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Biomedical subjects

Z Farfel

Publications and source records attributed to Z Farfel.

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

Bordetella pertussis adenylate cyclase toxin: intoxication of host cells by bacterial invasion.

Bordetella pertussis produces extracytoplasmic adenylate cyclase toxin (AC toxin) which penetrates target cells and, upon activation by host calmodulin, generates high levels of intracellular cyclic AMP (cAMP). As a result, bactericidal functions of immune effector cells are impaired. Since a considerable amount of AC toxin is associated with the bacterium, it was proposed that the toxin may be delivered by direct interaction of the organism with the target cells (E. L. Hewlett, M. C. Gray, and R. D. Pearson, Clin. Res. 35:477A, 1987). Incubation of CHO cells with intact B. pertussis led to formation of intracellular cAMP at levels comparable to those produced in CHO cells by equivalent activities of isolated AC toxin. cAMP accumulation induced by the whole bacteria appeared after a lag of 40 to 60 min and reached high levels within 2 to 3 h, whereas adherence of the bacteria proceeded rapidly and reached a maximal level within 80 min. Sera of pertussis patients completely blocked cAMP accumulation induced by the whole bacteria without having a major effect on either bacterial adherence or cAMP production by the AC toxin. Cytochalasins B and D, inhibitors of bacterial invasion, abrogated the cAMP response to the whole bacteria but not the response to the AC toxin. These agents did not affect bacterial adherence. Transmission electron micrographs revealed that B. pertussis, within the time course of cAMP induction, invaded CHO cells. We suggest that cAMP induction by B. pertussis is caused by the entry of the whole bacteria into CHO cells rather than by delivery of AC toxin during bacterial adherence. This route of cell intoxication may be relevant to the pathogenesis of whooping cough.

Adenylate Cyclase Toxin↗
PubMed1990

Spurious hypoglycemia, hyperkalemia and hypoxemia in chronic hemolytic anemia.

Spurious hypoglycemia and hyperkalemia were found in a patient with chronic hemolytic anemia due to an unidentified hemoglobinopathy. The patient had massive reticulocytosis, and many nucleated red blood cells were present in his blood smear. Hypoxemia was induced in vitro. No correlation was found between in vitro hypoglycemia and hyperkalemia. Reticulocytosis and the presence of nucleated red blood cells, as occurs in hemolytic anemia, should be added to the list of hematological causes of spurious hypoglycemia, hyperkalemia and hypoxemia.

Adult↗
PubMed1989

Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis.

STUDY OBJECTIVE: To determine whether a single-dose of thiazide administered to patients with previous thiazide-induced hyponatremia will cause hyponatremia and, if so, to analyze its pathogenesis. DESIGN: Prospective controlled study comparing patients with previous thiazide-induced hyponatremia with two control groups. PATIENTS AND CONTROLS: Eleven patients with thiazide-induced (Kaluril [hydrochlorothiazide, 50 mg; amiloride, 5 mg]) hyponatremia of less than 130 mmol/L at least 1 week before the study. Two groups of controls: 10 young healthy volunteers and 11 elderly hypertensive patients previously treated uneventfully with thiazide. INTERVENTIONS: Administration of a single dose of hydrochlorothiazide, 50 mg, and amiloride, 5 mg. MEASUREMENTS: Blood pressure, pulse rate, body weight, serum urea, creatinine, sodium, potassium, magnesium, osmolality, plasma antidiuretic hormone, renin, aldosterone and also urinary sodium, potassium, osmolality, and cyclic adenosine monophosphate (cAMP) before and 6 to 8, 12, and 24 hours after drug administration. RESULTS: Within 6 to 8 hours serum sodium decreased in patients, young controls, and elderly controls by 5.5 +/- 1.1 (mean +/- SE), 1.2 +/- 0.4, and 1.8 +/- 0.9 mmol/L, respectively (Py less than 0.001 [patients versus young controls], Pe = 0.017 [patients versus elderly controls]). Serum osmolality decreased in patients, young controls, and elderly controls by 14.9 +/- 2.6, 2.8 +/- 1.6, and 6.6 +/- 1.5 mmol/kg, respectively (Py less than 0.001, Pe = 0.012). All patients and only one control subject reached osmolality of less than 280 mmol/kg. At 6 to 8 hours all patients gained weight (0.85 +/- 0.13 kg) whereas young and elderly controls lost weight (0.47 +/- 0.23 and 0.45 +/- 0.2 kg, respectively) (Py much less than 0.001, Pe much less than 0.001). Patients' responses to the drug did not differ from both control groups regarding sodium and potassium urinary excretion, osmolar and free water clearance, and antidiuretic hormone blood levels. Water restriction in one patient attenuated serum sodium reduction. CONCLUSIONS: Use of a single-dose of a thiazide diuretic may predict the development of hyponatremia. Increased body weight apparently due to polydipsia may play a major role in the pathogenesis of thiazide-induced hyponatremia.

Adult↗
PubMed1989

High incidence of primary cerebral lymphoma in tumor-induced central neurogenic hyperventilation.

An awake patient presented with central neurogenic hyperventilation induced by a cerebral tumor. Corticosteroid therapy and brain irradiation while the patient was anesthetized and respiration controlled under pancuronium-induced respiratory paralysis were followed by tumor regression and resolution of hyperventilation. Recurrence of tumor 6 weeks later was not accompanied by recurrence of hyperventilation. Cytologic study of cerebrospinal fluid revealed B-cell lymphoma. This patient brings to 10 the number of cases recorded with tumor-induced central neurogenic hyperventilation. Five of the eight patients with known tumor histology had a primary cerebral lymphoma, a rare neoplasm that comprises only 1% of all intracranial neoplasms. The disproportionately high frequency of central neurogenic hyperventilation in patients with cerebral lymphoma has therapeutic implications that are briefly reviewed.

Adrenal Cortex Hormones↗
PubMed1989

[AIDS dementia].

Explore the source record for details and available documents.

AIDS Dementia Complex↗
PubMed1988

Bordetella pertussis adenylate cyclase. Identification of multiple forms of the enzyme by antibodies.

Two forms of Bordetella pertussis adenylate cyclase of 200 and 47 kDa have been purified from dialyzed urea extract of the bacteria to specific activities of 466 and 1685 mumol.min-1.mg-1, respectively. Both forms are activated 50-200-fold by calmodulin. The half-maximum concentration required for the activation of the 200-kDa catalyst is 5.4.10(-9) M, whereas the one required for activation of the 47-kDa catalyst is 1.8.10(-10) M. Polyclonal antibodies raised against the 47-kDa catalyst specifically recognize both forms of the enzyme in purified state as well as in bacterial extracts on immunoblots. The antibody inhibits at similar titer adenylate cyclase activity of the purified forms as well as the activity present in dialyzed urea extract of the bacteria. It also prevents the penetration of the invasive B. pertussis adenylate cyclase into human lymphocytes. The inhibition induced by the antisera is specific to B. pertussis enzyme, since both calmodulin-dependent brain and sperm adenylate cyclase are not affected by the antibody.

Adenylyl Cyclases↗
PubMed1988

Sinus arrest associated with clonidine therapy.

A 65-year-old male with diabetes, hypertension, and mild renal failure developed dizziness and syncope one week after starting clonidine 0.45 mg/day. A continuous ECG recording revealed sinus bradycardia, nodal rhythm, and multiple episodes of sinus arrest lasting up to 4.5 seconds. Upon discontinuation of clonidine, serial continuous ECG recordings revealed gradual decrease in the number and duration of the sinus arrest episodes, until their complete disappearance shortly after the third day off clonidine. This report shows that clonidine may cause a concentration-dependent sinus node dysfunction in addition to the atrioventricular (AV) node abnormalities previously ascribed to it.

Aged↗
PubMed1988

Complex interaction of rifampin and warfarin.

Rifampin is known to lower plasma warfarin concentrations by increasing the rate of warfarin clearance. We have described a patient in whom an additional potentiating influence on warfarin effect was observed during treatment with rifampin and isoniazid. After cessation of rifampin and isoniazid, prothrombin time was maintained within the same range by a 50% reduction of warfarin doses, despite a twofold rise in the plasma warfarin concentration. This rise in warfarin concentrations can be explained by the known mechanism by which rifampin increases warfarin clearance. After cessation of rifampin, warfarin fractional clearance decreased from 15.2 to 4.2 ml/min; however, the unchanged prothrombin time in the face of the increased warfarin concentration can be explained only by the removal of a potentiating effect that had been present during the coadministration of rifampin and isoniazid. It is likely that rifampin is responsible for this additional potentiating interaction, probably not through a change in warfarin binding, but through a differential effect on warfarin stereoisomer metabolism or through an altered dynamic effect. The role of isoniazid in this interaction cannot be completely ruled out.

Adult↗
PubMed1988

Sodium cromoglycate in asthma: correlation between response and serum concentrations.

The clinical response to sodium cromoglycate treatment was compared with its concentration in serum. Twenty five children with asthma entered a 10 week trial of two baseline weeks followed by eight weeks of treatment by the inhalation of 20 mg of sodium cromoglycate spincaps four times a day. Individual clinical response was determined by the differences between baseline and treatment periods of: (a) percentage of symptomless days (delta score 0); (b) diary derived daily score for four symptoms (delta DS); and (c) peak expiratory flow rate (delta PEFR). At the end of the treatment period, patients inhaled a 20 mg spincap of sodium cromoglycate and the technique of inhalation was graded. Concentrations of sodium cromoglycate in serum were measured by radioimmunoassay in samples withdrawn 5 to 120 minutes after inhalation. Delta Score 0, delta DS, and delta PEFR correlated significantly with the area under the concentration time curve. Both the area under the sodium cromoglycate concentration time curve and clinical response correlated significantly with inhalation technique score. We suggest that response of children with asthma to inhalation treatment with sodium cromoglycate is correlated to its serum concentrations.

Administration, Inhalation↗
PubMed1987

Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats. Characterization and mode of action.

The effect of oral administration of vanadate, in normalizing blood glucose levels of streptozotocin-treated rats (ST-rats), is further characterized and its mode of action is determined. We have examined the effects of two orally administered doses of sodium metavanadate. High concentrations of orally administered vanadate (0.8 mg/ml in drinking water) reduced blood glucose levels within 2-4 days of application and led to the appearance of hypoglycemia in test animals. Lower concentrations of vanadate (0.2 mg/ml in drinking water) also lowered blood glucose levels within 4 days, but did not lead to hypoglycemia for at least 3 weeks. These effects of vanadate were found to be reversible; hyperglycemia recurred within 2 days after removal of vanadate from the drinking water. In streptozotocin-treated rats receiving low vanadate treatment, circulating levels of vanadate were about 0.8 microgram/ml after 3 weeks of treatment. These rats became anabolic, while rats receiving high vanadate treatment remained catabolic. Subsequent to vanadate treatment, adipocytes derived from ST-rats responded to lower insulin concentrations. In addition, vanadate treatment lowered the increased insulin binding capacity of liver plasma membranes derived from ST-rats. Insulin binding capacity under these conditions approached that of control non-ST-rats. Basal rates of hexose uptake in muscle and liver tissues were doubled in vanadate-treated ST-rats. It is concluded that the oral administration of vanadate leads to normoglycemia by stimulating glucose uptake. Treatment with "low vanadate" leads to the formation of a stable anabolic and normoglycemic state in ST-rats and appears to restore insulin responsiveness of target tissues, without apparent signs of toxicity. Vanadate treatment did not impair either kidney or liver function, as assayed by the measurement of serum urea, creatinine, and glutamic-oxaloacetic transaminase.

Adipose Tissue↗
PubMed1987

The invasive adenylate cyclase of Bordetella pertussis. Properties and penetration kinetics.

Bordetella pertussis, the causative organism of whooping cough, produces a calmodulin-sensitive adenylate cyclase. Confer & Eaton [(1982) Science 217, 948-950] have shown that an extract from B. pertussis increases intracellular cyclic AMP levels in neutrophils and suggested that this increase is caused by the bacterial adenylate cyclase which penetrates these cells. We demonstrate in the present study that adenylate cyclase activity in lysates from lymphocytes exposed to a partially purified preparation of the bacterial enzyme has properties completely different from those of the intrinsic membrane-bound enzyme. Adenylate cyclase activity in lysates from lymphocytes exposed to the invasive enzyme is insensitive to N-ethylmaleimide, readily inactivated by acetic anhydride and relatively stable to SDS. Similar properties are exhibited by the bacterial enzyme itself. By contrast, the intrinsic membrane-bound enzyme activated by forskolin and guanosine 5'-gamma-thiotriphosphate is sensitive to N-ethylmaleimide and SDS and relatively stable to acetic anhydride. This strongly supports the notion that B. pertussis adenylate cyclase penetrates cells. Using the partially purified preparation of the invasive enzyme, we have studied the kinetics of its penetration. The intracellular catalytic activity reaches a steady state within 20 min, irrespective of enzyme or cell concentration. Steady-state levels are maintained for at least 2 h provided that the invasive enzyme is present in the incubation medium. Upon its removal, a rapid decrease (t1/2 approximately equal to 15 min) in the intracellular cyclase level is observed. This decrease reflects intracellular inactivation of the bacterial enzyme and is not caused by the release of the enzyme to the cell medium.

Adenylyl Cyclases↗
PubMed1987

The invasive adenylate cyclase of Bordetella pertussis. Intracellular localization and kinetics of penetration into various cells.

The penetration of Bordetella pertussis adenylate cyclase into various mammalian cells exhibits similar kinetics; the accumulation of both intracellular cyclase activity and cyclic AMP is rapid, reaching constant levels after 15-60 min of incubation. The kinetics of enzyme penetration into turkey erythrocytes is different; cyclase activity and cyclic AMP accumulate linearly and do not reach constant levels even after 6 h of incubation. In the preceding paper [Friedman, Farfel & Hanski (1987) Biochem. J. 243, 145-151] we have suggested that the constant level of intracellular cyclase activity reflects a steady state formed by continuous penetration and intracellular inactivation of the enzyme. In contrast with other mammalian cells, no inactivation of cyclase is observed in turkey erythrocytes. These results further support the notion that there is continuous penetration and deactivation of the invasive enzyme in mammalian cells. A 5-6-fold increase in specific activity of the invasive cyclase is detected in a pellet fraction of human lymphocytes in which a similar increase in specific activity of the plasma-membrane marker 5'-nucleotidase is observed. A similar increase in the invasive-cyclase specific activity is detected in a membrane fraction of human erythrocytes. Cyclase activity in a membrane-enriched fraction of human lymphocytes reached a constant level after 20 min of cell exposure to the enzyme. Similar time courses were observed for accumulation of cyclase activity and cyclic AMP in whole lymphocytes [Friedman, Farfel & Hanski (1987) Biochem, J. 243, 145-151]. We suggest therefore that cyclic AMP generation by the invasive enzyme as well as the intracellular inactivation process occur while it is associated with a membrane fraction identical, or closely associated, with the plasma membrane.

Adenylyl Cyclases↗
PubMed1987

Review of echocardiographically diagnosed right heart entrapment of pulmonary emboli-in-transit with emphasis on management.

2DE permits detection of thromboemboli transiently entrapped in the right heart chambers while en route to the pulmonary arteries. Review of the 49 cases recorded to date reveals that the supple elongated clot produces a 2DE picture--a mass of changing configuration and striking mobility--that is highly characteristic. Since emboli that become entrapped are large, when managed by medical measures alone they have an attendant mortality rate of 50%, usually soon after 2DE diagnosis, upon completion of pulmonary embolization. Death occurred in 8 of 16 patients treated with anticoagulants, thrombolytic agents, or antiaggregants and in 6 of 13 who received supportive measures only. Of 20 patients referred for surgery (cardiotomy and, in 17, pulmonary embolectomy), only three died, two of them failures of preceding anticoagulant treatment. These data indicate that thromboemboli entrapped in the right heart chambers are best handled as a surgical emergency.

Echocardiography↗
PubMed1987

Measles epidemic in young adults. Clinical manifestations and laboratory analysis in 40 patients.

Between February and June 1985, 40 military personnel were hospitalized because of measles. Diagnosis in all patients was entirely clinical, and serologic investigations were noncontributory. A transient disturbance in liver function occurred in 70% of patients, and its extent correlated with duration of fever and disease complications. Spontaneously resolving, measles-specific hypocalcemia, which was not associated with hepatic dysfunction, was noted in about one third of the patients. All these patients were asymptomatic, except one patient who developed tetany. The pathophysiologic basis for the hypocalcemia is still unknown. The disease course in three previously immunized patients was benign and uncomplicated.

Adolescent↗