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51.
A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a “basic isoferritin”. The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia. 相似文献
52.
Edward D. Levin Todd C. Brady Elizabeth Crapo Hochrein Tim D. Oury Lena M. Jonsson Stefan L. Marklund James D. Crapo 《Behavior genetics》1998,28(5):381-390
Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O
2
-
), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. In the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift 8-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impaired by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. NO systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (NG-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular (O
2
-
) may be more vital than merely reduction of brain extracelluar (O
2
-
) in maintaining adequate learning function. 相似文献
53.
L. Stefan Levin John M. Brady Michael Melnick John M. Optiz 《American journal of medical genetics. Part A》1980,5(2):189-199
Scanning electron microscopic studies were performed on 25 deciduous and permanent teeth from members of 7 kindreds with dominant nonlethal osteogenesis imperfects (OI). Two families had normal teeth on clinical and radiological examination; five familes had blue or brown opalescent teeth with specific radiologic findings. Enamel surfaces and prism organization were normal on all teeth. On fractured surfaces, the dentin tubules of normal teeth from patients with OI were evenly distributed and coursed regularly to the dentin-enamel junction. Opalescent teeth had few tubules and those present were short, narrow, and tortuous. Dentin calcification fronts of normal teeth were composed of many nodules with regularly spaced openings on their surfaces. Calcification fronts of opalescent teeth were composed of irregularly spaced, small nodules, which varied greatly in size and the nodules lacked tubule openings on their surfaces. The results of this study support the concept that at least two dominant forms of OI exist – one in which all individuals with IO have normal teeth, and the other in which all with OI have blue or brown opalescent teeth with characteristic changes on SEM. 相似文献
54.
Gene conversion is a likely cause of mutation in PKD1 总被引:3,自引:0,他引:3
Watnick TJ; Gandolph MA; Weber H; Neumann HP; Germino GG 《Human molecular genetics》1998,7(8):1239-1243
Approximately 70% of the gene responsible for the most common form of
autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in
several highly homologous copies located more proximally on chromosome 16.
We recently have described a novel technique for mutation detection in the
duplicated region of PKD1 that circumvents the difficulties posed by these
homologs. We have used this method to identify two patients with a nearly
identical cluster of base pair substitutions in exon 23. Since pseudogenes
are known to be reservoirs for mutation via gene conversion events for a
number of other diseases, we decided to test whether these sequence
differences in PKD1 could have arisen as a result of this mechanism. Using
changes in restriction digest patterns, we were able to show that these
sequence substitutions are also present in N23HA, a rodent-human somatic
cell hybrid that contains only the PKD1 homologs. Moreover, these changes
were also detected in total DNA from several affected and unaffected
individuals that did not harbor this mutation in their PKD1 gene copy. This
is the first example of gene conversion in PKD1 , and our findings
highlight the importance of using gene-specific reagents in defining PKD1
mutations.
相似文献
55.
Predominance of null mutations in ataxia-telangiectasia 总被引:15,自引:4,他引:15
Gilad S; Khosravi R; Shkedy D; Uziel T; Ziv Y; Savitsky K; Rotman G; Smith S; Chessa L; Jorgensen TJ; Harnik R; Frydman M; Sanal O; Portnoi S; Goldwicz Z; Jaspers NG; Gatti RA; Lenoir G; Lavin MF; Tatsumi K; Wegner RD; Shiloh Y; Bar-Shira A 《Human molecular genetics》1996,5(4):433-439
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving
cerebellar degeneration, immunodeficiency, chromosomal instability,
radiosensitivity and cancer predisposition. The responsible gene, ATM, was
recently identified by positional cloning and found to encode a putative
350 kDa protein with a Pl 3-kinase-like domain, presumably involved in
mediating cell cycle arrest in response to radiation-induced DNA damage.
The nature and location of A-T mutations should provide insight into the
function of the ATM protein and the molecular basis of this pleiotropic
disease. Of 44 A-T mutations identified by us to date, 39 (89%) are
expected to inactivate the ATM protein by truncating it, by abolishing
correct initiation or termination of translation, or by deleting large
segments. Additional mutations are four smaller in-frame deletions and
insertions, and one substitution of a highly conserved amino acid at the Pl
3-kinase domain. The emerging profile of mutations causing A-T is thus
dominated by those expected to completely inactivate the ATM protein. ATM
mutations with milder effects may result in phenotypes related, but not
identical, to A-T.
相似文献
56.
Developmental alterations in GABAergic synaptic transmission were examined physiologically and biochemically in hippocampus of rats from 3 days of age to adulthood. Neither antidromic nor orthodromic stimulation could elicit identifiable inhibitory postsynaptic potentials in CA1 neurons in slices from rats 5 or 6 days of age. In contrast, at this age these stimuli result in large inhibitory postsynaptic potentials in CA3 pyramidal cells. In the latter cells orthodromic stimulation produced a brief monosynaptic excitatory postsynaptic potential which was followed by a large prolonged biphasic hyperpolarization. These signals were strikingly similar to those recorded in 1-month-old rats. In addition, large recurrent inhibitory postsynaptic potentials were produced by antidromic stimulation. By postnatal day 9 similar inhibitory postsynaptic potentials could be elicited in a majority of neurons of the CA1 subfield. As in mature pyramidal cells, application of GABA antagonists, such as bicuculline, selectively eliminated the antidromic inhibitory postsynaptic potential and the first component of the biphasic inhibitory postsynaptic potential generated by stimulation of stratum radiatum. In the CA3 subfield, this blockade of GABA receptors resulted in prolonged afterdischarges in slices from immature but not month-old rats. Measurements of the equilibrium potential and the conductance of antidromic inhibitory postsynaptic potentials in CA3 neurons were very similar when made during the first postnatal week and at 1 month of age. While on days 10-11 the equilibrium potential was very similar to measurements made at these other ages, the conductance was 3-4 times greater. The activity of glutamate decarboxylase, the synthetic enzyme for GABA, was very low at 3 days in hippocampus, and increased until 30 days of age at which time adult values were obtained. By comparison, hippocampal GABA levels were high early in postnatal life. Glutamate decarboxylase activities in microdissected CA3 and CA1 subfields were similar in immature hippocampus. These results demonstrate dramatic differences in the ontogenesis of functional GABAergic inhibitory synaptic transmission in the CA1 and CA3 subfields of rat hippocampus. The late development of GABA-mediated synaptic inhibition in the CA1 subfield could play a role in the susceptibility of immature hippocampus to seizures. However, the large GABA-mediated inhibitory postsynaptic potentials present in the CA3 subfield at the same age have a critical role in dampening neuronal excitability.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
57.
The use of additive and subtractive approaches to examine the nuclear localization sequence of the polyomavirus major capsid protein VP1. 总被引:14,自引:0,他引:14
A nuclear localization signal (NLS) has been identified in the N-terminal (Ala1-Pro-Lys-Arg-Lys-Ser-Gly-Val-Ser-Lys-Cys11) amino acid sequence of the polyomavirus major capsid protein VP1. The importance of this amino acid sequence for nuclear transport of VP1 protein was demonstrated by a genetic "subtractive" study using the constructs pSG5VP1 (full-length VP1) and pSG5 delta 5'VP1 (truncated VP1, lacking amino acids Ala1-Cys11). These constructs were used to transfect COS-7 cells, and expression and intracellular localization of the VP1 protein was visualized by indirect immunofluorescence. These studies revealed that the full-length VP1 was expressed and localized in the nucleus, while the truncated VP1 protein was localized in the cytoplasm and not transported to the nucleus. These findings were substantiated by an "additive" approach using FITC-labeled conjugates of synthetic peptides homologous to the NLS of VP1 cross-linked to bovine serum albumin or immunoglobulin G. Both conjugates localized in the nucleus after microinjection into the cytoplasm of 3T6 cells. The importance of individual amino acids found in the basic sequence (Lys3-Arg-Lys5) of the NLS was also investigated. This was accomplished by synthesizing three additional peptides in which lysine-3 was substituted with threonine, arginine-4 was substituted with threonine, or lysine-5 was substituted with threonine. It was found that lysine-3 was crucial for nuclear transport, since substitution of this amino acid with threonine prevented nuclear localization of the microinjected, FITC-labeled conjugate. 相似文献
58.
Prostaglandin F and E levels during endotoxin-induced pulmonary hypertension in calves 总被引:10,自引:0,他引:10
Anderson FL; Tsagaris TJ; Jubiz W; Kuida H 《The American journal of physiology》1975,228(5):1479-1482
59.
A laboratory-developed analog signal processor, driven by a conventional polygraph recorder and associated signal conditioning devices, provides automatic heart beat-by-heart beat preprocessing of various cardiovascular functions for input to a laboratory-type minicomputer. The technique of preprocessing individual functions, integrated with the minicomputer system which includes an A/D converter and teletype as input-output peripherals, provides a low-cost data acquisition and reduction system for the on-line computation and analysis of cardiovascular functions in experimental research applications. Such preprocessing more efficiently uses the minicomputer's memory to handle large amounts of information since the digitized data is in the form of one data sample, per function, per heart beat. Preprocessing analog data provides a low density data format and simplified software programs that are ideally suited for the utilization of a minicomputer in this on-line application. 相似文献
60.