Trifluoperazine inhibits phagocytosis in a macrophagelike cultured cell line.

Trifluoperazine, a drug that binds to Ca2+-calmodulin and inhibits its interaction with other proteins, was found to inhibit growth and phagocytosis in a macrophagelike cell line, J774.16. Both effects were reversible and occurred at the same concentrations of drug (25--50 microM) that inhibited the activation of cyclic nucleotide phosphodiesterase by calmodulin in vitro. Fc-mediated phagocytosis was also depressed by W-7, a sulfonamide derivative that inhibits the activity of Ca2+-calmodulin. In contrast, taxol, a drug that stabilizes cellular microtubules, had no effect on Fc-mediated phagocytosis although it inhibited cell growth at nanomolar concentrations. The inhibitory effects of trifluoperazine and W-7 on phagocytosis suggest that calmodulin may be involved in this complex cellular function.

Pyroglutamyl peptidase II, a thyrotropin releasing hormone degrading enzyme: purification and specificity studies of the rabbit brain enzyme.

Pyroglutamyl peptidase II (EC 3.4.19.-) a membrane-bound thyrotropin releasing hormone degrading enzyme was purified 5000-fold to apparent homogeneity from the particulate fraction of a rabbit brain homogenate. The enzyme displayed a broad pH optimum in the neutral range. It was inhibited by metal chelators but was unaffected by inhibitors of serine, cysteine or aspartyl proteases. The molecular weight determined on a calibrated Sephadex G-200 column was 230,000. A series of pyroglutamyl peptidyl naphthylamides were synthesized for substrate specificity studies. The K(m) and V(max) of hydrolysis of the naphthylamide (NA) analog of TRH (pGlu-His-Pro-NA) was similar to TRH. The enzyme cleaved pGlu-His-tripeptidyl naphthylamides but did not cleave the pGlu-His bond of the dipeptide pGlu-His-NA or the tetrapeptide pGlu-His-Pro-Ala-NA. The degradation of substrates lacking a chromogenic group was studied by HPLC. The enzyme did not cleave pGlu-His, the pGlu-His decapeptide LHRH, Phe(2)-TRH or the ring opened Glu(1)-TRH. The specificity studies are consistent with the designation of pyroglutamyl peptidase II as the first characterized neuropeptide specific peptidase. On the basis of its localization and specificity, pyroglutamyl peptidase II may control the biological activity of neuronally released TRH.

Occurrence of pyroglutamyl peptidase II, a specific TRH degrading enzyme in rabbit retinal membranes and in human retinoblastoma cells.

Pyroglutamyl peptidase II, a highly specific thyrotropin releasing hormone (TRH)-degrading enzyme is found in highest concentration in brain where it is localized to synaptic membranes. Retina contains relatively high concentrations of both immunoreactive TRH and TRH receptors. We report that the specific activity of pyroglutamyl peptidase II in rabbit retinal membranes exceeds that of all non-CNS tissues thus far studied. Nine clonal cell lines were screened for this enzymatic activity. The specific activity of pyroglutamyl peptidase II in Y79 retinoblastoma cells was greater than the highest activity found in other cell lines by approximately one order of magnitude. These studies further support a functional relationship between pyroglutamyl peptidase II and TRH and identify a cell line suitable for studies on the regulation of this enzyme.

Localization of immunoreactive glutamyl aminopeptidase in rat brain. I. Association with cerebral microvessels.

Glutamyl aminopeptidase (aminopeptidase-A, EC 3.4.11.7) is an ectoenzyme that selectively hydrolyses N-terminal glutamyl and aspartyl residues from oligopeptides, including (Asp1) angiotensin II. Here we sought to determine the distribution of glutamyl aminopeptidase (EAP) in rat brain. EAP was purified to homogeneity from rat kidney and polyclonal antiserum raised in rabbits. Immune serum inhibited EAP enzyme activity in kidney homogenates and labeled two major protein bands of M(r) = 136,000 and M(r) = 101,000 in immunoblots of kidney protein. EAP-like immunoreactivity was concentrated on kidney proximal tubule brush borders. Immunocytochemical staining of rat brain indicated that EAP-like immunoreactivity was primarily associated with cerebral microvessels. Positive staining was detected in microvessels ranging in size from capillaries up to vessels approximately 50 microns in diameter. Isolated cerebral microvessels had a 23-fold enrichment in EAP enzyme activity (193.1 +/- 40.4 nmol/mg protein/h) compared to brain homogenates. Finally, immunoblots of isolated cerebral microvessels resulted in a pattern of labeling similar to that seen with kidney homogenates. These results indicate that EAP activity in brain is primarily associated with cerebral microvessels, and suggest that EAP may be involved in the metabolism of circulating or locally formed peptides.

[Performance of the Dutch health care from an international perspective: background and implications for policy]. / De prestaties van de Nederlandse gezondheidszorg in internationaal perspectief: achtergronden en implicaties voor beleid.

The 'World Health Report 2000' has stimulated discussions on the Netherlands' performance in health and healthcare from an international perspective. The only concrete result it provided was a world ranking in which the Netherlands stood in 17th place. The comparative data which have appeared in several other recent reports, are more useful to policy makers, a notable example being those from the Organization for Economic Cooperation and Development (OECD). One issue arising from these reports is that the increase in life expectancy in the Netherlands is lagging behind the European Union average. This is particularly the case for women and a major cause of this is smoking. Developments in Dutch perinatal mortality are also unfavourable and are associated with a strong increase in the age at which women bear children. International comparisons of public health data are valuable inputs for health policy development and it is therefore important to invest in the international harmonisation of such data collection.

[Inhalation heat shock]. / Untersuchungen zum Inhalations-Hitzeschock.

Using the example of a recent case, we examine the possibilities of trace analysis and fire protection techniques in the investigation of fire deaths. The effective cooperation between forensic pathologists and fire inspectors is presented and we discuss the mathematical-physical uses of fire simulation calculations. We review the trace analysis results and discuss the variety of technical possibilities of modern engineering techniques for fire protection.

[Significant injury of the neck including the cervical spine and soft tissue in suicidal strangulation]. / Uber eine erhebliche Verletzung des Halses einshcliesslich der Halswirbelsäule und der Halsweichteile im Rahmen einer suizidalen Strangulation.

A 46-year-old man committed suicide by jumping from a height of app. 4.5 m with a running noose round his neck. The neck was nearly cut through by the tightened ligature, so that there was only a small "bridge" of soft tissue between head and trunk.

[Clinical and morphological picture of adrenal gland carcinoma with characteristics of early embryonal development]. / Kliniczny i morfologiczny obraz raka nadnerczy z cechami rozwoju wczesnozarodkowego.

A two year old girl with symptoms of virilization was investigated and an adrenal gland tumor with morphological sings of malignancy was diagnosed. After surgery, irradiation and chemotherapy, a complete recovery was observed. The authors point out the diagnostical difficulties in similar cases. Our observation seems to confirm earlier suggestions, that in cases with predominant androgen activity the better prognosis is expected.

[Selected chemical compounds as potential sources of massive poisoning. Physicochemical properties, poisoning symptoms, treatment]. / Wybrane zwiazki chemiczne stanowiace potencjalne zródlo zatruc masowych. Wlasciwosci fizyko-chemiczne, objawy zatrucia, postepowanie lecznicze.

Characteristics of 42 chemical compounds (17 gases and 24 liquids) sustaining potential danger of massive poisonings in case of accident or chemical disaster is presented. Description of each substance includes: physiocochemical properties, pathophysiology and symptoms of acute poisonings with those chemicals. Rules and procedures of treatment are presented including premedical first aid and medical treatment.

[Incidence of goiter in children of the Tarnobrzeg district and environmental factors]. / Czestosc wystepowania wola u dzieci w województwie tarnobrzeskim a czynniki srodowiskowe.

A group of 1897 school children from Tarnobrzeg district were examined out of this number 1241 (65.4%) children displayed goiter. Goiter incidence was also established depending upon age and sex. The analysis also included goiter incidence in relation to its size according to the WHO classification. In certain patients, newborns and their mothers, determinations of iodine excretion were made; the values were found to be within the normal. This range suggests that other etiological factors than iodine deficiency might possibly contribute to goiter development in the studied children.

[Blood serum cortisol, insulin and somatotropin concentration in children with hypothalamo-hypophyseal insufficiency]. / Stezenie kortyzolu, insuliny i hormonu wzrostu w surowicy u dzieci z niedomoga powzgórzowo-przysadkowa.

In 22 patients with restricted growth the consecutive stimulation with arginine and insuline was applied for the diagnosis of somatotropic insufficiency. 13 children showed GH insufficiency. Simultaneously cortisol level during hypoglycemia for ACTH reserve and insulin level after arginine application were estimated.

[Dietary iodine intake in children and clinical and biochemical features of iodine deficiency in chosen districts of south-east Poland]. / Spozycie jodu w pokarmach dzieci a kliniczne I biochemiczne cechy niedoboru jodu w wybranych województwach Polski Poludniowo-wschodniej.

The study on the effects of Czarnobyl accident on thyroid gland function in children (MZ XVII program) revealed a high incidence of goiter in the population of children in district Kraków and Nowy Sacz. Other study on Tarnobrzeg population showed that the frequency of goiter in school children was 67%. The goiter prevalence, urine iodine excretion and iodine food consumption in the same populations were compared. The detailed investigation of iodine intake in children by feeding questionnaire shows a low consumption of iodine. The urine iodine excretion in the population of Kraków-district was low, but higher than in Nowy Sacz-district and nearly normal in Tarnobrzeg. High frequency of goiter in children and of IDD in newborns screened for CH, as well as low urine iodine excretion, together with low iodine intake with food are the markers of iodine deficiency in Kraków and Nowy Sacz districts. The improvement of feeding as well as iodine salt supplementation is necessary. The situation in Tarnobrzeg district looks differently and needs additional study.

[Epidemiologic studies after the disaster in Czernobyl in the population of children in the Krakow region]. / Badania epidemiologiczne po awarii w Czarnobylu w populacji dzieci w regionie krakowskim.

In 1989-1990 the epidemiologic studies about the impact of of Czarnobyl events on the health of children in Kraków and Nowy Sacz region were performed. The morphologic and functional changes of thyroid gland in children were estimated. Almost 90% of children in both districts received the iodine preparations for prophylactic reason. The mean time of intake was between 5-10 days following the Czarnobyl explosion. There were no relationship between the dose of iodine absorbed during prophylactic action and incidence of goiter. The prevalence of goiter amounted to 34.8-47.6% in boys and girls consecutively in Kraków district and 53.8-70.5% in Nowy Sacz. No hormonal changes in T3, T4 and TSH serum concentration were found in children with goiter and those without goiter. The complications after iodine intake were transient and seen only in a small number of children.