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PubMed2001

Features of somatization predict the onset of chronic widespread pain: results of a large population-based study.

OBJECTIVE: Chronic widespread pain, the clinical hallmark of the fibromyalgia syndrome, is associated with other physical and psychological symptoms both in patients studied in a clinical setting and in those identified in the community. The present study was undertaken to examine the hypothesis that psychological and physical indicators of the process of somatization predict the development of new chronic widespread pain. METHODS: In this population-based prospective study, 1,658 adults ages 18-65 years completed a detailed pain questionnaire, which included a pain drawing. They also completed the following psychosocial instruments: General Health Questionnaire, Somatic Symptom Checklist, Fatigue Questionnaire, and Illness Attitude Scales. Individuals were followed up at 12 months, at which time 1,480 (93% of subjects still living at their baseline address) provided data on pain status, using the same instruments. RESULTS: At baseline, 825 subjects were classified as pain free and 833 as having pain not satisfying criteria for chronic widespread pain. Of those, 18 (2%) and 63 (8%), respectively, were classified as having chronic widespread pain at followup. After adjustment for age and sex, there were strong relationships between baseline test scores and subsequent risk of chronic widespread pain (odds ratio for the Somatic Symptom Checklist 3.3; odds ratio for the Illness Behavior subscale of the Illness Attitude Scales 9.0). All 95% confidence intervals excluded unity. These associations were independent of baseline pain status. CONCLUSION: Subjects who are free of chronic widespread pain are at increased future risk of its development if they display other aspects of the process of somatization. Data from this population-based prospective study lend powerful support to the hypothesis that chronic widespread pain can be one manifestation of the somatization of distress.

Adolescent↗
PubMed2004

Preoperative somatic symptoms are associated with disease progression in patients with bladder carcinoma after cystectomy.

BACKGROUND: A link between patient psychologic factors and bladder carcinoma outcome has not been demonstrated. The purpose of the current study was to assess the association of psychologic factors measured preoperatively with bladder carcinoma progression after cystectomy. METHODS: The Brief Symptom Inventory (BSI)-18 was administered prospectively to 65 patients with clinically localized bladder carcinoma before surgery. The BSI-18 measures distress in three specific domains-depression, anxiety, and somatization (i.e., distress due to somatic symptoms)-as well as general distress. Preoperative BSI-18 scores, tumor pathologic stage, and certain clinical variables were compared with disease status. Disease progression was defined as the development of either local disease recurrence or distant metastasis. Univariate and multivariate Cox proportional hazards models were constructed for statistical analysis. RESULTS: Of the 65 patients, 49 (79.4%) had no evidence of disease, 4 (6.2%) had local disease recurrence, and 12 (18.5%) had metastatic disease at last follow-up. The mean follow-up time was 1.3 years and did not differ significantly between survival outcomes (P = 0.577). Both tumor pathologic stage and preoperative somatic distress scores were associated with time to disease progression by univariate analysis (P = 0.038 and P = 0.055, respectively). After adjusting for tumor pathologic stage, a somatic distress score of > or = 2.00 was a significant predictor of disease progression (P = 0.044, hazard ratio = 3.31, 95% confidence interval = 1.03-10.60). Patient age, gender, reconstruction type, and BSI-18 scores for depression, anxiety, and general distress were not significantly associated with disease outcome. CONCLUSIONS: The authors found no correlation between psychologic symptoms measured preoperatively (i.e., depression, anxiety, and general distress) and bladder carcinoma progression. However, they reported an association between somatic symptoms and cancer outcome. If confirmed by other studies, these results may have important implications for the diagnosis, staging, and potential treatment of patients with bladder carcinoma.

Aged↗
PubMed1984

Somatic and visceral primary afferents in the lower thoracic dorsal root ganglia of the cat.

Anterograde transport of horseradish peroxidase (HRP) through somatic and visceral nerves was used to estimate the proportions of somatic and visceral dorsal root ganglion (DRG) cells of the lower thoracic ganglia of the cat. A concentrated solution of HRP was applied for at least 5 hours to the central end of the right greater splanchnic nerve and of the left T9-intercostal nerve of adult cats. Some animals remained under chloralose anaesthesia for the duration of the HRP transport time (up to 53 hours) whereas longer HRP application and transport times (4-5 days) were allowed in animals that recovered from barbiturate anaesthesia. Visceral DRG cells were found in approximately equal numbers in all ganglia examined (T7-T11). Population estimates were obtained for the T8 and T9 ganglia where visceral DRG cells were found to be 6.2% (T8) and 5.2% (T9) of the total cell population. In contrast, somatic DRG cells were found in large numbers in the ganglia examined (T8 and T9) where they amounted to over 90% of the cell population. Measurement of cross-sectional areas and estimates of cell diameters of the DRG cells showed greater proportions of large somatic cells (diameter greater than 40 micron) than of large visceral cells. Similar distributions of cell size were found for both somatic and visceral DRG cells with diameters less than 40 micron. These results show that the proportion of visceral afferent fibres in the dorsal roots that mediate the spinal cord projection of the splanchnic nerve is very small. Since viscerosomatic convergence in the thoracic spinal cord is very extensive, the present results suggest considerable divergence of the visceral afferent input to the central nervous system.

Animals↗
PubMed1991

Embryonic development of choline acetyltransferase in thoracic spinal motor neurons: somatic and autonomic neurons may be derived from a common cellular group.

This investigation focused on the relationship between neurotransmitter phenotype expression and rat motor neuron development, as studied with choline acetyltransferase (ChAT) immunocytochemical techniques. The development of two subclasses of motor neurons, somatic and autonomic efferents, was examined in the upper thoracic spinal cord. ChAT was first detected in a few neurons on embryonic day 12 1/2 (E12 1/2), and in numerous cells located in a single, ventrolaterally located column in the intermediate zone on E13. By E14, this group of ChAT-positive neurons was more intensely immunoreactive, and their axons could be traced to appropriate targets in developing somatic muscle and paravertebral sympathetic ganglia. During the E15-16 period, somatic and autonomic motor neurons separated into two distinct subgroups, with the latter cells being observed to translocate dorsally. By E17, these autonomic motor neurons reached their final positions in the midportion of the intermediate zone. The autonomic motor neurons were observed to extend transverse dendritic bundles across the spinal cord between E15-16, but evidence of the longitudinal bundles of sympathetic preganglionic dendrites was not observed until after birth. A recent study of cholinergic thoracic motor neurons found that both somatic and autonomic cells were generated synchronously during the E11-12 period (Barber et al., Soc Neurosci Abstr 15:588, 1989). In combination with the present results, these data indicate that no more than 1 1/2 days are necessary after motor neuron genesis before a few cells begin to express detectable levels of ChAT, and that no more than 2 days are required before large numbers express this marker of the cholinergic phenotype. Further comparisons of the present findings with those of previous investigations of the development of both somatic and autonomic motor neurons (Dennis et al., Dev Biol 81:266, 1981; Rubin, J Neurosci 5:685, 697, 1985) indicate that these cells contain ChAT at the time their axons are growing toward their respective peripheral targets 1 day before the time when physiological evidence of function is manifest. Furthermore, the present results suggest that both subclasses of motor neurons initially migrate together from the ventricular zone into a single motor column within the ventral intermediate zone, and that the autonomic neurons subsequently translocate dorsally. Thus, autonomic motor neurons appear to be an exception to the generalization that postmitotic neurons migrate directly from the germinal zone to their final positions within the central nervous system.

Animals↗
PubMed2005

Does somatization influence quality of life among older primary care patients?

BACKGROUND: Among older people, somatization has been reported to be common and to be predictive of high attendance in primary care. Its relationship with quality of life among older people has not been investigated. OBJECTIVES: The objective was to establish whether, among older primary care attenders, somatized symptoms are independently associated with relevant measures of quality of life. METHOD: Older primary care attenders (n = 127) completed measures of somatized symptoms, psychiatric status, physical health and health-related quality of life. Logistic regression analyses established independent relationships of health and sociodemographic variables with reports of overall quality of life, overall health, restriction of physical activities by health and restriction of social activities by health. RESULTS: For all four outcomes, somatized symptoms independently predicted poorer quality of life ratings. CONCLUSIONS: Somatized symptoms independently influence quality of life in older primary care patients and are worthy of clinical attention.

Aged↗
PubMed2002

Somatic mutations in the BRCA2 gene and high frequency of allelic loss of BRCA2 in sporadic male breast cancer.

Breast cancer occurs rarely in men and risk factors for the disease include germline mutations of the BRCA2 gene. High frequency of allelic loss at the BRCA2 locus has been reported in sporadic breast tumors, but somatic mutations of BRCA2 are very rare. Here we report the first case of somatic BRCA2 mutation in male breast cancer with demonstrated loss of heterozygosity. We analyzed a series of 27 archival samples from male breast cancer patients for BRCA2 mutations and loss of heterozygosity at BRCA2 locus. The mutation analysis of BRCA2 gene was performed using SSCA-HA and sequencing methods. PCR was used to detect LOH at 3 highly polymorphic microsatellite markers spanning BRCA2 region on 13q by comparing the allelic pattern in matched tumor and blood DNA samples. In this study LOH at the BRCA2 locus was observed in 82.6% of informative cases, confirming previous observations on high frequency of LOH affecting the BRCA2 region in male breast cancer. We identified 5 somatic BRCA2 mutations in a set of 23 sporadic male breast cancers (21%). Two silent and 1 missense alterations were novel BRCA2 variants. Here we also report first somatic frameshift BRCA2 mutation in male breast cancer 8138del5. In 3 tumors with somatic BRCA2 alterations, 1 missense, 1 silent and frameshift LOH at chromosome 13q12-13 were detected and losses involved a wild-type allele of BRCA2 gene.

BRCA2 Protein↗
PubMed2004

Frequent somatic mutations of mitochondrial DNA in esophageal squamous cell carcinoma.

Recent studies of various cancers, such as those of the breast, head and neck, bladder and lung, reported that 46-64% of somatic mutations in the D-loop region of mitochondrial DNA (mtDNA) are observed. However, in esophageal cancer, only a low rate (5%) of somatic mutations has so far been reported in one article (Hibi, K. et al., Int J Cancer 2001;92:319-321). Thus, to confirm this we analyzed the somatic mutations for hypervariable regions (HVR-I and HVR-II) in the D-loop of mtDNA to reevaluate the possibility of mitochondrial genetic instability in this cancer. We amplified both HVRs by PCR and DNA samples obtained from 38 esophageal tumors and matched normal tissues, and then sequenced them. Comparing the sequences of tumors to those of normal tissues, we found 14 somatic mutations in 13 patients (34.2%). Eleven mutations were at the C consecutive stretch from position 303 to 309 of MITOMAP in the mitochondria databank (http://www.mitomap.org/), 1 at position 215 in HVR-II and 2 at positions 16,304 and 16,324 in HVR-I. There were 41 types of germ line variations in HVR-I including 2 not so far recorded in the mtDNA databank and 17 in HVR-II including 1 not yet recorded. We also determined nuclear genome instability of these 38 specimens by analyzing 3 independent microsatellite sequences. While 4 specimens showed a single microsatellite change, which is tumor specific, we did not find any co-relation between a somatic mtDNA mutation and microsatellite instability of nuclear genome DNA. These results suggest that mtDNA mutations might show a genetic instability in esophageal cancer independently from a nuclear genome instability.

Age Distribution↗
PubMed2006

Somatic mutations of the ERBB4 kinase domain in human cancers.

The EGFR family consists of 4 receptor tyrosine kinases, EGFR (ERBB1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Recent reports revealed that the kinase domains of both EGFR (ERBB1) and ERBB2 gene were somatically mutated in human cancers, raising the possibility that the other ERBB members possess somatic mutations in human cancers. Here, we performed mutational analysis of the ERBB4 kinase domain by polymerase chain reaction-single-strand conformation polymorphism assay in 595 cancer tissues from stomach, lung, colon and breast. We detected the ERBB4 somatic mutations in 3 of 180 gastric carcinomas (1.7%), 3 of 104 colorectal carcinomas (2.9%), 5 of 217 nonsmall cell lung cancers (2.3%) and 1 of 94 breast carcinomas (1.1%). The 12 ERBB4 mutations consisted of 1 in-frame duplication mutation and 8 missense mutations in the exons, and 3 mutations in the introns. We simultaneously analyzed the somatic mutations of EGFR, ERBB2, K-RAS, PIK3CA and BRAF genes in the 12 samples with the ERBB4 mutations and found that 1 gastric carcinoma with ERBB4 mutation also harbored K-RAS gene mutation. Our study demonstrated that in addition to EGFR and ERBB2, somatic mutation of the kinase domain of ERBB4 occurs in the common human cancers, and suggested that alterations of ERBB4-mediated signaling pathway by ERBB4 mutations may contribute to the development of human cancers.

Adult↗
PubMed1991

Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication.

We have previously demonstrated that B lymphocyte specific somatic mutations are introduced into the variable regions of immunoglobulin kappa transgenes in two independent transgenic mouse lines. The frequency, distribution and nature of these mutations strongly suggest that they arose as a result of the process of somatic hypermutation, which is responsible, in part, for affinity maturation during an immune response. Unexpectedly, in these multiple copy transgenic lines, many of the transgene copies showed no evidence of somatic mutation. This paradox was addressed by determining the sequence of each transgene copy in several B cell hybridomas derived from a mouse line carrying three copies of the kappa transgene. It was found that the somatic hypermutation process in different B cells from the same mouse preferentially targets one, but not the same, transgene copy. We present a model, based on the pattern of this targeting, which links somatic hypermutation to the orientation of the Ig gene relative to the direction of DNA replication.

Animals↗
PubMed1991

Somatic hypermutation of immunoglobulin kappa may depend on sequences 3' of C kappa and occurs on passenger transgenes.

We have compared the pattern of somatic mutation in different immunoglobulin kappa transgenes and suggest that an element(s) located between 1 kb and 9 kb 3' of C kappa is necessary for somatic hypermutation of the antibody V gene. The sequences of transgenic and endogenous Ig V regions were determined in antigen-specific B cell hybridomas specific for 2-phenyloxazolone from independent lines of hyperimmunized transgenic mice. We analysed somatic mutation of the transgene both in hybridomas in which the transgenic kappa chain contributes to the antigen combining site as well as in hybridomas in which the transgene is a passenger with the expressed antibody being composed of endogenously-encoded heavy and light chains. In both cases, nucleotide changes in the transgene are correctly targeted to the V region and are absent from the C region. They accumulate at a similar rate to that in the endogenous Ig genes within the same cell and we find that, irrespective of whether or not the transgene kappa is directly selected by antigen, somatic mutation occurs at a similar rate and involves only single base substitutions. Furthermore, the pattern of mutations in passenger transgenes gives information about the intrinsic sequence specificities of the somatic hypermutation mechanism.

Amino Acid Sequence↗
PubMed2003

Display of different modes of transcription by the promoters of an early embryonic gene, Zfp352, in preimplantation embryos and in somatic cells.

We have previously reported a Krupple-like finger protein gene, Zfp352, which is expressed temporarily in two- to eight-cell mouse embryos. The Zfp352 gene is intron-less in the coding region but carries a solitary 4.3-kb intron in the 5'-untranslated region. In this study, we have analyzed the Zfp352 promoter activity in early embryos and in somatic cells. We determined that the major Zfp352 promoter, designated P1 and located upstream of exon 1, is utilized in both early embryos and in somatic cells. A TATA-like box and a transcription initiator element are discernible in the P1 promoter. We uncovered an alternative promoter, designated P2, in the intron. 5'-Rapid amplification of cDNA ends and real-time RT-PCR experiments indicated that the P2 promoter is weak and is probably fortuitous in early embryos. In somatic cells, however, transfection experiments showed that P2 is as active as P1 as a promoter. Furthermore, P2 appears to be composed of two different subdomains used differentially for transcription initiation in embryos and in somatic cells. Our observations may bear relevance in explaining developmental deficiencies associated with somatic cell cloning experiments.

Animals↗
PubMed2007

Cloning of Asian yellow goat (C. hircus) by somatic cell nuclear transfer: telophase enucleation combined with whole cell intracytoplasmic injection.

Our and other previous studies have shown that telophase enucleation is an efficient method for preparing recipient cytoplasts in nuclear transfer. Conventional methods of somatic cell nuclear transfer either by electro-fusion or direct nucleus injection have very low efficiency in animal somatic cell cloning. To simplify the manipulation procedure and increase the efficiency of somatic cell nuclear transfer, this study was designed to study in vitro and in vivo development of Asian yellow goat cloned embryos reconstructed by direct whole cell intracytoplasmic injection (WCICI) into in vitro matured oocytes enucleated at telophase II stage. Our results demonstrated that the rates of cleavage and blastocyst development of embryos reconstructed by WCICI were slightly higher than in conventional subzonal injection (SUZI) group, but no statistic difference (P > 0.05) existed between these two methods. However, the percentage of successful embryonic reconstruction in WCICI group was significantly higher than that in SUZI group (P < 0.05). After embryo transfer at 4-cell stage, the foster in both groups gave birth to offspring. Therefore, the present study suggests that the telophase ooplasm could properly reprogram the genome of somatic cells, produce Asian yellow goat cloned embryos and viable kids, and whole cell intracytoplasmic injection is an efficient protocol for goat somatic cell nuclear transfer.

Animals↗
PubMed2003

The characterization of somatic APC mutations in colonic adenomas and carcinomas in Ashkenazi Jews with the APC I1307K variant using linkage disequilibrium.

Mutations of the adenomatous polyposis coli (APC) gene play a critical role in the development of colorectal neoplasms. A novel mechanism involves a germline variant, at codon 1307 of the APC gene. The mutation is thought to create an unstable segment of DNA, which facilitates the development of somatic mutations. I1307K has been shown to be ancestral in Middle Eastern populations. The aim of the present study was to confirm this observation for a Western population and to utilize this information in the characterization of the somatic changes in colorectal neoplasia in carriers of I1307K. DNA from 182 US Ashkenazim was screened for the I1307K variant, which was found in 22 (12.1%), and the ancestral nature of this variant was confirmed in this population by showing that all of those with the I1307K variant carried a specific allele at the D5S346 locus, while the majority shared a D5S1385 allele. Subsequently, 79 neoplasms were analysed from 15 I1307K carriers for loss of heterozygosity (LOH) at the D5S346 locus. LOH was detected in 18 neoplasms (23%). Of these 18, four neoplasms showed loss of the I1307K-associated allele, while 14 neoplasms had retained the I1307K-associated allele and, by implication, the I1307K variant. PCR products were also cloned into a plasmid vector to isolate individual APC alleles. For those neoplasms with LOH, 13 of the 18 neoplasms (72%) had a somatic mutation, of which 12 involved the I307K-bearing chromosome. This study is consistent with two previous studies in showing that additional somatic mutations close to codon 1307 are almost always on the I1307K-bearing chromosome, but either allele may demonstrate LOH. Further evidence for the interpretation of the action of I1307K as producing DNA instability is provided by analysing multiple neoplasms from the same person and by showing that these neoplasms have differing patterns of LOH and associated somatic mutations.

Adenoma↗
PubMed2001

Induction of desiccation tolerance in plant somatic embryos: how exclusive is the protective role of sugars?

Plant somatic embryos usually lack desiccation tolerance. They may acquire such a tolerance upon preculture in the presence of abscisic acid (ABA), followed by slow drying, but not fast drying. ABA causes torpedo-shaped somatic embryos to lose their chlorophyll, suspend growth, exhibit low rates of respiration, and maintain elevated sucrose contents. The subsequent slow drying leads to a partial conversion of sucrose into oligosaccharides and the expression of dehydrin transcripts. Slow-dried, desiccation-tolerant somatic embryos have stable membranes, retain their native protein secondary structure, and have a densely packed cytoplasmic glassy matrix. Fast-dried, desiccation-sensitive somatic embryos experience some loss of phospholipids and an increase in free fatty acids. Their proteins show signs of denaturation and aggregation, and the glassy matrix has reduced hydrogen bonding. The reduced conversion of sucrose into oligosaccharides appears not to underlie dehydration injury. Proteins in slow-dried somatic embryos, not pretreated with ABA, also show signs of denaturation, which might be attributed to low sugar contents. We conclude that by reducing cellular metabolism, ABA maintains high sugar contents. These sugars contribute to the stability of membranes, proteins, and the cytoplasmic glassy matrix, whereas slow drying permits a further fine tuning of this stability. Partitioning of endogenous amphiphiles from the cytoplasm into membranes during drying may cause membrane perturbance, although it might confer protection to membranes in the case of amphiphilic antioxidants. The perturbance appears to be effectively controlled in desiccation-tolerant systems but not in sensitive systems, for which we suggest dehydrins are responsible. In this context, the low desiccation tolerance in the presence of ample sugars is discussed.

Abscisic Acid↗
PubMed1996

Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors.

The second messenger cAMP has been implicated in the regulation of mammalian and amphibian oocyte maturation. Although a decrease in intraoocyte levels of cAMP precedes germinal vesicle breakdown (GVBD), the gonadotropin induction of ovulation and oocyte maturation is associated with major increases of cAMP in ovarian follicles. In the mammalian system, isolated oocytes undergo spontaneous maturation in vitro but this process is blocked by treatment with a phosphodiesterase (PDE) inhibitor, IBMX, which increases intraoocyte cAMP levels. In contrast, the same inhibitor, when added to cultured follicles for a brief time, increases follicle cAMP levels, followed by the induction of GVBD. To resolve the paradoxical actions of this PDE inhibitor on the maturation of isolated and follicle-enclosed oocytes, we hypothesized that meiotic maturation requires opposing fluctuations of cAMP levels in the somatic granulosa and germ cells. Such opposing fluctuations may result from selective expression and regulation of PDEs in the somatic and germ cell compartments of the follicle. To test this hypothesis, PDE activity was manipulated in different follicular cells using type-specific inhibitors. The impact of the ensuing changes in cAMP levels in the two compartments was monitored by the induction of GVBD. In isolated oocytes, spontaneous GVBD was blocked by two inhibitors of type 3 PDE (cGMP-inhibited: CGI-PDE), milrinone and cilostamide. In contrast, treatment with an inhibitor for type 4 PDE (cAMP-specific), rolipram, was ineffective. These findings suggest that the oocyte expresses type 3 but not type 4 PDE and that increases in intraoocyte cAMP suppress GVBD. This hypothesis was confirmed by in situ hybridization studies with PDE3 and PDE4 probes. PDE3B mRNA was concentrated in oocytes while PDE4D was mainly expressed in granulosa cells. In cultured follicles, LH treatment induced oocyte maturation but the gonadotropin action was blocked by inhibitors of type 3 but not the type 4 PDE inhibitors. Furthermore, treatment with the type 4, but not the type 3, PDE inhibitor mimics the action of LH and induces oocyte maturation, presumably by increasing cAMP levels in granulosa cells. Our findings indicate that PDE subtypes 4 and 3 are located in follicle somatic and germ cells, respectively. Preferential inhibition of PDE 3 in the oocyte may lead to a delay in oocyte maturation without affecting the cAMP-induced ovulatory process in the somatic cells. Conversely, selective suppression of granulosa cell cAMP-PDE may enhance the gonadotropin induction of ovulation and oocyte maturation. Thus, in addition to the well-recognized differential expression and regulation of adenylate cyclase in the somatic and germ cell compartments of the follicle, we suggest that selective regulation and expression of PDEs may be involved in the regulation of cAMP levels and control of oocyte maturation in the preovulatory mammalian follicle.

Animals↗
PubMed1996

Sequential triggering of apoptosis, somatic mutation and isotype switch during germinal center development.

Using an approach similar to that used to study primary B-lymphocyte development within bone marrow and primary T-lymphocyte development within thymus, the peripheral B-cell maturation pathway within secondary lymphoid tissue (human tonsils) was analysed on the expression of discrete surface antigens. sIgD and CD38 permit the identification of four subpopulations of tonsillar B lymphocytes, including sIgD+ CD38-, sIgD+, CD38+, sIgD-CD38+ and sIgD-CD38- B cells. Further phenotypic, functional and Ig gene analysis (IgV gene sequences, expression of sterile transcripts and DNA switch circles) allowed us to conclude the following: (1) sIgM+ IgD+ CD38- B cells are naive B cells (Bm1 + 2), which carry unmutated antigen-receptors; (2) sIgM+ IgD+ CD38+ B cells are germinal center founder cells (Bm2'), which become prone to undergo apoptosis before the onset of somatic mutation; (3) sIgM-IgD+ CD38+ are germinal center B cells (Bm 3 delta), that have accumulated the highest number of somatic mutations ever reported in normal B cells; these cells may have undergone C mu-deletion by homologous recombination through sigma mu-sigma delta sequences: (4) sIgD-CD38+ CD77+ B cells are centroblasts (Bm3), in which somatic mutation machinery is activated; (5) sIgD-CD38+ CD77- B cells are centrocytes (Bm4), in which the isotype switching machinery is activated; (6) sIgD-CD38- cells (Bm5) represent somatically mutated resting memory B cells. In conclusion, human peripheral B-cell subpopulations corresponding to the differentiation stages before, during and after the triggering of apoptosis program, somatic mutation and isotype switch have been identified and isolated using a combination of surface markers.

Apoptosis↗
PubMed2004

Accumulation of somatic mutation in mitochondrial DNA and atherosclerosis in diabetic patients.

A point mutation of mitochondrial DNA at nucleotide position 3243 A to G is responsible for the genetic cause of diabetes. Otherwise, this mutation is also reported to occur as a somatic mutation, possibility because of oxidative stress. Because diabetes may cause oxidative stress, we hypothesized that accumulation of the somatic A3243G mutation in mitochondrial DNA may be accelerated by diabetes. DNA was extracted from blood samples of 290 nondiabetic healthy subjects (aged 0-60 years) and from 383 type 2 diabetic patients (aged 18-80 years). Then, the extent of somatic A3243G mutation in total mitochondrial DNA was detected by real-time polymerase chain reaction (PCR) using the TaqMan probe. The genotyping of ACE I/D or p22phox C242T was done by PCR or PCR-restriction fragment length polymorphism. Although the level of the A3243G mutation was negligible in the newborn group, it increased in healthy subjects aged 20-29 and 41-60 years. In diabetic patients, the mutational rate increased along with age and the duration of diabetes. In the middle-aged group (41-60 years old), the A3243G mutation accumulates fourfold higher in the diabetic patients than in the healthy subjects. Moreover, multiple regression analysis revealed that the most critical factor associated with this mutation in diabetic patients was the duration of diabetes. Furthermore, the genotype of DD, DI-CC (ACE-p22phox) has the highest mutational rate and the thickest intima-media thickness of the carotid artery. In conclusion, diabetes accelerates the accumulation of the somatic A3243G mutation in mitochondrial DNA, and this somatic mutation may be a marker for the duration of diabetes and atherosclerosis.

Adolescent↗
PubMed1993

Identification of a RAPD marker associated with somatic embryogenesis in alfalfa.

The current study was conducted to identify random amplified polymorphic DNA (RAPD) markers linked to genes controlling somatic embryogenesis in alfalfa. Segregation analyses of the somatic embryogenesis trait and the RAPD markers in an F1 population of 83 plants, derived from a cross between embryogenic A70-34 and non-embryogenic Arrow36 alfalfa plants, identified a polymorphic band that is associated with somatic embryogenesis. Based on the assumptions that somatic embryogenesis in alfalfa is controlled by two dominant genes with complementary effects and that the genotypes of A70-34 and Arrow36 are AAaaBbbb and aaaabbbb, respectively, the segregation data for the marker and the somatic embryogenesis trait in the F1s indicate that the marker is linked to the A locus. The maximum recombination fraction estimated for the linkage between the marker and the gene is 36.3%.

Base Sequence↗