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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
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↗
PubMed1991

Adaptation of sleep and circadian rhythms to the Antarctic summer: a question of zeitgeber strength.

Adaptation of sleep and circadian rhythms was examined in three temperate zone dwellers arriving in Antarctica during summer. Rectal temperature, wrist activity, and heart rate were monitored continuously, sleep timing and quality noted on awakening, and mood and fatigue rated every 2 h while awake. Sleep was poorer in 2/3 subjects in Antarctica, where all subjects reported more difficulty rising. Sleep occurred at the same clock times in New Zealand and Antarctica, however, the rhythms of temperature, activity, and heart rate underwent a delay of about 2 h. The subject with the most Antarctic experience had the least difficulty adapting to sleeping during constant daylight. The subject with the most delayed circadian rhythms had the most difficulty. The delay in the circadian system with respect to sleep and clock time is hypothesized to be due to differences in zeitgeber strength and/or zeitgeber exposure between Antarctica and New Zealand.

Activities of Daily Living↗
PubMed1991

Psychological and sexual aspects of the menopause.

Female psychiatric morbidity appears to be highest during the middle years, with an apparent increase around the time of the menopause. Oestrogen replacement therapy may improve psychological symptoms, but the effects of testosterone and progestogens are less clear. There appears to be an adverse effect of both increasing age and the menopause on sexuality, with no clear benefit of oestrogen therapy. Exogenous testosterone may have a role in the treatment of sexual dysfunction.

Depressive Disorder↗
PubMed1990

Effects of temperature on nervous system: implications for behavioral performance.

Temperature change has a major impact on the function of the nervous system and its components, including altering synaptic gain and changing synaptic and conduction delays. Although many animals are subject to changes in body temperature, the degree of temperature change actually experienced by many poikilotherms is not well documented. The fact that many animals continue to exhibit coordinated sensorimotor function during changes in body temperature indicates that some form of temperature compensation has occurred within the nervous system. Compensations may occur automatically (opposing effects of temperature offsetting each other), they may be an inherent property of closed-loop systems, or they may be effected by more sophisticated control mechanisms such as those of the vertebrate cerebellum.

Action Potentials↗
PubMed1988

Temperature compensation in the vestibulo-ocular reflex: a novel hypothesis of cerebellar function.

Some ectothermic animals are subject to changes of body temperature during routine activity. How are they able to maintain co-ordinated behaviour? Analysis of the available evidence on the effects of temperature on the vestibulo-ocular reflex suggests that there will be a degree of automatic temperature compensation. Temperature will increase the gain of some components of the reflex, and decrease the gain of others resulting in a reduced temperature sensitivity of the overall reflex. It is suggested that the cerebellum may provide the balance of temperature compensation required to maintain adequate reflex function. The hypothesis is that type III (bidirectionally sensitive) Purkinje cells receive temperature information as a common-mode signal from the opposing labyrinths, and use this information to regulate the gain of the vestibulo-ocular reflex pathway.

Animals↗
PubMed1987

Effect of oestrogen and testosterone implants on psychological disorders in the climacteric.

In a double-blind trial oestradiol, oestradiol/testosterone, or placebo implants were assessed for their effects on psychological symptoms in women attending a menopause clinic. After two months, women receiving active treatment scored better than the placebo group on a self-rating scale of distress, on anxiety, and on depression (p less than 0.05). Postmenopausal but not perimenopausal women improved after placebo, and at 4 months the scores in the three groups no longer differed significantly.

Adult↗
PubMed1986

A vestibulo-ocular reflex with no head movement.

Eye movements were produced in an elasmobranch preparation by electrical stimulation of the horizontal canal ampullary nerves. A pseudorandom binary sequence of stimulus pulse trains was delivered bilaterally. Eye position during this stimulus was cross-correlated with the stimulus pattern to obtain a linear model of the response. Sums of exponential functions were fitted to the crosscorrelogram data to estimate time-constants and transfer functions. The data was examined in the frequency domain by using Fourier transformation. The response is accurately described by a second order linear filter, which is essentially a low pass filter with a cutoff at 0.22 Hz. This nearly two octaves below the cutoff frequency of the eye motor plant, which has been estimated by the same method. Our data shows that there is no central phase compensation or prediction which might offset the substantial delay in eye motor plant response. We hypothesise that the necessary phase compensation may be achieved by driving the vestibulo-ocular reflex with sensory neurons having a phase advance at high frequency.

Animals↗
PubMed1986

Elasmobranch eye motor dynamics characterised using pseudorandom stimulus.

A pseudorandom binary sequence electrical pulse rate stimulus was delivered to the abducens nerve of an elasmobranch preparation. Ipsilateral eye movements were recorded using a position-sensitive photodiode to measure the position of a reflective patch attached to the fish's eye. Eye position data was cross-correlated with the stimulus pattern, and exponential decay curves were fitted to the cross-correlograms to estimate the time constant of a linear first order low-pass filter model. The cross-correlograms were transformed into the frequency domain using a Digital Fourier Transform, and Bode plots of eye dynamics were plotted. Eye motor plant dynamics in the elasmobranch Cephaloscyllium isabella can be accurately characterised by a linear first order low-pass filter model with a corner frequency of 0.73 +/- 0.10 Hz. Non-minimum phase lag reaches 90 degrees at about 4 Hz, indicating a time delay of some 50-60 ms. Integration of the canal signal is not required for producing compensatory eye movements above the characteristic frequency of the eye motor plant. However, the canal signal may be integrated to ensure that the vestibulo-ocular reflex is compensatory at lower frequencies. Substantial phase compensation or prediction is required for effective control of the vestibulo-ocular reflex.

Abducens Nerve↗
PubMed1985

Comparison of the 5' regions of human and mouse carbonic anhydrase II genes and identification of possible regulatory elements.

The nucleotide sequence of the 5' region of the human carbonic anhydrase II gene has been determined. This sequence begins 643 base pairs upstream from the ATG start site and continues through exon 1, intron 1, exon 2 and the adjoining 125 nucleotides of intron 2. The human sequence is compared with homologous regions of the mouse (YBR strain) carbonic anhydrase II gene by aligning the two sequences for optimal homology. In addition to a TATA box and a putative CCAAT box (CCACC in human and CCACT in mouse), three conserved tandem-repeat elements in mouse and two in human (consensus: cCNGTCACCTCCgC) are located 15 and 22 base pairs upstream, respectively, from the CCAAT boxes in the human and mouse sequences. This repeat element is similar to a tandem repeat sequence located at about the same position in mammalian beta-globin genes, and may represent regulatory elements common to both the carbonic anhydrase and beta-globin genes. The regions surrounding exon 1 are extremely G + C-rich in both human and mouse genes. In addition, several CCGCCC or GGGCGG sequences which may be important for transcriptional efficiency are found in the 5' flanking regions of the human and mouse genes.

Amino Acid Sequence↗
PubMed1985

Structure and exon to protein domain relationships of the mouse carbonic anhydrase II gene.

We have isolated a cosmid clone containing the entire mouse (YBR strain) carbonic anhydrase (CA) II gene in 38 kilobase pairs of genomic DNA. The gene was found to be composed of seven exons and six introns. A TATA box (TATAAAA) and a possible CCAAT box (CCACT) have been located beginning 92 and 142 base pairs, respectively, upstream from the initiation codon ATG. When the regions encoded by exons and protein domains are examined, all but 1 of the 30 putative active site residues are encoded by four exons: exons 2 and 3 mainly code for hydrophilic residues and exons 4 and 6 mostly hydrophobic residues. Two intron splice positions, one between the codons for Glu-116 and Leu-117 and the other interrupting the codon for Gly-143, are located at the bottom of the active site cavity, and the former separates two of the three histidine residues forming ligands to the active site zinc ion. The other four splice sites map to the exterior of the molecule. Thus, except for the possible association of the 29 active site residues encoded by four exons, no obvious correspondence is seen between the regions coded by exons and the functional or secondary structural domains of the mouse CA II molecule. During this study, the possible basis for the two electrophoretic types, CA IIa and CA IIb, of inbred mouse strains was detected as a Gln/His interchange at position 38.

Amino Acid Sequence↗