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Biomedical subjects

D R Johns

Publications and source records attributed to D R Johns.

At least 73 records · Page 4Linked to original sources
PubMed1990

Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine.

The hypothesis that brain mitochondria are directly affected in several phenotypes associated with disordered oxidative phosphorylation was tested using phosphorus 31 (31P) magnetic resonance spectroscopy. Abnormal phosphorylation potentials in skeletal muscle have been demonstrated by 31P magnetic resonance spectroscopy in patients with mitochondrial cytopathies (heritable disorders of oxidative phosphorylation), but abnormalities of phosphorylation potentials in other organs have not been documented. Several lines of evidence suggest that these mutations may affect mitochondria in nonmuscle tissue. In this study we found that phosphocreatine-to-ATP ratios in brain were significantly reduced and that calculated brain ADP concentrations, phosphorylation potentials, and percentage of maximal rate of ATP synthesis were significantly altered in the 5 patients examined. This study indicates a primary abnormality of mitochondrial function in the brain, even in the absence of clinically evident cerebral dysfunction.

Adenosine Triphosphate↗
PubMed1990

Heteroplasmy in chronic external ophthalmoplegia: clinical and molecular observations.

Chronic progressive external ophthalmoplegia (CPEO) describes a recognizable clinical syndrome frequently associated with variable dysfunction in other organ systems. Histochemical and biochemical studies suggested primary dysfunction of oxidative phosphorylation. This has recently been confirmed by demonstration of partially deleted as well as normal mitochondrial DNA--heteroplasmy--in some of these patients, most of them sporadic. In the six heteroplasmic CPEO patients that we have examined to date, the partially deleted species has been detected in all tissues tested, albeit in vastly different proportions. We report here detection of physiologically significant proportions of partially deleted mitochondrial DNA in several organs taken at autopsy from a CPEO patient with severe multisystem disease. We discuss the relationship of CPEO to several other clinical phenotypes associated with mitochondrial dysfunction, and discuss the possible implications of heteroplasmy for the development of variable phenotypes.

Child↗
PubMed1990

Optic nerve sheath distention in Leber's optic neuropathy and the significance of the "Wallace mutation".

We recently encountered a 27-year-old man who presented an atypical clinical picture of Leber's hereditary optic neuropathy: His family history was negative, visual loss continued steadily for over 8 months, circumpapillary microangiopathy was equivocal, the optic discs showed large physiologic cups, and both optic nerve sheaths were notably distended with increased subarachnoid fluid. The latter was confirmed by ultrasonography, computed tomography, and magnetic resonance imaging. The patient's asymptomatic brother also showed unimpressive circumpapillary microangiopathy in the fundi. The asymptomatic mother from France was then seen, and she showed classic circumpapillary microangiopathy in the fundi. Studies of mitochondrial DNA showed the classic point mutation at position 11778 as reported by Wallace in all three family members. Another patient previously seen with classic Leber's hereditary optic neuropathy recently had mitochondrial DNA studies along with three other affected family members and five unaffected family members in the maternal lineage. All nine of these individuals were completely normal at the Wallace locus. In fact, sequencing of the entire ND-4 gene from one affected individual revealed it to be perfectly normal at the amino acid level. The importance of obtaining quantitative ultrasonography and the 30 degrees test, and studying mitochondrial DNA in patients suspected of having Leber's optic nerve disease is emphasized.

Adult↗
PubMed1989

Preferential amplification and molecular characterization of junction sequences of a pathogenetic deletion in human mitochondrial DNA.

Deletions of mitochondrial DNA have been detected in skeletal muscle of some patients with mitochondrial encephalomyopathies, but their junctions have been defined only approximately. We developed a procedure, using widely spaced primers for the polymerase chain reaction, that amplifies preferentially the sequences bracketing the deletion. This procedure permits detection of minor proportions, not detectable by Southern analysis, of deleted mitochondrial DNA species in a heteroplasmic mixture. Different proportions of intact mitochondrial DNA and species deleted from nucleotide 8708 to 13,722 were found in skeletal muscle, blood, and urinary epithelial cells from a patient with chronic progressive external ophthalmoplegia. These data indicate that the mutation occurred at or before early embryonic development and provide the first definition at the nucleotide level of a human disease caused by a deletion of mitochondrial DNA.

Adenosine Triphosphatases↗
PubMed1989

Directly repeated sequences associated with pathogenic mitochondrial DNA deletions.

We determined the nucleotide sequences of junctional regions associated with large deletions of mitochondrial DNA found in four unrelated individuals with a phenotype of chronic progressive external ophthalmoplegia. In each patient, the deletion breakpoint occurred within a directly repeated sequence of 13-18 base pairs, present in different regions of the normal mitochondrial genome-separated by 4.5-7.7 kilobases. In two patients, the deletions were identical. When all four repeated sequences are compared, a consensus sequence of 11 nucleotides emerges, similar to putative recombination signals, suggesting the involvement of a recombinational event. Partially deleted and normal mitochondrial DNAs were found in all tissues examined, but in very different proportions, indicating that these mutations originated before the primary cell layers diverged.

Base Sequence↗
PubMed1989

Dystrophin analysis in clonal myoblasts derived from a Duchenne muscular dystrophy carrier.

Clonal myogenic cell cultures were established from a potential heterozygote for a mutant Duchenne muscular dystrophy (DMD) gene who was also heterozygous for isozymes of the X-linked enzyme glucose-6-phosphate dehydrogenase. Previous tissue culture studies of this muscle donor demonstrated equal proliferative capacity of myoblasts that had lyonized either the paternal or maternal X-chromosome, indicating that mutation of the DMD gene does not affect growth of myoblasts. If this muscle donor were a gonadal mosaic, this conclusion would be incorrect. In the present study, only those myogenic colonies expressing the glucose-6-phosphate dehydrogenase-A isozyme were found to express dystrophin, indicating that this woman was indeed a heterozygote for DMD. By documenting dystrophin deficiency in a specific population of myogenic cells from this woman, we verify our previous conclusion regarding the normal proliferative capacity of DMD myoblasts. Somatic cell testing of dystrophin expression may offer an alternative to established genetic carrier tests for those women in whom deletions of the DMD are not detectable, whose pedigree structure does not permit linkage analysis, or in whom standard phenotypic analyses are ambiguous.

Blotting, Western↗
PubMed1987

Spinal cord compression due to ethmoid adenocarcinoma.

Adenocarcinoma of the ethmoid sinus is a rare tumor which has been epidemiologically linked to woodworking in the furniture industry. It has a low propensity to metastasize and has not been previously reported to cause spinal cord compression. A symptomatic epidural spinal cord compression was confirmed on magnetic resonance imaging (MRI) scan in a former furniture worker with widely disseminated metastases. The clinical features of ethmoid sinus adenocarcinoma and neoplastic spinal cord compression, and the comparative value of MRI scanning in the neuroradiologic diagnosis of spinal cord compression are reviewed.

Adenocarcinoma↗
PubMed1987

Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus.

Within the past 18 months, we have seen four cases of neurosyphilis at our institution (two of meningovascular syphilis, one of acute syphilitic meningitis, and one of asymptomatic neurosyphilis) in young homosexual men with serologic evidence of exposure to human immunodeficiency virus (HIV). Two of the four patients had neurosyphilis despite previous adequate therapy for early syphilis with benzathine penicillin. Meningovascular syphilis developed in one patient within four months after a primary infection, in a manner consistent with an accelerated course of syphilitic infection. These findings suggest the possibility that HIV infection may alter the natural course of syphilis because of the profound defects in cell-mediated immunity it causes. The possible potentiating effects of HIV on Treponema pallidum infection suggest the need for lumbar puncture in the evaluation of HIV-seropositive patients with syphilis, as well as modifications of the currently recommended treatment regimens for primary, secondary, and latent syphilis and neurosyphilis in this patient population. Neurosyphilis should probably be added to the growing list of infectious complications of the acquired immunodeficiency syndrome (AIDS) and may be the first such complication to appear.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Pure motor hemiplegia due to meningovascular neurosyphilis.

Two young male homosexuals developed prodromal syndrome followed by penicillin-responsive meningitis and the acute onset of pure motor hemiplegia. The clinical and laboratory features are consistent with meningovascular neurosyphilis. Basis pontis infarctions were subsequently demonstrated on magnetic resonance imaging scans. To our knowledge, this is the first description of syphilitic arteritis as a pathophysiologic basis for pure motor hemiplegia.

Adult↗
PubMed1987

Rapid response to acyclovir in herpes zoster-associated encephalitis.

A previously healthy patient became acutely encephalopathic, with complete disorientation and amnesia, several days after the onset of thoracic herpes zoster. She had transiently abnormal electroencephalographic results, abnormalities on radionuclide brain scanning, and cerebrospinal fluid pleocytosis. There was no evidence of a toxic/metabolic encephalopathy except for a mildly elevated ammonia level. Intravenously administered acyclovir (30 mg/kg per day) induced a dramatic response, with complete resolution of the encephalopathy within 72 hours and normalization of the electroencephalographic results. The scant clinical experience with the successful use of acyclovir in the treatment of herpes zoster-associated encephalitis is reviewed.

Acyclovir↗
PubMed1987

Spontaneous arteriovenous fistula of the superficial temporal artery.

A case of a nontraumatic arteriovenous fistula of the superficial temporal artery, documented on selective external carotid arteriography, is described in a 42-year-old man who was successfully treated by complete surgical excision. The clinical features, differential diagnosis, and treatment of arteriovenous fistulas of the superficial temporal artery are reviewed.

Adult↗
PubMed1986

Benign sexual headache within a family.

The occurrence of the vascular type of benign sexual headache (BSH) is described within members of a family. The most severely affected of the four sisters was successfully treated with propranolol hydrochloride prophylaxis. The literature on headache related to sexual activity is reviewed and the clinical features of BSH are formulated. The familial occurrence is put forth as further evidence to consider the vascular type of BSH as a migraine variant.

Adolescent↗