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T R King

Publications and source records attributed to T R King.

29 records · Page 2Linked to original sources

Electrocardiographic diagnosis of remote posterior wall myocardial infarction using unipolar posterior lead V9.

The accuracy of four electrocardiographic criteria for diagnosing remote posterior myocardial infarction was assessed prospectively in 369 patients undergoing exercise treadmill testing with thallium scintigraphy. Criteria included the following: 1) R-wave width greater than or equal to 0.04 s and R-wave greater than or equal to S-wave in V1; 2) R-wave greater than or equal to S-wave in V2; 3) T-wave voltage in V2 minus V6 greater than or equal to 0.38 mV (T-wave index); 4) Q-wave greater than or equal to 0.04 s in left paraspinal lead V9. Twenty-seven patients (7.3 percent) met thallium criteria for posterior myocardial infarction, defined as a persistent perfusion defect in the posterobase of the left ventricle. Sensitivities for the four criteria ranged from 4 to 56 percent, and specificities ranged from 64 to 99 percent. Posterior paraspinal lead V9 provided the best overall predictive accuracy (94 percent), positive predictive value (58 percent), and ability to differentiate patients with and without posterior myocardial infarction of any single criterion (p less than .0001). Combining the T-wave index with lead V9 further enhanced the diagnostic yield: the sensitivity for detecting posterior infarction by at least one of these criteria was 78 percent, and when both criteria were positive, specificity was 98.5 percent. It is concluded that a single, unipolar posterior lead in the V9 position is superior to standard 12-lead electrocardiographic criteria in diagnosing remote posterior myocardial infarction, and that combining V9 with the T-wave index maximizes the diagnostic yield.

Electrocardiography↗

Saturation germ line mutagenesis of the murine t region including a lethal allele at the quaking locus.

The proximal region of mouse chromosome 17 contains many genes affecting embryonic development, germ cell differentiation, and the immune system. Although the study of natural variation, including t haplotypes, has yielded some information about the function of these genes, spontaneous variants often exhibit manifold genetic effects and are generally not carried on inbred backgrounds. To clearly connect phenotypes with the actions of individual genes, mutants in which genes are altered singly are needed. Therefore, we used a highly efficient point mutagen, N-ethyl-N-nitrosourea, in combination with classical breeding schemes to induce and identify recessive lethal mutations in the t region. Of 350 mutagenized gametes examined, at least 10 independent recessive embryonic lethal mutations have been identified; an additional two are perinatal lethals. A spontaneous brachyury mutation, TWis, arose on a genetic background that permits high-resolution mapping of the induced recessive mutations against cloned DNA sequences from the t region. One lethal mutation is an allele at the quaking locus. The multiple alleles of quaking and the feasibility of high-resolution mapping permit investigation of the pleiotropic action of this locus in mammalian development.

Alleles↗

Neuroendocrine and behavioral effects of intrathecal capsaicin in adult female rats.

Neural feedback from the gonads and the reproductive tract has an integral role in normal reproductive function in female rats. To further assess the role of sensory feedback in neuroendocrine control, the effects of an intrathecal injection of the neurotoxin, capsaicin (100-125 micrograms) into the lumbosacral region of the spinal cord on reproductive function was tested in female rats. In addition, the effects of capsaicin on the response to noxious heat and pressure were tested. Intrathecal capsaicin had no effect on estrous cycles, ovarian compensatory hypertrophy or female sexual behavior. However, capsaicin treated animals showed a dramatic reduction in fertility, relative to vehicle treated control rats and this was shown to be due to the reduced capacity of vaginal/cervical stimulation to produce pseudopregnancy. Consistent with a selective loss in the effectiveness of cervical stimulation, immobilization produced by vaginal probing was reduced in capsaicin treated rats, but this response slowly recovered across time in some animals. Similarly, the ability of vaginal probing to induce a lordotic response during estrogen treatment was reduced in the capsaicin treated animals. The capsaicin treated animals showed analgesia to noxious heat, as measured by the tail flick test, but showed a normal foot withdrawal in response to pressure. The analgesic effect of vaginal stimulation on noxious pressure was unaltered in the capsaicin treated rats. Finally, the neurotoxic effect of capsaicin was verified in terms of a quantitative reduction in substance P immunoreactivity in the dorsal horns of the lumbosacral region of the spinal cord of capsaicin treated rats, relative to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypersensitivity reaction to desipramine.

Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been described and include eosinophilia, pulmonary infiltrates with eosinophilia, and elevated total serum IgE levels. The immunologic mechanism accounting for these adverse reactions has not been elucidated. This article describes a patient manifesting bronchospasm, profound eosinophilia, and elevated serum IgE levels after therapy with desipramine that resolved rapidly after withdrawal of the drug. Immunologic investigations failed to demonstrate specific IgE directed against a protein conjugate of desipramine but demonstrated the ability of desipramine to induce mast cell degranulation with direct intradermal skin challenges.

Desipramine↗

Neuroestrogenic control of feeding behavior and body weight in rats with kainic acid lesions of the lateral septal area.

The role of the lateral septal area (LS) in the regulation of energy balance and the estrogenic control of feeding behavior in the female rat has been examined. Food intake (FI) and body weight (BWt) were measured daily following kainic acid (KA) LS lesions (KALS) to assess any regulatory changes in energy balance. In all animals KA lesions of the LS produced major cell loss in the LS; however the extent of damage was variable. Associated with KA lesions of the LS was the concurrent loss of CA3-CA4 cell groups in the hippocampus which was comparable for all the lesioned animals. The extent of septal damage was quantified morphometrically and correlated with changes in FI and BWt following estrogen treatment. The significant effects of the KALS lesions, relative to the control animals were: an increase in BWt which was statistically significant 22 days following brain surgery, an increase in daily FI which was significant by day 6 post surgery, an attenuation in the anorexic effects of estrogen on FI and BWt, and a significant decrease in the present days of vaginal estrus. Moreover, the anorexic effects of estrogen were significantly correlated with the extent of LS damage, but not the amount of hippocampal damage. The present study confirms that an increase in BWt is produced by KA lesions of the LS and further indicates that a sustained period of increased FI precedes the increase in BWt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential effects of neurotoxic lesions on psychoneuroendocrine functions.

The use of neurotoxic agents has provided new insight into the functions of the septal region. The psychoneuroendocrine effects of kainic acid (KA) lesions in the lateral septum (LS) have been confirmed, and we have compared the effects of these lesions to those following lesions of the medial septum (MS) and hippocampus (HP). In addition, the effects of the cytotoxin ibotenic acid (Ibo), have been studied. The alterations in psychoneuroendocrine functions resulting from the cytotoxic lesions have been compared to those from electrolytic septal lesions (DCLS) and sham operations. KA and Ibo lesions of the LS resulted in extensive bilateral loss of neurons in the LS; however, KALS lesions also resulted in cell loss in the CA3-CA4 cell regions of the HP. In contrast, KA and Ibo lesions of the MS did not produce any obvious cell loss in the MS. KA lesions of the HP produced extensive CA3-CA4 cell loss and a reduction in the size of the fornix and rostral septum. The behavioral and endocrine effects of these lesions were, relative to controls: the KALS group exhibited fewer percent days of vaginal estrus, increased ovarian compensatory hypertrophy (OCH), increased body weight (BWt), attenuation in the anorexic effects of estrogen, and decreased female sexual behavior. The KAMS group exhibited a transitory increase in BWt and increased male sexual behavior. IboLS group demonstrated a greater percent days of vaginal estrus and increased female sexual behavior whereas the IboMS group exhibited a decrease in OCH. The KAHP group exhibited a partial attenuation in the anorexic effects of estrogen on food intake and BWt gain. The DCLS group demonstrated increased female sexual behavior. These results indicate that the septal region is involved in both facilitatory and inhibitory modulation of a variety of estrogen responsive processes and further suggest that the MS and LS have different psychoneuroendocrine functions.

Animals↗

The effects of unilateral frontolateral hypothalamic knife cuts and asymmetrical unilateral septal lesions on lordosis behavior of rats.

It has been shown that the medial hypothalamus exerts facilitatory control over female sexual behavior in the rat whereas the septal area exerts inhibitory control over lordosis behavior. The present study assessed whether the septal area exerts its inhibitory control over lordosis behavior via efferent connections with the mediobasal hypothalamus. Anatomical studies using retrograde tracers verified that cell bodies located in the lateral septal area project ipsilaterally to the mediobasal hypothalamus. Based upon the predominantly ipsilateral connection between the lateral septum and mediobasal hypothalamus, unilateral frontolateral knife cuts were produced on the left or right side of the mediobasal hypothalamus or else sham surgeries. Subsequently all animals were given unilateral electrolytic septal lesions on the right side of the brain. These animals had septal damage that was located either ipsilateral or contralateral with respect to the knife cuts. Female sexual behavior was tested following the hypothalamic knife cuts and retested after unilateral septal lesions. Unilateral hypothalamic knife cuts on either side of the brain had no detectable effect on female sexual behavior when compared to the sham group. However, following unilateral septal lesions a significant increase in lordosis behavior was observed in all groups following treatment with estrogen alone. There were no differences in lordosis behavior between the groups which had septal lesions located ipsilateral vs. contralateral with respect to the hypothalamic knife cuts. These results support the hypothesis that the facilitation in lordosis behavior associated with electrolytic septal lesions is not mediated by neural connections between the septal area and mediobasal hypothalamus. These two brain areas thus appear to exert separate and independent control over female sexual behavior.

Animals↗

Shorn (shn): a new mutation causing hypotrichosis in the Norway rat.

We report the identification of an autosomal recessive mutation in the Norway rat that causes an almost complete absence of normal hair. The mutation, named shorn (gene symbol shn), is distinct from fuzzy, hairless, and Rowett nude, and is not closely linked with any of these markers or with albino.

Animals↗

The hypotrichosis-generating shorn (shn) mutation maps to distal chromosome 7 in the Norway rat.

We have recently identified an autosomal recessive mutation in the Norway rat that generates an almost complete absence of normal hair. Here we describe a multilocus backcross analysis that was used to map this mutation, named shorn (gene symbol shn), to the distal end of rat chromosome 7. Although this region in rat carries no previously mapped similar mutations, the homologous genomic regions in mouse and human contain several potential homologues and candidate genes.

Animals↗

The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.

Recent evidence has indicated that the recessive mutation affecting hypotrichosis in the Charles River (CR) "hairless" rat does not involve the hairless gene (hr) on rat chromosome 15. To determine if this mutation might be allelic (or orthologous) with any other previously mapped hypotrichosis-generating mutation in mammals, we have produced a panel of backcross rats segregating for the CR hairless rat mutation as well as numerous other markers from throughout the rat genome. Analysis of this panel has located the CR hairless rat's hypotrichosis-generating mutation on chromosome 1, near Myl2, where only the fuzzy mutation in rat (fz) and the frizzy mutation in mouse (fr) have been previously localized. Intercrossing fz/fz and CR hairless rats produced hybrid offspring with abnormal hair, showing that these two rat mutations are allelic. We suggest that the CR hairless rat mutation and fuzzy be renamed frizzy-Charles River (fr(CR)) and frizzy-Harlan (fr(H)), respectively, to reflect their likely orthology with the mouse fr mutation.

Alleles↗