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PubMed2000

Frequency distribution of mitochondrial DNA haplogroups in Corsica and Sardinia.

Mitochondrial DNA (mtDNA) polymorphisms were analyzed by polymerase chain reaction amplification and haplogroup-specific restriction screening in populations from Corsica and Sardinia. These included 56 individuals from the area of Corte, central Corsica (France), 51 individuals from Gallura, northern Sardinia (Italy), and 45 individuals from Barbagia, central Sardinia. The screening revealed that about 95% of mtDNAs could be grouped in 8 of the 9 European haplogroups, including H-K, T-V, and X. Our results confirmed that these haplogroups encompass virtually all the mitochondrial lineages present in Europe and can be detected in both northern and southern European populations. We also discovered 2 restriction sites (-73 Alw441 and +75 SphI) that allow the detection of informative nucleotide changes in the second hypervariable segment of the control region, which help to detect the haplogroup identity of mtDNAs without requiring further DNA sequencing. Haplogroup H was the most common mtDNA lineage in this sample, reaching frequencies from about 40% in Corsican and Gallurese populations, to about 65% in the Barbagian population. Haplogroup V, possibly originating in the Iberian peninsula, was found only in the central Sardinian sample. Of the 5 Corsican mtDNAs belonging to the haplogroup T, 4 had a restriction fragment length polymorphism found only in this population. It seems that this mutation originated in Corsica and has had time to spread in the area, since the maternal grandmothers of the subjects came from different villages of the island. The sample from central Sardinia shows a remarkable discontinuity with those from the northern part of the island and from Corsica. Gallura and Corsica seem to have undergone a more recent peopling event, possibly related to the arrival of new mitochondrial variability from continental Italy, while Barbagia has apparently maintained more archaic haplotypes.

Complementarity Determining Regions↗
PubMed1975

[The significance of speaking for the transfer of bacteria, and of the tuberculin skin test for the diagnosis of tuberculosis (author's transl)].

A Korean nurse was employed in Germany after having passed the routine medical checkup without discovery of apparent disease. Five months later she fell ill with fever due to pneumonia. Work was suspended for 8 days and then continued in an infants' ward for another 8 weeks. Because of increasing weakness the nurse was reexamined medically. This revealed an open Tuberculosis of the lung. The sputum culture was positive. The following treatment was successfull. No infant or other person with previous contact to the nurse contracted tuberculosis. The explanation for this is presumably given by the virtual speechlessness of the foreign nurse. --The importance of the tuberculin skin test for the diagnosis of tuberculosis is discussed with regard to the declining incidence of new infections, and practicability of mass screening for this disease.

Female↗
PubMed1997

[Diagnosis of chlamydia and gardnerella infection in patients with acute gynecological diseases].

Chlamydial infection was diagnosed by indirect immunofluorescence in 26.3% and Gardnerella infection in 28.7% of patients with acute gynecological diseases. The degree of vaginal contamination in patients with chlamydiasis was virtually the same as in all other examinees, whereas in patients with gardnerellosis the third and fourth degrees of purity predominated. Hence, assessment of the vaginal contamination (purity) is an additional criterion for screening for gardnerellosis but providing no clinically significant information for the detection of chlamydiasis.

Acute Disease↗
PubMed1994

True three dimensional stereographic display of 3D reconstructed CT scans of the pelvis and acetabulum.

Fractures of the acetabulum can cause the pelvis to shatter into a wide array of complex configurations which can be difficult to fully delineate preoperatively. In addition to plain radiography and standard computed tomography, technology now allows the reconstruction of magnetic resonance imaging (MRI) and computed tomography (CT) data into virtual objects; three dimensional (3D) representations of anatomy which exist only within the computer memory. Printouts and photographs of 3D reconstructions provide another level of anatomic information to the orthopaedic surgeon. However, current standard displays such as computer and video screens and photographic and radiographic film are all two dimensional (2D) modalities. Displaying 3D reconstructions in this standard 2D fashion, inescapably robs the images of up to one third of the information contained within them--all the true depth information which is the essence of 3D. Shading techniques and perspective have both been utilized to simulate depth, but true depth is still lacking. Recently, the authors have begun using a technique of computerized 3D reconstruction and recording which provides a true 3D display of the reconstructed images. The resultant gain in image realism is profound, somewhat similar to hearing full stereo audiophonic recording compared to monophonic, or to seeing in color rather than black and white. The image generation and display process is a computerized mathematical adaptation of the photographic technique of stereophotography. Once in place, the technique is relatively simple to use and can be achieved in several ways with a minimum of additional hardware. Potential benefits lie in the method's ability to convey, in one 3D display, the true 3D, spatial anatomic configuration of the imaged pelvis. The methods described are common to those forming the fundamental basis for virtual reality imaging. Current users of some 3D reconstruction systems can now easily generate images which can be viewed with all of the depth information restored, into a true 3D display.

Acetabulum↗
PubMed2001

Prevalence and significance of retinopathy in subjects with type 1 diabetes of less than 5 years' duration screened for the diabetes control and complications trial.

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated the powerlul impact of glycemic control on the progression of diabetic retinopathy. A large number of individuals (2,771) underwent stereoscopic color photography and fluorescein angiography as part of screening for participation in the DCCT. A subgroup of those individuals screened participated in the DCCT and underwent evaluation of their retinal vasculature semiannually for 4-9 years. These data were evaluated to determine how the 2000 American Diabetes Association position statement would apply to the DCCT experience. Specifically, the position statement indicates that the first dilated eye examination should be performed after 3-5 years' duration of diabetes because vision-threatening retinopathy virtually never develops in patients with type 1 diabetes during that interval RESEARCH DESIGN AND METHODS: We examined the experience of the DCCT in evaluating retinal photographs in 1,613 patients with type 1 diabetes of <5 years' duration and follow-up photographs every 6 months for 4-9 years in 855 members of that group. RESULTS: Of 1,613 subjects with type 1 diabetes of <5 years' duration screened for the DCCT, 716 (44.4%) had stereo-color photographic evidence of diabetic retinopathy, and 6 had preproliferative or worse pathology. Fluorescein angiography revealed retinopathy in 158 of 713 subjects with no evidence of retinopathy on color photographs. Thus, 874 (54.2%) of the original 1,613 subjects had retinopathy at baseline. DCCT follow-up identified 341 additional individuals in whom retinopathy was developing before 5 years; 1,083 of 1,613 (67.1%) individuals screened for the DCCT had retinopathy before 5 years' duration of diabetes. Those with retinopathy before 5 years had more rapid three-step progression of vascular pathology than those with no retinopathy. CONCLUSIONS: Dilated eye examinations and retinal photography should be included in the routine management of type 1 diabetes during the first 5 years to identify the individuals at greatest risk for vision-threatening problems.

Blood Glucose↗
PubMedDate not supplied

Identifying patients with depression in the primary care setting: a more efficient method.

OBJECTIVE: To determine if there is a core subset of depressive symptoms that could be used to efficiently diagnose depression after administering the 2-item PRIME-MD a screening questionnaire for depression. METHODS: One thousand patients selected randomly and by convenience from 4 primary care clinics were assessed by PRIME-MD and completed a questionnaire measuring the following validation variables: functional status and well-being, disability days, somatic symptoms, depression severity, suicidal thoughts, health care utilization, and the physician-patient relationship. RESULTS: Four symptoms (sleep disturbance, anhedonia, low self-esteem, and decreased appetite) accounted for virtually all the depression symptom-related variance in functional status and well-being, with 8.3% of patients having 2 of these symptoms and 8.2% having 3 or 4 of these symptoms. There was excellent agreement between diagnosis based on core symptoms and major depression (K= 0.77; overall accuracy rate, 94%). There were significant differences (P<.001) among patients with negative depression screen, 0 to 1, 2, and 3 to 4 core symptoms with scores on each of the validation variables getting progressively worse in these 4 groups. A cutoff point of 2 core symptoms identified all but 3 patients with major depression and an additional 5% of the entire sample without major depression who were significantly (P<.05) worse than patients without depression on each of the validation variables. CONCLUSION: A strategy that includes the use of a 2-item depression screener followed by the evaluation of 4 core depressive symptoms is an efficient and effective way of identifying and classifying primary care patients with depression in need of clinical attention.

Alabama↗
PubMed2006

Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation.

Tumor cells generally proliferate rapidly and the demand for essential nutrients as well as oxygen always exceeds the supply due to the unregulated growth and the insufficient and inappropriate vascular supply. However, cancer cells show an inherent ability to tolerate extreme conditions, such as that characterized by low nutrient and oxygen supply, by modulating their energy metabolism. Thus, targeting nutrient-deprived cancer cells may be a novel strategy in anticancer drug development. Based on that, we established a novel screening method to discover anticancer agents that preferentially inhibit cancer cell viability under the nutrient-deprived condition. After screening 500 medicinal plant extracts used in Japanese Kampo medicine, we found that a CH(2)Cl(2)-soluble extract of Arctium lappa exhibited 100% preferential cytotoxicity under the nutrient-deprived condition at a concentration of 50 microg/mL with virtually no cytotoxicity under nutrient-rich condition. Further bioassay-guided fractionation and isolation led to the isolation of arctigenin as the primary compound responsible for such preferential cytotoxicity; the compound exhibited 100% preferential cytotoxicity against nutrient-deprived cells at a concentration of 0.01 microg/mL. Furthermore, arctigenin was also found to strongly suppress the PANC-1 tumor growth in nude mice, as well as the growth of several of the tested pancreatic cancer cell lines, suggesting the feasibility of this novel antiausterity approach in cancer therapy. Further investigation of the mechanism of action of arctigenin revealed that the compound blocked the activation of Akt induced by glucose starvation, which is a key process in the tolerance exhibited by cancer cells to glucose starvation.

Animals↗
PubMed1997

Identification of compact, hydrophobically stabilized domains and modules containing multiple peptide chains.

Compactness has been used to locate discontinuous structural units containing one or more polypeptide chains in proteins of known structure. Rather than exhaustively calculating the compactness of all possible units, our procedure uses a screening algorithm to find discontinuous regions that are potentially compact. Precise calculations of compactness are restricted only to units in these regions. With our procedure, compactness can be used to discover discontinuous domains with virtually any number of disjoint peptides. Small, single-domain proteins may contain several compact regions: thus, compact regions do not always correspond to folding domains. Because a domain is an independent folding unit and should contain a hydrophobic core, compact units were further examined for the presence of hydrophobic clusters (Zehfus MH, 1995, Protein Sci 4:1188-1202). This added constraint limits the number of acceptable units and helps greatly in the location of the true structural domains. The larger hydrophobically stabilized compact units correspond to domains, while the smaller units may correspond to folding intermediates.

Algorithms↗
PubMed2000

RET proto-oncogene mutations in thyroid carcinomas: clinical relevance.

Different forms of RET mutations are found in papillary and medullary thyroid carcinomas. Rearrangements with other genes (RET/PTC oncogene) play a causative role in a significant proportion of papillary thyroid carcinomas. In this case, several factors influence the frequency and the type of RET/PTC, such as exposure to radiation, age and histological variant of the papillary tumor. On the other hand, the presence of the mutation does not seem to influence the biological behavior of the tumor or its response to conventional treatment modalities. In the setting of medullary thyroid cancer, germline RET point-mutations are implicated in the pathogenesis of virtually all hereditary forms and somatic point-mutations in nearly half of the sporadic forms. The clinical impact of this finding is that family members at-risk of hereditary MTC may be screened by genetic analysis, to distinguish those carrying or not-carrying the mutation. The last can be reassured on their status and relieved from further follow-up. Those with the mutation may be treated at a pre-clinical stage of the disease or even before the disease is started. The present review is focused on the clinical implication of RET gene mutations in thyroid cancer patients.

Carcinoma, Medullary↗
PubMedDate not supplied

The preparation of red cells depleted of leukocytes. Review and evaluation.

The most commonly used methods for depleting red cells of leukocytes are the inverted spin procedure, which results in excessive red cell loss and poor leukocyte depletion, and washing, which is expensive and yields a product with a 24-hour shelf life. Clinical data now available suggest that nonhemolytic febrile transfusion reactions can be prevented in most clinical situations by microaggregate filtration of red cells during transfusion using the spin-cool-filter procedure with a screen filter. This procedure holds advantages for leukocyte removal, red cell recovery, cost, normal shelf-life, and simplicity over other washing and buffy coat removal procedures currently used. For highly alloimmunized patients requiring virtually total leukocyte removal and where alloimmunization is to be avoided at any cost, adhesion filtration or freezing and deglycerolization should be used.

Cell Separation↗
PubMed1987

Cell-surface antigens of melanoma recognized by human monoclonal antibodies.

Human monoclonal antibodies (mAbs) were derived from lymph node lymphocytes and peripheral blood lymphocytes (PBL) from patients with melanoma. Four methods for generating human mAbs were compared: fusion with human [LICR-LON-HMy-2 (LICR-2)] or mouse (NS-1) cells; transformation by Epstein-Barr virus (EBV); and EBV transformation followed by NS-1 fusion. NS-1 fusion with lymph node lymphocytes resulted in a higher number of growing hybrids than LICR-2 fusion. Virtually no hybrids were obtained from NS-1 or LICR-2 fusions with PBL. EBV transformed lymphocytes from lymph node and peripheral blood with equal efficiency, and the yield of proliferating cultures for antibody screening was more than 10- to 30-fold greater than that obtained by fusion techniques. However, once antibody-producing cultures had been identified, stability and clonability of EBV-transformed cells were poorer than that of NS-1 hybrid cells. To combine the strengths of both methods, cultures of EBV-transformed cells were fused with NS-1; and hybrid clones were isolated that showed vigorous growth, clonability, and stable antibody secretion. Detailed specificity analysis of the mAbs produced by six of these clones indicated detection of a class 1 (unique) melanoma antigen, a class 3 melanoma antigen, and four ganglioside antigens (GD3, GM3, and two other, as yet uncharacterized, heterophile antigens).

Antibodies, Monoclonal↗
PubMed1999

Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency.

Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age, patients with CDSP may present with cardiomyopathy and muscle weakness. A linkage with D5S436 in 5q was reported in a family. A recently cloned homologue of the organic cation transporter, OCTN2, which has sodium-dependent carnitine uptake properties, was also mapped to the same locus. We screened for mutation in OCTN2 in a confirmed CDSP family. One truncating mutation (Trp132Stop) and one missense mutation (Pro478Leu) of OCTN2 were identified together with two silent polymorphisms. Expression of the mutant cDNAs revealed virtually no uptake activity for both mutations. Our data indicate that mutations in OCTN2 are responsible for CDSP. Identification of the underlying gene in this disease will allow rapid detection of carriers and postnatal diagnosis of affected patients.

Amino Acid Sequence↗
PubMed2001

Developments in the pathology of ovarian tumours.

The understanding of the pathogenesis and pathology of ovarian tumours is constantly evolving. Dominant themes in recent studies of ovarian tumours include prognostic features in borderline tumours, molecular events in the pathogenesis of ovarian tumours, the assessment of tumour features that may have prognostic or treatment implications, and the development of techniques that may enhance diagnostic accuracy. The literature has been reviewed with an aim to identifying those studies that can potentially impact practice and improve patient care. The most noteworthy developments include: the understanding that so-called 'tumours of low malignant potential' are virtually always benign, and that one can identify those rare cases with malignant potential; the importance of the recognition of micropapillary serous carcinomas; an improved understanding of early invasive carcinomas and their impact on screening practices; an understanding of the association of endometriosis with ovarian cancer; further awareness of factors in ovarian tumours that influence prognosis, such as refinements in grading and molecular markers such as P27; and refinements in diagnosis so as to distinguish primary from metastatic cancer and benign lesions from malignant tumours more effectively.

Diagnosis, Differential↗
PubMed2003

Size-selection of cDNA libraries for the cloning of cDNAs after suppression subtractive hybridization.

Here we describe the establishment of size-selected cDNA libraries for the cloning of full-length cDNAs that were initially identified by suppression subtractive hybridization (SSH) technology as being differentially expressed. First, the SSH-cDNA fragments were used as 32P-probes to verify their level and differential pattern of expression by virtual Northern and to establish their corresponding full-length cDNA size. Second, cDNAs were separated by size on agarose gels and used to construct size-selected cDNA plasmid libraries, which were then screened by colony hybridization with the SSH-cDNA fragments. We conclude that the described approach complements SSH technology by allowing efficient cloning and characterization of the corresponding full-length cDNA from any desired cell type or species. This approach will give researchers the ability to specifically target and study differentially expressed genes in an efficient manner for functional genomic studies.

Animals↗
PubMed1994

The diabetic dental patient.

DM is such a common disease in the United States that virtually every dentist encounters patients with known or undiagnosed diabetes. The dentist should be alert for both general and oral signs and symptoms suggestive of uncontrolled or poorly controlled DM, and laboratory or interoffice screening tests should be a part of dental practice. Under no circumstances, however, should the dentist attempt to diagnose the disease. Patients with suggestive symptoms or with abnormal blood glucose levels identified by screening tests should be referred to a physician for diagnosis and any treatment necessary. Uncontrolled DM may be associated with increased frequency and severity of oral infections, including periodontal disease and dental caries. In some diabetic patients, susceptibility to oral disease may continue despite establishment of effective metabolic control. Dental treatment can safely be performed on the controlled diabetic patient, but some adjustment of office protocol and of antihyperglycemic drug administration may occasionally be necessary. Finally, the dental treatment team must always be alert for signs and symptoms of developing diabetic emergencies and be prepared to provide treatment as necessary.

Dental Care for Chronically Ill↗
PubMed2002

Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease.

BACKGROUND: Mutations in the SCO2 gene have been associated with fatal cardioencephalomyopathy. OBJECTIVE: To report a novel SCO2 mutation with prominent spinal cord involvement mimicking spinal muscular atrophy (Werdnig-Hoffmann disease). PATIENT AND METHODS: An infant girl presented at birth with generalized weakness, hypotonia, and lactic acidosis. At 1 month of age she developed hypertrophic cardiomyopathy and died of heart failure 1 month later. Neuroradiological studies were unremarkable. Muscle biopsy specimens showed groups of atrophic and hypertrophic fibers, but mutation screening of the SMN gene was negative. Histochemical and biochemical studies of respiratory chain complexes were performed, and the whole coding region of the SCO2 gene was sequenced. RESULTS: Findings from muscle histochemistry studies showed virtually undetectable cytochrome c oxidase activity, but normal succinate dehydrogenase reaction. Biochemical analysis in muscle confirmed a severe isolated cytochrome c oxidase deficiency. Pathologic findings of the brain were unremarkable, but the ventral horns of the spinal cord showed moderate-to-severe loss of motor neurons and astrocytosis. Sequencing of the SCO2 gene showed the common E140K mutation, and a novel 10 base-pair duplication of nucleotides 1302 to 1311, which disrupts the reading frame of the messenger RNA and gives rise to a truncated protein. CONCLUSION: The SCO2 mutations should be considered in the differential diagnosis of children with spinal muscular atrophy without mutations in the SMN gene.

Amino Acid Sequence↗
PubMed1994

Detection of lectin activity on western blots using erythrocytes.

A method is described for the direct detection of lectins, agglutinating erythrocytes, on nitrocellulose membranes after Western blotting, thus avoiding protein extraction from specific bands in the gel, followed by agglutination assays. The methodology essentially involves exposing the lectin band on a nitrocellulose strip to trypsinized rabbit erythrocytes (2%, in 0.15 M NaCl) for 30 min at 37 degrees C and then carefully transferring the membrane to saline (4 degrees C) for a few gentle washes and then fixing it in a solution (0.2% glutaraldehyde in 0.15 M NaCl) for 30 min. Later, the membrane is gently washed several times in 0.15 M NaCl containing 10 mM beta-alanine. The lectin band is visualized as a red agglutinated patch. The method is specific for lectins that can agglutinate red blood cells and virtually has no cross reactivity with the various nonlectin proteins tested. Binding of erythrocytes to the lectin band on the nitrocellulose strip can be prevented by specific competing sugars. The method can be applied to screen for the presence of lectins in natural materials and to monitor lectin fractions during purification.

Animals↗
PubMed1989

Evaluation of the developmental toxicity of five compounds with the frog embryo teratogenesis assay: Xenopus (FETAX) and a metabolic activation system.

The potential teratogenic hazard of five compounds was evaluated using the Frog Embryo Teratogenesis Assay--Xenopus (FETAX) and a metabolic activation system. Embryos of the South African clawed frog, Xenopus laevis, were exposed to (i) three compounds suspected to be proteratogenic in mammalian test systems--[2-acetylaminofluorene (2-AAF), rifampicin (RA) and benzo[a]pyrene (BP)] for 96 h; (ii) one compound unaffected by mixed-functional oxidase (MFO) metabolism--ZnSO4; (iii) one compound thought to be inactivated by cytochrome P-450--cytochalasin D (CD). Two separate static renewal tests were conducted with and without the presence of an exogenous metabolic activation system (MAS). The metabolic activation system consisted of Aroclor 1254-induced rat liver microsomes. The teratogenic potential of each compound and the effects of metabolic activation were based on teratogenic indices [TI = 96 h LC50/96 h EC50 (malformation)], types and severity of malformation, and effects on embryo growth. Metabolic activation increased the potential teratogenic hazard of 2-AAF, RA and BP by TI factors of 1.3, 2.8 and 6.8, respectively. The teratogenic potential of ZnSO4 was virtually unaffected by the MAS. The MAS significantly reduced the teratogenic potential of CD by a TI factor of 2.7. These results demonstrate the utility and importance of a MAS for in vitro developmental toxicity screens such as FETAX. Consistent use of a MAS with FETAX should reduce the number of potential false-positive and false-negative test results.

Animals↗