Redox reactions associated with iron release from mammalian ferritin.

The early redox events involved in iron reduction and mobilization in mammalian ferritin have been investigated by several techniques. Sedimentation velocity measurements of ferritin samples with altered core sizes, prepared by partial reduction and Fe2+ chelation, suggest two different events occur during iron loss from the ferritin core. Reductive optical titrations confirm this biphasic behavior by showing that the first 20-30% of core reduction has different optical properties than the latter 70-80%.

Comparison of high-risk and mass strategies for the prevention of high blood pressure.

A mass strategy for the prevention of high blood pressure and its complications is likely to be more effective than high-risk strategies for several reasons: there is no practicable way of identifying in advance a large proportion of future hypertensives; a minority of hypertensive complications occur in individuals with pressures high enough to warrant treatment; and treatment has little or no effect on the incidence of the major hypertensive complication, coronary heart attacks. The effect of a broad-based dietary prevention programme is not proven, but such a strategy offers a reasonable prospect of a broad range of benefits, and is likely to prove acceptable to the general public. A family-based approach may contribute to aetiological research, and make pragmatic sense in clinical practice, but does not provide a scientific basis for a high-risk strategy of prevention.

Rapid diagnosis of tuberculous meningitis by using an enzyme-linked immunosorbent assay to detect mycobacterial antigen and antibody in cerebrospinal fluid.

Rapid diagnostic tests for tuberculous meningitis are urgently needed because delayed treatment increases the already high mortality rate of this disease. Direct acid-fast staining of cerebrospinal fluid is the only quick method generally available, but it lacks sensitivity. Therefore, we evaluated the use of an enzyme-linked immunosorbent assay (ELISA) to mycobacterial antigen and antibody in the cerebrospinal fluid of 29 patients with proven tuberculous meningitis, 83 patients with nontuberculous central nervous system infections, and 15 normal controls.

Redox reactivity of bacterial and mammalian ferritin: is reductant entry into the ferritin interior a necessary step for iron release?

Both mammalian and bacterial ferritin undergo rapid reaction with small-molecule reductants, in the absence of Fe2+ chelators, to form ferritins with reduced (Fe2+) mineral cores. Large, low-potential reductants (flavoproteins and ferredoxins) similarly react anaerobically with both ferritin types to quantitatively produce Fe2+ in the ferritin cores. The oxidation of Fe2+ ferritin by large protein oxidants [cytochrome c and Cu(II) proteins] also occurs readily, yielding reduced heme and Cu(I) proteins and ferritins with Fe3+ in their cores.

Bites by the Philippine cobra (Naja naja philippinensis): prominent neurotoxicity with minimal local signs.

We studied 39 patients envenomed by the Philippine cobra (Naja naja philippinensis). Neurotoxicity occurred in 38 cases and was the predominant clinical feature. Respiratory paralysis developed in 19 patients, and was often rapid in onset--in 3 cases apnea occurred within 30 min of the bite.

A serologic survey of rice-field leptospirosis in Central Luzon, Philippines.

Although human cases of leptospirosis have been reported from the Philippines, there is a lack of data on its prevalence. We therefore surveyed three rice-farming villages for the presence of leptospiral antibody. Out of 155 sera tested, 63 (43.

Comparison of redox and EPR properties of the molybdenum iron proteins of Clostridium pasteurianum and Azotobacter vinelandii nitrogenases.

Both heterologous crosses of the Clostridium pasteurianum and Azotobacter vinelandii nitrogenase components are completely inactive, although the reasons for this incompatibility are not known. We have compared a number of properties of the MoFe proteins from these organisms (Cp1 and Av1, respectively) in an attempt to find differences that could explain this lack of functional activity. Optical and CD spectroscopic titrations are similar for both Av1 and Cp1, but EPR titrations are significantly different, suggesting different chemical reactivity patterns and/or magnetic interaction behavior.

Tourniquet application after cobra bite: delay in the onset of neurotoxicity and the dangers of sudden release.

The effects of tourniquet application were prospectively studied in 36 hospitalized patients who developed neurotoxic symptoms after bites by the Philippine cobra (Naja naja philippinensis). Tourniquets had been applied in 94% of cases and delayed the onset of symptoms. Four patients were asymptomatic prior to the release of their tourniquet and in 11 patients symptoms worsened precipitously.

Praziquantel pharmacokinetics and side effects in Schistosoma japonicum-infected patients with liver disease.

Praziquantel undergoes extensive first-pass hepatic biotransformation, but there is little information on its disposition or toxicity when administered to patients with liver disease. To define the influence of liver disease on the pharmacokinetics of praziquantel, we administered it orally to 30 patients with proven Schistosoma japonicum infection whose liver disease was carefully assessed as being severe, moderate, or absent. Both the peak plasma concentration of praziquantel and the bioavailability (measured as the area under the plasma concentration time curve) were significantly greater in the two groups of patients with liver disease (P less than .

Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis.

The effect of a 7-day course of intravenous penicillin (6 million units/day) on severe, advanced leptospirosis was examined in a randomised, placebo-controlled, double-blind trial involving 42 patients. Every measurable aspect of the disease was favourably affected by penicillin. Fever lasted more than twice as long in the placebo group (11.

Chloroquine and quinine: a randomized, double-blind comparison of efficacy and side effects in the treatment of Plasmodium falciparum malaria in the Philippines.

Chloroquine (25 mg/kg over 3 d) was compared to quinine (10 mg/kg 3 times daily for 5 d) in 20 adult Filipino males with uncomplicated Plasmodium falciparum malaria in a double-blind, randomized trial. Asexual parasitaemia was cleared in all patients, with no statistically significant difference (P = 0.13) in the rate of clearance between the chloroquine-treated patients (76.

Does "susceptibility" explain the weak epidemiological relationship between dietary sodium and blood pressure?

It is often suggested that the weak epidemiological relationship between dietary sodium and blood pressure may reflect a stronger relationship within a susceptible subgroup. The evidence in favour of this explanation is reviewed, and found to be insubstantial. A more consistent explanation of the available data is that there is a weak general effect of dietary sodium on blood pressure acting on the general population.

Electron paramagnetic resonance studies of the tungsten-containing formate dehydrogenase from Clostridium thermoaceticum.

The redox centers in the tungsten-containing formate dehydrogenase from Clostridium thermoaceticum were examined by potentiometric titration and electron paramagnetic resonance spectroscopy. At low temperature two overlapping iron-sulfur signals which correlated with enzymatic activity were observed with formal potentials near -400 mV vs. SHE.

Bites by the Philippine cobra (Naja naja philippinensis): an important cause of death among rice farmers.

We investigated mortality from cobra (Naja naja philippinensis) bite among Filipino rice farmers. Village records in one area were examined and we conducted a careful survey in this and two additional areas among inhabitants at varying risk for snakebite. The death rate from cobra bite was estimated to be as high as 107.

Identification of rat erythrocyte antigens with a new non-radioactive immunoprecipitation technique.

In order to examine how rat erythrocytes stimulate erythrocyte autoantibody production at the molecular level, we have identified rat erythrocyte antigens by immunoprecipitation and western blotting using monoclonal antibodies and antisera. A novel non-radioactive immunoprecipitation technique was used, which employed biotin as a label and a luminescent detection system. The new method was validated by comparison with conventional immunoprecipitation using 125I.

In vitro drug response of Plasmodium falciparum in the Philippines: increased resistance to amodiaquine.

A long term study was carried out at San Lazaro Hospital, Manila, Philippines, monitoring the in vitro response of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, and quinine. The in vitro effective dose giving 50% inhibition of schizogony was: 0.68 X 10(-6) M/liter blood for chloroquine; 0.

Distribution of methacholine inhalation challenge responses in a selected adult population.

To determine bronchial reactivity patterns in adults, 211 subjects, 22 to 86 years of age, underwent a methacholine challenge in a Natural History of Asthma study. The diagnosis of asthma or nonasthmatic allergic diseases was based on a standardized respiratory questionnaire. Subjects were nonsmokers and had not had an infection for 1 month.