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Biomedical subjects

J Garner

Publications and source records attributed to J Garner.

At least 19 recordsLinked to original sources
PubMed2000

Corticotropin releasing hormone: therapeutic implications and medicinal chemistry developments.

Corticotropin releasing hormone (CRH, sometimes known as CRF) is an endogenous 41 amino acid peptide that has been implicated in the onset of pregnancy, the 'fight or flight' response, in addition to a large number of physiological disorders. Recently, medicinal chemists have developed a number of potent and selective compounds that show promise in a vast array of therapeutic uses. Herein we review the current status of research.

Amino Acid Sequence↗
PubMed2000

Reduplication phenomena: body, mind and archetype.

The many biological and few psychodynamic explanations of reduplicative syndromes tend to have paralleled the dualism of the phenomenon with organic theories concentrating on form and dynamic theories emphasising content. This paper extends the contribution of psychoanalytic thinking to an elucidation of the form of the delusion. Literature on clinical and aetiological aspects of reduplicative phenomena is reviewed alongside a brief examination of psychoanalytic models not overtly related to these phenomena. The human experience of doubles as universal archetype is considered. There is an obvious aetiological role for brain lesions in delusional misidentifications, but psychological symptoms in an individual can rarely be reduced to an organic disorder. The splitting and doubling which occurs in the phenomena have resonances in cultural mythology and in theories from different schools of psychodynamic thought. For the individual patient and doctor, it is a diverting but potentially empty debate to endeavour to draw strict divisions between what is physical and what is psychological although both need to be investigated. Nevertheless, in patients in whom there is clear evidence of an organic contribution to aetiology a psychodynamic understanding may serve to illuminate the patient's experience. Organic brain disease or serious functional illness predispose to regression to earlier modes of archetypical and primitive thinking with concretization of the metaphorical and mythological world. Psychoanalytic models have a contribution in describing the form as well as the content of reduplicative phenomena.

Brain↗
PubMed1999

Pharmacophore development for corticotropin-releasing hormone: new insights into inhibitor activity.

Corticotropin-releasing hormone (CRH) is an endogenous 41-amino acid peptide involved in a wide ranging series of systems including the brain, the coordination of the body's overall response to stress, and more recently as a crucial initiator in the onset of labor, also known as the placental clock. Although more physiological data on CRH is emerging shedding more light on the processes involved and their integration, the mode of action of the hormone and the postulated binding site(s) remain unknown. Recently, a number of small-molecular-weight ligands have emerged as potent antagonists but, as therapeutics, suffer from a lack of solubility. Additionally, despite a number of exhaustively large patents, the lack of structural diversity with these antagonists has enabled little scope for comprehensive and wide ranging studies into the structure of the binding sites of this hormone. As part of a program investigating new, structurally diverse antagonists and agonists of CRH, we have developed a preliminary pharmacophore based on the known small-molecular-weight ligands as an initial step in our program. This pharmacophore was validated by comparison with some of the compounds we postulated to be active.

Adrenocorticotropic Hormone↗
PubMed1999

Predictors of brain morphology for the men of the NHLBI twin study.

BACKGROUND AND PURPOSE: Cross-sectional studies show that cerebrovascular risk factors are associated with increased brain atrophy, accumulation of abnormal cerebral white matter signals, and clinically silent stroke. We extend these findings by examining the relationship between midlife cerebrovascular risk factors and later-life differences in brain atrophy, amount of abnormal white matter, and stroke on MRI. METHODS: Subjects were the 414 surviving members of the prospective National Heart, Lung, and Blood Institute Twin Study, who have been examined on 4 separate occasions, spanning the 25 years between 1969-1973 and 1995-1997. Quantitative measures of brain volume, volume of abnormal white matter signal (WMHI), and volume of stroke, when present, were obtained from those participating in the fourth examination. RESULTS: The mean+/-SD age of the subjects was 47.2+/-3.0 years at initial examination and 72. 5+/-2.9 years at final examination. Average blood pressure (BP) levels were normal, although 32% of the subjects had received or were currently taking antihypertensive medications. As a group, 31% had symptomatic cardiovascular disease, 11% had symptomatic cerebrovascular disease, and 8% had symptomatic peripheral vascular disease. Both systolic and diastolic BP levels at initial examination were inversely related to brain volume and positively related to WMHI volume. Multiple regression analysis identified BP-related measures and vascular risk factors as significant predictors of brain and WMHI volumes. In addition, the magnitude of orthostatic BP change was significantly associated with WMHI volume. Subjects with extensive amounts of WMHI had significantly higher systolic BP at the final examination and a higher prevalence of symptomatic cardiovascular and cerebrovascular disease, without significant differences in the prevalence of hypertension treatment. CONCLUSIONS: Midlife BP measures are significantly associated with later-life brain and WMHI volumes and the prevalence of symptomatic vascular disease. Since WMHI share cerebrovascular risk factors and extensive WMHI are associated with symptomatic vascular disease, extensive WMHI may be a subclinical expression of cerebrovascular disease. Careful treatment of midlife BP elevations may diminish these later-life brain changes.

Age Factors↗
PubMed1998

Membrane-mediated release of nucleotide from an initiator of chromosomal replication, Escherichia coli DnaA, occurs with insertion of a distinct region of the protein into the lipid bilayer.

DnaA protein, the initiator protein of E. coli chromosomal replication, can be rejuvenated from an inactive ADP form to active ATP-DnaA protein by acidic phospholipids in a fluid bilayer. Cross-linking studies with the photoactivable phospholipid analog 1-O-hexadecanoyl-2-O-[9-[[[2-[125I]iodo-4-(trifluoromethyl-3H- diazirin -3-yl)benzyl]oxy]carbonyl]nonanoyl]-sn-glycero-3-phosphocholine reveal insertion of DnaA protein into the hydrophobic region of the bilayer; this insertion is accompanied by membrane-mediated dissociation of the tightly bound allosteric nucleotides ADP and ATP. Photolabeling of DnaA protein occurred with membrane properties that resembled those needed for reactivation of ADP-DnaA protein; efficient labeling of DnaA protein was observed only when the lipid analog was incorporated into anionic vesicles and the temperature during treatment was above the gel to liquid crystalline phase transition. Predominant hydrophobic photolabeling was localized within a single region of DnaA protein, a region that contains putative amphipathic helices and has been shown to contain information essential for functional interaction with membranes.

Adenine Nucleotides↗
PubMed1997

A molecular phylogeny of Mobile River drainage basin pleurocerid snails (Caenogastropoda: Cerithioidea).

Sequences from the mitochondrial 16S rRNA gene were obtained to construct a molecular phylogeny for Mobile River drainage basin pleurocerid snails. Data from 876 aligned positions generated a single most-parsimonious tree for each of three analytical approaches: (1) equal weighting, (2) transversions weighted 2 x transitions; and (3) transversions weighted 4 x transitions. Identical topologies for the resulting trees depict the genera Elimia and Pleurocera as monophyletic sister taxa. The genus Leptoxis is paraphyletic with Leptoxis plicata sister to the Elimia + Pleurocera clade. L. taeniata and L. ampla are sister taxa and L. picta is the most basal pleurocerid examined. When transversions were weighted 10x transitions a single most-parsimonious tree was obtained with the only topological difference being L. picta depicted as sister to L. taeniata and L. ampla and L. plicata is now the most basal pleurocerid examined. Many of the Elimia species are closely related, but we await further data before making any taxonomic recommendations. L. picta and L. plicata are quite distinct from each other and all other pleurocerid species examined. These data serves as an important foundation for future studies examining conservation genetics and systematics of this diverse and imperiled family.

Animals↗
PubMed1997

Dementia: an intimate death.

This paper focuses on the loss of intimacy and mutuality in the relationship when one partner has Alzheimer's disease and suggests that the paradigm of anticipatory grief described in terminal care work may need to be reconsidered in relation to organic brain disease. An attempt is made to link some of the psychoanalytic literature of grief and the experience of clinicians in old age psychiatry working with patients and their relatives. Mention is made of implications for management. The paper includes illustrative clinical material.

Aged↗
PubMed1996

Membrane regulation of the chromosomal replication activity of E. coli DnaA requires a discrete site on the protein.

The capacity of DnaA protein to initiate DNA synthesis at the chromosomal origin is influenced profoundly by the tightly bound nucleotides ATP and ADP. Acidic phospholipids can catalyze the conversion of inactive ADP-DnaA protein into the active ATP form. Proteolytic fragments of the nucleotide form of DnaA protein were examined to determine regions of the protein critical for functional interaction with membranes. A 35 kDa chymotryptic and 29 kDa tryptic fragment retained the tightly bound nucleotide. The fragments, whose amino-termini are within three residues of each other, but differ at their carboxyl ends, showed strikingly different behavior when treated with acidic phospholipids. The larger chymotryptic fragment released the bound nucleotide in the presence of acidic, but not neutral phospholipids. In contrast, the smaller tryptic fragment was inert to both forms of phospholipids. Acidic membranes, but not those composed of neutral phospholipids, protect from tryptic digestion a small portion of the segment that constitutes the difference between the 29 and 35 kDa fragments. The resulting 30 kDa tryptic fragment, which possesses this protected region, interacts functionally with acidic membranes to release the bound effector nucleotide. Inasmuch as the anionic ganglioside GM1, a compound structurally dissimilar to acidic glycerophospholipids, efficiently releases the nucleotide from DnaA protein, an acidic surface associated with a hydrophobic environment is the characteristic of the membrane that appears crucial for regulatory interaction with DnaA protein.

Adenosine Triphosphate↗
PubMed1996

Membrane regulation of the chromosomal replication activity of E.coli DnaA requires a discrete site on the protein.

The capacity of DnaA protein to initiate DNA synthesis at the chromosomal origin is influenced profoundly by the tightly bound nucleotides ATP and ADP. Acidic phospholipids can catalyze the conversion of inactive ADP-DnaK protein into the active ATP form. Proteolytic fragments of the nucleotide form of DnaA protein were examined to determine regions of the protein critical for functional interaction with membranes. A 35 kDa chymotryptic and 29 kDa tryptic fragment retained the tightly bound nucleotide. The fragments, whose amino-termini are within three residues of each other, but differ at their carboxyl ends, showed strikingly different behavior when treated with acidic phospholipids. The larger chymotryptic fragment released the bound nucleotide in the presence of acidic, but not neutral phospholipids. In contrast, the smaller tryptic fragment was inert to both forms of phospholipids. Acidic membranes, but not those composed of neutral phospholipids, protect from tryptic digestion a small portion of the segment that constitutes the difference between the 29 and 35 kDa fragments. The resulting 30 kDa tryptic fragment, which possesses this protected region, interacts functionally with acidic membranes to release the bound effector nucleotide. Inasmuch as the anionic ganglioside GM1, a compound structurally dissimilar to acidic glycerophospholipids, efficiently releases the nucleotide from DnaA protein, an acidic surface associated with a hydrophobic environment is the characteristic of the membrane that appears crucial for regulatory interaction with DnaA protein.

Adenosine Triphosphate↗
PubMed1992

Antimicrobial susceptibility of anaerobic bacteria in Auckland 1987-90.

The antimicrobial susceptibility of 292 clinical isolates of anaerobic bacteria was determined by a standard agar dilution method. Metronidazole was the most active agent with only one Bacteroides fragilis, two anaerobic cocci, and Propionibacterium acnes being resistant. For B fragilis itself and other members of the B fragilis group: 35/35 (100%) and 43/44 (98%) respectively, were susceptible to amoxycillin-clavulanic acid; 47/47 (100%) and 55/56 (98%) respectively, were susceptible to cefoxitin; and 20/28 (71%) and 7/25 (28%) respectively, were susceptible to ceftriaxone. All four agents and penicillin were almost always active against anaerobic cocci and Fusobacterium species. All agents were active against clostridium isolates except for cefoxitin where only 47/57 (82%) were susceptible. These results allow comparison with isolates from other locations and may be considered when choosing an antimicrobial agent for prophylaxis or therapy of anaerobic infections.

Amoxicillin↗
PubMed1991

Immunolocalization of epidermal growth factor (EGF), EGF receptor and transforming growth factor alpha (TGF alpha) during murine palatogenesis in vivo and in vitro.

The distribution of epidermal growth factor, the epidermal growth factor receptor and transforming growth factor alpha during murine palatogenesis was investigated immunocytochemically. On embryonic day 12 staining for transforming growth factor alpha was present throughout the palatal mesenchyme, with little in the epithelia. On embryonic day 13 staining increased in the palatal epithelia and in the mesenchyme at the tip of the palate. As the palatal shelves fused together (embryonic day 14.5) intense staining for transforming growth factor alpha was seen in the midline epithelial seam and in the subjacent mesenchyme. On embryonic day 15 there was a generalised increase in palatal epithelial staining; this was most marked in the remnants of the degenerating epithelial seam. Mesenchymal staining was, however, uniform. Whilst palatal staining for epidermal growth factor was sparse, at all stages, staining for its receptor was present throughout the palatal epithelia and mesenchyme. This was most intense in the palatal medial edge epithelia at the time of midline epithelial seam degeneration. The regional and temporal differences in staining for the epidermal growth factor receptor and transforming growth factor alpha suggested that these molecules may play an important role in normal palate development in vivo, particularly in degeneration of the midline epithelial seam.

Animals↗