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Biomedical subjects

K J Jones

Publications and source records attributed to K J Jones.

At least 91 records · Page 5Linked to original sources

Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy.

Lactate infusions are anxiogenic in patients with panic disorder or agoraphobia with panic attacks, but few neuroendocrine profiles of this effect have appeared. The authors measured the number and intensity of panic symptoms and blood hormone levels during double-blind lactate infusions in 25 patients and 10 normal subjects and during placebo infusions in another five patients. Each patient was rechallenged with an identical infusate after chronic double-blind outpatient treatment with alprazolam or placebo. The results confirm the effectiveness of lactate infusions in evoking anxiety, extend previous hormone profiles of this maneuver, and indicate that chronic alprazolam treatment minimizes the neuroendocrine response to lactate challenges in patients with panic disorder or agoraphobia with panic attacks.

Adolescent↗

Early estrogen-induced nuclear changes in rat hypothalamic ventromedial neurons: an ultrastructural and morphometric analysis.

Alterations in the fine structure of nuclei of ventromedial hypothalamic neurons in ovariectomized (OVX) rats after either a 2-hour exposure to estradiol (E2) or a discontinuous exposure (2 hours E2/7 hours off/2 hours E2), previously shown sufficient for female rat sexual behavior (Parsons et al., '82a), were examined with the electron microscope. Morphometric measurements of nucleolar, nuclear, and somal areas, and nuclear shape and perimeter were accomplished at the light microscope level. After 2 hours of E2, the appearance of the nucleoplasm was altered, with a decrease in the small, scattered clumps of heterochromatin. Nuclear shape appeared dramatically altered from nonspherical, invaginated profiles toward spherical, smooth profiles. Nucleolar, nuclear, and somal hypertrophy were evident. In addition, stacked rough endoplasmic reticulum was present more frequently in E2-treated than control OVX neurons. After the discontinuous (2 hours/7 hours/2 hours) E2 treatment, progressive loss of small clumps of heterochromatin along the nuclear envelope as well as in the nucleoplasm had occurred. Decrease in a large heterochromatin clump along the nuclear envelope was correlated with an increase in nucleolus-associated chromatin. As determined by a distribution analysis, these estrogen-induced nuclear changes co-occurred more frequently than predicted from mutual independence. These findings, the marked co-occurrence of E2-induced changes in 30% or more of the cells, and the differences between the 2-hour E2 and the 2-hour/7-hour/2-hour group are consistent with a cascade of cell nuclear changes in the first few hours after estrogen onset.

Animals↗

An unusual nucleolar ring-like structure in axotomized hamster facial motoneurons.

Structures consisting of connecting rings surrounding a fibrillar core were observed within nucleoli of developing normal and axotomized hamster facial motoneurons. A few appeared in the nucleoplasm, attached to coiled bodies. Their peculiar structure and temporal association with neuronal maturation may reflect a transient state of ribosomal RNA transcription.

Animals↗

Changes in nuclear envelope invaginations in axotomized immature and mature hamster facial motoneurons.

In this study, changes in the amount of nuclear envelope invaginations (NEI) were quantitatively assessed after axotomy during the late nuclear maturation stages (15, 20 and 25 days postnatal age) and in the adult (100-day-old) hamster facial motoneurons. These changes were expressed as boundary density or BA (length of nuclear envelope per unit area of nucleus). Absolute nuclear areas and perimeters were also estimated after axotomy at these ages. At 1/2 and 1 day after axotomy, no differences in the above parameters were noted at any of the operative ages. At 4 days postoperative, the peak of chromatolysis for all these ages, axotomy resulted in significant decreases in BA and nuclear perimeter in the immature neurons and no changes in BA and nuclear perimeter in the adult neurons. In addition, 4 days after axotomy at 20 days postnatal and later ages, pronounced increases in nuclear area occurred. These quantitative results are interpreted as evidence that the accelerated loss of NEI after axotomy during the final stages of nuclear maturation in these neurons is related to the formation of rough endoplasmic reticulum (RER) or Nissl substance. The hypothesis that an 'excess' of RER is accumulated during the late maturation stages and may account for the lack of NEI in the adult axotomized facial motoneuron is presented.

Aging↗

Causal links between plasma and CSF endorphin levels in stress: vector-ARMA analysis.

To explore causal links between vital sign responses and immunoreactive beta-endorphin ("i-BE") rises in blood and CSF during ovine endotoxin stress, we analyzed concurrent i-BE levels in these two compartments by a "vector-ARMA" (= autoregressive moving average) method. This technique--widely used for modeling in other applications--has not to our knowledge been employed to study dynamic relationships of neuropeptides. Log-transformed i-BE levels were first "filtered" by repeated observations ANOVA to confirm significance of rises in both compartments. Next, vector-ARMA methodology was applied to derive an optimal causal model of vital sign changes and i-BE entry into plasma vs. CSF pools. The model indicated that reflux of i-BE from blood into CSF contributed to increases in CSF levels of this hormone. This novel application to neuroendocrinology of this approach illustrates its utility in evaluating changes in one or more neuropeptide levels in multiple compartments to indicate potentially causal relationships.

Animals↗

Some biochemical correlates of panic attacks with agoraphobia and their response to a new treatment.

Thirty-two patients with chronic debilitating agoraphobia and panic attacks participated in a comparative study of the triazolobenzodiazepine alprazolam and the anti-inflammatory agent ibuprofen. After a 2-week placebo washout period, patients were randomly assigned to 8 weeks of treatment with alprazolam (2 to 6 mg/day) or ibuprofen (0.8 to 2.4 g/day). Medication was identically packaged and patients were blind to the treatment condition, but investigators were aware of which medication was dispensed. Alprazolam recipients (mean daily dose: 5.4 mg) improved markedly with respect to physician and patient global rating of disease severity, frequency and severity of panic attacks, and phobic anxiety target symptoms on the 90-Item Hopkins Symptom Check List. Ibuprofen recipients (mean daily dose: 2.13 g) experienced significantly less clinical improvement than patients on alprazolam. After 8 weeks of treatment, ibuprofen patients were crossed over to alprazolam, while the original alprazolam group continued on that drug. The daily dosage ceiling was increased to 10 mg. In the ensuing 4 weeks (mean daily alprazolam dose: 6.3 mg), all patients achieved comparably marked clinical improvement relative to baseline. Pretreatment plasma concentrations of platelet factor 4 and beta-thromboglobulin--two measures of platelet turnover and release--were significantly elevated in patients relative to normal controls. The elevated platelet factor 4 and beta-thromboglobulin normalized during treatment with both drugs. Alprazolam appears to produce rapid and specific clinical improvement in patients with severe agoraphobia and panic attacks and deserves further evaluation under double-blind conditions.

6-Ketoprostaglandin F1 alpha↗

Macrophage origin of Reed-Sternberg cells: an immunohistochemical study.

In an immunohistochemical study of 26 biopsies from 24 patients with Hodgkin's disease a granular staining pattern for alpha-1-antitrypsin (alpha(1)AT) and alpha-1-antichymotrypsin (alpha(1)ACT) was seen in Reed-Sternberg (RS) cells and mononuclear Hodgkin's (H) cells in over half the cases. The pattern of staining for these antiproteases seen in RS and H cells has previously only been observed in normal and malignant cells of the monocyte/macrophage lineage within the lymphoreticular system. A faintly granular evenly distributed staining for IgG was found in viable RS and H cells. This staining was associated with a similar distribution of both light chains but not J chain, suggesting that the immunoglobulin had not been synthesised by these cells but had been taken up from the extracellular environment. It is suggested that this uptake is an active process occurring in viable RS and H cells, possibly via Fcgamma receptors and further supports an origin from cells of the monocyte/macrophage lineage. IgA, IgD, albumin, fibrinogen, C1q, C4 and C3 were present in some cells, IgM was more rarely found and lysozyme was absent. The fact that cells staining for these serum proteins generally showed signs of degeneration and that the extent of staining correlated with the molecular weight, but not serum concentration, of the protein suggests that they are passively acquired by dead or dying cells and thus represent a separate phenomenon from IgG uptake. The function of IgG uptake and accumulation by RS cells and the alpha(1)AT and alpha(1)ACT markers may prove of use in identifying the macrophage subtype from which these cells are derived.

Blood Proteins↗

Interaction of Sindbis virus glycoproteins during morphogenesis.

In cells infected with the Sindbis temperature-sensitive mutants ts-23 and ts-10 (complementation group D), which contain a defect in the envelope glycoprotein E1, the precursor polypeptide PE2 is not cleaved to the envelope glycoprotein E2 at the nonpermissive temperature. This defect is phenotypically identical to the defect observed in the complementation group E mutant, ts-20. The lesion in ts-23 is reversible upon shift to permissive temperature, whereas that of ts-10 is not. Antiserum against whole virus, E1, or E2 also prevents the cleavage of PE2 in cells infected with wild-type Sindbis virus. Because the cleavage of PE2 is inhibited by the lesion in mutants that are genotypically distinct and by anti-E1 or -E2 serum, it appears that PE2 and E1 exist as a complex in the membrane of the infected cell.

Cell Membrane↗

Virus-directed post-translational cleavage in Sindbus virus-infected cells.

The viral polypeptides synthesized in cells coinfected with group C and group D or E Sindbis virus mutants were studied. Cleavage of the ts2 protein occurs in cells coinfected with ts2 and ts20. Since the ts2 protein fails to chase in cells infected with ts2 alone, the activity effecting this cleavage must be, at least in part, virus specified.

Animals↗

Cleavage of a viral envelope precursor during the morphogenesis of Sindbis virus.

In cells infected with a temperature-sensitive mutant of Sindbis virus, the cleavage of the precursor to one of the viral envelope proteins does not occur at the nonpermissive temperature. This precursor is found associated with the plasma membrane fraction obtained from the infected cell. Since this is the site at which the virus matures, this finding suggests that during Sindbis virus replication the precursor to the smaller proteins associates with the cell membrane and is then cleaved during the maturation of the virus.

Animals↗

Age and sex-dependent decreases in ChAT in basal forebrain nuclei.

Microdissection techniques were utilized to measure the activity of choline acetyltransferase (ChAT) (enzyme responsible for synthesis of acetylcholine) in individual basal forebrain nuclei of aged (24 month) and young (4 month) male and female rats. Small but consistent decreases in the activity of ChAT in aged rats were found, and the location of the changes was dependent on the sex of the rat. Aged female rats showed approximately 30% lower ChAT and 40% lower acetylcholinesterase (AChE) activity in the ventral globus pallidus (vGP). Aged males did not show decreased ChAT in the vGP but activity in the medial aspect of the horizontal diagonal band nucleus was 50% lower than in the young males. ChAT activity in four other closely aligned basal forebrain nuclei was not different between the young and aged rats. Analysis of cell number, density and area in the vGP by AChE histochemistry showed no significant differences between aged and young females. In addition, age and sex-dependent changes were measured in pituitary glucose-6-phosphate dehydrogenase activity. The relationship of the changes to age-dependent decrements in memory, the possible influence of gonadal hormones on aging, and the mechanisms responsible for age-related declines in ChAT activity are discussed.

Age Factors↗