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At least 739 records · Page 41Linked to original sources
PubMed2003

Molecules mimicking Smad1 interacting with Hox stimulate bone formation.

Bone morphogenetic proteins (BMPs) induce osteoblast differentiation and bone formation. Smads, a group of functionally and structurally related intracellular effectors, mediate signaling initiated by BMPs and regulate cell definite commitment. Previously, we showed that Smad1 activates osteopontin and osteoprotegerin gene expression by dislodging Hoxc-8 from its DNA binding sites. A domain of Smad1, termed Smad1C, was characterized as interacting with Hoxc-8 and then crippling its DNA-binding ability. Ectopic expression of Smad1C is able to bypass BMP signaling in the induction of osteoblast differentiation and bone formation in vitro. To test the function of Smad1C on osteogenesis in vivo, we generated transgenic mice in which Smad1C expression was induced with doxycycline and localized in bone by using a tetracycline-inducible expression system (Tet-on) modified with a bone-specific gene promoter, type I collagen alpha1. The mice expressing Smad1C showed increased skeletal bone mineral density compared with their littermates. Bone histomorphometric analysis of mouse tibiae showed that Smad1C significantly increases trabecular bone area and length of trabecular surface covered with osteoid and up-regulates bone marker gene (OPN, Cbfa1, Col I alpha1, BSP, ALP) expression in vivo. Moreover, stromal cells isolated from mice expressing Smad1C displayed a higher potential for differentiating into osteoblasts than the other mice. These results indicate that Smad1C mimics BMPs in the induction of osteogenesis in vivo. Most important, using a high throughput screening assay based on mimicking Smad1C's displacement of Hoxc-8 binding to DNA, we identified chemical entities that exhibit bone anabolic activity in cell and bone organ cultures, suggesting the possibility that the compounds may be used as bone anabolic agents to treat bone pathologies.

Animals↗
PubMed2006

Leucine 135 of tropomodulin-1 regulates its association with tropomyosin, its cellular localization, and the integrity of sarcomeres.

Tropomodulin-1 (Tmod-1) is a well defined actin-capping protein that interacts with tropomyosin (TM) at the pointed end of actin filaments. Previous studies by others have mapped its TM-binding domain to the amino terminus from amino acid 39 to 138. In this study, we have identified several amino acid residues on Tmod-1 that are important for its interaction with TM5 (a nonmuscle TM isoform). Glutathione S-transferase affinity chromatography and immunoprecipitation assays reveal that Tmod sense mutations of either amino acid 134, 135, or 136 causes various degrees of loss of function of Tmod TM-binding ability. The reduction of TM-binding ability was relatively mild (reduced approximately 20-40%) from the G136A Tmod mutant but more substantially (reduced approximately 50-100%) from the I134D, L135E, and L135V Tmod mutants. In addition, mutation at any of these three sites dramatically alters the subcellular location of Tmod-1 when introduced into mammalian cells. Further analysis of these three mutants uncovered a previously unknown nuclear trafficking function of Tmod-1, and residues 134, 135, and 136 are located within a nuclear export signal motif. As a result, mutation on either residue 134 or residue 135 not only will cause a significant reduction of the Tmod-1 ability to bind to TM5 but also lead to predominant nuclear localization of Tmod-1 by crippling its nuclear export mechanism. The failure of the Tmod mutations to fully associate with TM5 when introduced into neonatal rat cardiomyocytes was also associated with an accelerated and severe fragmentation of sarcomeric structures compared with overexpression of wild type Tmod-1. The multiple losses of function of Tmod engendered by these missense mutations are most severe with the single substitution of residue 135.

Chromatography, Affinity↗
PubMed1993

Turning symptoms into allies: utilization approaches with posttraumatic symptoms.

Adult patients with symptoms connected to the trauma of childhood sexual abuse often present in therapy with multiple symptoms and life difficulties and offer a challenge to even the most experienced clinician. In this paper, I describe my work with three such patients who were crippled in different ways by symptoms that had proved resistant to years of various therapeutic interventions. In every case, I accepted and utilized these symptoms as positive resources for successful and rapid change. Patients were then taught self-utilization approaches which allowed them to sustain and extend initial improvements. I conclude that the indirect utilization principle introduced by Milton Erickson provides an effective method to use in approaching some of the more persistent patterns of posttraumatic symptomatology related to childhood sexual abuse.

Adolescent↗
PubMed2005

Awake-alert hypnosis in the treatment of panic disorder: a case report.

An individual developed a lifestyle-limiting case of Panic Disorder that threatened to interfere with her raison d'etre: To participate in the exclusive lifestyle of her community. The panic episodes started to cripple her social calendar and as the "season" came into full swing her coveted role of chairwoman of various philanthropic functions came into peril. A variant of awake-alert hypnosis had to be created for this case. Hypnosis consisting of eye closure with relaxation was out of the question. The authors created an induction technique and specific suggestions based on the Waterford glassware, as focal point, with the purpose of not only inducing awake-alert hypnosis but also of executing a series of specific strategies, tailored to abort the incipient panic episodes.

Aged↗
PubMed1990

Personality characteristics of eating-disordered outpatients as measured by the Hand Test.

The Hand Test was administered to 34 eating-disordered and 26 noneating-disordered college-age women to determine discriminating projective personality features. Eating-disordered women scored higher on response time, overall pathology, and passivity. Anorexics present more tension, aggression, and acting out potential whereas bulimics demonstrate significantly more passive responses. The more severely affected women scored higher on crippled, passive, and withdrawal variables. Similarities as well as differences between the groups may have important implications for the diagnosis of subgroups of eating-disordered women and for treatment planning.

Adult↗
PubMed1992

Nonarticular pain syndromes. Differentiating generalized, regional, and localized disorders.

Nonarticular pain syndromes, although not inherently crippling, can have significant impact on patients' comfort, daily activities, and job performance. These syndromes include fibromyalgia, bursitis, tendinitis, and localized myofascial pain syndromes. Although differentiating these conditions from one another may be difficult, early diagnosis and follow-up are important for determining appropriate treatment. Depending on the diagnosis, treatment may include use of nonsteroidal anti-inflammatory drugs, analgesics, or corticosteroid injections; trigger-point desensitization therapy; physical therapy; and patient education.

Bursitis↗
PubMed1990

Advances in the management of victims struck by ruptured intracranial aneurysms.

The advances in management of victims struck by the rupture of an intracranial aneurysm is reviewed. In the 1970s the management outcome was still far from acceptable; many victims who had 'recovered' following a major aneurysmal subarachnoid haemorrhage (SAH) succumbed or became crippled as the result of repeat bleeds and/or delayed SAH-induced ischaemic deterioration ('cerebral vasospasm'). The era of prosperity for microneurosurgery, the introduction of the calcium channel blocker nimodipine and the accumulation of cases in centres with a team of dedicated aneurysm surgeons form the basis of a recent breakthrough in the previously gloomy management outcome. With microsurgical techniques elective surgery can now be performed in the acute stage thereby preventing disastrous reruptures which occur frequently in the early phase after the first bleed. The concomitant use of nimodipine minimizes delayed SAH-induced ischaemic deterioration. Today a management regime including early operation combined with nimodipine has led to grossly improved results. Nevertheless cognitive disturbances and psychosocial maladjustment are frequent sequelae following a major aneurysmal bleed. Hope for further improvements could depend on the development of techniques which may allow identification of intracranial aneurysms before they rupture and increased knowledge of the aetiology of such cerebral arterial wall lesions.

Aged↗
PubMed1997

Avascular necrosis secondary to postoperative steroid therapy.

Hypothalamic and pituitary tumours may present with vague symptoms owing to excess or lack of hormone production, including diabetes insipidus. Corticosteroids are commonly employed to limit cerebral oedema and at much lower doses to treat secondary hypocorticalism. Continuation of steroids at inappropriately high doses predisposes to the development of avascular necrosis as in the case we describe in a young woman of 34 years. This is a potentially preventable crippling disorder. When prescribing steroids the lowest effective dose should be used.

Adult↗
PubMed1984

Juvenile tropical pancreatitis syndrome in northern Nigeria: a case report.

A six-year-old boy with abdominal pain since the age of two years is described. Physical examination revealed no abnormality but under general anaesthesia a mass could be felt in the left upper abdominal quadrant. An X-ray showed calcification in that quadrant, anterior to the vertebrae and an IVP revealed incomplete duplication of the left ureter. At laparotomy, small multiple calculi were removed from the pancreatic duct and pancreatico-jejunostomy was performed. Following surgery, his crippling abdominal pain ceased dramatically and he has remained symptom-free.

Calcinosis↗
PubMed1987

Familial hyperphosphatasaemia in a Nigerian child.

A 5-year-old Nigerian girl of normal intelligence had grotesque crippling skeletal deformities, multiple pathological fractures and dwarfism dating back to the end of the first year of life. She also suffered from recurrent lower respiratory tract infection since infancy. The clinical, biochemical and radiological profile were compatible with the diagnosis of familial hyperphosphatasaemia.

Alkaline Phosphatase↗
PubMed1998

Carnitine and antioxidants levels in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a heterogeneous disorder with a spectrum of clinical severity ranging from mild arthritis to a crippling joint disease with involvement of internal organs. Carnitine is essential for muscle energy production and is required for the transport of long chain fatty acids and the acyl coenzyme A derivatives across the inner mitochondrial membrane. The levels of malondialdehyde (MDA), an index of lipid peroxidation, and the antioxidants copper-zinc superoxide dismutase (CuZnSOD), glutathione (GSH), ceruloplasmin (CP), catalase (CAT), and carnitine were assessed in 42 patients with RA and 24 control subjects. While plasma carnitine and erythrocyte CuZnSOD levels were significantly lower in the patients with RA compared with the control group (p<0.01 and p<0.001, respectively), the CAT level was not different from controls (p>0.05). Plasma MDA, CP, and erythrocyte GSH levels were significantly higher than in the control group (p<0.001, p<0.001 and p<0.01, respectively). MDA levels showed a positive correlation with CP and GSH levels (r=0.716, p<0.001 and r=0.492, p<0.01, respectively). However, MDA, GSH, and CP demonstrated a negative correlation with carnitine (r=-0.719, p<0.001; r=-0.559, p<0.01, and r=-0.635, p<0.001, respectively) in the patient group but not in controls. There was also a significant positive correlation between CP and GSH levels (r=0.561, p<0.01). However, neither CuZnSOD nor CAT levels demonstrated correlation withcarnitine, MDA, GSH, or CP levels. It was interesting that CAT activity was not altered and CuZnSOD activity decreased when compared with the control group. These results suggest that while CP, MDA and GSH levels increased, carnitine and CuZnSOD levels decreased, but CAT activity was unchanged.

Adult↗
PubMed2006

Resource allocation for community-based therapy.

PURPOSE: Adequate and equitable resourcing of services for children with disabilities and their families is a challenge that is faced by agencies as the growth in client numbers outstrips any increase in available funding. While funding models have been developed within the acute health care and education sectors, there have been few attempts to develop funding models for therapy (occupational therapy, physiotherapy, psychology, and speech pathology) provided within community-based, paediatric disability services. This paper outlines a model for allocating staff resources to provide therapy services for children with physical disabilities based on a project conducted by Novita Children's Services (formerly the Crippled Children's Association of South Australia, Inc.). METHOD: Services were mapped using a framework based on the International Classification of Function developed by the World Health Organization and adopted by the Australian Institute of Health and Welfare. An action research methodology was employed that included focus groups held with staff to identify potential resource drivers; collection of travel time data, client caseload numbers; and developing profiles of services and client groups. A model for allocating staff time was developed to reflect the differing service demands, travel time, leave allowances and time for activities to develop the social environment for individuals with disabilities. RESULTS AND CONCLUSIONS: Analysis indicated that the drivers of staff resources were the type of service delivery (early intervention versus school aged services), model specific (e.g., time required to provide community-based services and work within multi-disciplinary teams), and specific client (need for complex technology or equipment; school/preschool transition times; high health care needs due to dysphagia, deteriorating conditions with changing needs, or post surgery/medication rehabilitation) and family well-being issues. While further data collection and refinement of the model is needed, it provides the organization with more objective and equitable resource allocation and enables improved advocacy for client needs.

Child↗
PubMed1997

Three head injuries: the Biblical account of the deaths of Sisera, Abimelech and Goliath.

Three head injuries are described in the Bible: the death of Sisera at the hands of Jael, the skull fractures inflicted on Abimelech near the walls of Thebez, and the slaying of Goliath by David. The various attempts to understand the mechanisms of these head injuries are reviewed. We shall try to identify the site of the mortal blow on Sisera's head, to understand why Abimelech, still conscious, asked to die, and to clarify whether the Philistine giant from Gat was a rugged warrior or just an endocrinological cripple.

Bible↗
PubMed2003

Pathobiology of primary mediastinal B-cell lymphoma.

Controversy still exists over the response to therapy and prognosis of patients with primary mediastinal B-cell lymphoma (PMBL). Recent data from the International Extranodal Lymphoma Study Group (IELSG) suggest that a MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin) chemotherapy regimen followed by radiotherapy may be a better induction strategy than other previously used treatments. Although the pathobiology of PMBL has been widely studied, its precise histology, phenotype, and molecular characteristics are still not clear. To date, phenotypic analysis has revealed the following phenotype: positivity for CD45 and CD20, but negativity for CD3, CD10, CD21, Class I/II major histocompatibility antigens, and a variety of other immunohistochemical markers. CD79a is generally detected, despite an absence of surface immunoglobulins (Igs). CD30 staining is observed in most cases, but is weaker and less homogeneous than in classic Hodgkin's lymphoma or anaplastic large cell lymphoma. BCL-2 protein is usually expressed but there are few data describing the expression of MUM1/IRF4, PAX5/BSAP, BCL-6, or the B-cell transcription factors BOB.1, Oct-2, and PU.1. Cytogenetic studies reveal gains in segments of chromosome 9p, including amplification of the REL proto-oncogene and the tyrosine kinase gene JAK2. Other molecular findings include: C-myc mutations or rearrangements, p53 mutations, IgV(H), gene mutations, and bcl-2 and mal over-expression. bcl-6 mutations and bcl-2 gene rearrangements are generally absent, suggesting that PMBL is of pre-germinal center (GC) origin. However, two recent reports show isotype-switched Ig genes with a high frequency of somatic hypermutations as well as variants in the 5' noncoding region of the bcl-6 gene. The IELSG collected 137 PMBL cases for extensive pathologic review. Histologically, the lymphomatous growth was predominantly diffuse with sclerosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. Molecular analysis was performed on 40 cases and showed novel findings. More than half of the cases displayed bcl-6 gene mutations, which usually occurred together with functioning somatic IgV(H) gene mutations, and BCL-6 and/or MUM1/IRF4 expression. The present study supports the concept that PBML is derived from activated GC or post-germinal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective Ig production despite the expression of Oct-2, BOB.1, and PU.1 transcription factors, and a lack of IgV(H) gene crippling mutations.

Diagnosis, Differential↗
PubMedDate not supplied

Working together for health and human rights.

The right to a standard of living adequate for health and well-being is being denied to vast numbers of people all over the world through increasing disparities in income and in wealth. In the name of economic development, a number of international and national policies have increased the grossly uneven distribution of income, with ever-growing numbers of people living in poverty as well as in increasing depths of poverty. Globalization, crippling levels of external debt, and the 'structural adjustment' policies of international agencies have expanded the numbers and the suffering of people living in poverty and have resulted in the neglect of government-funded social programs, of regulations protecting the environment, and of human development. Access to medical care, an essential element in the protection of health, is difficult for many, including the 44 million people in the United States who lack insurance coverage for the cost of medical care services. Working together for health and human rights also requires promotion of the right to peace. The right to life and health is threatened not only by the existence and active deployment of weapons of mass destruction, including nuclear, chemical and biological weapons and anti-personnel landmines, but also other weapons. The twentieth century has been the bloodiest in human history, with an estimated 250 wars, more than 110 million people killed, countless people wounded and at the least 50 million refugees. Health workers must work together with people in our communities for the promotion of health and human rights, which, in Sandwell and elsewhere, are inextricably intertwined.

Health↗
PubMed1981

Chronic obstructive pulmonary disease.

While the prospects of "curing" a patient of emphysema, chronic bronchitis, or asthma are poor, prompt institution of appropriate drug therapy and adjunctive measures can keep the patient from becoming a respiratory cripple.

Biofeedback, Psychology↗
PubMed1958

Fatal keratomas due to deep homografts of the benign papillomas of tarred mouse skin; normal proclivities and neoplastic disabilities as determinants of tumor course.

Six out of eight epidermal papillomas, induced with tar in mice of homogeneous strain, have grown after transfer to the subcutaneous tissue of sucklings and weanlings. Five of them have been thus maintained for nearly or quite a year and a half, and in seven to nine successive groups of mice. The tumor studied longest has been kept going in five parallel lines since its primary implantation. The papillomas have all grown progressively in most instances, and proved fatal. None has altered except through the occurrence of derivative cancers, but these have arisen so often as only to be excluded on transfer by a rigorous selection of grafts. Histologically the papillomas have been of a single, completely unaggressive kind, yet transfer has disclosed great differences in their abilities. The tumors they form are of unique sorts. The cells of some are able-bodied (Type A), capable of spreading along bare connective tissue and keratinizing like normal, reparative epidermis. They line graft pockets, differentiate into the free space these provide, and form cysts densely packed with keratin. The papilloma is thus turned outside in. The cysts become huge as keratin accumulates in them, and eventually they rupture with result either in subcutaneous dissecting cysts or keratinizing surface growths that are often prodigious in size and fantastic in shape, but sometimes are completely like the cutaneous papillomas ordinarily induced by carcinogens, and tend, when small, to regress or come away as these frequently do. One growth of Type A was placed in the peritoneal cavity or in the liver, spleen or lung, and at all these situations it formed introverted cysts resembling the subcutaneous. The cells of other papillomas are more or less crippled (Type C). In extreme instances they are unable to spread laterally, and produce relatively little keratin. They fail to line graft pockets, but their keratin inflames the exposed connective tissue, extravasation ensues, and a continually enlarging, fluid-filled cyst forms, with walls that are bare except where a stalked or cauliflower papilloma exists, projecting inwards. At last the cyst ruptures and a second dissecting cyst forms, also devoid of papilloma tissue; or else the overlying skin undergoes pressure necrosis, the cyst fluid escapes through a rent, and fatal infection ensues. All gradations exist between Type A and Type C. The cancers derivative from both exhibit a marked disability,-though invasive they are almost or quite unable to extend along bare connective tissue. The papillomas that are possessed of this faculty spread beyond them along the cyst wall, and kill the host through their unceasing activity. In collateral work a papilloma was transplanted that was found protruding from the external auditory canal of a mouse which had received an intramuscular injection of methylcholanthrene many months previously. The tumor is now in its 5th generation, after 15 months. The growths it forms are of Type A. All of the papillomas are functioning tumors, with their own cells as the functioning product. Their papilliferous shape, when on the skin, is due solely to inability of their cells to gain space in other ways. Intrinsically they are keratomas. The papillomas do well after transfer to deep situations because the growth of their cells is indirectly promoted, through favoring local conditions. No direct promotion takes place like that when the cells of prostatic and mammary tumors are stimulated to multiply by hormones. Doubtless many agents act in both ways, that is to say by dual promotion.

Allografts↗
PubMed1983

Long-term erythropoietic repopulating ability of old, young, and fetal stem cells.

It is possible that erythropoietic stem cells do not age. This would mean that stem cells from old donors can function as well as those from young or fetal donors. The competitive repopulation assay has been used to test long-term stem cell function by directly comparing how well competing stem cells repopulate a recipient and produce differentiated cell types. C57BL/6J (B6) mice were used as donors, while recipients and competitors were WBB6F1 hybrids with genetically distinguishable hemoglobin. Lethally irradiated young WBB6F1 recipients were given a mixture of 2.5 X 10(6) cells from B6 old marrow, young marrow, or fetal liver donors; each recipient also received a standard dose of 1 X 10(6) marrow cells from a pool of young WBB6F1 competitors. Surprisingly, the old marrow cells competed the best in repopulating the recipients. This pattern was maintained even after recovery from sublethal irradiation, a treatment that severely stresses stem cells. This stress was demonstrated when sublethal irradiation caused a 20-fold decline in repopulating ability measured using hemoglobin markers, and a 3- to 7-fold decline using chromosome markers. Stem cells from old marrow competed better than young or fetal cells in similar experiments using immunologically crippled recipients or using unirradiated W/Wv recipients that are immunologically intact. In both types of recipients, the advantage of old marrow cells again persisted after recovery from sublethal irradiation. Other genotypes were tested, and marrow cells from old B6CBAF1 donors competed better than those from young donors of that genotype. However, marrow cells from young CBA donors completed better than those from old CBA donors. These results support the hypothesis that stem cells do not age, and suggest that regulatory changes with age promote rapid stem cell repopulation in B6 and B6CBAF1 mice, but inhibit it in CBA mice.

Aging↗