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Biomedical subjects

R Drummond

Publications and source records attributed to R Drummond.

At least 19 recordsLinked to original sources
PubMed1996

Fever duration in hospitalized acute pyelonephritis patients.

PURPOSE: To study persistence of fever in treated pyelonephritis with respect to guidelines recommending investigation and modification of therapy after 2 to 3 days of fever. PATIENTS AND METHODS: A retrospective chart review was made of 70 patients hospitalized for febrile pyelonephritis at a community hospital in Canada. RESULTS: Median duration of fever was 34 hours; persistence of fever at 48 and 72 hours was 26% and 13%, respectively. No patients had complications such as intrarenal or perirenal abscess. Prolonged fever was independently associated with increasing baseline creatinine (P = 0.0001), younger age (P = 0.027), and increasing total leukocyte count (P = 0.026). Results of ultrasonography and intravenous urograms were not predictors of fever duration. CONCLUSION: Fever in treated pyelonephritis can take 4 days to resolve, and routine urologic investigation after 2 to 3 days of fever may be unwarranted.

Acute Disease↗
PubMed1996

The role of the nucleus in organogenesis: Part 1.

Organogenesis is the result of cell allocation followed by cell differentiation, and the processes involved are still to be elucidated. Present-day teaching suggests that the cytoplasmic membrane, the extracellular matrix and the cytoskeleton, in combination, are responsible, but the literature also suggests that other factors must be working as well. Because organogenesis is under strict genetic control, the controlling mechanism must reside in the nucleus and when the biology of the embryonic stem cell's nucleus was looked into, some interesting features emerged. One noteworthy feature was that the cytoplasm formed an incomplete ring around the nucleus so that part of the nuclear envelope was bare of cytoplasm, and in the aggregates of stem cells which made up an organ rudiment, the bare margins were in intimate contact. Another noteworthy feature was that the cytoplasm of the embryonic cells then underwent dissolution prior to differentiation, and the specialized cytoplasm arose progressively from the bare nuclei. The argument is put that, when embryonic stem cells join to form an organ rudiment, the bare margins of the nuclei of adjoining cells make intimate contact, allowing the correct spatial orientation of the cells to be achieved by means of positional cues in the nuclei. The cytoplasm of the embryonic cells then undergoes dissolution and the specialized cytoplasm of the differentiated cells is constructed by the denuded nuclei.

Animals↗
PubMed1996

The role of the nucleus in organogenesis: Part 2.

In a previous paper, it was proposed that the spatial orientation of stem cells was dependent on nucleus/nucleus contact. This proposition is discussed in more detail here. The correct spatial orientation of the cells making up the organs of the adult demands a molecular plan of some type to be encoded in the DNA, and it is suggested that the plan is encoded in the nontranscribed DNA. This DNA is present in the form of loops and folds, giving rise to a spatial array of enormous complexity, and the general belief is that the spatial array is dependent on sequence-specific proteins which firmly bind to the DNA. It is proposed that the binding proteins can also join the DNA of two adjacent stem-cell nuclei once nucleus/nucleus contact has been made, and in this way determine the spatial orientation of the future specialized cells. There is enough information encoded in the spatial arrays to correctly position the myriad of cells that make up the adult organism. If cell alignment is carried out by nuclear union, then the development of the neuron can be better understood. It is suggested that malignancy may be due to a fault in either the nontranscribed DNA responsible for spatial orientation or in the sequence-specific binding proteins.

Adult↗
PubMed1995

The paradox of Ferrata and the fate of the extruded red cell nucleus: two problems concerning erythropoiesis in the human.

A critical analysis of the present erythropoietic pathway reveals two problems which require resolving. One is the paradox of the basophilic erythroblast, and the other is the fate of the extruded red cell nucleus. The problems can be overcome if erythropoiesis is looked at differently, and the orthochromatic normoblast considered to arise directly from a denuded stem cell nucleus as has been previously suggested. The orthochromatic normoblast extrudes its nucleus leaving behind a reticulocyte. The extruded but functionally impaired nucleus of the orthochromatic normoblast then gives rise to a polychromatic normoblast, a defective cell. The poorly made cytoplasm of the polychromatic normoblast is shed and its nucleus, now non-functional, undergoes complete dissolution into an aggregate of ultrafine particles. The theory has the advantage that the fate of the extruded red cell nucleus can be explained without having to introduce phagocytosis by macrophages and all the immunological difficulties which this entails. The new pathway does away with the basophilic erythroblast as a haemoglobin-producing cell, and it is argued that the cell instead is a ferritin storage cell, and that erythropoiesis is the result of two separate but interdependent pathways, a ferritin storage pathway and a haemoglobin production pathway. Evidence is put forward to support the new pathways.

Biology↗
PubMed1995

An analysis of thymic function and the possible role of the thymus in stem cell production.

The thymus is considered to be essentially an organ of the immune system, its purpose being to supply T cells. The role of the T cell is to regulate the immune reaction which it does by liberating lymphokines. The lymphokine function of the T cells was not deciphered in vivo, but in explanted T cells, and it is debatable if explanted cells behave in the same way as their counterparts in the intact animal, so the liberated lymphokines may not represent nature's intent. Adding to the disquiet are those biological properties of the thymus which are difficult to explain on an immunological basis, in particular why the thymus is essential in the child but not in the adult. Thus, there is room for a different approach to the role of the thymus. There is sound evidence that the thymus plays a part in somatic growth and differentiation, and one explanation is that the thymus provides the stem cells for somatic growth. A stem cell role is supported by studies on mastopoiesis and eosinophilopoiesis, and also supported by the way embryonic organs grow after their initial development. From the arguments put forward, the hypothesis is put that the role of the thymus is to store and propagate the stem cells required for the organ growth which takes place subsequent to their initial development. If the thymus is a repository for stem cells, the varied aspects of thymic behaviour, including its role in immunity, can be explained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The role of cell fusion in erythropoiesis--Part 2.

In a prior study, cell fusion was found to play an important part in erythropoiesis in both the chicken and frog. Erythropoiesis in both organisms could be traced back to groups of embryonic cells which first fused to form an aggregate structure consisting of multiple nuclei enclosed by a common cytoplasm. The cytoplasm of the fused aggregate underwent dissolution to give rise to a set of denuded nuclei which, by manufacturing a haemoglobinized cytoplasm, were transformed into erythroblasts. Following these findings, the question of cell fusion in erythropoiesis in the human was investigated, and the results are reported here. Leishman stained smears of marrow aspirate were used, and care taken to prevent the immature cells coming into contact with plasma. The reason for this was that plasma was found to alter the normal structure of the immature haemopoietic cells, particularly the megakaryocyte series. Free from plasma contact, the nucleus of the megakaryocyte was found to be not multilobulated, but composed of a compact set of small nuclei. The mode of development of the megakaryocyte and its fate could be deciphered in the smears. The megakaryocytes arose as a result of fusion of small basophilic embryonic-like cells. After the megakaryocyte had attained a certain size, fusion ceased and the cytoplasm of the megakaryocyte underwent dissolution and was shed in the form of platelets, thus denuding the nuclei. The latter, bared of cytoplasm, were transformed directly into erythroblasts. The fate of the denuded nuclei in this manner goes against the accepted view that the denuded nucleus is phagocytosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The malignant stem cell.

A recent study of embryonic cells at organogenesis revealed that their nucleus was bare of cytoplasm along one section of the envelope, and that they formed aggregates in which nucleus to nucleus contact was a feature. Their behaviour could be divided into three stages, the first when the embryonic cell was small and motile, the second when cell aggregation took place and the third when differentiation occurred. The embryonic cell at organogenesis was considered to be committed and hence stem cell in nature. It is hypothesized that stem cells in the adult also start off as small, motile embryonic-like cells and progress through the same three stages. This embryonic-like structure and behaviour also applies to the malignant stem cell, and evidence is put forward to support this view. Finally the suggestion is made that metastases are due to the small size and motile nature of the malignant stem cell, and not due to a decrease in any adhesive forces between tumour cells.

Cell Differentiation↗
PubMed1994

Haemopoietic stem cells and basophils.

In a recent paper it was argued that all stem cells are small motile cells, the haemopoietic stem cell being no exception. Although haemopoietic stem cells arise and mature in an extravascular milieu, they are present in small numbers in the peripheral circulation, where they have a lymphocyte-like appearance, and in the peripheral circulation their fate can be linked to the development of basophils. The basophil is a cell shrouded in mystery, and one of the most mysterious aspects of the basophil is its small numbers in bone marrow, a finding which does not fit in with a marrow origin. A simple experiment provides an alternative explanation as to how they develop. If peripheral blood smears are prevented from drying out, after a few hours new basophils develop from a lymphocyte-like cell. The findings suggest that the basophil may arise, not in the marrow, but in the peripheral circulation, and may represent an aberrant development of the haemopoietic stem cell caused by the plasma. The pathology of the basophil supports this view.

Animals↗
PubMed1993

The role of cell fusion in erythropoiesis--Part 1.

The present haemopoietic pathways have been deduced from fixed material, and can be criticised on the grounds that they are an interpretation of a highly complex cytological picture and open to error. Furthermore, the pathways have not helped in the search for the haemopoietic stem cell, the initiating and most essential element of the pathways. Hence a different approach to the study of haemopoiesis may be useful, and in this regard Sabin's work is valuable. Sabin is one of the few investigators who has carried out a study of erythropoiesis on the living organism. She studied hanging drop preparations of explanted blastoderms of the chicken, and found that special embryonic cells called angioblasts fused to form well demarcated aggregates which were transformed into erythroblastic islands. In this paper, cell fusion leading to erythropoiesis has been further explored. Leishman stained smears of the blastoderm of the chicken, the splanchnic mesenchyme of the tadpole, the bone marrow of the juvenile chicken and the bone marrow of the juvenile frog were studied. Aggregates consisting of a set of nuclei enclosed by a common cytoplasm were found in all four tissues, and the origin and fate of the aggregates could be deciphered. The aggregates arose by a fusion of embryonic cells, and after the aggregate had attained a certain size, the cytoplasm underwent dissolution, denuding the nuclei. The bare nuclei, by manufacturing a haemoglobinised cytoplasm, were transformed into erythroblasts. The findings not only confirmed Sabin's observations on erythropoiesis in the chicken blastoderm but also showed that cell fusion was an integral part of erythropoiesis on a wider scale.

Animals↗
PubMed1991

Stimulation of megakaryocytopoiesis in mice by human recombinant interleukin-6.

The in vivo effects of purified human recombinant interleukin-6 (IL-6) on murine megakaryocytopoiesis were examined. IL-6 was administered subcutaneously to Swiss Webster mice, followed by evaluation of bone marrow megakaryocyte ploidy, size and frequency, and median platelet volume 24, 48, and 72 hours after the initiation of IL-6 administration. In addition, bone marrow megakaryocyte morphology was examined using electron microscopy at 72 hours. IL-6 (10,000 U per subcutaneous injection) was administered three times during the first 24 hours, three times during the second 24 hours, and twice during the last 24-hour period. IL-6 bioactivity (10 U/ng) was determined using the IL-6-dependent murine hybridoma cell line B9. Megakaryocyte ploidy distribution, measured by two-color flow cytometry, demonstrated a shift in the modal ploidy class from 16N to 32N and a significant increase in the relative frequency of 64N megakaryocytes 48 and 72 hours (but not 24 hours) after initiation of IL-6 administration (cumulative doses of 60,000 and 80,000 U at 48 and 72 hours, respectively). In addition, ploidy levels were increased in animals that received a cumulative IL-6 dose of only 40,000 U (evaluated after 72 hours). The size of recognizable bone marrow megakaryocytes, determined by the cross-sectional areas of plastic embedded bone marrow megakaryocytes, was increased at the 48-hour (60,000 U IL-6) and 72-hour (80,000 U IL-6) time points. Megakaryocyte frequency, measured by flow cytometry, was unaffected at all time points and doses of IL-6. Median platelet volume, measured by electrical impedance, was not consistently altered by administration of IL-6. Electron microscopic examination of bone marrow megakaryocytes showed an increase in the proportion of megakaryocytes with a wide, peripheral, organelle-deficient zone from 20% +/- 9% (SD) in control animals to 50% +/- 7% (SD) (P less than .02) in animals that received IL-6. No changes were observed in the distribution of the demarcation membranes. IL-6 is a potent stimulator of murine megakaryocytopoiesis, in vivo, and appears to act early in megakaryocyte differentiation.

Animals↗
PubMed1989

Isolation, characterization, and expression in Escherichia coli of the DNA polymerase gene from Thermus aquaticus.

The thermostable properties of the DNA polymerase activity from Thermus aquaticus (Taq) have contributed greatly to the yield, specificity, automation, and utility of the polymerase chain reaction method for amplifying DNA. We report the cloning and expression of Taq DNA polymerase in Escherichia coli. From a lambda gt11:Taq library we identified a Taq DNA fragment encoding an epitope of Taq DNA polymerase via antibody probing. The fusion protein from the lambda gt11:Taq candidate selected an antibody from an anti-Taq polymerase polyclonal antiserum which reacted with Taq polymerase on Western blots. We used the lambda gt11 clone to identify Taq polymerase clones from a lambda Ch35:Taq library. The complete Taq DNA polymerase gene has 2499 base pairs. From the predicted 832-amino acid sequence of the Taq DNA polymerase gene, Taq DNA polymerase has significant similarity to E. coli DNA polymerase I. We subcloned and expressed appropriate portions of the insert from a lambda Ch35 library candidate to yield thermostable, active, truncated, or full-length forms of the protein in E. coli under control of the lac promoter.

Amino Acid Sequence↗
PubMed1988

Interleukin-one induced inositol phospholipid breakdown in murine macrophages: possible mechanism of receptor activation.

Stimulation of mouse peritoneal macrophages by Interleukin-one (IL-1) provoked rapid increases in the levels of inositol mono, bis, tris and tetrakisphosphates (IP1, IP2, IP3 and IP4 respectively). IP3 was by far the major metabolite formed and time course studies revealed that IP2 and IP3 were formed more rapidly than IP1 and IP4 in response to IL-1 stimulation. The IP2 and IP3 levels peaked at five seconds while there was a time lag of five seconds in the IP4 response and the IP1 levels increased relatively steadily over the time course of the experiments. Levels of IP2, IP3 and IP4 all returned almost to control levels by 60s. The rapid formation of the inositol phosphate metabolites was concomitant with a decrease (84%) in the levels of phosphatidyl-inositol 4,5-bisphosphate (PIP2) in the macrophages. These results suggest that the mechanism of IL-1 receptor activation is by the rapid hydrolysis of phosphoinositides and generation of the second messenger IP3.

Animals↗
PubMed1988

Synergistic interaction of hematopoietic colony stimulating and growth factors in the regulation of myelopoiesis.

Synergistic interactions in the regulation of myelopoiesis have been noted in vitro and in vivo and are discussed. Moreover, data is presented to highlight such synergistic interactions in vitro and in vivo. It is shown that purified recombinant human B-cell stimulating factor-1/interleukin-4 (rh BSF-1/IL-4) synergizes with rh Granulocyte (G)-Colony Stimulating Factor (CSF), but not with rh Granulocyte-Macrophage (GM)-CSF, rh IL-3, or rh Macrophage CSF (CSF-1) to enhance colony formation in vitro by normal human bone marrow cells. This synergism is restricted to granulocyte progenitors. Also, it is shown that rh G-CSF or rh CSF-1 enhance the proliferation of granulocyte-macrophage progenitor cells (CFU-GM) in vivo in mice pretreated with human lactoferrin, and when added together these preparations of CSF act synergistically. It is apparent that a true understanding of how myeloid blood cell production is regulated requires insight into how molecules collaborate with or antagonise one another.

Animals↗
PubMed1987

Protective effect of gamma-linolenic acid on aspirin-induced gastric hemorrhage in rats.

The effects of feeding with gamma-linolenic acid (GLA) in comparison with linoleic acid on aspirin-induced gastric hemorrhage were studied in the rat. Gastric damage was examined macroscopically and histologically. Intragastric administration of 100 mg aspirin daily for 4 weeks produced hemorrhage in 3 of 8 rats receiving a linoleic-acid-enriched diet, but none in 8 rats receiving GLA-enriched diet. The levels of linoleic acid in plasma and liver phospholipids were significantly increased, whereas those of arachidonic acid (AA) were reduced in plasma and liver phospholipids of aspirin-treated animals fed linoleic acid. Similar, more pronounced changes occurred in those animals with hemorrhage. The reduced ratios of arachidonate/linoleate suggest that fatty acid desaturation in these animals was depressed. Treatment with GLA prevented these changes. Our results demonstrated that GLA could protect the gastric mucosa from aspirin-induced damage by bypassing the depressed delta-6-desaturation and thus providing a precursor for the synthesis of AA and prostaglandins.

Animals↗
PubMed1982

Some thoughts on the origin of RNA, and the roles of ribosomes, the nucleolus and the nucleus.

The deciphering of DNA's structure led to the formulation of Crick's central dogma, implicit in which is that all RNA is chromosomal in origin. The detection of RNA synthesis at nucleolar sites, plus the similarity between r RNA and nucleolar RNA has firmly established the idea that the nucleolus is responsible for r RNA production. But neither of these considerations actually prove that this is so. An analysis of RNA synthesis in E coli suggests that its r RNA is not chromosomal in origin, but arises by semi conservative replication. The likelihood therefore exists that eukaryotic r RNA also arises by self replication and is not a product of the nucleolus. This concept is favoured by the behaviour of the nucleolus in the differentiating cell in which it seems to have an important role.

Cell Nucleolus↗