Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 54-yr-old man was admitted to Hokkaido University Hospital, complaining of fever, multiple arthralgia, edematous erythema and face and muscular weakness of extremities during the last 2 months. He was diagnosed as dermatomyositis by acceleration of ESR, elevation of GOT, GPT, CPK, aldolase, moderate increases of collagen fibers in biopsy specimen of skin and his clinical signs. Although stools were positive for occult blood, the routine radiographic examination failed to detect the bleeding site in the upper GI. tract. However, in the double contrast picture of the stomach, a very fine abnormal linear shadow was observed at the upper corpus of the lesser curvature. This linear shadow was a margin of the tumor, retrospectively. About 4 months later, abnormal pain occurred and a mass was palpable in the left lumbar region, suggesting a pancreatic tumor. He was operated on excising the tumor, but was performed only exploratory laparotomy because of the presence of intra-abdominal metastases. Death occurred 40 days after the operation and necropsy was done. The gross anatomical findings of the abdomen showed a stomach tumor as large as an infant's head and its metastases to pancreas, lymph nodes, and greater and lesser omentum. Esophageal mucosa including esophagocardiac junction was intact. Histological examination of the intragastric tumor revealed a typical squamous cell carcinoma with keratinization. According to the absence of the components of adenocarcinoma and squamous metaplastic gastric mucosa of non-cancerous areas in the stomach, it seemed likely to be a heterotopic squamous cell carcinoma. It was unknown about the precedence between the stomach cancer and dermatomyositis. There have been 11 cases of primary pure squamous cell carcinoma in the world literature since 1968, but this is the first case report of coexistence of these two diseases.
 ...
PMID:[A case report of a primary pure squamous cell carcinoma of the stomach associated with dermatomyositis (author's transl)]. 726 22

The in vitro test of direct granulation of basophils affected by specific antigens (cardial tissue, acid-soluble fraction of collagen, streptococcal allergens) was investigated in the course of treating 41 patients (29 women and 12 men aged from 20 to 50 years) suffering from a little active rheumatic fever. The patients received a complex of therapeutic measures including high-protein diet (130-140 g protein) and drugs (1.5-2.0 g acetylsalicylic acid and 15 mg of prednisolone a day). As a result of the treatment all the patients improved and demonstrated pain relief in the heart region, reduced palpitation, abatement of general weakness and fatigue. At the same time there was a decrease in the reactivity of basophilic leukocytes, shown by less number of degranulated cells in vitro, activated with specific antigens.
 ...
PMID:[Parameters of polynuclear cell activity in torpid and latent recurrent rheumocarditis in the process of treatment with a high-protein diet and drug preparations]. 736 68

Changes in perianal connective tissue were studied using specimens from juvenile cadavers and resected tissue from adults. The fibers of the anal sphincter muscles lie in a connective tissue mesh which anchors the muscle fibers, the anal mucosa and skin, and the entire anal canal. The connective tissue mesh is present in the newborn and has similar patterns in every age group, but the ratio of the amount of connective tissue/muscle tissue (C/M ratio) increases with age. The increase of the C/M ratio may have a role in the development of weakness of the sphincters and mucosal or rectal prolapse in the elderly. After injuries or operation no pure collagen scar formation was observed in the sphincter muscles, but there was an increase in the C/M ratio. In inflammatory bowel diseases, when severe anal stenosis is present, the connective tissue web and sphincter are intact and the scar formation is confined to the submucosal and subcutaneous layers.
 ...
PMID:Age-related changes and scar formations of perianal connective tissue. 737 69

Juvenile hyaline fibromatosis is a rare disorder characterised by multiple subcutaneous tumours, gum hypertrophy, muscle weakness, and flexion contractures of the large joints. Histology shows an abundance of a homogenous, amorphous, acidophilic extracellular matrix in which spindle shaped cells are embedded forming minute streaks. It has been previously suggested that collagen abnormalities may be involved. A 14 month old girl with this syndrome is described in whom postmortem western blot studies were performed. These studies revealed an absent pro-alpha 2(I) chain and an absent collagen type III chain in skin but not in the other organs examined.
 ...
PMID:Skin collagen defects in a patient with juvenile hyaline fibromatosis. 749 65

Congenital muscular dystrophies (CMDs), are heterogeneous autosomal recessive disorders. Their severe manifestations consist of early hypotonia and weakness, markedly delayed motor milestones and contractures, often associated with joint deformities. Histological changes seen in muscle biopsies consist of large variations in muscle fibre size, a few necrotic and regenerating fibres and a marked increase in endomysial collagen tissue. Diagnosis is based on clinical features and on morphological changes. In several CMD cases, we have demonstrated an absence of one of the components of the extracellular matrix around muscle fibres, the merosin M chain, now referred to as the alpha 2 chain of laminin-2 (ref.3). We localized this CMD locus to chromosome 6q2 by homozygosity mapping and linkage analysis. The laminin alpha 2 chain gene (LAMA2) maps to the same region on chromosome 6q22-23 (ref. 5). We therefore investigated LAMA2 for the presence of disease-causing mutations in laminin alpha 2 chain-deficient CMD families and now report splice site and nonsense mutations in two families leading presumably to a truncated laminin alpha 2 protein.
 ...
PMID:Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. 755 Mar 55

IBM has emerged as a clinicopathological entity during the past 25 years but with increasing complexity. It occurs primarily in elderly persons (over the sixth decade of life, with 3:1 male preponderance), but young adults or children may also be affected in some families. FIBM is by and large non-inflammatory though some autosomal dominant FIBM cases have inflammatory cell infiltrates. In IBM, slowly progressive weakness of proximal as well as distal muscle groups occurs and is usually not associated with skin rash or malignancy. The incidence of associated collagen-vascular disease is thought to be lower than in DM or PM but is reported to be as high as 15%. It is generally refractory to treatment with corticosteroids or other immunosuppressants. Muscle biopsy and electromyography may suggest a neurogenic process mixed with myopathic features. None of the histopathological features is specific enough to be a diagnostic criterion. The diagnostic criteria have to be collective, encompassing both clinical and pathological criteria in different combinations. The presence of eosinophilic intranuclear or cytoplasmic inclusions immunoreactive for both beta-amyloid and ubiquitin in affected myofibres may facilitate the diagnosis of IBM. The diagnosis no longer depends on the ultrastructural demonstration of characteristic microtubular filaments as previously thought. The identification of both beta-amyloid and ubiquitin may provide a new concept for the disease process in IBM. A chronic persistent intracytoplasmic synthesis of abnormal amyloid protein in IBM is suspected to be similar to that in Alzheimer's disease. IBM is considered to be intimately related to a heterogenous group of non-inflammatory IBMD, including DMY, OPMD, and both autosomal recessive and dominant FIBM. An inflammatory response has been seen, however, in muscles of both OPMD and autosomal dominant FIBM. The pathogenesis in IBM and in IBMD may not be the same. Unlike IBM, there is no abnormal sarcolemmal expression of MHC-I antigen in IBMD as a sign of T-cell-mediated cytotoxicity causing myofibre destruction. The prion theory derived from identification of amyloidogenic protein in the filament inclusions in the rimmed vacuoles is provocative. If one believes in the contention that the amyloidogenic filaments are the primary pathogen of either IBM or IBMD, one must account for the fact that these filaments are originally derived from sarcolemmal nuclei and not from autophagic vacuoles. Until this is clarified, the possibility that the filaments represent either abnormal or defective 'slow' virus nucleocapsids cannot be completely ruled out.
 ...
PMID:Inclusion body myositis. 815 43

Among the different subtypes of Ehlers-Danlos syndrome (EDS), the dominant types I-III have, so far, been uninformative biochemically and molecular genetically, and diagnostic problems with subgroup boundaries often arise. We have investigated the ultrastructural pattern of connective tissue macromolecules in skin biopsy specimens of some 85 patients aged 4 months-54 years who exhibit clinical symptoms or the suspicion of EDS I-IV. Based on the differential features of collagen fibrils and ground substance material, four distinct groups could be established. Group I (clinically EDS type I) showed disorganized collagen bundles and dense aggregations of collagen fibrils with bizarre shapes. Group II (clinically varying from EDS types I-III) revealed collagen bundles that regularly contained numerous "composite collagen fibrils" with enlarged "flower-like" cross-sections and rope-like longitudinal sections, often associated with increased amounts of matrix substances in the form of electron-dense irregular strands and filaments in a branched network. Group III (clinically EDS types II-III) presented smaller isolated collagen flowers and ropes associated with excessive filamentous ground substance material and flocculent material. Group IV (with clinical symptoms of EDS type IV) had a dermis thinned to one third of the normal and a reduced number of collagen bundles with small diameter fibrils. In 13 patients, the abnormal ultrastructural dermal architecture did not coincide with any of these four groups or with the pattern of any other inherited connective tissue disorder. In 16 additional patients with mostly mild clinical symptoms, such as muscle weakness and small joint hyperlaxity, no ultrastructural aberrations could be found. Even though the primary defects underlying the respective aberration of the collagen fibrils are still unknown, the differential ultrastructural changes of the collagen fibrils together with clinical symptoms should, as in other heterogeneous genetic disorders, facilitate the (provisional?) classification of EDS and permit the diagnosis of individual cases.
 ...
PMID:Differential ultrastructural aberrations of collagen fibrils in Ehlers-Danlos syndrome types I-IV as a means of diagnostics and classification. 816 10

Seven pseudophakic patients with severe anterior capsular shrinkage and opacities after continuous curvilinear capsulorhexis as a severe anterior capsular shrinkage group and seven pseudophakic patients without the complication as control group were studied in a slit lamp examination of zonular fibers and anterior vitreus body with an indentation mirror. A light and electron microscopic study of the shrunken anterior capsular edge was performed in one case of the severe anterior capsular shrinkage group. No morphological findings suggesting weakness of zonular fibers such as cleavage or scarceness were observed, but reduction in elasticity of the zonular fibers was surmised and degeneration and liquefacation of the anterior vitreus body was observed in the severe anterior capsular shrinkage group. Histological study revealed several layers of proliferated spindle cells and also abundant extracellular matrix, consisting of collagen types I, III and IV, under the monolayer of lens epithelium attached to the anterior capsule. Spindle cells were epithelial cells and considered to be derived from lens epithelium, because the spindle cells were connected by junctional apparatus, which is a feature of epithelium. Severe anterior capsular shrinkage and opacities were due to low ability of the lens supporting system of zonular fibers and anterior vitreus and severe scarring and shrinkage at the anterior capsular edge.
 ...
PMID:[Findings from slit lamp and histological examination of the anterior capsule in patients with severe anterior capsular shrinkage and opacities after implantation of intraocular lenses]. 832 39

The attachment of grafts of keratinocyte sheets is mediated in part by the presence and organisation of basement membrane components. The reappearance of basement membrane following keratinocyte autografting was examined in pigs. These studies showed that there was rapid expression of anchoring fibrils and hemidesmosomes, which reached normal numbers at 10 days. However, the length of hemidesmosomes did not reach normal size during the period of study. Weakness of attachment of keratinocyte autografted epidermis was found to lie between the basement membrane and the granulation tissue. This suggests that reported clinical problems with keratinocyte graft attachment may be mediated not only by delay in maturation of the basement membrane but also by its poor integration with collagen of the wound bed.
 ...
PMID:Restoration of basement membrane structure in pigs following keratinocyte autografting. 836 76

Endplate acetylcholinesterase (AChE) consists of globular catalytic subunits attached to the basal lamina by a collagen-like tail. Different genes encode the catalytic subunit and the tail portion of the enzyme. Endplate AChE deficiency was reported previously in a single case (Engel et al., 1977, patient 1). We describe here our observations in four additional patients (patients 2-5). Three cases were sporadic; patients 2 and 3 were sisters. All had generalized weakness increased by exertion but ophthalmoparesis was not a constant feature. All had mild slowing of the pupillary light reflex; other dysautonomic features were absent. None benefited from anticholinesterase therapy. All patients had a decremental electromyogram response; in four of the five patients, single nerve stimuli evoked a repetitive response. Miniature endplate potential amplitude was reduced in patient 5 only. Endplate amplitudes and currents were prolonged but the open-time of the acetylcholine receptor ion channel was normal. In patients 1-4 the quantal content of the endplate potential was reduced due to a reduced number of readily releasable quanta. Quantitative electron microscopy revealed abnormally small nerve terminals, abnormal encasement of the presynaptic membrane by Schwann cells and degeneration of junctional folds and of organelles in the junctional sarcoplasm. Acetylcholinesterase was absent from all endplates of all patients by cytochemical and immunocytochemical criteria. Density gradient ultracentrifugation of muscle extracts from patients 1, 3, 4 and 5 revealed an absence of the collagen-tailed form of the enzyme in patients 1, 3 and 4 but not in patient 5. The kinetic properties of the residual AChE in muscle were normal. Erythrocyte AChE activity and Km values, determined in three patients, were also normal. Studies of the catalytic subunit gene of AChE in patients 2 and 3 revealed no abnormality in those exons that encode the domain to which the tail subunit binds. In patients 1-4 the molecular defect is likely to reside in the gene encoding the tail subunit of AChE, or in a protein necessary to assemble the catalytic and tail subunits. In patient 5, the absence of AChE from the endplate may be due to a faulty tail subunit, a defect in the basal lamina site that binds the tail subunit or failure of transport of the assembled asymmetric enzyme from the cell interior to the basal lamina. The cause of the weakness in these patients is not fully understood but possible mechanisms are discussed.
 ...
PMID:Congenital endplate acetylcholinesterase deficiency. 839 Mar 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>