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PubMed2001

Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells.

The absence of immunoglobulin (Ig) expression in B-cell-derived Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD) was initially suggested to be caused by crippling mutations in the Ig promoter or coding region. More recent investigations have, however, challenged this concept. This study addressed the role of mutations in the Ig promoter region in HRS cells. Nine cases of cHD and 3 B-cell-derived HD lines were analyzed for mutations in the TATA box and octamer motif of the Ig promoter. Mutations in the octamer motif were found in only 1 of the 9 cases and in 1 of the 3 HD cell lines (L1236). Furthermore, in all cases either a complete lack or strong reduction in the expression of the Oct2 transcription factor and the BOB.1/OBF.1 coactivator were found. The relevance of the rare promoter mutations was investigated by assaying the activity of Ig promoter reporter constructs transfected into the HD cell line L1236, which harbors a mutated octamer motif. These Ig reporter constructs were completely inactive in L1236 cells; however, their activity could be reconstituted by the cotransfection of a BOB.1/OBF.1 expression vector. The additional transfection with an Oct2 expression vector did not further enhance the Ig promoter activity. The conclusions drawn from these results are that crippling mutations in the Ig promoter and coding region are not the sole cause for the lack of Ig expression in HRS cells and that defects in the transcription machinery such as absence of BOB.1/OBF.1 are more important for this phenomenon.

Carrier Proteins↗

PubMed2004

PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina.

MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation.

Amino Acid Sequence↗

PubMed2005

Abnormal oral habits in the children of war veterans.

Any kind of stress has a negative effect on the mood of people and stress resulting from war is no exception. Stress from war has not only has effects on war veterans but also on the families. Children of these families have been more susceptible to abnormal oral habits. In this observational, analytical and historical research, attempts have been made to determine the prevalence of abnormal oral habits in the children of war veterans (martyrs, freed prisoners of war and war cripples) and compare them with a control group. In this study of 520 children aged between 7 and 11 years were (238 in the study group and 282 in the control group), information was gathered via a questionnaire completed by the mothers of the students. Analysis of the received information showed that the prevalence of para functional and abnormal oral habits was more in the study group (P = 0.005). The prevalence rate was highest in children, whose family members had been both crippled and freed prisoners of war, while the rate was lowest in children whose parents had been only prisoners of war without any lasting physical injury. Most of these children had acquired these habits at the age of seven and these abnormal habits were most prevalent in children aged eight and nine.

Child↗

PubMed1998

Irving S. Cooper (1922-1985): a pioneer in functional neurosurgery.

Irving S. Cooper (1922-1985), the son of a salesman, worked his way through high school, college, and medical school to become one of the pioneers in functional neurosurgery. He developed several novel techniques for the surgical management of Parkinson's disease and other crippling movement disorders. A keen interest in the physiology of movement disorders was kindled by his doctoral research and continued during his neurosurgical training. He began to apply this knowledge to surgical practice in 1952 when he began his faculty career as Assistant Professor of Surgery at New York University. At the time, surgical treatment of parkinsonian tremor focused on various techniques used to interrupt the pyramidal tract. During a subtemporal approach for a cerebral pedunculotomy, he inadvertently injured and, subsequently, was forced to occlude the anterior choroidal artery. Much to Cooper's surprise, following emergence from anesthesia the patient's tremor and rigidity were abolished without any residual hemiparesis. This serendipitous observation, together with Meyer's earlier work on the role of the basal ganglia in motor control, helped focus surgical efforts on targets within the basal ganglia and, subsequently, within the thalamus to alleviate the movement disorders associated with Parkinson's disease. While at New York University, Cooper developed chemopallidectomy and, later at St. Barnabas Hospital in the Bronx (1954-1977), he used cryothalamectomy as a surgical technique for primary control of tremor in patients with Parkinson's disease. Cooper authored many original papers on surgical techniques and several textbooks on the lives of patients afflicted with Parkinson's disease and other crippling movement disorders. Although considered controversial, this fascinating and complex neurosurgeon made significant contributions to this field.

Cryosurgery↗

PubMed2000

Appliances and surgery for poliomyelitis in developing countries.

Death before maturity is the usual fate of the untreated crawling crippled child in developing countries. Most children with poliomyelitis, however, when upright and walking with supports or following surgery, are accepted by the community, educated by parents and relatives, and employable when they reach maturity. It is more economical to prevent 100 polio cases than to treat one hopelessly crippled child. It is often quicker to straighten 100 deformed limbs by simple subcutaneous surgeries than to treat a single patient with complicated procedures. It costs less for 100 crawling paralyzed children to walk in simple, locally made braces and clogs, than for 1 patient to be mobile in expensive imported appliances and boots. It is essential to educate or rehabilitate patients in addition to making them mobile. The final aim should be patients returned to their own village or town, accepted and integrated into their own communities, and earning their own living among their own friends. This chapter is discussed in further detail in both English and French in my Website, . This site also includes comprehensive information on both the manufacture of the simple appliances described and various surgical details. This information is also available on CD-ROM.

Adolescent↗

PubMed2003

Typing the histogenetic origin of the tumor cells of lymphocyte-rich classical Hodgkin's lymphoma in relation to tumor cells of classical and lymphocyte-predominance Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is separated into the classical (c) and lymphocyte-predominance (lp) forms. Whereas classical Hodgkin-Reed/Sternberg (HRS) cells carry mutated immunoglobulin (Ig) gene rearrangements that are often "crippled" and lack intraclonal diversity, and are likely derived from preapoptotic germinal center (GC) B cells, the lymphocytic and histiocytic cells of lpHL are presumably derived from selected GC B cells and often show ongoing somatic hypermutation. The recently identified lymphocyte-rich classical (lrc) HL is characterized by HRS cells with the immunophenotype of classical HRS cells (CD30(+)CD15(+)CD20(-)CD45(-)) but an infiltrate similar to lpHL and a clinical behavior resembling lpHL. To identify the histogenetic origin of the HRS cells in lrcHL and to determine the relationship to the lymphoma cells of cHL and lpHL we characterized seven cases of lrcHL by immunohistochemistry and sequenced the rearranged Ig genes of single micromanipulated HRS cells. The expression patterns of BCL6, CD138, Oct2, and BOB1 in HRS cells of lrcHL showed differences to those of both cHL and lpHL. Analyses of rearranged Ig genes identified clonal HRS cell expansions carrying mutated Ig rearrangements without significant intraclonal diversity in all seven of the cases. In two cases crippling mutations, rendering originally functional V gene rearrangements nonfunctional, were observed. Thus, the mutation pattern of rearranged Ig genes of HRS cells in lrcHL is clearly different from those in lymphocytic and histiocytic cells of lpHL, and resembles the pattern in HRS cells of cHL, suggesting that HRS cells in lrcHL derive from (preapoptotic) GC B cells that silenced hypermutation. In one case in addition to the dominant HRS cell clone, CD30(+) EBV-infected HRS-like cells unrelated to the tumor clone were observed, suggesting development of an expanded population of EBV-harboring HRS-like cells in the microenvironment of HL.

Adult↗

PubMed1953

The allergic aspects of multiple sclerosis.

For the past ten years there has been an increasing acceptance of the theory that allergenic reaction is a causative factor in multiple sclerosis. In the study of a series of patients the author traced many attacks directly to allergenic insults. When the offending substances were removed, a quiescent period often ensued. The severest symptoms of multiple sclerosis were most often associated with food allergens, the moderately severe with molds and fungi and the least severe with pollens and chemical offenders. The earlier the diagnosis and the beginning of treatment, the better the chance of arresting the disease and preventing serious crippling conditions. In cases of longer duration where the patient has become crippled or bedridden, physical therapy with relaxing medication is of great value.

Allergens↗

PubMed1958

Musculoskeletal complications of hemophilia.

Persons with hemophilia may be crippled by hemorrhages into soft tissue, the pressure destroying nerve and muscle. Recurrent bleeding into joints produces severe arthritis with synovitis and damage to cartilage and bone. The resulting deformities, even of long standing, may be greatly lessened, so far as impairment of function is concerned, by conservative orthopedic treatment. Treatment also may slow the progress of crippling deformities.

Arthritis↗

PubMed1992

New federal policy for children with special health care needs: implications for pediatricians.

Title V of the Social Security Act of 1935 established the nation's first categorical health care program for children: the Crippled Children's Service. In 1985, federal legislation changed the name of the Crippled Children's Service to the Program for Children With Special Health Care Needs. Four years later, new amendments to Title V dramatically altered the Program's mission. States are now required to spend 30% of the funds from the Maternal and Child Health Services block grant on children with special health care needs and to take specific steps toward improving the service system for these children and their families. The new mandate is the only current foundation of a national health policy for children with special health care needs. The 1989 law substantially broadens the mission of the state programs and explicitly recognizes that all children with a special health care need should have access to an appropriate, community-based system of care monitored by state Children with Special Health Care Needs agencies. In addition, states are now required to conduct needs assessments pertaining to these children, to foster local systems of care, and to ensure a high quality of community-based services. Understanding the implications of the new amendments is essential because pediatricians and other child health care professionals have key roles to play in implementing these new policies.

Child↗

PubMed1977

Stereotypic attitudes and behavioral intentions toward handicapped children.

Fifty-six junion-high-school pupils were questioned about their attitudes toward mentally retarded and crippled children. Same- and opposite-sex ratings of stereotypes and behavioral intentions were obtained. Results indicated a significant main effect for handicap condition, with stereotypic attitudes toward the crippled child being more favorable than attitudes toward the mentally retarded child. No differences in attitudes toward the two handicapping conditions emerged on the measure of behavioral intentions. Sex of the subject and sex of the handicapped child being rated did not significantly affect attitude scores in this study. The data were discussed in relation to the many methodological difficulties encountered in attitude research toward handicapped populations.

Adolescent↗

PubMed2003

Informed consent in clinical research: policies and practices in Singapore.

The policies and practices for obtaining informed consent from research subjects in clinical research play a vital role in determining a nation's success as a center for clinical research. The difficulty lies in the fact that while on the one hand, informed consent is a necessary pre-condition for ethical clinical research, a scrupulous observance of the guidelines for informed consent could, on the other hand, cripple medical research. Crippling of ethical medical research can be adverse to public interest, and consequently, unethical. Hence, a fine balance must be struck in the application of the guidelines for obtaining informed consent. This, in turn, would depend on the constitution and skill of research ethics committees who are appointed to consider and approve clinical research proposals. The discussion below addresses the above difficulty with recommendations that could further enhance Singapore's image as a regional clinical trial hub.

Clinical Trials as Topic↗

PubMed1991

[50 years of health care of war invalids in Finland. A good 20 years of work remains].

During the years 1939-1945 Finland was involved in the Second World War, divided for her part into three different wars: The Winter War, The Continuation War and The Lappish War. Finland was not occupied and she was spared wholesale bombing. The country suffered most of her casualties through the battles at the front, the majority being men born in 1886-1926. Some 700,000 men and women took part in her defence and almost half of them were wounded or killed. Finland was compelled to build up her health and medical services from scratch for the rehabilitation and care of those wounded in War. During the 1980's the geriatric problems of the war cripples have increased and many new patients are now complaining about their war wounds for the first time. The medical care of war cripples in Finland will cover 70 years; thus 20 years work remains.

Finland↗

PubMed1989

Handicapping and genetic disorders in Zimbabwean institutions: a diagnostic survey.

A diagnostic survey was undertaken in twelve Zimbabwean institutions for deaf, crippled and mentally handicapped individuals. A total of 1396 persons were evaluated of whom 885 were deaf, 356 physically disabled and 155 were mentally retarded. Acquired causes formed the largest aetiological group throughout the survey, but a high frequency of inherited crippling disorders was encountered (125 individuals). Down Syndrome accounted for almost one third of children with mental handicap. Undifferentiated autosomal recessive deafness was found in 87 persons, most of whom were from the Shona people.

Deafness↗

PubMed1985

[The development of legal premises in the rehabilitation of the physically handicapped from Bismarck to today--a brief overview].

The legal bases for rehabilitation and integration of the physically disabled have developed from public welfare provisions, the beginnings of disability care having been part of public poor relief schemes. Ensueing developments range from cripple care programmes to today's efforts to establish a uniform social code, which is expected to benefit the individual disabled person by bringing about a marked simplification of the current legal and administrative situation. The extension of the scope of rehabilitative efforts, which since Bismarck's time had comprised nursing and institutional care in cases of physical and mental ailings within the framework of poor relief, had initially occurred outside Prussia by including education and vocational training for disabled people (the beginnings of "rehabilitation"). A more comprehensive approach to disability care in the sense of extended assistance was embodied in the Prussian cripple welfare act of 1920. The Federal Social Assistance Act of 1962, in the final analysis, had developed from this tradition. This 1962 act not only established a duty to provide public welfare but also gave those concerned a legal title to this kind of assistance.

Persons with Disabilities↗

PubMed1985

[Psychotherapeutic possibilities in patients with definitive movement disorders].

Since traumas leading to severe and permanent physical handicaps affect the whole personality, the psychological approach plays a major role in the rehabilitation of patients with locomotory handicaps owing to injury. The harmful effects become apparently more easily on account of the disturbed personality development of the cripple, and the consequent mental changes complicate his or her reintegration into society. Rehabilitation measures intended to restore, as far as possible, the physical functions can only yield satisfactory results if they prepare the whole personality of the cripple--as a combined psychological and somatic entity--for life of a different quality.

Combined Modality Therapy↗

PubMed1986

Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease.

Endemic skeletal fluorosis is a chronic metabolic bone and joint disease caused by ingesting large amounts of fluoride either through water or rarely from foods of endemic areas. Fluoride is a cumulative toxin which can alter accretion and resorption of bone tissue. It also affects the homeostasis of bone mineral metabolism. The total quantity of ingested fluoride is the single most important factor which determines the clinical course of the disease which is characterized by immobilization of joints of the axial skeleton and of the major joints of the extremities. A combination of osteosclerosis, osteomalacia and osteoporosis of varying degrees as well as exostosis formation characterizes the bone lesions. In a proportion of cases secondary hyperparathyroidism is observed with associated characteristic bone changes. Contrary to earlier thinking, severe crippling forms of skeletal fluorosis are seen in paediatric age group too. Increased metabolic turnover of the bone, impaired bone collagen synthesis and increased avidity for calcium are features in fluoride toxicity. Osteosclerotic picture is evident when small doses of fluoride are ingested over a long period of time during which calcium intakes are apparently normal while osteoporotic forms are common in paediatric age group and with higher body load of the element. Alterations in hormones concerned with bone mineral metabolism are seen in fluorosis. Kidney is the primary organ of excretion for fluorides. Age, sex, calcium intake in the diet, dose and duration of fluoride intake and renal efficiency in fluoride handling are the factors which influence the outcome. Serum parameters rarely help in the diagnosis. Elevated urinary fluoride and increased bone fluoride content are indicators of fluoride toxicity. Fluorosis is a preventable crippling disease. No effective therapeutic agent is available which can cure fluorosis. Industrial fluorosis is on the increase on a global basis. Bone density measurement is a tool for early diagnosis.

Bone Diseases↗

PubMed1987

Endemic fluorosis in the Ethiopian Rift Valley.

Between 1977 and 1985, the fluoride content of drinking water and the incidence of endemic fluorosis were assessed and correlated in 16 large farms, villages and towns in the Ethiopian Rift Valley. The fluoride level of drinking-water collected from wells there ranged from 1.2 mg/litre to 36.0 mg/l (mean 10.0 mg/l). Dental fluorosis was observed in more than 80% of sampled children resident in the Rift Valley since birth, with maximum prevalence in the age-group 10-14 years; 32% of the children showed severe dental mottling. Males were affected more than females. Three areas, Wonji-Shoa, Alemtena and Samiberta, were identified as having cases of skeletal fluorosis. The highest incidence was at Wonji-Shoa sugar estates, where a linear relationship was observed between the development of crippling fluorosis, fluoride concentration of drinking-water, and period of exposure to it. The first cases of skeletal fluorosis there appeared among workers (98% males) who had been consuming water with fluoride content of more than 8ppm for over 10 years. Among 30 workers with crippling skeletal fluorosis, cervical radiculo-myelopathy was found to be the commonest incapacitating neurologic complication. As a preventive measure, low-fluoride surface water should be supplied for drinking wherever feasible; if this is not possible, the development of partial defluoridation should be considered.

Adolescent↗

PubMedDate not supplied

[The treatment of hypospadias complexes].

OBJECTIVES: To explain the preoperative assessment of the hypospadias cripple and define the fundamental principles of correction of the failed hypospadias repair. METHODS: Through case presentation and literature review, the defects associated with the failed hypospadias repair including persistent chordee, urethral stricture, urethrocutaneous fistula, urethral diverticulum, meatal retraction and stenosis, failed glansplasty are elaborated. Decision-making points in selecting a method of repair are also provided. RESULTS: The principles of successful reoperative hypospadias surgery are discussed and listed. CONCLUSIONS: A thorough assessment of the defect and precise application of standard principles of hypospadias repair allows for successful correction of even complex hypospadias cripples.

Humans↗