PubMed Health⌕ Search

Biomedical subjects

Y Harati

Publications and source records attributed to Y Harati.

At least 37 records · Page 2Linked to original sources
PubMed1994

Muscle mitochondrial ATP production in progressive supranuclear palsy.

Six patients with progressive supranuclear palsy (PSP) and 12 age-matched disease-free subjects participated in this study designed to compare rates of ATP production by intact mitochondria from biopsied skeletal muscle. When pyruvate and malate were used as metabolic substrates, rates of ATP production were 0.184 +/- 0.025 mumol/min/U of citrate synthase (CS) activity (a mitochondrial marker) in control subjects and 0.131 +/- 0.051 mumol/min/U of CS in PSP patients. In the presence of succinate, rates of ATP formation were 0.137 +/- 0.02 mumol/min/U of CS in controls and 0.109 +/- 0.04 mumol/min/U of CS in patients. With N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and ascorbate, rates were 0.034 +/- 0.008 mumol/min/U of CS in controls and 0.022 +/- 0.01 mumol/min/U of CS in PSP subjects. Differences between the control and PSP populations reached statistical significance with pyruvate/malate and TMPD/ascorbate. No differences in either muscle histopathology or histochemistry were found between patient and control subjects. Results of this study suggest that oxidative phosphorylation defects occur in muscle mitochondria from patients with PSP.

Adenosine Triphosphate↗
PubMed1993

Chronic immune activation in the eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a multisystem illness of uncertain pathogenesis that occurred in an epidemic related to the ingestion of contaminated L-tryptophan. To investigate the role of immune dysfunction in EMS we prospectively measured a serologic index of T-cell activation, the soluble interleukin-2 receptor (sIL-2R), in 7 patients followed into the late stages of the illness. As a group, EMS patients had significantly elevated sIL-2R levels throughout the study. Five patients suffered chronic symptoms of myalgia, arthralgia, muscle cramps, fatigue, or subjective memory impairment and all had persistently elevated sIL-2R levels. Two patients had near-resolution of EMS and normal sIL-2R levels. We conclude that chronic symptoms are common in EMS and are associated with persistent T-cell activation as measured by serum sIL-2R levels. These findings suggest that immunosuppressive treatment may be beneficial in EMS.

Adult↗
PubMed1993

Somatic instability of CTG repeat in myotonic dystrophy.

An unstable expansion of the CTG repeat in the 3' untranslated region of the myotonin protein kinase (MT-PK) gene is the mutation specific for myotonic dystrophy (DM). To examine somatic stability of the repeat, we studied tissue variability of the repeat size. In five DM patients, the restriction fragment containing the repeat region was substantially larger in skeletal muscle than in peripheral blood leukocytes (PBL). In addition, one normal subject showed a size discrepancy in one of the normal alleles by one repeat on the polymerase chain reaction analysis. In most DM patients, the repeat size of native PBL differed from the transformed lymphoblastoid cells after passages. In contrast, various tissues from a congenital DM patient showed a similar size of the expanded repeat, including the transformed lymphoblastoid cells. We conclude that somatic instability of the CTG repeat may cause substantial tissue variability of the CTG repeat size in adult-onset DM, providing a potential mechanism for the variable pleiotropism.

Alleles↗
PubMed1992

Tryptophan metabolism via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome.

OBJECTIVE: To investigate the metabolism of L-tryptophan (LT) via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome (EMS). METHODS: Measurement of LT, L-kynurenine, and quinolinic acid in plasma and cerebrospinal fluid (CSF) from subjects with EMS, from asymptomatic users of LT, and from normal subjects. RESULTS: Plasma LT concentrations were lower in untreated EMS patients (n = 5) than in corticosteroid-treated EMS patients (n = 5; P less than 0.05) and in asymptomatic users of LT (n = 5; P less than 0.05). Untreated EMS patients, who had discontinued LT weeks to months prior to study, had significantly higher plasma levels of L-kynurenine and quinolinic acid than did corticosteroid-treated EMS patients (P less than 0.05), normal subjects (P less than 0.02), and asymptomatic users of LT (P less than 0.05). EMS patients also had significantly elevated levels of L-kynurenine (P less than 0.05) and quinolinic acid (P less than 0.001) in CSF compared with normal subjects. After a 1-gm oral dose of LT, untreated EMS patients (n = 4) showed lower peak levels of LT and accentuated synthesis of L-kynurenine and quinolinic acid, compared with these values in corticosteroid-treated EMS patients (n = 2), who responded like normal subjects (n = 5). CONCLUSION: These data demonstrate that during the active phase of EMS, LT metabolism via the kynurenine pathway was accentuated, probably secondary to induction of the enzyme indoleamine-2,3-dioxygenase. Ingestion of large amounts of LT (median daily dose 1.5 gm) resulted in high concentrations of kynurenine-pathway metabolites in blood and extrahepatic tissues, which was accentuated in EMS patients and which may have played a significant role in the pathogenesis of the disease.

Adrenal Cortex Hormones↗
PubMed1992

Decreased polyphosphoinositide metabolism accompanies myelinated fiber loss in human peripheral neuropathies.

The distribution of incorporated 32P in phospholipids of sural nerve biopsy samples from patients with several peripheral neuropathies was measured. Both the absolute amount and the proportion of isotope in polyphosphoinositides was decreased in nerves that displayed substantial (> 50%) depletion of myelinated fibers as compared to nerves that exhibited minimal depletion. The results suggest that diminished metabolism of these substances is an indicator of myelin loss, and are consistent with the conclusion that polyphosphoinositide turnover in human nerve is nearly entirely localized to the myelin sheath.

Adult↗
PubMed1992

Clinical features of Todd's post-epileptic paralysis.

Two hundred and twenty nine patients with generalised tonic-clonic seizures were prospectively evaluated. Fourteen were identified who had transient focal neurological deficits thought to be Todd's post-epileptic paralysis (PEP). Eight of these 14 patients had underlying focal brain lesions associated with the postictal deficits. All patients with PEP were weak, but there was wide variation in the pattern (any combination of face, arm, leg), severity (plegia to mild), tone (spastic, flaccid, or normal), and reflexes (increased, decreased, or normal). Significant sensory loss occurred in only one patient. The only other signs of PEP were aphasia (in five patients all with underlying lesions) and gaze palsy (in four patients). Post-epileptic paralysis persisted from half an hour to 36 hours (mean of 15 hours). Post-epileptic paralysis may occur with the first seizure or after many years of seizures and does not appear after every seizure. The clinical features of PEP are thus heterogeneous.

Electroencephalography↗
PubMed1989

Effects of cyclosporine therapy on plasma lipoprotein levels.

Accelerated atherosclerosis is a leading cause of death in long-term survivors of heart and renal transplantation and may be exacerbated by the frequent occurrence of posttransplant hyperlipidemia. Attempts to define the mechanism for hyperlipidemia in transplant recipients are confounded by dramatic changes in metabolism and nutritional status after transplantation, as well as by treatment with multiple immunosuppressive and antihypertensive drugs. To avoid these pitfalls and to determine if cyclosporine alone adversely affects lipid levels, we measured lipoprotein levels in a prospective, double-blind, randomized, placebo-controlled trial of cyclosporine in 36 men with amyotrophic lateral sclerosis. Plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein B levels were measured at baseline, 2 weeks, 1 month, and 2 months. Significant increases of 21% in total cholesterol, 31% in low-density lipoprotein cholesterol, and 12% in apolipoprotein B levels occurred only in the cyclosporine group. Cyclosporine therapy alone adversely affects plasma lipoprotein levels by increasing total cholesterol levels, primarily due to an increase in low-density lipoprotein cholesterol level.

Adult↗
PubMed1989

Muscle pain associated with tubular aggregates and structures resembling cylindrical spirals.

A 42-year-old man complained of muscle pain in the legs and episodes of left-sided limb weakness. Light microscopy of his quadriceps muscle showed abundant subsarcolemmal accumulations with typical histochemical features for tubular aggregates. Electron microscopy showed areas filled with tubular aggregates and vesicular profiles. Scattered within some of the tubular aggregates circular profiles reminiscent of cylindrical spirals were seen. The presence of structures resembling cylindrical spirals within tubular aggregates suggest that they may arise from a component of the sarcoplasmic reticulum. There appears to be an intimate relationship between myalgia and these various types of abnormal membranous profiles; however, the pathophysiology remains to be elucidated.

Adult↗
PubMed1988

A double-blind study of the effectiveness of cyclosporine in amyotrophic lateral sclerosis.

In a double-blind placebo-controlled trial of cyclosporine in amyotrophic lateral sclerosis, no differences were observed in the monthly rate of progression or the relative risk of progression in comparing 38 patients randomized to the placebo group and 36 patients randomized to the cyclosporine group. In comparing three subgroups of patients, cyclosporine appeared to benefit men who entered the study within 18 months of the onset of first symptoms, whereas it was of no value to women or to men who entered later than 18 months. For the men with recent onset of disease, the relative risk of progression was 0.403; the monthly rate of progression was 5.2 +/- 1.1 points with placebo and 3.5 +/- 0.7 points with cyclosporine. These provocative results support the need for a full study of cyclosporine in men with recent onset of disease.

Amyotrophic Lateral Sclerosis↗
PubMed1988

Sympathetic skin response in diabetic peripheral neuropathy.

There were 72 diabetic patients with clinical evidence of sensorimotor peripheral neuropathy investigated to determine the sensitivity of the sympathetic skin response test (SSR) for detection of sudomotor dysfunction and its correlation with other autonomic function tests, autonomic symptoms, and degree of peripheral neuropathy. Nerve conduction velocities (NCV) were abnormal in all patients, SSR was absent in 60 of 72 patients (83%), Valsalva test was abnormal in 32 of 67 patients (48%) who had the test, and 6 of 72 (9%) had orthostatic hypotension. Statistically significant correlation was found between the Valsalva test abnormality, the degree of peripheral neuropathy, and the SSR in our patients. All patients with orthostatic hypotension had an absent SSR and an abnormal Valsalva test. Most patients had one or more autonomic signs or symptoms. Orthostatic dizziness only correlated with SSR, however. These results suggest that sudomotor activity detected by sympathetic skin response is a valuable test for investigation of dysautonomia in diabetic peripheral neuropathy.

Adult↗
PubMed1987

Diabetic peripheral neuropathies.

Diabetic peripheral neuropathies are a group of heterogeneous syndromes with considerable morbidity. At least 50% of diabetic patients develop one or several of these neuropathies within 25 years after the diagnosis. In recent years several pathogenetic mechanisms have been proposed, with the newest findings suggesting a link between several of these hypotheses. The hypoxic hypothesis has revived the role of vascular factors in the pathogenesis of diabetic peripheral neuropathies. Although the exact role of hyperglycemia in the development of peripheral neuropathy is not known, the balance of evidence indicates that attainment and maintenance of normal blood glucose remains the cornerstone of treatment of diabetes and diabetic neuropathies. There is no convincing evidence that any of the treatments devised to correct the metabolic derangements in nerve are of sufficient value or safety to be recommended for routine use.

Aldehyde Reductase↗
PubMed1986

Immunosuppressive drug therapy in myasthenia gravis.

We reviewed the records of 37 patients with myasthenia gravis treated with azathioprine (n = 10) or cyclophosphamide (n = 27). All patients had received prednisone and anticholinesterase therapy, and most had undergone thymectomy prior to immunosuppressive therapy. Thirty patients (81%) responded to treatment. Both azathioprine and cyclophosphamide were found to be effective in the treatment of myasthenia gravis. The degree of improvement was more pronounced in patients with thymoma.

Adolescent↗
PubMed1986

Diabetic autonomic neuropathy.

The incidence of autonomic dysfunction as a complication of diabetes mellitus is reported to be as high as 20% to 40%. Symptoms of diabetic autonomic neuropathy (DAN) are often vague, and signs difficult to detect on routine physical examination. The early diagnosis of DAN is possible by utilizing several simple noninvasive tests, which may also be helpful in localizing the lesion(s) to specific autonomic pathways. DAN may affect multiple organ systems, to include cardiovascular, gastrointestinal, genitourinary and/or neuroendocrine, and may, in fact, be life-threatening. The same metabolic disturbances of somatic peripheral nerve may also be responsible for DAN. Like somatosensory neuropathy, definitive therapy for DAN is not yet satisfactory, although multiple chemotherapeutic agents have been tried and warrant further investigation.

Autonomic Nervous System Diseases↗
PubMed1986

The clinical spectrum of inflammatory-angiopathic neuropathy.

Thirty-three patients with inflammatory-angiopathic neuropathy diagnosed by sural nerve biopsy, were investigated to determine the underlying disease. Twenty-six patients had symmetrical sensorimotor polyneuropathy and seven had mononeuropathy multiplex. An aetiology for inflammatory-angiopathic neuropathy was found in only eight patients: typical collagen vascular disease in five and malignant tumour in three. Sixteen patients received prednisone and/or immunosuppressive drug therapy and 12 (75%) responded to treatment. This study demonstrates that typical collagen vascular diseases are not the most common cause of inflammatory-angiopathic neuropathy, that symmetrical polyneuropathy is seen in 75.8% of inflammatory-angiopathic neuropathy patients. Prednisone and/or immunosuppressive agents appear effective regardless of aetiology.

Adolescent↗