Comparison of antiviral and antitumor activity of activated macrophages.

The antiviral and antitumor activity in vitro of normal, stimulated, vaccinia virus “immune”, and activated peritoneal macrophages were compared. Activated (pyran or corynebacteria induced) PEC exhibited both antitumor and antiviral activity. Stimulated (thioglyocollate) and vaccinia virus “immune” PEC inhibited virus growth but did not possess antitumor activity. Normal (unstimulated) PEC were relatively ineffective in either activity. The antiviral activity was nonspecific, being expressed against herpes simplex and EMC viruses in addition to vaccinia. Although a possible role for interferon was suggested by the lack of activity of mouse PEC on vaccinia virus growth in heterologous FLK cells, definitive proof was not obtained. The activity was most pronounced against multiple cycles of viral infection initiated at a low multiplicity of infection. Single cycle virus growth was not affected, suggesting that the major inhibition was on subsequent cycles of virus growth.     

Inhibition of human seminal fluid and Leishmania donovani phosphatases by molybdate heteropolyanions

Inhibition of a tartrate-resistant acid phosphatase (ACP) from Leishmania donovani and the tartrate-sensitive ACP from human seminal fluid (prostatic ACP) was examined using a series of 13 molybdate-containing heteropolyanions. The heteropolyanions were divided into four groups based on the number of molybdenum atoms they contain: Group I, Mo4; Group II, Mo6-8; Group III, Mo12; Group IV, Mo18. Two of the four groups, those consisting of compounds that contain either an Mo4 unit or an Mo18 unit with a heteroatom in the central cavity, were potent inhibitors and exhibited the highest degree of selectivity against the leishmanial and seminal fluid ACPs. The inhibition of prostatic ACP by complex E2 could be completely reversed by dialysis. Little inhibition of the acid phosphatase, beta-glucuronidase, or alpha-mannosidase from human spleen was observed with complexes B' and E2. For the seminal fluid phosphatase, the Ki values obtained with arsenate and vanadate depended markedly on pH, suggesting that, unlike most other phosphatases, the conformation of the inhibitor binding site on human seminal fluid ACP is pH-dependent. Results of competition experiments performed with various inhibitor pairs indicated that complex D2 binds to the active site of prostatic ACP while complex M binds at some site on the enzyme that affects the active site. Binding of complex M also modifies the affinity of the enzyme for other inhibitors such as vanadate. The potency of several heteropolyanion complexes and their selective inhibition of pathophysiologically significant acid phosphatases indicate that these compounds may have value as tools for study of the structure and function of this class of enzyme and perhaps in the therapy of human disease.     

Evolutionary conservation of the human nucleolar protein fibrillarin and its functional expression in yeast

NOP1 is an essential nucleolar protein in yeast that is associated with small nucleolar RNA and required for ribosome biogenesis. We have cloned the human nucleolar protein, fibrillarin, from a HeLa cDNA library. Human fibrillarin is 70% identical to yeast NOP1 and is also the functional homologue since either human or Xenopus fibrillarin can complement a yeast nop1- mutant. Human fibrillarin is localized in the yeast nucleolus and associates with yeast small nucleolar RNAs. This shows that the signals within eucaryotic fibrillarin required for nucleolar association and nucleolar function are conserved from yeast to man. However, human fibrillarin only partially complements in yeast resulting in a temperature-sensitive growth, concomitantly altered rRNA processing and aberrant nuclear morphology. A suppressor of the human fibrillarin ts-mutant was isolated and found to map intragenically at a single amino acid position of the human nucleolar protein. The growth rate of yeast nop1- strains expressing Xenopus or human fibrillarin or the human fibrillarin suppressor correlates closely with their ability to efficiently and correctly process pre-rRNA. These findings demonstrate for the first time that vertebrate fibrillarin functions in ribosomal RNA processing in vivo.     

Prevalence of psammoma bodies in Papanicolaou-stained cervicovaginal smears

Reports from sequential series of 234,318 cervicovaginal smears from a period of three years were reviewed to ascertain the prevalence and significance of psammoma bodies. Seven smears contained psammoma bodies. Three of the seven were associated with benign conditions and four were associated with a cancer (two serous papillary endometrial adenocarcinomas, one ovarian serous cystadenocarcinoma and one serous papillary carcinoma of the peritoneum). The prevalence of psammoma bodies in benign cases was much higher than reported in previous studies, in which most findings of psammoma bodies were associated with malignancy, particularly ovarian carcinoma. A consistent and useful feature in distinguishing psammoma bodies associated with benign or malignant disease was the presence of a few adherent small bland-appearing glandular cells in benign disorders and adherent malignant glandular cells in cases of carcinoma. A more conservative work-up may be merited in young women with clearly benign cells associated with psamoma bodies in a cervicovaginal smear and an otherwise negative physical examination and noncontributory endometrial sampling.     

Psychophysical studies of the itch sensation and itchy skin ("alloknesis") produced by intracutaneous injection of histamine.

Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 micrograms in 10 microliters of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-microgram dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15 degrees C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 micrograms of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical demonstration of villin in the normal human pancreas and in chronic pancreatitis

Summary Human pancreatic tissue was investigated by immunohistochemistry using a polyclonal antibody against the actin binding protein villin, which participates in the formation of actin filament bundles in the microvilli. In cells of the different parts of the pancreatic duct system as well as in the acinar cells villin immunoreactivity was located mainly at the apical cell surface. This was confirmed by the ultrastructural demonstration of microvilli on the surface of duct and acinar cells, which exhibited the typical actin bundles. In chronic pancreatitis the staining for villin in duct-like structures of degenerative pancreatic tissue was irregular or even absent. This correlated with the electron microscopic observation of duct-like structures known as tubular complexes composed of cells devoid of microvilli at the apical cell surface. At the light microscopical level degenerative structures without lumen and of unknown origin showed a strong staining for villin at their basal cell surface.     

Brain Tubulin Microheterogeneity in the Mouse During Development and Aging

Abstract: Mouse brain tubulin was analyzed on isoelectric focusing gels. High-resolution gels utilizing Bio-Rad ampholytes (pH 4-6) revealed 5-6 bands in the region corresponding to the α-subunit of tubulin and 10 or more for the β-subunit. The same general banding pattern was observed regardless of the method of preparation of the tubulin. Two species prominent in the brains of immature mice, α6 and β2, virtually disappeared during maturation, while species β6 to β10 appeared. No significant changes from the mature pattern were seen during aging (examined at 12, 23, and 30 months of age).     

Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells II. Test validation and interpretation

The L5178Y Mouse Lymphoma TK assay was studied extensively to determine if this mammalian cell assay for gene mutations at the thymidine kinase (TK) locus could provide valid, interpretable determinations of mutagenic potential, and whether this information is of value in the safety evaluation of chemicals. We first determined that test-derived TFT^R mutants were phenotypically stable, possessing little or no thymidine kinase activity as measured by labeled thymidine uptake, but demonstrating 100% cross resistance to bromodeoxyuridine. Common solvent vehicles such as acetone, dimethylsulfoxide and ethanol were shown to produce little cytotoxicity and no mutagenic activity when present at 1% levels. Out of a total of 10 noncarcinogens tested, all were negative when results were analyzed by a 2-sample log_et test on control and treated mutant count means. Of the 13 putative animal carcinogens tested, 10 were positive, 2 were negative (auramine O and sodium phenobarbital), and 1 showed sporadic activity (hydrazine sulfate) in the TK assay on the basis of test-derived t statistics. 2 compounds, 1,2-epoxybutane and ICR 191, which have been described as Ames positive non-carcinogens, were also positive in the TK assay. Although this sampling of a total of 29 compounds is insufficient for precise estimations of expected false-positive or false-negative frequencies, these data indicate the TK assay can be expected to detect a majority of carcinogens as mutagens including some missed by more established point-mutation assays.     

Révision systématiquedu genre Steginoporella smitt, 1873 (Bryozoa Cheilostomata)

Systematic revision of the genus Steginoporella: until now about eighty species were described. Only twenty recent species and thirty-four fossil ones are maintained. Several species and subspecies are new.The main interest of this revision is to establish a biostratigraphical scale: the settlement of this scale is based on the known stratigraphical distribution and on an attempt of phylogeny.The second advantage is ecological: all recent species live in marine tropical environment. The Steginoporella are good paleoecological indicators.At last, the establishment of a paleobiogeography, even incomplete and not definitive, allows to understand more easily recent distribution of Steginoporella connected with the great events of earth evolution.