Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.     

Symptoms of tobacco withdrawal. A replication and extension

Smokers (n = 315) who wished to quit were randomly assigned in a double-blind manner to groups using either nicotine or placebo gum. Self-reported and observed symptoms of tobacco withdrawal were collected before cessation and at follow-ups of 1 to 2 weeks, 1 month, and 6 months. Self-reported and/or observed anger, anxiety, craving, difficulty concentrating, hunger, impatience, and restlessness were the most prominent symptoms of tobacco withdrawal. These symptoms had returned to precessation levels by 1 month except increased weight, hunger, and craving continued for 6 months in many smokers. Nicotine gum decreased most symptoms, including craving and hunger but not weight. Abstinent smokers with more intense withdrawal were not more likely to relapse. Abstinent smokers who gained more weight were less likely to relapse.     

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.     

Nicotine vs placebo gum in general medical practice

Three hundred fifteen smokers who attended a family practice clinic and wished to quit smoking were assigned in a random, double-blind manner to receive either nicotine (2 mg) or placebo gum. Smokers initially received brief advice from a physician and nurse, a slide presentation and written materials (29 to 35 minutes), and a single follow-up visit (12 to 20 minutes) one week after cessation. After corrections for marital status and income, 10% of those who received nicotine gum and 7% of those who received placebo gum reported continuous abstinence for 11 months and passed observer and biochemical verification (this difference was not statistically significant). We conclude that, when used in a nonselected group of smokers along with a brief intervention in a general medical practice, the pharmacologic effects of nicotine gum to increase cessation are either small or nonexistent.     

Prevalence of tobacco dependence and withdrawal

In a sample of 1,006 middle-aged male smokers drawn from the general population, 90% (N = 905) fulfilled DSM-III criteria and 36% (N = 362) fulfilled Fagerstrom's criteria for tobacco dependence. Among the 875 who had stopped smoking in the past for at least 24 hours, 21% (N = 184) fulfilled DSM-III criteria and 46% (N = 403) fulfilled the authors' own criteria for tobacco withdrawal. Concordance of results among the criteria for diagnosing tobacco dependence and withdrawal was low. These results suggest that the DSM-III criteria for tobacco dependence are overinclusive and that there is little consensus among the definitions of tobacco dependence and withdrawal.     

Environmental and developmental signals modulate proline homeostasis: evidence for a negative transcriptional regulator.

In many plants, osmotic stress induces a rapid accumulation of proline through de novo synthesis from glutamate. This response is thought to play a pivotal role in osmotic stress tolerance [Kishor, P. B. K., Hong, Z., Miao, G.-H., Hu, C.-A. A. and Verma, D. P. S. (1995) Plant Physiol. 108, 1387-1394]. During recovery from osmotic stress, accumulated proline is rapidly oxidized to glutamate and the first step of this process is catalyzed by proline oxidase. We have isolated a full-length cDNA from Arabidopsis thaliana, At-POX, which maps to a single locus on chromosome 3 and that encodes a predicted polypeptide of 499 amino acids showing significant similarity with proline oxidase sequences from Drosophila and Saccharomyces cerevisiae (55.5% and 45.1%, respectively). The predicted location of the encoded polypeptide is the inner mitochondrial membrane. RNA gel blot analysis revealed that At-POX mRNA levels declined rapidly upon osmotic stress and this decline preceded proline accumulation. On the other hand, At-POX mRNA levels rapidly increased during recovery. Free proline, exogenously added to plants, was found to be an effective inducer of At-POX expression; indeed, At-POX was highly expressed in flowers and mature seeds where the proline level is higher relative to other organs of Arabidopsis. Our results indicate that stress- and developmentally derived signals interact to determine proline homeostasis in Arabidopsis.     

A study of the prevalence of rotavirus infection in children with gastroenteritis admitted to an infectious diseases hospital.

In a 12 month survey of infants and children with gastroenteritis admitted to Fairfield Hospital, Melbourne, rotavirus was found in approximately 42% of patients. This virus was detected more often during the winter months, particularly in children aged between 12 months and 3 years. Detection of rotavirus by electron microscopy was found to be more sensitive than by counterimmunoelectrophoresis. Routine bacterial and viral studies revealed that bacterial pathogens and common enteric viruses were associated with relatively few cases of gastroenteritis. There is little doubt that rotavirus is the most important aetiological agent of acute gastroenteritis in yvirus is the most important aetiological agent of acute gastroenteritis in young children in Melbourne.     

Characterization of a precipitating antigen detected in the serum of patients with viral hepatitis

During a search for the aetiological agent of non-A non-B hepatitis, a precipitating antigen was detected in the sera of some patients during the acute phase of their illness. The antigen was detected by agar gel diffusion using antibody from convalescent sera obtained from patients with non-A non-B hepatitis, and from haemophiliac sera. The antigen was usually detected early in the patient's illness, disappearing as liver function tests returned to normal. In some patients specific antibody appeared during the convalescent phase of the disease. The antigen does not appear to be specific for non-A non-B hepatitis, as it could be detected with similar frequency in patients with hepatitis A or hepatitis B and some patients with other liver disorders. Biochemical and biophysical studies suggest that the antigen is probably an abnormal lipoprotein produced as a result of acute liver damage.