Time-resolved optical Kerr response of C84 in CS2.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
F Sun
Publications and source records attributed to F Sun.
The polymerase chain reaction and branching processes.
We construct a mathematical model for the polymerase chain reaction and its mutations using the theory of branching processes. Under this model we study the number of mutations in a randomly chosen sequence after n PCR cycles. A method for estimating the mutation is proposed and the variance of this estimator is studied. We also study the distribution of the Hamming distance between two randomly chosen sequences and a method for estimating the mutation rate based on pairwise differences is proposed.
Base Sequence↗
Tetrandrine vs nicardipine in cerebral ischemia-reperfusion damages in gerbils.
AIM: To study the effects of tetrandrine (Tet) vs nicardipine (Nic) on cerebral ischemia-reperfusion damages. METHODS: Cerebral ischemia was produced by 10-min occlusion of bilateral carotid arteries followed by 5-min reperfusion in gerbils. The changes in electroencephalogram (EEG), calcium and water contents, lipid peroxide (LPO) content and ultrastructure in gerbil brains were compared. RESULTS: Pretreatment with Tet (15 mg.kg-1, i.v.) and Nic (0.25 mg.kg-1, i.v.) enhanced the recovery of EEG amplitude, reduced the calcium (151.2 +/- 1.1 and 155.3 +/- 2.4 mg/kg dry wt in Tet and Nic groups vs 193 +/- 8 mg/kg dry wt in ischemia-reperfusion group, P < 0.05) and water contents, attenuated the increase in LPO content (293 +/- 29 and 276 +/- 23 mumol.kg-1 wet wt in Tet and Nic groups vs 427 +/- 24 mumol.kg-1 wet wt in ischemia-reperfusion group, P < 0.01), and diminished the ultrastructural abnormalities of cortex and hippocampus in gerbil brain during ischemia and reperfusion. CONCLUSION: Tet and Nic had protective effects against ischemia-reperfusion brain damages in gerbils. The effects of Tet were similar to, but less potent than those of Nic.
Alkaloids↗
Recent progress in the studies on weight reduction by acupuncture and moxibustion.
Explore the source record for details and available documents.
Acupressure↗
[Growth pattern and metastatic behaviour of orthotopically metastatic model of human hepatocellular carcinoma in nude mice].
Growth pattern, metastatic behaviour and serial alph-a-fetoprotein (AFP) level of highly metastatic model of human hepatocellular carcinoma in nude mice (LCI-D20), which constructed by using orthotopic implantation of histologically intact patient specimens, were studied by implanting into the liver, subcutis and peritoneum of nude mice. Pathologic (by light and electronmicroscopic examination) and biologic (chromosome karyotype and DNA contents by flow cytometry) characteristics of LCI-D20 were also observed. The results showed that transplantability of LCI-D20 was 100% in 12 generations (passage time: 20 days) and all of these mice implanted tumors died within 40 days after transplantation due to serious metastasis. After LCI-D20 implanted into the liver of nude mice, growing implant-tumors in progress were negatively related to their double time during animal survival. LCI-D20 maintained 100% (70/70) metastatic rate in nude mice that showed early intrahepatic metastasis and late lymphatic and pulmonary metastasis. The high metastatic potentials of LCI-D20 tumor cells were kept in subcutis and peritoneum (70%, 100% respectively). The increase of the serial AFP secreting from the tumor cells was correlated with the implantation tumor growth rate (797.5 micrograms/L/5th week). The data from histological and electronmicroscopic findings, chromosome karyotype and DNA content analysis of the tumor cells revealed characteristics of human hepatocellular carcinoma. The results indicated that LCI-D20 exhibited the variety of clinical behaviours seen in hepatoma patients and it could be a useful model for investigating the metastasis mechanism of human hepatoma and anti-metastasis therapy.
Adult↗
Paracrine interactions among parathyroid cells: effect of cell density on cell secretion.
Cell-cell interactions are important in the regulation of endocrine cell secretion. To investigate the possibility that cell communication may alter the regulation of parathyroid cell secretion, we utilized the reverse hemolytic plaque assay (RHPA) to measure parathyroid hormone (PTH) release from individual cells. Bovine parathyroid cells were dispersed and plated with protein A-conjugated erythrocytes at cell densities ranging from 0.9 to 36 x 10(2) cells/cm2 in 0.2 mM calcium. Cell populations were greater than 98% homogenous as determined by immunocytochemistry and in situ hybridization for PTH mRNA. Plaques were developed and data analyzed for the amount of PTH per cell released (plaque area in microns 2 x 10(4)) and the determination of cell recruitment (% plaques formed). A positive correlation existed between parathyroid cell density and the amount of PTH released. As the distance between cells increased, the plaque area (amount of PTH released per cell) decreased (ranging from 1.0 x 10(4) microns 2 at 0.9 x 10(2) cells/cm2 versus 1.6 x 10(4) microns 2 at 36 x 10(2) cells/cm2). The percentage of cells releasing PTH (recruitment) also decreased (16% at 0.9 x 10(2) cells/cm2 versus 47% at 36 x 10(2) cells/cm2). These data suggest that parathyroid cells in close proximity are stimulated to secrete more hormone than those at lesser densities. In addition, parathyroid cells are recruited to secrete PTH when plated at high density. Factor(s) released by the parathyroid cell may increase cell responsiveness and stimulate secretion in a paracrine fashion.
Animals↗
Search for a third susceptibility gene for maturity-onset diabetes of the young. Studies with eleven candidate genes.
Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. This cohort of families will be useful for identifying other diabetes-susceptibility genes. Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid-binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. None of these loci showed evidence for linkage with MODY, implying that mutations in these genes do not make a major genetic contribution to the development of MODY. In addition to these linkage analyses, one or two affected subjects from each family were screened for the presence of the A to G mutation at nucleotide 3,243 of the mitochondrial tRNA(Leu(UUR)) gene. This mutation was not found in any of these subjects. Finally, we report the localization of the gene encoding the regulatory protein of glucokinase to chromosome 2, band p22.3 and the identification of a restriction fragment length polymorphism at this locus.
Adolescent↗
Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique.
We have reported that 56% of French families with maturity-onset diabetes of the young (MODY) carry a mutation in the glucokinase gene (GCK). Therefore, we have established a quick and sensitive nonradioactive technique (with the PhastSystem based on single-strand conformation polymorphism [SSCP] analysis) to routinely screen the 12 exons of GCK for mutations. We have studied GCK in 12 young hyperglycemic patients with a strong family history of type II diabetes. SSCP variants were observed in 6 of those 12 patients (50%), which cosegregated with diabetes in five families where DNA from additional members was available. Direct sequencing identified a 10-bp (base pair) deletion in exon 3; a 33-bp deletion at the exon 5/intron 5 junction, including the two consensus bases (GT) of the donor splice site; a nonsense mutation in exon 5 (Arg186-->Stop) in a Black-African family, which has been identified previously in a Caucasian family; and three missense mutations: Thr209-->Met209 in exon 6, Gly261-->Glu261 in exon 7, and Arg36-->Trp36 in exon 2. The missense mutation in exon 2 was found only in the second and third generation of the tested family but not in the first. To our knowledge, this is the first time that a de novo mutation of GCK is reported within a family. All six families carrying a mutation in GCK were typical MODY and most of their affected members had a mild form of diabetes. This nonradioactive SSCP technique may be useful to routinely diagnose glucokinase deficiency, which is an important cause of hyperglycemia among young type II diabetic patients.
Adult↗
[Studies on morphological superstructure of inactivated rabies virus and uninactivated rabies virus].
Rabies is widely epidemic in human and animals. It is a very dangerous disease at present. In 1919, semple has shown that antigenicity was not destroyed by chemicals. After that inactivated rabies vaccine was widely used in human being up to more than seventy years. But the afferration of morphological superstructure between inactivation and uninactivated, we have not see any report on the world.
Formaldehyde↗
Nonradioactive screening of glucokinase mutations in maturity onset diabetes of the young.
DNA mutations were previously identified in the glucokinase gene in 56% of French families affected with maturity onset diabetes of the young (MODY), an early onset autosomal dominant form of non-insulin-dependent diabetes mellitus (NIDDM). Mutations were found on almost all exons using the common radioactive single-strand conformation polymorphism (SSCP) technique. In this paper, we describe a non-isotopic SSCP method using the Pharmacia Biotech PhastSystem for the routine screening of new mutations in diabetic patients or in offsprings of diabetic patients. The use of the PhastSystem allowed us to easily and reproducibly optimize the electrophoretic conditions for each exon. We demonstrate the efficiency of this technique by identifying 8 mutations, 7 of which have never previously been detected, in patients referred to us for diagnostic purposes. It appears to be a sensible, easy and reliable method to improve the routine diagnosis of MODY in diabetic subjects or relatives and should be applicable to other genetic diseases.
DNA Mutational Analysis↗
Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus.
BACKGROUND AND METHODS: Non-insulin-dependent diabetes mellitus (NIDDM) is a genetically heterogeneous disorder. Maturity-onset diabetes of the young, a form of NIDDM with an early age of onset and autosomal dominant inheritance, can result from mutations in glucokinase, a key enzyme of glucose metabolism in beta cells and the liver. We studied 32 French families with maturity-onset diabetes of the young as well as 21 families with late-onset NIDDM to determine the frequency and clinical features of mutations of glucokinase. Fasting plasma glucose concentrations and oral glucose-tolerance tests were used to determine metabolic status. DNA was isolated from lymphocytes, and DNA polymorphisms in the glucokinase gene were tested for linkage with diabetes. Individual exons of the glucokinase gene from one affected member in each family were amplified by the polymerase chain reaction and screened for mutations by analysis of the conformation-dependent polymorphisms of single-stranded DNA and by DNA sequencing. RESULTS: We found substantial evidence of linkage between the glucokinase locus and maturity-onset diabetes of the young but not between this locus and late-onset NIDDM: Sixteen mutations were identified in 18 of the 32 families with maturity-onset diabetes of the young, but none were found in families with late-onset NIDDM: They included 10 mutations that resulted in an amino acid substitution, 3 that resulted in the synthesis of a truncated protein, and 3 that affected RNA processing. The affected subjects with glucokinase mutations usually had mild hyperglycemia that began during childhood, whereas in subjects with maturity-onset diabetes of the young not due to glucokinase mutations, hyperglycemia usually appeared after puberty. CONCLUSIONS: Mutations in glucokinase are the primary cause of hyperglycemia in a substantial fraction of French patients with maturity-onset diabetes of the young and result in a relatively mild form of NIDDM that can be diagnosed in childhood.
Adult↗
Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships.
The glycolytic enzyme glucokinase plays an important role in the regulation of insulin secretion and recent studies have shown that mutations in the human glucokinase gene are a common cause of an autosomal dominant form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) that has an onset often during childhood. The majority of the mutations that have been identified are missense mutations that result in the synthesis of a glucokinase molecule with an altered amino acid sequence. To characterize the effect of these mutations on the catalytic properties of human beta-cell glucokinase, we have expressed native and mutant forms of this protein in Escherichia coli. All of the missense mutations show changes in enzyme activity including a decrease in Vmax and/or increase in Km for glucose. Using a model for the three-dimensional structure of human glucokinase based on the crystal structure of the related enzyme yeast hexokinase B, the mutations map primarily to two regions of the protein. One group of mutations is located in the active site cleft separating the two domains of the enzyme as well as in surface loops leading into this cleft. These mutations usually result in large reductions in enzyme activity. The second group of mutations is located far from the active site in a region that is predicted to undergo a substrate-induced conformational change that results in closure of the active site cleft. These mutations show a small approximately 2-fold reduction in Vmax and a 5- to 10-fold increase in Km for glucose. The characterization of mutations in glucokinase that are associated with a distinct and readily recognizable form of NIDDM has led to the identification of key amino acids involved in glucokinase catalysis and localized functionally important regions of the glucokinase molecule.
Amino Acid Sequence↗
On the structures of crambescins B and C1.
Revised structures have been assigned to the cyclic guanidine-containing crambescins B [3] and C1 [5], from the Mediterranean sponge Crambe crambe. The revisions were based on the fabms/cid/ms spectra of the [M+H]+ ions from crambescins B and C1 and hrfabms measurements on key fragment ions in the ms/ms spectra, which identify losses of C9H19 and C8H18N3O side-chains.
Animals↗
Mycoplasma corogypsi sp. nov., a new species from the footpad abscess of a black vulture, Coragyps atratus.
Strain BV1 was isolated from the exudate of the footpad abscess of a black vulture (Coragyps atratus). The colonies had a "fried-egg" appearance consistent with that of mycoplasmal species. Electron microscopic examination of the cells revealed irregular elongated or elliptical forms and smaller circular budding processes. Profuse growth was observed in Frey medium supplemented with 20% swine serum at 37 degrees C in a humidified atmosphere of 10% CO2 and air. Typical of mycoplasma, strain BV1 required sterol for growth and catabolized glucose but did not hydrolyze arginine or urea. The guanine-plus-cytosine content of the DNA was 28 mol%. The organism demonstrated the ability to hemolyze, absorb onto, and agglutinate the erythrocytes from several animal species. Strain BV1 was serologically unrelated by the growth inhibition test to previously established Mycoplasma, Acholeplasma, Entomoplasma, and Mesoplasma species, as well as to strains belonging to these genera but not identified to species level. Moreover, BV1 had a 16S rRNA gene with a nucleotide sequence distinct from reported sequences of other mycoplasmas. This organism represents a new species for which the name Mycoplasma corogypsi is proposed. Strain BV1 (ATCC 51148T) is the type strain of Mycoplasma corogypsi sp. nov.
Abscess↗
Heterogeneous response to calcium by individual parathyroid cells.
Classical stimulus-secretion theory suggests that each individual cell responds to a given stimulus. We tested this theory by determining the response of single bovine parathyroid cells to calcium with the reverse hemolytic plaque assay (RHPA), an assay that measures hormone release from individual cells. As calcium concentrations decreased, the amount of parathyroid hormone (PTH) released per cell increased, and cells were recruited to release PTH. To confirm that adequate stores of PTH were present, immunocytochemistry and in situ hybridization were performed. To test if cells that did not release PTH were capable of secretion, we performed a sequential RHPA; 47.8% of cells did not release PTH after the first stimulus. After the second exposure to low concentrations of calcium, 26.5% of these "nonsecretory" cells were able to release PTH. We conclude that parathyroid cells are homogeneous for PTH content and synthetic capability. Parathyroid cells respond to changes in extracellular calcium heterogeneously in that more PTH per cell is released, and individual parathyroid cells are "recruited" to release PTH at low calcium concentrations. In addition, parathyroid cells can be induced to secrete suggesting that cells are viable but in a depressed secretory state. Parathyroid cells may exist in an "on" or "off" secretory state.
Adrenocorticotropic Hormone↗
Deletion of the donor splice site of intron 4 in the glucokinase gene causes maturity-onset diabetes of the young.
Missense and nonsense mutations in the glucokinase gene have recently been shown to result in maturity-onset diabetes of the young (MODY), a subtype of non-insulin-dependent diabetes mellitus with early age of onset. Glucokinase catalyzes the formation of glucose-6-phosphate and is involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism. Nucleotide sequence analysis of exon 4 and its flanking intronic regions of the glucokinase gene, in four hyperglycemic individuals of a MODY family, revealed a deletion of 15 base pairs, which removed the t of the gt in the donor splice site of intron 4, and the following 14 base pairs. This deletion resulted in two aberrant transcripts, which were analyzed by reverse transcription of RNA from lymphoblastoid cells obtained from a diabetic patient. In one of the abnormal transcripts, exon 5 is missing, while in the other, the activation of a cryptic splice site leads to the removal of the last eight codons of exon 4. This intronic deletion in a donor splice site seems to cause a more severe form of glucose intolerance, compared with point mutations described in glucokinase. This might be due to a more pronounced effect on insulin secretion.
Adult↗
Linkage analysis and molecular scanning of glucokinase gene in NIDDM families.
Mutations in the glucokinase gene are a major cause of maturity-onset diabetes of the young. To evaluate the contribution of this gene to the development of late-onset NIDDM, linkage analyses between DNA polymorphisms at the glucokinase locus and NIDDM were performed in 79 multigenerational French families. In addition, all exons and the islet promoter region of glucokinase gene from 1 affected member from each family as well as from 17 unrelated women with previous gestational diabetes were amplified by polymerase chain reaction and screened for mutations by single-strand conformational polymorphism and DNA sequencing. Linkage of glucokinase and NIDDM was significantly rejected under all models tested. However, in 1 family, the lod score was 2.30, and we found a nucleotide substitution at the position -30 in the islet promoter region that cosegregated with diabetes. The proband of this family was a gestational diabetic individual. No other mutation in glucokinase was found in the 79 NIDDM families. We identified a missense mutation (TGG257-->CGG257) in exon 7 of glucokinase gene from 1 of 17 women with gestational diabetes, which was present in all diabetic members of her family. This family is likely to be a cryptic maturity-onset diabetes of the young, as 4 younger members, carrying this mutation, were subsequently found to be hyperglycemic. In conclusion, no evidence was obtained to incriminate glucokinase as a major gene for late age of onset NIDDM. Diabetic families with mutations in glucokinase must be carefully investigated, to differentiate cryptic maturity-onset diabetes of the young from late-onset NIDDM. Furthermore, pregnancy reveals diabetes in women carrying a glucokinase defect.
Adolescent↗
Effect of acupuncture on weight loss evaluated by adrenal function.
In order to understand the relationship between patients' adrenal function and simple obesity and effect of acupuncture on it, the obesity indices, lipid indices, fasting blood-glucose, noradrenaline, dopamine, adrenalin and cortisol were observed. The results indicated that patients with simple obesity had hypofunction of the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system. Acupuncture treatment not only affected weight loss but also enhanced functioning of the two systems, suggesting that the effect of acupuncture on weight loss may be produced by enhancing the functions of both the sympathetic-adrenal system and the hypothalamus-pituitary-adrenal system.
Acupuncture Therapy↗