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Biomedical subjects

J Halperin

Publications and source records attributed to J Halperin.

At least 19 recordsLinked to original sources
PubMed2000

Molecular basis for a link between complement and the vascular complications of diabetes.

Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes.

Amino Acid Sequence↗
PubMed2000

Bimodal breathing in the estuarine crab Chasmagnathus granulatus Dana 1851--physiological and morphological studies.

Chasmagnathus granulatus is an estuarine crab which actively moves from subtidal to supratidal areas. To elucidate the possible existence of extrabranchial sites for aerial gas exchange, we measured respiratory and acid-base variables in animals with and without branchial water (controls and experimental crabs, respectively) during air exposure. An histological study of the branchiostegite was also performed. Throughout 4 h of emergence C. granulatus did not suffer venous hypoxia, even without branchial water. The rate of oxygen uptake (M(O(2))) was similar in both groups. The rate of carbon dioxide excretion (M(CO(2))) and the gas exchange ratio (R) significantly decreased during emergence in both groups, with R significantly lower for experimental crabs. Consequently, CO(2) was accumulated in the hemolymph. This variable stabilized after 90 min in control animals, but experimental crabs continued accumulating CO(2). Histological study of the branchiostegites demonstrated the presence of an attenuated and greatly perfused epithelium facing the branchial chamber lumen, with a shortest diffusion distance of 0.5 microm. Simple folds and lobulated projections increase the respiratory surface area. These results suggest that C. granulatus is a bimodal breathing crab, active both in water and air. When emerged, this species extract oxygen directly from air through branchiostegal lungs, but relies on branchial exchange to eliminate carbon dioxide.

Animals↗
PubMed1999

Warfarin safety and efficacy in patients with thoracic aortic plaque and atrial fibrillation. SPAF TEE Investigators. Stroke Prevention and Atrial Fibrillation. Transesophageal echocardiography.

Patients with atrial fibrillation and with documented aortic plaque who were assigned to adjusted-dose warfarin therapy (international normalized ratio 2.0 to 3.0) had an annual rate of cholesterol embolization of 0.7% (95% confidence interval [CI] 0.1% to 5.3%/patient-year). Warfarin-assigned patients with plaque had a lower rate of embolic events (5.9%/year; 95% CI 3.0 to 12) than those on combination low-dose warfarin (international normalized ratio <1.5) plus aspirin (17.3%/year; 95% CI 11 to 27; p = 0.01).

Aged↗
PubMed1998

Neuropsychological testing in adult attention deficit hyperactivity disorder: a pilot study.

Diagnosing adult ADHD is frequently problematic because behavioral information from the patient's childhood, and multiple informants who can delineate the patient's current behavior, are often unavailable. This preliminary study was designed to explore whether objective neuropsychological testing may be a useful adjunct in the diagnosis of adult ADHD. Nineteen adults diagnosed with ADHD according to DSM-IV criteria, along with 10 controls, were assessed using a neuropsychological battery which comprised tests assessing linguistic, visual-spatial perceptual, academic, attentional and inhibitory control, mnestic and executive functions. Following preliminary analyses, designed to determine which variables best discriminated the groups, receiver operating characteristic (ROC) curves were constructed to determine the sensitivity and specificity of the best measures both alone and in combination. Only three measures significantly (p < 0.01) distinguished the groups; Digits Backwards from the WAIS-R and two reaction time measures from a computerized task modeled after Luria's Competing Motor Programs. ROC curve analyses indicated that in combination these measures had greater than 90% accuracy for classifying ADHD and non-ADHD patients. While further research is necessary these preliminary findings suggest that neuropsychological testing may be a useful adjunct in the differential diagnosis of adult ADHD.

Adolescent↗
PubMed1994

Congenital Horner's syndrome does not alter Lisch nodule formation.

A 21-year-old woman with neurofibromatosis type 1 (NF-1) had a unilateral congenital Horner's syndrome with resultant hypopigmentation of the affected iris. Lisch nodules, which are melanocytic hamartomas, were similar in number, size, and pigmentation in both eyes. The present findings suggest that the formation of Lisch nodules is not influenced by the presence or absence of sympathetic innervation of the iris.

Adult↗
PubMed1991

Mesenteric blood flow in patients with diabetic neuropathy.

We examined flow velocities in the superior mesenteric artery and celiac artery in normal controls (group C, n = 11), diabetic patients (group D, n = 8), and diabetic patients with clinically evident autonomic neuropathy (group DN, n = 6) to further define the usefulness of duplex examination in the evaluation of the mesenteric circulation in normal and disease states. By use of a 3 MHz duplex scanner, peak systolic velocity, peak diastolic forward velocity, end-diastolic forward velocity, and peak diastolic reverse velocity were measured in centimeters per second before and after a standardized meal. The vessels' diameters in centimeters were also measured. After the meal peak diastolic reverse velocity disappeared in all patients. The average vessel diameter in the superior mesenteric artery (0.7 cm) and celiac artery (0.8 cm) did not change. Flow velocities in the celiac artery were not significantly altered by the meal. In the control group, peak systolic velocity in the superior mesenteric artery increased 38%, peak diastolic forward velocity rose 66%, and end-diastolic forward velocity increased by 70%. In the diabetic nonneuropathic group the changes were 15%, 98%, and 100%, respectively. These changes were statistically significant (p less than 0.01). On the other hand, the patients with diabetic autonomic neuropathy presenting a picture of gastroparesis did not exhibit the expected increases in postprandial velocities. Moreover, this alteration in blood flow velocity, although similar to that encountered in patients with intestinal angina, did not appear to be due to occlusive arterial disease on the basis of clinical examination and B-mode scanning.

Autonomic Nervous System Diseases↗
PubMed1990

Lyme neuroborreliosis. Peripheral nervous system manifestations.

An ever increasing number of apparently unrelated peripheral nervous system (PNS) disorders has been associated with Lyme borreliosis. To ascertain their relative frequency and significance, we studied prospectively 74 consecutive patients with late Lyme disease, with and without PNS symptoms: 53% had intermittent limb paraesthesiae, 25% the carpal tunnel syndrome, 8% painful radiculopathy, and 3% Bell's palsy; 39% had disseminated neurophysiological abnormalities. To assess the interrelationships among these syndromes, we reviewed the neurophysiological findings in all 163 such patients that we have studied to date. Reversible abnormalities of distal conduction were the most common finding. Demyelinating neuropathy was extremely rare. The pattern of abnormality was similar in all patient groups, regardless of whether the symptoms suggested radiculopathy, Bell's palsy, or neuropathy. We conclude that (1) reversible PNS abnormalities occur in one-third of our patients with late Lyme borreliosis, and (2) the pattern of electrophysiological abnormalities is the same in all and is indicative of widespread axonal damage, suggesting that these different presentations reflect varying manifestations of the same pathological process.

Adolescent↗
PubMed1988

Noninvasive evaluation of the extracranial carotid arteries in patients with cerebrovascular events and atrial fibrillations.

Noninvasive carotid artery testing was performed in 73 patients with nonvalvular atrial fibrillation who were referred because of symptoms or signs of cerebrovascular disease. Thromboembolism related to atrial fibrillation without valvular heart disease was the probable source of cerebral ischemia in 25 (80%) of 31 patients with stroke and coexisting atherosclerotic disease at the carotid artery bifurcation in six (20%). Nonvalvular atrial fibrillation was the probable source of symptoms in nine (70%) of 13 of patients with transient cerebral ischemia, while coexisting carotid artery disease was present in four (30%). Nonvalvular atrial fibrillation accounted for the symptoms in four of five patients with amaurosis fugax, with atherosclerotic carotid artery disease present in one. The remaining 24 patients had nonhemispheric symptoms of cerebrovascular disease, including vertebrobasilar insufficiency, dizziness, and syncope, and only one had a carotid lesion. A significantly higher proportion of patients with focal hemispheric symptoms had coexisting carotid disease than patients with nonfocal symptoms had, suggesting that atherosclerotic cerebrovascular disease contributes to stroke in patients with nonvalvular atrial fibrillation. Noninvasive carotid artery testing may be helpful in identifying atherosclerotic lesions at the carotid artery bifurcation in patients with atrial fibrillation and cerebrovascular disease, because different therapeutic modalities may be appropriate when two potential sources of cerebral ischemia are present.

Atrial Fibrillation↗
PubMed1984

Acute effects of oral labetalol on myocardial conduction after coronary artery bypass grafting.

Cardiac electrophysiologic effects of a single oral dose of labetalol were determined in seven patients 4 to 9 days after a coronary artery bypass graft. Surface ECG and bipolar electrograms recorded from temporary pacing wires affixed to the normal right ventricle and abnormal left ventricle at the time of surgery were used to determine conduction intervals. Electrophysiologic parameters were recorded during fixed-rate atrial pacing. Sinus heart rate and blood pressure were monitored. Three patients received 100 mg and four patients received 200 mg labetalol. The drug had no significant effect on intraventricular conduction intervals or QRS duration. It did not significantly influence sinus heart rate or AV conduction time, but in two patients there was prolongation in AV conduction that may have been drug-induced. Labetalol induced a modest but significant decrease in systolic and diastolic blood pressure. In another study propranolol, unlike labetalol, had prolonged AV and intraventricular conduction in the abnormal left ventricle, but not in the normal right ventricle. The absence of these effects with labetalol may reflect lesser local anesthetic effect on intraventricular conduction and an alpha-adrenergic blocking effect that interferes with beta-blockade-induced prolongation of AV conduction.

Administration, Oral↗
PubMed1983

Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin.

Fatal infantile mitochondrial myopathy with lactic acidosis, morphologically abnormal mitochondria, deficient cytochromes aa3 and b, and a Fanconi-like aminoaciduria has been described. We report two infants, second cousins, with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in one child and to liver in the other. The first child at 3 months of age had weight loss, hypotonia, external ophthalmoplegia, and a severe lactic acidosis with a high lactate/pyruvate ratio. Electron microscopy of muscle showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae. In skeletal muscle mitochondria, cytochromes aa3 and b were not detectable but cytochrome cc was found to be normal by spectroscopy. Cytochrome c oxidase activity was less than 1% of normal. Mitochondria from kidney, liver, heart, lung, and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. The second cousin at 5 months of age had weight loss and hepatomegaly but no systemic lactic acidosis. Liver biopsy showed hepatocytes packed with enlarged mitochondria. The liver mitochondria showed deficient cytochromes aa3 and b postmortem, and cytochrome c oxidase activity was less than 10% of normal. Kidney mitochondria had normal cytochromes. Muscles was not studied. The mitochondrial abnormality in the two cousins presumably is related. Unexplained are the mode of genetic transmission or environmental exposure and the apparent involvement of a single different organ in each child.

Acidosis↗
PubMed1981

Cranial computed tomography in Whipple's disease.

Cranial computed tomography (CT) in a 58-year-old man disclosed enhancing lesions in the medial right temporal lobe and the right pons. Biopsy of the sural nerve was positive for Whipple's disease, and one of the temporal lobe lesions showed unprecedented histological findings. This case, to our knowledge, is unique in its demonstration of cranial CT findings in association with Whipple's disease. It is suggested that a cranial CT scan with the use of intravenous contrast material should be performed in patients presenting with the signs or symptoms of Whipple's disease.

Biopsy, Needle↗
PubMed1975

Effect of cephalic glucose infusion on insulin secretion.

The continuous infusion of glucose (1 mg/kg/min) via the carotid artery in anesthetized dogs produces a biphasic pattern of insulin secretion. The first peak reaches a maximum 3 min after glucose infusion and drops to basal level at 7 min. As long as the glucose infusion persists a slow and mantained increase in insulin level in the pancreaticoduodenal vein can be observed. The same amount of glucose infused in the general circulation via the jugular vein provoked a different pattern of insulin secretion. Cerebral glucose infusion to vagotomized dogs also produced a two phase response to insulin secretion, but the levels reached in the first phase were lower that those observed in the normal dogs. The infusion of glucose, via the jugular vein, in vagotomized dogs, failed to induce any change in plasma insulin levels. Our data suggest that a glucose load to the brain induces pancreatic insulin secretion mediated partially by the vagus nerves. These results are also compatible with the hypothesis that a humoral factor could be involved in the pancreatic response.

Animals↗