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Biomedical subjects

J C Montgomery

Publications and source records attributed to J C Montgomery.

At least 19 recordsLinked to original sources
PubMed2000

Responses of anterior lateral line afferent neurones to water flow.

The mechanoreceptive lateral line system detects hydrodynamic stimuli and plays an important role in a number of types of fish behaviour, including orientation to water currents. The lateral line is composed of hair cell receptor organs called neuromasts that occur as superficial neuromasts on the surface of the skin or canal neuromasts located in subepidermal canals. Both are innervated by primary afferents of the lateral line nerves. Although there have been extensive studies of the response properties of lateral line afferents to vibrating sources, their response to water flow has not been reported. In this study, we recorded extracellularly from anterior lateral line afferents in the New Zealand long-fin eel Anguilla dieffenbachii while stimulating the eel with unidirectional water flows at 0.5-4 cm s(-)(1). Of the afferents, 80 % were flow-sensitive to varying degrees, the response magnitude increasing with flow rate. Flow-sensitive fibres gave non-adapting tonic responses, indicating that these fibres detect absolute flow velocity. Further studies are needed to confirm whether flow-sensitive and flow-insensitive fibres correlate with superficial and canal neuromasts, respectively.

Anguilla↗
PubMed1998

The murine Fhit locus: isolation, characterization, and expression in normal and tumor cells.

The murine Fhit locus maps near the centromere nu proximal Ptprg locus on mouse chromosome 14. The cDNA sequence and structure are similar to those of the human gene, with exons 5-9 encoding the protein. The predominant mRNA in the tissues and cell lines tested was an alternatively spliced form missing exon 3. Most murine cell lines tested, including lines established from normal mouse embryos and tumors, expressed very low or undetectable levels of Fhit mRNA. Most normal mouse tissues expressed wild-type Fhit mRNA, whereas approximately 40% of murine lung carcinomas expressed wild-type and aberrant Fhit RT-PCR products that lacked various exons. Several tumorigenic mouse cell lines exhibited homozygous deletions of Fhit exons. We conclude that the murine Fhit gene, like its human counterpart, is a target of alterations involved in murine carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed1997

Reln(rl-Alb2), an allele of reeler isolated from a chlorambucil screen, is due to an IAP insertion with exon skipping.

The reeler Albany2 mutation (Reln(rl-Alb2) in the mouse is an allele of reeler isolated during a chlorambucil mutagenesis screen. Homozygous animals had drastically reduced concentrations of reelin mRNA, in which an 85-nt exon was absent. At the genomic level, the mutation was shown to be due to an intracisternal A-particle insertion leading to exon skipping. This appears to be the first observation of retrotransposon insertion during chlorambucil mutagenesis.

Alleles↗
PubMed1997

Chromosome 11.

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Animals↗
PubMed1997

Identification of a conserved family of Meis1-related homeobox genes.

Meis1 locus was isolated as a common site of viral integration involved in myeloid leukemia in BXH-2 mice. Meis1 encodes a novel homeobox protein belonging to the TALE (three amino acid loop extension) family of homeodomain-containing proteins. The homeodomain of Meis1 is the only known motif within the entire 390-amino-acid protein. Southern blot analyses using the Meis1 homeodomain as a probe revealed the existence family of Meis1-related genes (Mrgs) in several diverged species. In addition, the 3' untranslated region (UTR) Meis1 was remarkably conserved in evolution. To gain a further understanding of the role Meis1 plays in leukemia and development, as well as to identify conserved regions of the protein that might reveal function, we cloned and characterized Mrgs from the mouse and human genomes. We report the sequence of Mrg1 and MRG2 as well as their chromosomal locations in murine and human genomes. Both Mrgs share a high degree of sequence identity with the protein coding region of Meis1. We have also cloned the Xenopus laevis ortholog of (XMeis1). Sequence comparison of the murine and Xenopus clones reveals that Meis1 is highly conserved throughout its coding sequence as well as the 3' UTR. Finally, comparison of Meis1 and the closely related Mrgs to known homeoproteins suggests that Meis1 represents a new subfamily of TALE homeobox genes.

Animals↗
PubMed1997

AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins.

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

Animals↗
PubMed1994

GABA, muscarinic cholinergic, excitatory amino acid, neurotensin and opiate binding sites in the octavolateralis column and cerebellum of the skate Raja nasuta (Pisces: Rajidae).

As part of a study of signal processing in the electro- and mechanosensory systems we have screened the octavolateralis column of the skate for GABAA, muscarinic cholinergic, excitatory amino acid, neurotensin and opiate binding sites using autoradiography following in vitro labelling of cryostat sections with tritiated ligands. The presence and distribution of these binding sites is compared between the octavolateralis column and the corpus cerebellum. GABAA binding sites were located in high concentrations in the granule cell regions of the cerebellum and octaval columns, with much lower concentrations in the Purkinje cell layer of the corpus cerebellum. Little or no labelling was evident in all molecular layer areas. Displacement studies using the discriminating ligand CL218,872 indicated that the GABAA binding sites were predominantly of the GABAA/benzodiazepine Type II variety. M1 muscarinic cholinergic binding sites were found in high concentrations in all granule cell areas and in lower concentrations in the molecular layer of the octavolateralis column, with an absence of labelling in the molecular layer of the corpus cerebellum. Kainic acid and AMPA binding sites were present in very high concentrations in all molecular layer areas. Glutamate binding was present in the molecular layer of the octavolateralis column and in some restricted regions of the dorsal granular ridge, whereas phencyclidine binding sites were sparse or absent. Neurotensin binding sites were strongly present in all granule cell areas and evident in the molecular layer of the octavolateralis column. There was evidence for opiate binding sites in the molecular layer of both the dorsal and medial octavolateralis nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

An adaptive filter that cancels self-induced noise in the electrosensory and lateral line mechanosensory systems of fish.

In lateral line and electrosensory systems of fish, the animal's own movements create unwanted stimulation that could interfere with the detection of biologically important signals. Here we report that an adaptive filter in the medullary nuclei of both senses suppresses self-stimulation. Second-order electrosensory neurons in an elasmobranch fish and mechanosensory neurons in a teleost fish learn to cancel the effects of stimuli that are presented coupled to the fish's movements. A model is proposed for how the adaptive filter is realized by the cerebellar-like circuits of the hindbrain nuclei in these senses.

Adaptation, Physiological↗
PubMed1994

High-resolution genetic map and YAC contig around the mouse neurological locus reeler.

Mutations at the recessive reeler locus (rl) on mouse Chromosome (Chr) 5 result in abnormal development of multiple central nervous system components, including the cerebral and cerebellar cortices. These abnormalities are characterized by highly disorganized laminar structures thought to have arisen from a post-migration failure of neuronal organization events that are probably mediated through cell-cell interactions. As a result of a mutagenesis scheme designed to generate visible recessive mutations induced by the drug chlorambucil, we had previously recovered a new allele of the reeler locus (rlAlb) that is likely to involve a deletion based on the known mechanisms of chlorambucil action. We have constructed a high-resolution genetic map from two intercrosses segregating this allele. Our first cross, in which the mutation was outcrossed to the 101 strain prior to intercrossing, consisted of 196 meioses and resulted in the positioning of four loci proximal to rl, with D5Mit1 being the closest (2.6 +/- 1.1 cM). The second cross consisted of intercrossing rl heterozygotes derived from an outcross to the C57BL/6 strain. A total of 318 mice (636 meioses) gave rise to a panel of 41 recombinants, which were used to map a total of 14 loci within a 6.4-cM interval bounded by D5Mit1 and the En-2 gene. A yeast artificial chromosome contig consisting of clones containing two of these loci, D5Mit72 (located 0.31 cM distal to rl), and D5Mit61 (no recombinants with rl), has been assembled and is being used to locate the rl gene.

Alleles↗
PubMed1994

Uncoupling of visual and somatic growth in the rainbow trout Oncorhynchus mykiss.

Hatchery reared juvenile rainbow trout of common parentage were reared on measured low or high rations, or fed ad libitum for 4.3 months to produce fish with different growth rates. Fish from the different groups differed in size by up to 40 and 290% for length and weight, respectively, by the end of the trial. Slow somatic growth was not accompanied by correspondingly slow growth of either the eyes, optic tectum or the cerebellum, suggesting that above a certain maintenance ration, growth of these parts of the CNS is strongly age-dependent. Retinal characteristics were also found to be age-dependent and not affected by the somatic growth rate of the fish. The corollary that age-dependent ocular growth should also be reflected in different relative eye sizes in fish with differential growth rates in the wild was tested by comparing fish of known age from lakes in which fish have markedly different growth profiles. Fish stocked from a single hatchery were recaptured from Lakes Okataina and Tarawera (rapid fish growth) and Lake Taharoa (slow fish growth) at times up to 5 years after release. As predicted, eye sizes of fish from Lakes Okataina and Tarawera were smaller for any given body size, than those of fish from Lake Taharoa. Absolute eye size was correlated with fish age, although there was some variation in eye size for any given age. Taken together, these results show that up to a certain level of food deprivation, growth of the eye is maintained at the expense, or in spite, of low somatic growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Comparison of behavioural and morphological measures of visual acuity during ontogeny in a teleost fish, Forsterygion varium, tripterygiidae (Forster, 1801).

Ocular morphology was examined in larval, juvenile and adult F. varium. There was a 26-fold increase in eye size from 0.28 mm in the smallest larva (5.0 mm in length) to a maximum diameter of 7.2 mm in a 110 mm long adult. Larval fish had pure cone retinae at hatching, however, putative rod precursor cells were also present. Juvenile and adult fish had a duplex retina with cones arranged in a square mosaic in which 4 equal double cones surrounded a central single cone. Hypertrophy of cone ellipsoids with increasing eye size resulted in maintenance of a closely packed array in fishes of all sizes. Theoretical sensitivity, assessed in terms of convergence of rods:bipolars, rod density, and photoreceptor outer segment length, increased during the juvenile phase but was constant across the adult size range. Angular density of cones increased with increasing eye size such that theoretical spacial acuity was poor in smallest fish (1 degree 8') and improved to an asymptotic value of about 9' in adults. Behavioural acuity of a 1-day-old larva determined using the optokinetic response (29 degrees), was very much poorer than histological estimates (1 degree 8'). Behavioural acuity improved to 4 degrees 18' at 14 days of age, compared to a theoretical value of 54'. An estimate of Matthiessen's ratio based on histological measurements suggests that the larval eye is initially strongly myopic, and grows into focus. Development of the retractor lentis muscle was first apparent 7 days after hatching with the result that larval eyes are incapable of accommodative lens movements to correct for a refractive error. This apparent myopia is thought to account for at least part of the mismatch between theoretical and behavioural spatial acuity.

Animals↗
PubMed1993

Coordinate regulation of collagen II(alpha 1) and H19 expression in immortalized hamster cells.

Loss of tumor suppressor gene function is essential in the multistep progression of cells to neoplasia. Immortalized cells were established by carcinogen treatment of Syrian hamster embryo cells. At early passages, these nontumorigenic cells retained the ability to suppress tumorigenicity in cell hybrids with malignant cells. Upon passage and subcloning of these suppressor-positive (supB+) cells, variant clones that had lost tumor suppressor activity were isolated. These suppressor-negative (supB-) clones remained nontumorigenic. The mRNAs encoding collagen II(alpha 1a), a chondrocyte differentiation marker, and H19, a developmentally controlled gene, were more abundant in supB+ cells than in supB- cells. Nuclear run-on analysis indicated that the transcription of these genes is differentially regulated. Transient transfection experiments revealed that a cis-acting element in the rat collagen II 5' flanking sequences directs differentially regulated transcription. Gel retention analysis demonstrated the presence of a nuclear DNA-binding factor(s) that specifically recognizes a DNA sequence common to both the rat collagen II sequences and the mouse H19 enhancer. In one set of clones, transcriptional regulation could account for differential collagen II and H19 expression in supB+ and supB- cells. In another set of clones, posttranscriptional controls are responsible for the decreased expression of these genes in supB- cells. The emergence of two independent mechanisms that cause differential expression of collagen II and H19 related to tumor suppressor loss suggests that coordinate regulation of these genes, or others regulated by common mechanisms, may be important in tumor suppression.

Animals↗
PubMed1991

Loss of a tumor suppressor gene function is correlated with downregulation of chondrocyte-specific collagen expression in Syrian hamster embryo cells.

We previously described the isolation of closely related, preneoplastic Syrian hamster cell lines that have retained (supB+) or lost (supB-) the ability to suppress the anchorage-independent growth and tumorigenicity of a sarcoma cell line (BP6T) in cell hybrids. In this report, we have used differential cDNA screening to clone several genes that are expressed in supB+ cells and downregulated in supB- cells. The nontumorigenic supB+ and supB- variants are advantageous for differential cDNA cloning because multiple independent cell lines differing in their tumor suppressor activity have been isolated. Differentially expressed cDNAs were isolated and placed into one of four groups based on DNA cross-hybridization. Representative cDNAs from Groups I and II, which were expressed at relatively high levels in two independently derived supB+ cell lines (DES4 and 10W) and downregulated in the supB- and tumor cell lines, were sequenced. The DNA and predicted amino acid sequences of these genes were found to be highly homologous to the chondrocyte-specific collagens type II and type IX. In contrast to the chondrocyte-specific collagens, another collagen isoform, collagen type I, was expressed at similar levels in both supB+ and supB- cells. These results suggest that carcinogen-induced immortalization selected for chondrocyte-like cell lines from the mixed embryo cell population. As these cells progressed toward tumorigenicity, the ability to express the chondrocyte differentiation markers was lost concomitantly with the ability to suppress the tumorigenicity of the BP6T sarcoma cell line. These results are consistent with the hypothesis that the supB+ tumor suppressor gene is involved in the regulation of differentiation. The identification of genes regulated by this suppressor gene may aid in its isolation.

Animals↗
PubMed1991

Characterization of the human gene for a newly discovered carbonic anhydrase, CA VII, and its localization to chromosome 16.

Six carbonic anhydrase (CA) isozymes (CA I-VI) in mammals and other amniotes have been described. We have isolated an additional CA gene from a human genomic library and designated its putative product carbonic anhydrase VII (CA VII). The gene is approximately 10 kb long and contains seven exons and six introns found at positions identical to those determined for the previously described CA I, CA II, and CA III genes. The finding of a 17-bp GT-rich segment in a position 28 bp downstream of the poly(A)+ signal and the high correspondence of the 5' and 3' splice sites of the six introns with consensus junction sequences are consistent with the gene being functional. The 5' flanking regions of the CA VII gene do not contain the TATA and CAAT promoter elements usually found within 100 bp upstream of transcription initiation, but do contain a TTTAA sequence 102 nucleotides upstream of the initiation codon. The 5' region of the gene (-243 to +551) is GC-rich and contains 80 CpG dinucleotides and four possible Sp1 (GGGCGG or CCGCCC) binding sites. Northern analysis has identified the salivary gland as a major site of expression. The derived amino acid sequence of the CA VII gene is 263 amino acids long and has 50, 56, and 49% identity with human CA I, CA II, and CA III, respectively. No differences were found at any of the 39 positions that have remained invariant in all mammalian CA isozymes sequenced to date. Based on analysis of interspecific somatic cell hybrids, the human CA VII gene, CA7, was assigned to chromosome 16, with localization to the long arm at the q21-23 region by in situ hybridization. This is in contrast to the location of the CA I, CA II, and CA III gene cluster on human chromosome 8 and that of the human CA VI gene on chromosome 1.

Amino Acid Sequence↗
PubMed1991

Lipid and carbohydrate metabolism in premenopausal women given subdermal estradiol implants.

Fifteen premenopausal women were studied before and 6 weeks after receiving subcutaneous implants of 100 mg estradiol. Serum estradiol levels doubled; increases were also seen in fasting serum total cholesterol and in high-density lipoprotein cholesterol (HDL). This increase was confined to the HDL2 subfraction, and was not reflected in the HDL apolipoproteins. Low density lipoprotein (LDL) cholesterol levels were unchanged, as were those of apolipoprotein B, the major protein component of LDL. Carbohydrate metabolism was assessed in a subgroup of 12 women. Estrogen implantation reduced fasting plasma glucose levels but did not alter the plasma glucose response to an oral glucose tolerance test. Plasma insulin levels were unchanged both in the fasted state and during the glucose tolerance test. Our findings indicate that parenteral administration of estradiol can alter lipid and carbohydrate metabolism in premenopausal women.

Adult↗
PubMed1991

Identification of genes associated with tumor suppression in Syrian hamster embryo cells.

Loss of a tumor-suppressor gene function appears to play a critical role in the multistep process of neoplastic transformation of Syrian hamster embryo (SHE) cells in vitro. Clonal variants of two independent, preneoplastic cell lines have been isolated that have either retained (termed supB+) or lost (termed supB-) the ability to suppress the tumorigenicity of a highly malignant benzo[alpha]pyrene-transformed SHE cell line (BP6T) in cell hybrids. We have pursued several approaches in an attempt to identify genes that are responsible for tumor suppression in these cells. The only consistent differences detected in two-dimensional gel analyses of supB+ and supB- cellular proteins were decreases in the levels of two high molecular weight isoforms of tropomyosin in supB- cells. Differential screening of a supB+ cDNA library for genes that are preferentially expressed in supB+ cells yielded cDNA clones for four genes, i.e., collagen type II, collagen type IX, H19, and a previously unidentified gene (clone 5). Nuclear run-on assays suggested that higher transcription rates were responsible for the increased steady-state levels of some of these transcripts in supB+ cells. DNA sequence comparisons showed that two copies of a 9 bp element, previously identified in each of the mouse H19 enhancers, were also present in the 5' flanking region of the rat type II collagen gene. A transcription factor that controls expression of the collagen and H19 genes through binding to this conserved motif would be an attractive candidate for the supB+ gene or at least a mediator of the supB+ phenotype.

Animals↗