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Biomedical subjects

M Land

Publications and source records attributed to M Land.

At least 37 records · Page 2Linked to original sources
PubMed1997

Structure and expression of the Caenorhabditis elegans protein kinase C2 gene. Origins and regulated expression of a family of Ca2+-activated protein kinase C isoforms.

The molecular and cellular basis for concerted Ca2+/lipid signaling in Caenorhabditis elegans was investigated. A unique gene (pkc-2) and cognate cDNAs that encode six Ca2+/diacylglycerol-stimulated PKC2 isoenzymes were characterized. PKC2 polypeptides (680-717 amino acid residues) share identical catalytic, Ca2+-binding, diacylglycerol-activation and pseudosubstrate domains. However, sequences of the N- and C-terminal regions of the kinases diverge. PKC2 diversity is partly due to differential activation of transcription by distinct promoters. Each promoter precedes an adjacent exon that encodes 5'-untranslated RNA, an initiator AUG codon and a unique open reading frame. PKC2 mRNAs also incorporate one of two 3'-terminal exons via alternative splicing. Cells that are capable of receiving and propagating signals carried by Ca2+/diacylglycerol were identified by assessing activities of pkc-2 gene promoters in transgenic C. elegans and visualizing the distribution of PKC2 polypeptides via immunofluorescence. Highly-selective expression of certain PKC2 isoforms was observed in distinct subsets of neurons, intestinal and muscle cells. A low level of PKC2 isoforms is observed in embryos. When L1 larvae hatch and interact with the external environment PKC2 content increases 10-fold. Although 77- and 78-kDa PKC2 isoforms are evident throughout post-embryonic development, an 81-kDa isoform appears to be adapted for function in L1 and L2 larvae.

Alternative Splicing↗
PubMed1995

Which parts of the road guide steering?

A driver steering a car on a twisting road has two distinct tasks: to match the road curvature, and to keep a proper distance from the lane edges. Both are achieved by turning the steering wheel, but it is not clear which part or parts of the road ahead supply the visual information needed, or how it is used. Current models of the behaviour of real drivers or 'co-driver' simulators vary greatly in their implementation of these tasks, but all agree that successful steering requires the driver to monitor the angular deviation of the road from the vehicle's present heading at some 'preview' distance ahead, typically about 1 s into the future. Eye movement recordings generally support this view. Here we have used a simple road simulator, in which only certain parts of the road are displayed, to show that at moderate to high speeds accurate driving requires that both a distant and a near region of the road are visible. The former is used to estimate road curvature and the latter to provide position-in-lane feedback. At lower speeds only the near region is necessary. These results support a two-stage model of driver behaviour.

Adult↗
PubMed1995

Peroxisomal membrane protein PMP68 of mouse liver: cloning of a cDNA encompassing the nucleotide binding fold and epitope mapping of monoclonal antibodies to the expressed protein.

We have isolated and sequenced a cDNA which encodes 376 amino acids toward the carboxy-terminus, and encompassing the putative nucleotide binding fold, of PMP68 (mouse liver peroxisomal integral membrane protein of 68 kDa) the major integral membrane protein of mouse liver peroxisomes. The protein sequence predicted from this cDNA shows 97.9% amino acid identity to this same region of rat liver PMP70, a member of the ATP-binding cassette protein superfamily (K. Kamijo, S. Taketani, S. Yokota, T. Osumi, and T. Hashimoto, 1990, J. Biol. Chem. 265, 4534-4540). The section of the cDNA encoding the hydrophilic and putative cytoplasmic domain of PMP68 was expressed as a recombinant fusion protein in bacteria. Two monoclonal antibodies raised against this protein have been epitope-mapped to peptides generated by cyanogen bromide cleavage of the fusion protein. Antibody 1A4 recognizes a peptide whose sequence contains the first motif of the putative nucleotide binding fold of PMP68, and antibody 8F11 recognizes a carboxy-terminal peptide which includes the second motif of this nucleotide binding fold. These antibodies are expected to be useful in the elucidation of the biological function of this putative membrane transporter.

ATP-Binding Cassette Transporters↗
PubMed1994

Origin, properties, and regulated expression of multiple mRNAs encoded by the protein kinase C1 gene of Caenorhabditis elegans.

Recently, we cloned and characterized cDNA encoding a novel, protein kinase C (designated PKC1B) from Caenorhabditis elegans. PKC1B (707 amino acid residues) is a developmentally regulated, calcium-independent kinase that is expressed exclusively in sensory neurons and related interneurons. We have now discovered a mechanism by which a second, distinct mRNA (PKC1A mRNA) with increased protein coding potential is generated from the C. elegans PKC1 gene. PKC1A mRNA is produced in a process that involves the utilization of an alternative, distal promoter, the incorporation of two unique exons into the mRNA, and alternative cis/trans splicing. Diversity among PKC1 gene transcripts is increased substantially by trans-splicing. The 5' end of PKC1A mRNA contains an acceptor site that is modified by the addition of either a classical spliced leader sequence 2 or one of four novel spliced leaders. PKC1A mRNA encodes a predicted kinase that contains the entire sequence of PKC1B as well as an N-terminal extension of 56 residues. The extension contains a preponderance of basic amino acids. The levels of transcripts arising from the distal (1A) and proximal (1B) promoters for the PKC1 gene are differentially regulated during C. elegans development. The ratio of 1B mRNA:1A mRNA varies from 40:1 to unity as the nematodes progress from early larval stages to mature adults. The novel exons in the PKC1A structural gene are not contiguous with the PKC1A promoter but are instead positioned downstream from a second gene, kinase upstream gene-1, in the context of a multicystronic operon. PKC1A and kinase upstream gene-1 mRNAs are coordinately expressed in a fixed ratio throughout C. elegans post-embryonic development, suggesting that a shared upstream promoter regulates transcription of both genes. Finally, PKC1A and PKC1B mRNA levels are differentially regulated by phorbol esters in a process that may involve the participation of another PKC isoform that is analogous to mammalian PKC delta.

Amino Acid Sequence↗
PubMed1994

Structure and expression of a novel, neuronal protein kinase C (PKC1B) from Caenorhabditis elegans. PKC1B is expressed selectively in neurons that receive, transmit, and process environmental signals.

The nematode Caenorhabditis elegans provides an advantageous system for investigating the regulation, expression, and functions of protein kinase C (PKC) isoforms. We cloned and characterized cDNAs encoding a novel C. elegans PKC designated PKC1B. The predicted PKC1B polypeptide contains features characteristic of the nPKC subfamily of PKC isoforms. The levels of PKC1B and its cognate mRNA vary over a 7-fold range during C. elegans postembryonic development. PKC1B protein and mRNA are abundant at the earliest larval stage, but their relative concentrations decrease coordinately in late larvae. Embryos, which are enriched in PKC1B mRNA, contain little PKC1B protein. Thus, PKC1B expression is regulated at a translational or post-translational level during early development. Cells engaged in PKC1B gene transcription were identified in transgenic C. elegans that carry the lacZ gene under the regulation of the PKC1B promoter. Staining for beta-galactosidase revealed PKC1B promoter activity exclusively in sensory neurons and interneurons. Immunofluorescence microscopy disclosed that the PKC1B polypeptide is located in the processes (axons and dendrites) and perinuclear regions of approximately 75 neurons that constitute the sensory circuitry of the nematode. The intracellular localization of PKC1B and the enzyme's differential solubility in ionic and nonionic detergents suggest that the kinase is associated with membranes and the cytoskeleton.

Amino Acid Sequence↗
PubMed1992

Glycerol-induced unraveling of the tight helical conformation of Escherichia coli type 1 fimbriae.

Glycerol was found to unravel the helical conformation of Escherichia coli type 1 fimbriae without appreciable depolymerization. The linearized fimbrial polymers have a diameter of 2 nm, react strongly with a monoclonal antibody directed at an inaccessible epitope on native fimbriae, and display greater mannose-binding activity and trypsin sensitivity than native fimbriae. Removal of glycerol by dialysis results in spontaneous reassembly of the linear polymers into structures morphologically, antigenically, and functionally indistinguishable from native fimbriae.

Escherichia coli↗
PubMed1992

Blastomycotic cranial osteomyelitis.

This is the second case report of a temporal bone osteomyelitis caused by Blastomyces dermatitidis, which presented as a chronic serous otitis media. The presenting serous otitis media was refractory to conventional medical and surgical management and progressed to a temporal bone osteomyelitis prior to diagnosis. B. dermatitidis is a rare fungal pathogen that causes a systemic pyogranulomatous disease that primarily manifests itself in the skin, bones, pulmonary, and genitourinary systems. If left untreated it is associated with a high rate of mortality. The otologic presentation of this rare disease is emphasized, while the clinical and therapeutic features are reviewed.

Adult↗
PubMed1990

The accuracy of simple ordinal scoring of tooth attrition in age assessment.

Tooth wear is frequently used as a method of ageing skeletal remains. Fundamental to this method is the ability to measure the amount of tooth wear. The Brothwell chart based on the Miles method of ageing, uses simple ordinal scoring and is frequently used by archeologists. The purpose of the present investigation was to evaluate the accuracy of simple ordinal scoring in recording tooth wear and ageing skulls. A group of Chinese skulls of known age at death was used. The age range was from 16 to 60 years. A single score per molar tooth was used to record occlusal wear. The data were analysed by regression methods using BMDP statistical software. The results showed that molar tooth wear continues throughout the life of the individual. The first molar teeth wear significantly more quickly than do second molar teeth. Use of a simple ordinal score method for recording wear gives an inaccurate estimate of an individual skull's age at death with a very wide 95% confidence interval.

Adolescent↗
PubMed1990

A comparison of the position of the mental foramen in Chinese and British mandibles.

The antero-posterior position of the mental foramen was studied in 68 Chinese and 44 British skulls of known or calculated age at death. All skulls showed low pre-mortem tooth loss and had a good occlusion. The position of the foramen was related to the body of the mandible as well as to the standing mandibular teeth using two previously published methods. There was no significant difference in the size of the Chinese and British mandibles. There was a significant difference between the two groups when measurements relating the foramen to the body of the mandible (symphysis menti) were considered, the foraminal position being more distal in the Chinese group. The modal position of the foramen in the Chinese sample was along the long axis of the second premolar, whereas in the British sample it lay between the apices of the first and second premolar. The foraminal position apparently moved distally in both groups with age and this was likely to be associated with mesial tooth drift and age-related attrition.

Adolescent↗
PubMed1987

Identification of a mineralocorticoid receptor binding substance in the urine of patients with congenital adrenal hyperplasia.

Increased amounts of circulating mineralocorticoid receptor binding substances presumed to be natural antagonists were previously demonstrated in congenital adrenal hyperplasia. In this study the feasibility of using urinary extracts for the identification of such binding substances was investigated. Urinary extracts from patients with the 21-hydroxylase defect did contain greater than normal amounts of mineralocorticoid receptor binding material. When subjected to chromatographic separation using a radioreceptor assay to follow the course of fractionation, a major aldosterone binding competitor was identified. On the basis of its chromatographic mobility in comparison with the labeled steroid, radioimmunoassay, ultraviolet absorption and radio-receptor assay of the native and acetylated derivative, the component was identified as 11-deoxycorticosterone and its structure confirmed by mass spectrometry. Although the major mineralocorticoid receptor binding component proved not to be an antagonist but an agonist, the results are in keeping with other evidence for overproduction of 11-deoxycorticosterone in the simple virilizing form of the disorder. Our finding did not disprove the existence of a circulating mineralocorticoid antagonist in congenital adrenal hyperplasia, but demonstrate that the major receptor binding substance in urinary extracts in that disorder is the mineralocorticoid agonist, 11-deoxycorticosterone.

Adrenocortical Hyperfunction↗
PubMed1986

Evidence for the secretion of an antimineralocorticoid in congenital adrenal hyperplasia.

Plasma extracts from patients with congenital adrenal hyperplasia were found to contain substances that competed with aldosterone for mineralocorticoid receptor-binding sites in a rat kidney cytosol system. In normal subjects and patients with other disorders, the mineralocorticoid receptor-binding activity in such extracts could be entirely accounted for by the sum of the contributions of the steroids known to bind to the mineralocorticoid receptor. The secretion of these binding substances in patients with the C-21 hydroxylation defect was ACTH dependent. While these substances could be either mineralocorticoid agonists or antagonists, the latter is more likely. Production of mineralocorticoid antagonists would account for the compensatory hyperaldosteronism that occurs in the simple virilizing form, in which there is minimal impairment of aldosterone secretory reserve, and for the tendency to Addisonian crisis in patients with the salt-losing form, who have a more severe defect in aldosterone biosynthesis.

Adolescent↗
PubMed1983

Biosynthesis of 18-oxocortisol by aldosterone-producing adrenal tissue.

Aldosterone-biosynthesizing adrenal tissue contains an angular methyl oxidase which converts corticosterone to 18-hydroxycorticosterone and aldosterone. Cortisol, when incubated with an active source of this oxidase, the bullfrog interrenal gland, was converted to 18-hydroxycortisol and a new C-18-oxygenated steroid identified as 11 beta, 17 alpha,21-trihydroxy-3,20-diketo-4-pregnene-18-al, or 18-oxocortisol. Proof of structure was based on the evidence that it was an alpha, beta-unsaturated ketone biosynthesized from cortisol with an empirical formula of C21H28O6. Low resolution gas chromatography-mass spectrometry of its fully derivatized methoxime trimethylsilyl ether confirmed a trioxopregnenetriol structure in which one aldehyde group was partially masked as an internal hemiacetal. That the oxo group had replaced the C-18 angular methyl was shown by oxidative degradation of the side chain with either periodic acid or sodium bismuthate to yield an hydroxy gamma-lactone rather than an etioacid. It is suggested that the corticosterone methyl oxidase system of aldosterone-producing cells has diminished substrate specificity enabling it to accept cortisol as a suboptimal substrate. Angular methyl oxidation of cortisol to its 18-hydroxy and 18-oxoderivative in two hypertensive disorders is attributed to a derangement in adrenocortical functional zonation permitting access of glucocorticoid products into the mineralocorticoid-biosynthesizing system.

Adrenal Glands↗
PubMed1983

18-oxocortisol, a naturally occurring mineralocorticoid agonist.

Two C-18-oxygenated corticosteroids, 18-hydroxy- and 18-oxocortisol, have recently been isolated from the urine of patients with primary and genetic (dexamethasone-suppressible) aldosteronism and from adrenal tissue. The relevance of these steroids to the manifestations of mineralocorticoid excess in these disorders was investigated by measuring their affinity to rat renal corticosteroid receptors. 18-Oxocortisol showed greater affinity than the 18-hydroxy derivative for both mineralocorticoid and the glucocorticoid receptors and was accordingly assayed in vivo for mineralocorticoid activity. The 18-oxo derivative was found to be an agonist with a sodium-retaining and kaliuretic action qualitatively similar to that of aldosterone. Although 18-oxocortisol was one-third as active as 11-deoxycorticosterone in this assay, it was a more potent mineralocorticoid at the same total plasma concentration because of its lower affinity for corticosteroid-binding globulin.

Adrenalectomy↗
PubMed1979

Pharmacists' clinical role expanded.

A hospital used management engineering to achieve more effective utilization of its pharmacy staff so that pharmacists' clinical role could be expanded without increases in staff or costs.

Hospital Bed Capacity, 300 to 499↗
PubMed1979

Interrelation of the pituitary-thyroid system at birth in man.

Samples of cord blood derived from 105 normal babies after uncomplicated deliveries were assayed for thyroxine (T4), tri-iodothyronine (T3), reverse tri-iodothyronine (rT3), thyroxine-binding globulin (TBG) and thyrotrophin (TSH). The values for T3, rT3 and TSH were log-normally distributed (geometric means 0.62 nmol/l, 3.28 nmol/l and 10.9 mu./l respectively) and those for T4 and TBG were normally distributed (means 126 nmol/l and 13.7 mg/l), The data were systematically analysed and no evidence was obtained to suggest that the concentration of TSH, which varied widely, was regulated by any of the thyroid hormones alone or in combination. There was a direct relation between the concentrations of T4 and T3 in the cord blood at birth but not between either of these and rT3. There is thus no evidence of a functional interdependence of the hypothalamic-pituitary-thyroid system in man at birth.

Fetal Blood↗
PubMed1978

Radioaffinity assay, a new approach to binding assays applied to the measurement of serum albumin.

The affinity adsorbent Cibacron Blue F3GA-Sepharose 4-B has been used to develop a binding assay for human serum albumin. The method is simple, accurate and precise. It agrees well with the 'rocket' immunoelectrophoretic method and is proposed as an alternative technique for the re-estimation of albumin levels in the low range (less than 30 g/l) where the bromocresol green dye-binding method overestimates. Bilirubin, several drugs, gammaglobulin, haemoglobin and heparin do not interfere with the estimations.

Bromcresol Green↗