Sarcolemmal defect and subsarcolemmal lesion in a patient with gamma-sarcoglycan deficiency

We report a case of gamma-sarcoglycanopathy with sarcolemmal defects and subsarcolemmal lesions indistinguishable from those in Duchenne muscular dystrophy. Both disorders share certain ultrastructure features that suggest a common pathogenesis related to primary deficiency of transmembrane glycoproteins (e.g., sarcoglycans) or deficiency in dystrophin, which produces a secondary deficiency in sarcoglycans. The lack of transmembrane glycoproteins may contribute to membrane lesions and associated muscle fiber degeneration and necrosis.     

A transketolase assembly defect in a Wernicke-Korsakoff syndrome patient

Thiamine deficiency, a frequent complication of alcoholism, contributes significantly to the development of damage in various organ systems, including the brain. The molecular mechanisms that underlie the differential vulnerabilities to thiamine deficiency of tissue and cell types and among individuals are not understood. Investigations into these mechanisms have examined potential variations in thiamine utilizing enzymes. Transketolase is a homodimeric enzyme containing two molecules of noncovalently bound thiamine pyrophosphate. In the present study, we examined a his-tagged human transketolase that was produced in and purified from Escherichia coli cells. Previous findings demonstrated that purified his-transketolase had a Km app for cofactor and a thiamine pyrophosphate-dependent lag period for attaining steady-state kinetics that was similar to transketolase purified from human tissues. Interestingly, the time of the lag period, which is normally independent of enzyme concentration, was found herein to be dependent on the concentration of the recombinant protein. This atypical behavior was due to production in E. coli. Generation of the normal, enzyme concentration-independent state required a cytosolic factor(s) derived from human cells. Importantly, the required factor(s) was found to be defective in a Wernicke-Korsakoff patient whose cells in culture show an enhanced sensitivity to thiamine deficiency.     

Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred

Urine activity product ratios of uric acid (APRua), sodium urate (APRna), and ammonium urate (APRau), and urinary excretion of 10 metabolites were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of 4 diets containing approximately 11% protein (dry weight) and various protein sources: a 72% moisture, casein-based diet; a 10% moisture, egg-based diet; a 72% moisture, chicken-based diet; and a 71% moisture, chicken-based, liver-flavored diet. Significantly (P < 0.05) higher APRua, APRna, and APRau were observed when dogs consumed the egg-based diet, compared with the other 3 diets; there were no differences in these ratios among the other 3 diets. Twenty-four-hour urinary excretions of chloride, potassium, phosphorus, and oxalic acid were significantly (P < 0.05) higher when dogs consumed the egg-based diet. Twenty-four-hour urinary excretions of sodium were significantly (P < 0.05) higher when dogs consumed the egg-based diet, compared with the casein-based diet and the chicken-based, liver-flavored diet, but were not significantly different between the egg-based diet and chicken-based diet. Twenty-four-hour urine volume was similar when dogs consumed the 4 diets. Twenty-four-hour endogenous creatinine clearance was significantly (P < 0.05) lower when dogs consumed the casein-based diet; there were no differences among the other 3 diets. Although consumption of all diets was associated with production of alkaline urine, the 24-hour urine pH was significantly (P < 0.05) higher when dogs consumed the egg-based diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular analysis of T cell receptor beta variability in a patient with orofacial granulomatosis

Treponema pallidum can be detected by conventional techniques such as dark-field microscopy, immunofluorescence or the rabbit infectivity test, in large numbers in the skin lesions of primary and early secondary syphilis. In the skin lesions of late secondary and tertiary syphilis, conventional techniques fail to detect spirochaetes in general, perhaps due to increasing degeneration and the disappearance of treponemal spirochaetes in late syphilitic skin lesions. We used the highly sensitive technique of polymerase chain reaction (PCR) to prove the presence of Treponema pallidum-specific DNA in six lesions of late secondary syphilis and seven lesions of tertiary syphilis, including one syphilitic gumma. A Whartin-Starry stain was carried out in all 13 specimens and did not reveal any treponemal structures. Treponema pallidum-specific DNA was amplified by PCR in four of six cases of secondary syphilis and in the syphilitic gumma. These results are in favour of a direct cell-mediated immune reaction directed against treponemal antigen rather than the concept of an Id-reaction. Beside the usefulness of a PCR-based assay for understanding the aetiology of lesions of late syphilis, the assay described can be of clinical importance in various situations where traditional methods fail to detect Treponema pallidum because of lack of sensitivity.     

Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria

Methionine synthase catalyzes the remethylation of homocysteine to methionine via a reaction in which methylcobalamin serves as an intermediate methyl carrier. Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin rendering the enzyme inactive. Regeneration of functional enzyme requires reductive methylation via a reaction in which S-adenosylmethionine is utilized as a methyl donor. Patients of the cblE complementation group of disorders of folate/cobalamin metabolism who are defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay, hyperhomocysteinemia, and hypomethioninemia. Using consensus sequences to predicted binding sites for FMN, FAD, and NADPH, we have cloned a cDNA corresponding to the "methionine synthase reductase" reducing system required for maintenance of the methionine synthase in a functional state. The gene MTRR has been localized to chromosome 5p15.2-15.3. A predominant mRNA of 3.6 kb is detected by Northern blot analysis. The deduced protein is a novel member of the FNR family of electron transferases, containing 698 amino acids with a predicted molecular mass of 77,700. It shares 38% identity with human cytochrome P450 reductase and 43% with the C. elegans putative methionine synthase reductase. The authenticity of the cDNA sequence was confirmed by identification of mutations in cblE patients, including a 4-bp frameshift in two affected siblings and a 3-bp deletion in a third patient. The cloning of the cDNA will permit the diagnostic characterization of cblE patients and investigation of the potential role of polymorphisms of this enzyme as a risk factor in hyperhomocysteinemia-linked vascular disease.     

Evidence for McKusick''s hypothesis of deficient collagen cross-linking in patients with homocystinuria

Fractionation of the venom of the spider Phoneutria nigriventer revealed that it was a mixture of several neurotoxic peptides. The peptides so far characterized either inhibited or induced neurotransmitter release. These effects were mediated by Ca2+ channels or increasing Na+ permeability through voltage sensitive Na(+)-channels, respectively. The pooled toxic components (fraction P4) showed stimulatory effects on acetylcholine release from brain cortical slices. In addition, a component of the observed effects resembling that of alpha-latrotoxin was identified, which was characterized by the ability to provoke release of acetylcholine (ACh) at low temperature and in a manner independent of extracellular Ca2+ and of voltage sensitive Na(+)-channels.     

A case report of incomplete endocardial cushion defect with mitral stenosis in an elderly patient

The following paper describes a mitral valve replacement (SJM 27 mm), the patch closure (EPTFE) of an ostium primum atrial septal defect and tricuspid annuloplasty (De Vega's method) in a 64-year-old female patient with an incomplete endocardial cushion defect and mitral stenosis. Surgery revealed thickened, mitral valve leaflets and the presence of a cleft, findings similar to those observed in case of rheumatic degeneration. Investigation of patient hemodynamics confirmed a diagnosis of Lutembacher syndrome and a lower with left ventricle volume. After surgery, the volume of left ventricle increased and the patients clinical course was uneventful.     

Survival of a patient with postinfarction ventricular septal defect following venoarterial bypass with centrifugal pump and reoperation for residual shunt

A 61-year-old man was hospitalized because of circulatory collapse due to postinfarction ventricular septal defect. As his hemodynamic condition deteriorated despite intraaortic counterpulsation, he underwent patch closure of VSP and patch reconstruction of the anterior left ventricular wall concomitant with coronary artery bypass grafting to the circumflex lesion immediately after admission. Femorofemoral circulatory assist with centrifugal pump was necessitated to wean from cardiopulmonary bypass because of severe left ventricular dysfunction. Circulatory assist was controlled to maintain mixed venous oxygen saturation of more than 70% under mild hypothermia. On the second postoperative day (POD), increased oxygen saturation from right atrium to pulmonary artery developed (Qp/Qs = 2.1). Further surgery was performed on an emergency basis for additional patch closure of VSP. Then he was successfully weaned from cardiopulmonary bypass successfully. The patient was extubated on the 14th POD and was ambulatory when he discharged on the 56th POD. Immediate surgical intervention should be performed for the patient with postinfarction ventricular septal defect when the hemodynamic state deteriorates under intraaortic counterpulsation.     

Polycythemia in a patient with HIV

A case of primary Nocardia otitidiscaviarum infection of a skin wound over an open fracture in a previously healthy adult who suffered multiple trauma in a car accident is reported. The organism was identified in cultures of pus specimens from the infected wound. The case demonstrated the difficulties of testing susceptibility of nocardiae in vitro and the necessity of prolonged antibiotic treatment. The prevalence of nocardial infections is underestimated, highlighting the need for adequate documentation of such infections and compilation of the information by public health authorities.     

A study of cardiovascular risk in heterozygotes for homocystinuria

Early atherosclerotic-like lesions and thromboemobolic problems are prominent in homocystinuric patients. Recent evidence suggested that mild homocyst(e)inemia, such as is present in heterozygotes for homocystinuria due to cystathionine synthase deficiency, may cause a marked excess in early ischemic heart disease. To evaluate the risk due to mild homocyst(e)inemia, the frequencies of heart attacks and strokes in parents and grandparents of homocystinuric children were assessed in the present study. No statistically significant increases in the incidence of heart attacks or strokes were consistently detected. The data available are sufficient to virtually exclude an increase in the cardiovascular risk for homocystinuria heterozygotes of as much as fivefold compared to controls, and to make very improbable a relative risk of as much as threefold. Less than 5% of homocystinuria heterozygotes are likely to have a fatal or nonfatal heart attack by age 50. These results fail to suggest that mild homecyst(e)inemia is an important contributory factor in the overall incidence of cardiovascular disease.     

Molecular diagnosis of Ureaplasma urealyticum in an immunocompetent patient with destructive reactive polyarthritis

Polymerase chain reaction (PCR) amplification, which is a useful method for detecting infectious agents in joints, has potential utility in the molecular diagnosis of venereal-associated arthritis. Among pathogens detected by this technique, Ureaplasma urealyticum, which is primarily associated with reactive arthritis (ReA), is also implicated in septic arthritis in immunocompromised patients. We report here a case of destructive polyarthritis, initially suggestive of septic arthritis, in an immunocompetent patient whose PCR positivity for U. urealyticum DNA in one joint, in conjunction with the disease outcome and histologic findings, led to the diagnosis of destructive ReA.     

Acute life-threatening event with rhabdomyolysis after starting on high-dose pyridoxine therapy in an infant with homocystinuria

A case of posttraumatic ischaemic stenosis is presented. The patient, a five year-old girl, was admitted to hospital with physical and radiological signs of small bowel obstruction about two weeks after sustaining blunt abdominal trauma in a car accident. At laparotomy two lesions of the distal jejunum were found. Proximal to this the small intestine was dilated. A segment of 25 cms. of small bowel including the two lesions was resected. Microscopic examination showed two ulcers with adjacent fibrosis consistent with ischaemic stenosis. The patient recovered completely after the operation. The entity of "seat belt syndrome" is presented.