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Biomedical subjects

J Pearson

Publications and source records attributed to J Pearson.

At least 145 records · Page 8Linked to original sources

Calcineurin and synaptophysin in the human spinal cord of normal individuals and patients with familial dysautonomia.

This report concerns the immunohistochemical demonstration of two neuronal Ca2(+)-binding proteins, calcineurin and synaptophysin, in the spinal cord of normal controls and from patients with familial dysautonomia. In controls, calcineurin immunoreactivity was highly concentrated in small nerve cells and fibers of the substantia gelatinosa. Synaptophysin immunoreactivity was normally distributed throughout the spinal cord gray matter, being highly concentrated in the substantia gelatinosa, the dorsal nucleus of Clarke and the anterior horn. In patients with familial dysautonomia, no apparent changes in calcineurin immunoreactivity were found in the substantia gelatinosa. By contrast, there was a significant depletion of synaptophysin-positive axon terminals in the substantia gelatinosa and in the dorsal nucleus of Clarke of patients with familial dysautonomia.

Adolescent↗

Zinc treatment, metallothionein expression, and resistance to cisplatin in mouse melanoma cells.

Metallothioneins (MTs) protect cells from the toxic effects of heavy metals. It has been suggested that they play a role in cellular resistance to alkylating agents and ionizing radiation because of the coincidence of cadmium- and drug-resistance and by virtue of the reactivity of MT with free radicals. We report the analysis of mouse B16 melanoma cell lines with high and low constitutive MT expression. In these cells, both cisplatin and cadmium resistance were associated with constitutive MT accumulation in the absence of heavy-metal induction. However, in cells with high constitutive MT expression (where zinc treatment did not induce increased MT expression), cisplatin resistance, but not cadmium resistance, was increased approximately twofold by zinc treatment. Methotrexate resistance also was increased by zinc treatment in some cases. We conclude that MT is associated with cisplatin resistance, but that effects of heavy-metal treatment other than MT induction are also responsible for cisplatin and methotrexate, but not cadmium, resistance.

Animals↗

Patterns of mRNA for epidermal growth factor receptor and keratin B-2 in normal cervical epithelium and in cervical intraepithelial neoplasia.

Patterns of epidermal growth factor receptor (EGFR) and keratin B-2 (KB2) mRNA localization were studied in samples of normal cervical squamous epithelium and in samples of cervical intraepithelial neoplasia (CIN). 35S-Labeled EGFR and KB2 DNA probes were used for in situ hybridization on formalin-fixed tissue sections. Normal cervical squamous epithelium showed predominantly basal and parabasal expression of EGFR mRNA and suprabasal and midepithelial localization of KB2 mRNA. CIN lesions with moderate to severe dysplasia were generally characterized by continued expression of EGFR mRNA and decreased KB2 mRNA in midepithelial locations. Ratios of KB2 mRNA levels at the basal layer to KB2 mRNA levels at the midepithelial location were increased in moderate and severe dysplasia (CIN II and III) compared with normal epithelium (P less than .01). Ratios of EGFR mRNA levels at the midepithelial level to those of EGFR mRNA at the basal layer were increased in moderate to severe dysplasia compared with normal epithelium. These findings indicate a possible in vivo role of EGFR gene expression in normal and neoplastic proliferation and in prevention of differentiation of the cervical epithelium.

Cell Differentiation↗

Assessment of four monoclonal antibodies as serum markers in breast cancer.

Four monoclonal-antibody-defined serum markers (CA15-3, HMFG1, HMFG2 and NCRC-11) were examined in five groups of subjects: controls, benign breast disease and stage I/II, stage III and metastatic breast cancer. None of the markers were significantly elevated in primary breast cancer (i.e. stage I/II or stage III) compared with controls or patients with benign breast disease. These markers therefore have no role in screening or in the diagnosis of primary breast cancer. CA15-3, HMFG2 and NCRC-11 were significantly increased in the patients with metastatic breast cancer (P less than 0.001), indicating a potential use in the diagnosis of symptomatic metastases. In patients with metastases, sequential changes in CA15-3 correlated significantly with clinical response to therapy. Thus CA15-3 is a powerful marker of response and in combination with other markers, may provide an objective measurement of response to therapy in patients with advanced breast cancer.

Adult↗

Custody after divorce: demographic and attitudinal patterns.

In a reanalysis of data from a large sample of divorced parents, joint residential custody--and joint legal custody to a lesser extent--was shown to be a favorable arrangement for couples who chose it and for their children. Parents with joint custody reported better cooperation with former spouses and greater financial resources than did those with sole custody. No association was found between children's adjustment and form of custody.

Attitude↗

Effects of enflurane and isoflurane in air-oxygen on changes in thermal balance during and after surgery.

The temperatures in the aural canal (core), skeletal muscle and skin surface were measured during anaesthesia and surgery in 32 healthy females undergoing total abdominal hysterectomy and for 4 h after operation. The patients were allocated randomly to one of four groups according to the end-tidal concentration of volatile anaesthetic: 1 MAC isoflurane, 1 MAC enflurane, 1.8 MAC isoflurane and 1.8 MAC enflurane. The lungs were ventilated with an air-oxygen mixture. Neuromuscular block was produced with pancuronium. Room temperature and i.v. fluid administration were standardized. Aural canal, muscle and mean skin temperatures decreased significantly in all groups during surgery (P less than 0.001). The decrease in core and muscle temperatures, and mean body heat was significantly greater in the 1.8 MAC groups than in the 1 MAC groups for both volatile agents (P less than 0.001). However, there was a significantly greater decrease in core temperature and mean body heat in the isoflurane compared with the enflurane group (P less than 0.026). Body temperature returned to preoperative values during the recovery period. There was a significantly greater rate of rewarming during the first 1 h of recovery in the 1.8 MAC groups compared with the 1 MAC equivalent (P less than 0.001), and this was independent of the volatile agent used. The present results are compared with those reported previously in which nitrous oxide was added to the volatile agents. The decrease in body temperature depends upon the concentration of vapour used. However, it appears that isoflurane, without nitrous oxide, caused greater loss of body heat than enflurane.

Adult↗

Spontaneous and radiation-induced genetic instability of heteromyeloma hybridoma cells.

We have examined the genetic stability of heteromyeloma cells both spontaneously and following ionizing radiation. Clones of E10 cells (SHM-D33 heteromyeloma X human lymphoblastoid) were examined for the stability of human immunoglobulin (Ig) production (mu, lambda), relative human and mouse DNA, and total DNA content. The stability of recloned E10 cells was improved more than fourfold relative to the stability of the nascent E10 cells. The spontaneous loss of human Ig production in the established E10 cells was approximately 1.5 x 10(-3) events/cell per generation, which is comparable to mouse hybridomas. In contrast to the relative stability of antibody production, the relative human DNA content of antibody producing clones of E10.26 cells showed considerable variation (median, 15%; range, 4 to 23% for 30 clones) although the total DNA content of the clones was relatively constant (1.2(+/- 0.1) x 10(-12)g/cell). The frequency of Ig(mu-) antibody loss variants was increased in three subclones of E10 cells following irradiation (P less than 0.05, 20 to 90 Ig(mu-) variants/10(5) cells per Gray. In addition, the human DNA content per cell was significantly reduced (P less than 0.001) in a sample of irradiated E10 clones, while the total DNA content per cell was constant. We conclude that, although the antibody production is relatively stable in heteromyeloma cells, the relative human DNA content is constantly drifting by small amounts while maintaining a constant DNA content.

Animals↗

Altered glucose metabolism in microvessels from patients with Alzheimer's disease.

Microvessels isolated from temporal cortex of patients with Alzheimer's disease showed decreased uptake of glucose when compared with vessels from age-matched or young control subjects. This was due to decreased hexokinase activity in the Alzheimer samples, as determined by ion exchange chromatography. This finding was confirmed independently by determination of the phosphorylation constant for hexokinase, K3, using positron emission tomography. The results suggest that Alzheimer's disease may result from a global defect in brain energy metabolism.

Adult↗

Enzymes for liberation of pantothenic acid in blood: use of plasma pantetheinase.

Reported normal concentrations for human whole-blood total pantothenic acid vary from 1.1 to 12 mumol/L. This wide range may partly arise from the various enzymes used for liberation of pantothenic acid from coenzyme A, particularly the source of pantetheinase. A purified pantetheinase from pig kidney had greater than 100 times the specific activity and less than 0.01 times the pantothenate content of other commonly used extracts. Endogenous pantetheinase activity in human plasma was identified (11.2 +/- 2.0 mumol pantothenate .min-1.L-1, n = 29) and found comparable to the activity usually added from exogenous sources for liberation of pantothenate from whole blood (1-13 mumol.min-1.L-1). Alkaline phosphatase alone liberated as much pantothenate from hemolyzed whole blood as did alkaline phosphatase with pantetheinase. Previous reports of total blood pantothenate may be elevated by pantothenate in the pantetheinase extracts, an unnecessary source of error. Whole-blood total pantothenate concentrations less than 4.6 mumol/L are normal and do not indicate deficiency, as is often currently quoted.

Alkaline Phosphatase↗

[Immunohistochemical absence of adrenergic neurons in the dorsal part of the solitary tract nucleus in sudden infant death].

The immunohistochemical distribution of TH and PNMT containing neuronal elements was investigated utilizing peroxidase anti-peroxidase methods in newborn control and sudden infant death syndrome (SIDS) brainstems. The TH immunoreactive neurons, within the medulla oblongata, displayed a similar distribution in both control and SIDS tissue. However, PNMT immunoreactive neurons seen in the dorsal part of the nucleus of tractus solitarius in control tissue were not observed in SIDS tissue. This alteration of adrenergic neurons in the dorsal part of NTS (region reported to be implicated in the control of blood pressure and respiration) could explain the cardiorespiratory disorders in SIDS.

Epinephrine↗

Brain histamine in Alzheimer's disease.

The concentration of histamine (HA) has been determined by high-performance liquid chromatography (HPLC) with fluorometric detection in 21 different regions of brains from patients with senile dementia of the Alzheimer type (SDAT) and subjects (CB) whose causes of death were not related to neuropsychiatric, neurological and/or neurodegenerative diseases. The highest levels of HA in the central nervous system (CNS) of both control (CB) and SDAT samples were found in the posterior hypothalamus (CB = 3.13 +/- 0.63 pmol/mg; SDAT = 7.75 +/- 1.43 pmol/mg, p less than 0.005), where the HA neurons are located, and in the anterior hypothalamus (CB = 1.77 +/- 0.33 pmol/mg; SDAT = 2.82 +/- 0.45 pmol/mg, p less than 0.005). The lowest HA levels were detected in the cerebellum (CB = 0.12 +/- 0.04 pmol/mg; SDAT = 0.24 +/- 0.09 pmol/mg, p less than 0.01) and medulla oblongata. HA levels were significantly higher in SDAT than in CB in the following areas: motor cortex (Brodmann's area 4) (A4), premotor cortex (A6), postcentral gyrus (A1,2), posterior parietal cortex (A5,7), superior temporal gyrus (A41,42), temporal pole (A38), primary and secondary visual cortices (A17,18), anterior and posterior regions of the hypothalamus, putamen, caudate nucleus, nucleus accumbens, thalamus, hippocampus, pons, medulla oblongata and cerebellum. No changes were seen in globus pallidus and corpus callosum. Since the origin of HA in the brain is dependent upon three main compartments (neuronal, mast cell, vascular smooth muscle), with approximately 60-80% of the total HA belonging to the neuronal pool, on the basis of neurochemical data we postulate that the increase in the levels of HA in SDAT might account for or be associated with alterations in neuroendocrine, cognitive, neurovascular and sleep-wakefulness functions.

Aged↗

Immunohistochemistry of tyrosine hydroxylase and phenylethanolamine N-methyltransferase in the human brain stem: description of adrenergic perikarya and characterization of longitudinal catecholaminergic pathways.

Using immunocytochemical method in conjunction with antibodies to tyrosine hydroxylase and phenylethanolamine N-methyltransferase, catecholaminergic cell groups and axon pathways are mapped in the human hind brain. Adrenergic perikarya are located mainly in the rostral medulla, as in lower animals, and contribute a subset of axons to the main longitudinal catecholaminergic bundle which runs through the medulla oblongata, pons and midbrain such as the dorsal part of the central nucleus of the medulla oblongata, the parvocellular reticular formation ventromedial to the facial nerve and ventrolateral to the locus coeruleus. Adrenergic terminals are present in the locus coeruleus and other medullary and pontine structures. The locus coeruleus contains only tyrosine hydroxylase-immunoreactive cells and appears to be the source of a discrete dorsal catecholaminergic bundle which runs through the central tegmental field just ventrolateral to the periaqueductal gray of the rostral pons and mesencephalon and which does not contain adrenergic axons. A ventral catecholaminergic bundle arising in the medullary cells does contain a subset of adrenergic axons in the mesencephalic tegmental field. These two longitudinal axon bundles run near each other in the mesencephalic reticular formation. Additional descriptions are provided of catecholaminergic axons near the dorsal and ventral surface of the human medulla.

Adrenergic Fibers↗

The reason for cardiac output reduction after aortic cross-clamping.

The hypothesis that a decrease in cardiac output during infrarenal aortic cross-clamping is related to a decrease in oxygen consumption in the perfused tissues (cross-clamp-adapted oxygen consumption) rather than to deterioration of myocardial performance has been tested. Twenty-two patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups of equal number. During aortic cross-clamping, Group 1 patients received nitroglycerin infusion, 1 to 2 micrograms.kg-1.min-1, whereas Group 2 patients did not receive a nitroglycerin infusion. During aortic cross-clamping, cross-clamp-adapted body oxygen consumption decreased equally in both groups by 40 to 42 percent of baseline values, whereas cardiac output decreased by 17 percent in Group 2 but did not change significantly in Group 1. Mixed venous oxygen content increased significantly after induction of anesthesia and prior to aortic cross-clamping in both groups. During cross-clamping, the values of mixed venous oxygen content remained increased in Group 2 and increased further in Group 1. The data support our hypothesis since a decrease in cardiac output was not associated with an increase in filling pressures during aortic cross-clamping, but was instead associated with an increase in mixed venous oxygen content and a decrease in the arteriovenous oxygen content difference. Nitroglycerin infusion was associated with a further increase in mixed venous oxygen content during aortic cross-clamping and a decrease in the arteriovenous oxygen content difference, without a concomitant increase in oxygen utilization.

Aorta, Abdominal↗