens from the procarcinogen, or the possible inhibition of the biotransformation of active carcinogens into their inactive conjugates. It will be necessary at all times to carry out control experiments with the so-called inactive metal ions. Without experiments designed specifically to investigate the mechanism of action of nickel as a carcinogen, this topic will continue to remain in the realm of pure speculation.

Animals↗

Solubility of nickel powder in human serum.

The solubility of nickel powder was studied to estimate the inertness of the nickel metal in contact with deionized distilled water, saline solution, a chelating agent, ethylenediamine tetraacetate, and human serum. The human serum dissolved more than two times as much nickel as the saline solution and almost six times as much nickel as the EDTA solution in the first 24 h of the experiment. The resultant solubility curve can be an indication of the level of toxicity of an individual nickel compound or alloy. The degree of solubility may also be important in further studies on the mechanisms of nickel carcinogenesis.

Edetic Acid↗

The temporal order of replication of murine immunoglobulin heavy chain constant region sequences corresponds to their linear order in the genome.

The time of replication during the S phase in a murine erythroleukemia (MEL) cell line was determined for immunoglobulin heavy chain constant region C alpha, C gamma 2b and C mu sequences whose boundaries are defined by EcoR1 restriction endonuclease sites (EcoR1 segments). Logarithmically growing cultures of MEL cells with an S phase of about 7.5 hours were pulse labelled with 20 micrograms/ml of 5-bromodeoxyuridine (BUdR). The cells were then fractionated by centrifugal elutriation into 10-12 distinct populations containing cells in different stages of the cell cycle. Flow microfluorimetric (FMF) analysis of DNA content, measurements of cell volume and autoradiography after 3H-thymidine pulse labelling were used to determine position in the cell cycle. Fractions were pooled to represent four selected intervals of S in which BU-DNA was synthesized for 2.5 hrs or less. Newly replicated DNA which had incorporated BUdR into one strand was isolated, cleaved with EcoR1, and separated on neutral Cs2S04 gradients. Equal amounts of BU-DNA replicated during these four intervals of S were electrophoresed in 0.8% agarose gels, transferred to diazotized aminobenzyloxymethyl paper and hybridized with 32p probes containing the C alpha, C gamma 2b and C mu genes and flanking sequences. The relative amounts of segments replicated were assessed by quantitation of the appropriate bands on the autoradiograms by microdensitometry. The results indicate that the 2.8 kb C alpha, 6.6 kb C gamma 2b and 12 kb C mu EcoR1 segments in these MEL cells replicated during defined intervals of the first half of the S phase. The order of replication of these EcoR1 segments as the cells proceeded through S was C alpha, C gamma 2b, C mu, corresponding to the linear order of the genes determined by restriction endonuclease mapping.

Animals↗

alpha-Globulin sequences are located in a region of early-replicating DNA in murine erythroleukemia cells.

The time of replication in the S phase of regions of the mouse genome including the alpha-globin genes was determined in the murine erythroleukemia cell line transformed by Friend virus. Cells grown for short times in the presence of BrdUrd were fractionated into synchronous populations by centrifugal elutriation. The DNA was cleaved by restriction endonucleases, and fragments containing bromouracil (BrU-DNA) were isolated in density gradients of Cs2SO4. BrU-DNA fractions replicated during selected S-phase intervals were subjected to electrophoresis in agarose gels, transferred to diazobenzyloxymethyl-paper, and hybridized to an alpha-globin probe. Reconstruction experiments using a cloned mouse EcoRI fragment including one alpha-globin gene demonstrated that the extent of hybridization provides an accurate measurement that the extent of hybridization provides an accurate measurement of the concentrations of specific fragments in a DNA sample. The alpha-globin fragments were detected primarily in the BrU-DNA replicated during early S phase (approximately the first quarter of S). This result was confirmed in other synchrony experiments and by Cot analysis. (Cot is the initial concentration of DNA in mol of nucleotide per liter multiplied by the time in sec.) The temporal replication of mouse satellite sequences, already known from previous studies, was used as an internal control for cell synchrony. To show that the globin sequences were not lost from the cells in late S phase during isolation of the DNA, we quantitated th alpha-globin fragments in BrU-DNA prepared from a mixture of cells in early and late S phase. The results demonstrate that the alpha-globin gene regions in these cells are replicated during early S phase.

Animals↗

Bioassay of metals for carcinogenesis: whole animals.

Metals have been evaluated as potential carcinogens by administering pure elements or compounds by a large variety of routes. These include mixing the agent in the food, dissolving the test compound in the drinking water, or administering the material by gavage. The respiratory tract routes tested include inhalation, intratracheal instillation, the direct injection of particulates into the pleural cavity, or the implantation of hooks by surgical intervention. The parenteral routes used were intravenous injection, intraperitoneal injection, subcutaneous implantation, as well as intrafemoral and intramuscular injection. This latter route is the most commonly used. There are major objections to the subcutaneous implantations route, and data generated from these experiments are difficult to interpret for the foreign body reaction may give rise also to fibrosarcomas. This then is a nonspecific reaction. Exotic routes tested include intrarenal, intratesticular, and intracranial injections. The endpoints of the carcinogenic reactions are, in the main, sarcomas of certain types with fibrosarcomas predominating. Rhabdomyosarcomas are the next most frequent cancer found, and squamous cell carcinoma may account for less than 2% of the cancers reported. Much more research is necessary to clarify the nature of metal carcinogenesis. Dose-response information is almost nonexistent; the divided dose problem has not been studied adequately, and very little information is available on interspecies reactions. More work is needed to help interpret the mechanism of action.

Administration, Oral↗

Diagnostic characteristics of patients referred to a secondary care military medical facility of the Israel Defense Forces.

A consistently high annual referral rate of over 20% from primary care clinics to secondary (specialist) care clinics in the Israel Defense Forces (IDF) prompted a study of 2,225 such referrals at the major IDF secondary care facility during 1978. This report details the diagnostic information obtained concerning the 1,329 (59.7%) medical referrals (i.e., excluding technical and administrative referrals). Fewer than one-quarter of the diagnoses from the list developed for the study (68 out of 275) accounted for more than two-thirds (906) of the 1,329 referrals studied. The implications of the impression that many of the diagnoses were simple and straightforward in nature are discussed. Further data concerning the type of investigation for each referral and the follow-up pattern are also presented. For only 351 (26.4%) of the 1,329 cases were any additional laboratory tests or other auxiliary investigations ordered: three procedures alone, simple radiology, electrocardiography, and audiometry, accounted for all such tests in 229 (62.5%) of these 351 cases. Of 979 new medical referrals 602 (73.5%) were discharged after their initial visit without need for follow-up. The possible significance of the diagnostic findings in relation to the referral rates and to the training of IDF medical officers is indicated, and the importance of additional studies, especially at the IDF primary care clinic itself, is stressed.

Ambulatory Care Facilities↗

Diabetes, blood lipids, lipoproteins, and change of environment: restudy of the "new immigrant Yemenites" in Israel.

Restudy of 306 "new immigrant Yemenite" Jews, an ethnic group in which, upon their arrival in Israel, no diabetes was detected, revealed, 25 yr after their immigration, an increased incidence of diabetes and higher plasma and lipoprotein-lipid levels. The prevalence of diabetes (defined as "glucose intolerance") rose to 11.8% (13.2% males and 9.7% females). Obesity in females resulted in increased prevalence of diabetes in all age groups, while in males it affected the older age group only. The male/female diabetic ratio was affected by weight status--in the underweight, diabetes was more prevalent in males, in the overweight, the rate of diabetes in females equaled that of males. In nondiabetics (those with normal glucose tolerance), neither the glucose tolerance nor the insulin response deteriorated with aging. Most diabetics had a delayed insulin response. However, about 50% of nondiabetics and diabetics had insulin response peak at 60 min and similar insulin levels. It appears that in newly discovered adult-onset diabetics in this population there is no shortage of insulin, but rather shortage of insulin action. In nondiabetics, the levels of plasma cholesterol and triglycerides (TG) were higher than levels upon their arrival. In diabetics, the plasma TG, cholesterol, and LDL-cholesterol levels were higher when compared to those of nondiabetics, especially in the group of overweight males. Hyperlipoproteinemia was diagnosed in 27.7% of diabetics and 11.0% of nondiabetics. In diabetics, the HDL/LDL cholesterol ratio was found to be reduced, significantly so in overweight diabetics.

Adult↗