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At least 145 records · Page 8Linked to original sources
PubMed1993

Biotechnology and bone graft substitutes.

Trauma, disease, developmental deformities, and tumor resection frequently cause bone defects that seriously challenge the skills of orthopedic and maxillofacial surgeons. Currently, repairing osseous deficiencies involves various medical surgical techniques, including autogenous grafts, allografts, internal and external fixation devices, electrical stimulation, and alloplastic implants. The existing technology, though effective in many cases, still is beset with numerous difficulties and disadvantages. A critical need for improved treatment methods exists today. Biotechnology now provides access to new bone repair concepts via administration of protein growth and morphogenic factors. Implantable device and drug delivery system technologies also have advanced. The converging biopharmaceutical, device, and delivery technologies represent an opportunity to improve the quality of health care for individuals with orthopedic and maxillofacial deficiencies. This report reviews current concepts in fracture healing and bone repair and examines existing treatment modalities. It also addresses novel protein drugs that stimulate osseous regeneration and delivery systems for these drugs.

Amino Acid Sequence↗
PubMed2004

Arsenic toxicity, mutagenesis, and carcinogenesis--a health risk assessment and management approach.

A comprehensive analysis of published data indicates that arsenic exposure induces cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and various types of cancer. Although exposure may occur via the dermal, and parenteral routes, the main pathways of exposure include ingestion, and inhalation. The severity of adverse health effects is related to the chemical form of arsenic, and is also time- and dose-dependent. Recent reports have pointed out that arsenic poisoning appears to be one of the major public health problems of pandemic nature. Acute and chronic exposure to arsenic has been reported in several countries of the world where a large proportion of drinking water (groundwater) is contaminated with high concentrations of arsenic. Research has also pointed significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. There is therefore a great need for developing a comprehensive health risk assessment (RA) concept that should be used by public health officials and environmental managers for an effective management of the health effects associated with arsenic exposure. With a special emphasis on arsenic toxicity, mutagenesis, and carcinogenesis, this paper is aimed at using the National Academy of Science's RA framework as a guide, for developing a RA paradigm for arsenic based on a comprehensive analysis of the currently available scientific information on its physical and chemical properties, production and use, fate and transport, toxicokinetics, systemic and carcinogenic health effects, regulatory and health guidelines, analytical guidelines and treatment technologies.

Arsenic↗
PubMed2003

Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups.

OBJECTIVE: To determine the prevalence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in women of different ethnic groups and to relate these common mutations to plasma homocysteine, red cell folate, and serum folate. DESIGN: A one-time fasting blood sample was obtained for MTHFR genotype (C677T and A1298C) determinations (n=433). Serum folate, red cell folate, and homocysteine analyses were performed in nonfolic acid supplement users (n=215). SUBJECTS/SETTING: This study involved 433 women from four ethnic groups, including 193 Hispanic women of Mexican descent, 139 white women, 53 Asian women of mixed descent, and 48 African American women. STATISTICAL ANALYSIS PREFORMED: Chi;(2), t Test, and analysis of variance were used. RESULTS: Mexican women (18.1%) had a higher frequency of the 677 TT genotype compared with white (7.2%), Asian (3.8%), and African American (0%) women. White women (7.9%) had a higher frequency of the 1298 CC genotype than the other ethnic groups (range=1.9% to 2.6%). The frequency of compound heterozygosity (677 CT + 1298 AC) was higher in Mexican (17.6%) and white (15.1%) women than Asian and African American ( approximately 4% to 6%) women. In the era of folic acid fortification, neither genotype, independently or together, was associated with homocysteine or blood folate concentrations when ethnic groups were combined. In Mexican women, however, a linear trend (P</=.05) was detected for the C677T variants with the lowest red cell folate in the TT genotype. APPLICATIONS/CONCLUSIONS: These data demonstrate ethnic differences in genetic polymorphisms that are diet responsive and may be useful when investigating ethnic variations in chronic disease, developmental anomalies, and folate requirements.

Adolescent↗
PubMed2002

Probiotics as an adjuvant to detoxification protocols.

Autism is a developmental disease characterized by a spectrum of symptoms ranging from decreased verbal skills and social withdrawal, to repetitive behavior and violent outbursts. Genetic analysis has yielded a few potentially interesting genes, however no clear linkage has been established. For this reason, it has been suggested that the etiology of autism may involve multiple loci. This, in large part, explains why so many different theories abound. One such theory is that of mercury poisoning. Environmentally acquired mercury, either through some causal contact or through vaccination, has been postulated as the culprit. Mercury is thought to be exerting its neurological effect on the brain. The standard treatment has been to apply chelating agents in an attempt to extricate the mercury. One missing component in the treatment is the utilization of the body's own detoxification mechanisms. Arguably the largest detoxification component of the body, the endogenous enteric bacteria are an enormous reservoir, which can be constantly and safely replenished. This paper discusses the use of high-dose probiotics as an adjuvant for detoxification protocols with an emphasis on use in autistics.

Autistic Disorder↗
PubMed2002

Enzyme-based therapy for autism spectrum disorders -- is it worth another look?

Autism is a developmental disease usually manifesting within the first three years of life. To date, no causative agent has been found. Similarly, treatment options have been limited. Of the treatment options available, a number of them have been nutritionally based in an attempt to address one or more of the theories regarding the etiology of the disease. An example would be enzyme therapy for the digestion of purported offending neuroactive peptides collectively known as exorphins. This paper discusses the exorphin theory of autism and subsequent treatment with dietary enzyme therapy. Novel data are presented in support of the theory that enzymes play a critical role in autism. Forty-six patients between the ages of 5 and 31 were selected for inclusion in the study based on a diagnosis placing them in the category of the autism spectrum disorders (ASD). The diets were supplemented with a novel dietary enzyme formulation, ENZYMAID, for a period of 12 weeks. Progress was tracked according to the Symptom Outcome Survey (SOS) (1) form method of symptom charting and presented in a table for further analysis. The novel enzyme formula, ENZYMAID, beneficially and safely affected all 13 of the parameters measured. Improvements ranged from 50-90%, depending on the parameter measured. Enzyme therapy to treat ASD may indeed a viable option in treatment protocols. These results indicate that further controlled studies are warranted.

Adolescent↗
PubMed1996

Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries.

A new and highly effective method, termed suppression subtractive hybridization (SSH), has been developed for the generation of subtracted cDNA libraries. It is based primarily on a recently described technique called suppression PCR and combines normalization and subtraction in a single procedure. The normalization step equalizes the abundance of cDNAs within the target population and the subtraction step excludes the common sequences between the target and driver populations. In a model system, the SSH technique enriched for rare sequences over 1,000-fold in one round of subtractive hybridization. We demonstrate its usefulness by generating a testis-specific cDNA library and by using the subtracted cDNA mixture as a hybridization probe to identify homologous sequences in a human Y chromosome cosmid library. The human DNA inserts in the isolated cosmids were further confirmed to be expressed in a testis-specific manner. These results suggest that the SSH technique is applicable to many molecular genetic and positional cloning studies for the identification of disease, developmental, tissue-specific, or other differentially expressed genes.

Base Sequence↗
PubMed1996

The faciogenital dysplasia gene product FGD1 functions as a Cdc42Hs-specific guanine-nucleotide exchange factor.

The Rho family of small GTP-binding proteins plays important roles in the regulation of actin cytoskeleton organization and cell growth. Activation of these GTPases involves the replacement of bound GDP with GTP, a process catalyzed by the Dbl-like guanine-nucleotide exchange factors, all of which seem to share a putative catalytic motif termed the Dbl homology (DH) domain, followed by a pleckstrin homology (PH) domain. Here we have examined the role of a Dbl-like molecule, the faciogenital dysplasia gene product (FGD1), which when mutated in its Dbl homology domain, cosegregates with the developmental disease Aarskog-Scott syndrome. We report that a polypeptide of FGD1 encompassing the DH and PH domains can bind specifically to the Rho family GTPase Cdc42Hs and stimulates the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. Microinjection of this FGD1 polypeptide into Swiss 3T3 fibroblast cells induces the formation of peripheral actin microspikes, similar to that previously observed when cells were injected with a constitutively active form of Cdc42Hs. This effect of FGD1 on actin organization is readily inhibited by coinjection of a dominant-negative mutant of Cdc42Hs. Examination of NIH 3T3 cells expressing the FGD1 fragment revealed that similar to cells expressing Dbl, two independent elements downstream of Cdc42Hs, the Jun NH2-terminal kinase and the p70 S6 kinase, became activated. Hence, our results indicate that FGD1, through its DH and PH domains, acts as a Cdc42Hs-specific guanine-nucleotide exchange factor and suggest that the Cdc42Hs GTPase may have a role in mammalian development.

3T3 Cells↗
PubMed1996

Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.

The development of the skeleton requires the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The activities of these two cell types are likely to be regulated by TGF-beta, which is abundant in bone matrix. We have used transgenic mice to evaluate the role of TGF-beta 2 in bone development and turnover. Osteoblast-specific overexpression of TGF-beta 2 from the osteocalcin promoter resulted in progressive bone loss associated with increases in osteoblastic matrix deposition and osteoclastic bone resorption. This phenotype closely resembles the bone abnormalities seen in human hyperparathyroidism and osteoporosis. Furthermore, a high level of TGF-beta 2 overexpression resulted in defective bone mineralization and severe hypoplasia of the clavicles, a hallmark of the developmental disease cleidocranial dysplasia. Our results suggest that TGF-beta 2 functions as a local positive regulator of bone remodeling and that alterations in TGF-beta 2 synthesis by bone cells, or in their responsiveness to TGF-beta 2, may contribute to the pathogenesis of metabolic bone disease.

Age Factors↗
PubMed2002

Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function.

Mutations in the human LIS1 gene cause type I lissencephaly, a severe brain developmental disease involving gross disorganization of cortical neurons. In lower eukaryotes, LIS1 participates in cytoplasmic dynein-mediated nuclear migration. We previously reported that mammalian LIS1 functions in cell division and coimmunoprecipitates with cytoplasmic dynein and dynactin. We also localized LIS1 to the cell cortex and kinetochores of mitotic cells, known sites of dynein action. We now find that the COOH-terminal WD repeat region of LIS1 is sufficient for kinetochore targeting. Overexpression of this domain or full-length LIS1 displaces CLIP-170 from this site without affecting dynein and other kinetochore markers. The NH2-terminal self-association domain of LIS1 displaces endogenous LIS1 from the kinetochore, with no effect on CLIP-170, dynein, and dynactin. Displacement of the latter proteins by dynamitin overexpression, however, removes LIS1, suggesting that LIS1 binds to the kinetochore through the motor protein complexes and may interact with them directly. We find that of 12 distinct dynein and dynactin subunits, the dynein heavy and intermediate chains, as well as dynamitin, interact with the WD repeat region of LIS1 in coexpression/coimmunoprecipitation and two-hybrid assays. Within the heavy chain, interactions are with the first AAA repeat, a site strongly implicated in motor function, and the NH2-terminal cargo-binding region. Together, our data suggest a novel role for LIS1 in mediating CLIP-170-dynein interactions and in coordinating dynein cargo-binding and motor activities.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1976

The effects of a 20-week nutritional insult on the skeletal development of Cebus albifrons during the 1st year of life.

Using an atlas constructed from records of a group of normal monkeys in the same colony, the effects of a 20-week low-calorie or low-protein nutritional insult on skeletal development were determined. The most significantly retarded sites were the late-forming ossifications (epiphyses, sesamoids, and tuberosites). A general increase in ossification anomalies and in individual variation was evident. The similarity of these findings to studies previously reported for man indicates the utility of nonhuman primate models for the further study of nutritional deficiency.

Age Determination by Skeleton↗
PubMed2026

TriosCompass: a snakemake workflow for integrated detection of SNVs, indels, STRs, and structural de novo variants in parent-child trios.

MOTIVATION: The accurate and sensitive identification of de novo variants, which are unique to an individual and not found in the parents' germlines, is critical for understanding the genetic basis of rare diseases, developmental disorders, and evolutionary processes. Existing de novo variant detection pipelines often lack the flexibility to handle multiple variant types, struggle with speed and reproducibility across computational environments, demand extensive manual configuration, or require bioinformatics expertise for downstream curation and analysis, limiting their scalability and usability for large genomic studies. Accordingly, there is a pressing need to better address these challenges. RESULTS: We introduce TriosCompass, an open-source Snakemake workflow that addresses these challenges by providing a modular, accelerated, and environmentally-configurable end-to-end solution for comprehensive de novo variant discovery. It integrates state-of-the-art tools into a reproducible framework, empowering researchers to discover novel genetic insights with greater efficiency and reliability. AVAILABILITY: TriosCompass is implemented as a Snakemake workflow and is freely available at https://github.com/NCI-CGR/TriosCompass_v2 or on Zenodo (10.5281/zenodo.17981062). SUPPLEMENTARY INFORMATION: Supplementary data is available on GitHub at https://github.com/NCI-CGR/TriosCompass_v2/tree/manuscript/report_dashboards. Supplementary methods on DeepTrio benchmark runs can be viewed at: https://github.com/NCI-CGR/TriosCompass_v2/blob/manuscript/TriosCompass_Supp_Methods_deeptrio_benchmark.md.

Software↗
PubMedDate not supplied

Analysis of randomly amplified polymorphic DNA (RAPD) for identifying genetic markers associated with canine hip dysplasia.

Canine hip dysplasia is a heritable developmental disease resulting, in part, from increased laxity in hip joints and is a precursor to degenerative joint disease. Identification of genetic markers linked to joint laxity would foster development of more accurate diagnostic methods, facilitate identification of the disease gene(s), and supplement efforts to establish physical/genetic maps of the canine genome. Work presented here describes analysis of randomly amplified polymorphic DNA in the search for markers which cosegregate with increased joint laxity in Canis familiaris, the domestic dog. The Boykin spaniel, a highly inbred breed afflicted with an extremely high incidence of hip dysplasia, served as a model for study of canine hip dysplasia. Only 5% of 200 random primers revealed significant polymorphisms within this breed. However polymorphisms were detected in seemingly nonpolymorphic amplification products when digested with restriction enzymes. Restriction digestion revealed polymorphisms in 15% of the monomorphic amplification products. Among the primers that revealed polymorphisms, one primer correctly identified 9 of 12 dogs with regard to joint laxity. However, extensive evaluation is required before any assertion can be made regarding linkage of this marker to joint laxity. Of interest, another primer amplified a genomic segment unique to the canine Y chromosome.

Animals↗
PubMed1988

Epidemiology of hip and knee osteoarthritis.

This review has focused on the prevalence and risk factors associated with knee and hip osteoarthritis. Risk factors for knee osteoarthritis are obesity and major injury, and knee osteoarthritis probably fits into the generalized osteoarthritis diathesis. Repetitive use, such as in jobs requiring heavy labor and knee bending, probably increases the risk of knee osteoarthritis. Hip osteoarthritis is probably frequently secondary to developmental defects. As Rothman (182) has pointed out in discussing causation, this does not necessarily mean that the same factors do not also contribute to causing hip osteoarthritis. Yet, it appears that, in many cases, developmental defects are severe enough to be sufficient causes of hip osteoarthritis. To delineate other causes, it may be necessary to examine risk factors separately in those with and in those without developmental disease. Although large epidemiologic studies are best able to identify the relative contributions of specific risk factors while controlling for other risk factors, new studies need to focus on important unresolved questions. First, longitudinal studies with comprehensive follow-up using repeated radiographic assessments are needed to identify factors that cause development of disease or the onset of symptoms. Second, cohorts with early and possibly asymptomatic disease need to be followed to determine the causes of progression or regression of disease and the natural history of disease. Such cohorts may include those at high risk of injury such as sports enthusiasts or manual laborers.

Animals↗
PubMed1999

Disorders of the stomach and duodenum in children.

Over the past year, there have been continued efforts to increase our understanding of the epidemiology, natural history, and pathogenic mechanisms of Helicobacter pylori infection in children. In an attempt to delineate the spectrum of disease associated with this organism, several teams of investigators have also examined the association of H. pylori infection with other disorders, from food allergy to inflammatory bowel disease. Developmental aspects of gastric and duodenal motility, risk factors for gastrointestinal bleeding in pediatric intensive care unit patients, and the use of uncooked cornstarch in the treatment of dumping syndrome are among other topics covered in this review.

Journal Article↗
PubMed2002

Craniomaxillofacial fibrous dysplasia.

Fibrous dysplasia is a nonneoplastic developmental disease of osseous tissue. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. In this series of 16 patients with fibrous dysplasia of the craniomaxillofacial bones, the disease was generally monostotic and most commonly maxillary in location. Two patients demonstrated typical symptoms of the McCune Albright syndrome. Marked deformity or functional disturbances were the major indications for treatment. Total excision of the involved bone was the most successful form of treatment but produced the greatest functional and cosmetic deficits and long-term postoperative complications. A conservative therapeutic approach with a modest reduction in the bulk of these lesions may be sufficient to relieve signs and symptoms effectively. Periodic follow-up is indicated to detect recurrences or malignant changes in the early stages.

Adolescent↗
PubMed1995

Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus.

Transforming growth factor beta (TGF-beta) has been proposed to play a number of roles in central nervous system (CNS) development and response to injury. To test these proposals, transgenic mice were generated which overproduce TGF-beta 1 in the CNS. Surprisingly, these mice developed severe hydrocephalus and died between birth and 3 weeks of age. Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known. These results also demonstrate that the developing CNS is highly sensitive to TGF-beta, and suggest a role for aberrant expression of TGF-beta in the pathogenesis of developmental disease of the CNS.

Animals↗
PubMed2004

Long-term changes in visual acuity and refractive error in amblyopes.

PURPOSE: To report long-term changes in visual acuity and refractive error for strabismic, anisometropic, and isoametropic amblyopes. METHODS: Records of patients with strabismic amblyopia, anisometropic amblyopia, and isoametropic amblyopia who were treated from 1983 to 1993 were reviewed. Excluded were patients having ocular or neurological diseases, developmental delay, and follow-up <4 years after treatment cessation. Data included best-correctable visual acuity and spherical equivalent refractive error of the amblyopic and the nonamblyopic eye at pretreatment, posttreatment, and long-term follow-up. RESULTS: Records for 61 patients met the inclusion criteria. For strabismic amblyopia (n = 22), mean visual acuity in amblyopic and nonamblyopic eyes improved 0.36 and 0.05 logarithm of the minimum angle of resolution (logMAR) units after a mean treatment time of 1 year. At long-term follow-up (mean = 9.3 years after treatment), visual acuity in the amblyopic eye regressed 0.09 logMAR and visual acuity in the nonamblyopic eye improved 0.10 logMAR units. For anisometropic amblyopia (n = 26), mean visual acuity in amblyopic and nonamblyopic eyes improved 0.30 and 0.02 logMAR units, respectively, after a mean treatment period of 1.1 year. At the long-term follow-up visit (mean = 7.1 years after treatment), visual acuity in the amblyopic eye regressed 0.09 logMAR unit and in the nonamblyopic eye improved 0.03 logMAR unit. Repeated-measures analysis of variance showed no significant effect of type of amblyopia on visual acuity of the amblyopic eye and a significant effect of visit due to treatment but not regression. The changes in visual acuity in the nonamblyopic eye from the pretreatment to the follow-up visit were significant and interacted with type, the changes being larger in strabismic amblyopia. For strabismic amblyopia, the mean refractive error in amblyopic and nonamblyopic eyes changed from +2.15 D and +1.85 D, respectively, initially to +0.45 D and +0.58 D, respectively, at the follow-up visit. For anisometropic amblyopia, the mean refractive error in amblyopic and nonamblyopic eyes changed from +1.04 D and +0.12 D, respectively, initially to +0.23 D and -0.94 D, respectively, at the follow-up visit. The effect of visit on amblyopic and nonamblyopic refractive errors was significant. For isoametropic amblyopia (n = 13), visual acuity in both right and left eyes initially was 0.39 logMAR unit and improved to 0.14 logMAR unit in each eye after a mean follow-up of 8.9 years. Refractive error in the right and the left eyes changed from -1.22 D and -1.14 D, respectively, to -2.68 D and -2.56 D, respectively, at follow-up. These differences were all significant. CONCLUSIONS: After treatment and with long-term follow up, visual acuity regresses but not significantly in the amblyopic eye in strabismic amblyopia and anisometropic amblyopia. At the same time, visual acuity in the nonamblyopic eye improves slightly. Visual acuity also improves significantly over time in isoametropic amblyopia. The refractive error of both amblyopic and nonamblyopic eyes tends to show a myopic shift regardless of the type of amblyopia.

Adolescent↗