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Stably transfected Balb-C 3T3 fibroblasts (clone 5), overexpressing a catalytically active tissue transglutaminase, showed a basal adenylate cyclase activity lower than control cells (clone 1). Several modulators of the adenylate cyclase activity (forskolin, Mn2+ and pertussis toxin) showed the existence of a marked negative control on the adenylate cyclase activity present in clone 5 cells. Very interestingly, this same marked negative control was also found in a Balb-C 3T3 fibroblast clone stably transfected with a mutagenized human tissue transglutaminase (mut277 cys > ser) virtually devoid of transglutaminase catalytic activity (clone Ser). Conversely, a significant increase of the adenylate cyclase activity was observed in bovine aortic endothelial cells after the lowering of tissue transglutaminase expression levels by the transfection of an eukaryotic expression vector containing the gene for tissue transglutaminase in antisense orientation. All these findings suggest a possible role for type II tissue transglutaminase as a negative modulator of the adenylate cyclase activity in different cell types, beside its transglutaminase enzyme activity.

Recent developments of the nuclear emulsion technology led to the production of films with nanometric silver halide grains suitable to track low energy nuclear recoils with submicrometric length. This improvement opens the way to a directional Dark Matter detection, thus providing an innovative and complementary approach to the on-going WIMP searches. An important background source for these searches is represented by neutron-induced nuclear recoils that can mimic the WIMP signal. In this paper we provide an estimation of the contribution to this background from the intrinsic radioactive contamination of nuclear emulsions. We also report the induced background as a function of the read-out threshold, by using a GEANT4 simulation of the nuclear emulsion, showing that it amounts to about 0.06 neutrons per year per kilogram, fully compatible with the design of a 10 kg$\times$year exposure., Revised version

The most convincing candidate as main constituent of the dark matter in the Universe consists of weakly interacting massive particles (WIMP). WIMPs must be electrically neutral and interact with a very low cross-section (σ < 10−40 cm2) which makes them detectable in direct searches only through the observation of nuclear recoils induced by the WIMP rare scatterings. In the experiments carried out so far, recoiled nuclei are searched for as a signal over a background produced by Compton electrons and neutron scatterings. Signal found by some experiments have not been confirmed by other techniques. None of these experiments is able to detect the track, typically less than one micron long, of the recoiled nucleus and therefore none is able to directly detect the incoming direction of WIMPs. We propose an R&D program for a new experimental method able to observe the track of the scattered nucleus based on new developments in the nuclear emulsion technique: films with nanometric silver grains, expansion of emulsions and very fast completely automated scanning systems. Nuclear emulsions would act both as the WIMP target and as the tracking detector able to reconstruct the direction of the recoiled nucleus. This unique characteristic would provide a new and unambiguous signature of the presence of the dark matter in our galaxy.

Tissue transglutaminase (tTGase) is a GTP-binding Ca2+-dependent enzyme which catalyses the post-translational modification via epsilon(gamma-glutamyl)lysine bridges. The physiological role of tTGase is not fully understood. It has been shown that in cartilage the expression of tTGase correlates with terminal differentiation of chondrocytes. Recent evidence suggests that the GTP-binding activity of tTGase may play a role in the control of cell cycle progression thus explaining some of the suggested roles for the enzyme. tTGase activity is present in primary cultures of epiphyseal chondrocytes and increases transiently upon retinoic acid (RA) treatment. Increase in enzyme activity occurs upon RA addition and is accompanied by a parallel increase in protein and mRNA levels. Stimulation of tTGase expression by RA correlates with suppression of cell growth and occurs independently of cell adhesion and cell differentiation. tTGase expression is not observed in MC2, a permanent chondrocyte cell line derived from retrovirus infected chondrocytes. RA treatment fails to activate tTGase expression in MC2 cells and to completely suppress cell proliferation. Our findings lend support to the idea that tTGase might play a role in non-dividing cultured chondrocytes. (C) 1999 Academic Press.

The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy.This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies.After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma.The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.

Transglutaminases (EC 2.3.2.13) catalyze the post-translational modifications of proteins by the formation of{var_epsilon}({gamma}-glutamyl)lysine insopeptide bonds. The number of transglutaminases recently described in eukaryotic cells includes at least five distinct enzymes that have been localized both intracellularly (tissue transglutaminase, keratinocyte transglutaminase, hair follicle transglutaminase) and extracellularly (factor XIIIa and prostate transglutaminase). Although these enzymes share some common features, such as the amino acid sequence in the active site and a strict calcium dependence for their catalytic activity, many differences in the biochemical and immunological properties have been described among the different members of this family. These findings suggest that each molecular form of transglutaminase, catalyzing the cross-linking of specific substrate proteins in specific biological districts, plays a different role in various physiological processes (i.e., blood coagulation, keratinocyte terminal differentiation, cell differentiation, apoptosis, seminal fluid coagulation, and sperm immunogenicity suppression). 10 refs., 1 fig.

The use of removable thin films for the abatement of hazardous particulates has many advantages. The easy removal and securing of materials, such as, broken glass, lead, beryllium, uranium, and biological agents, to name a few. Removable thin films are designed to trap and fix in the film's matrix by adhesion. Thin films can be applied to an existing contaminated area to fix and capture the particulates for removal. The nature of the removable thin films, after sufficient cure time, is such that it can typically be removed as one continuous entity. The removable thin films can be applied to almost any surface type with a high success rate of removal

A cDNA encoding for the human tissue transglutaminase gene has been used to identify the chromosomal localization of the corresponding structural gene. The precise chromosomal and subregional localizations have been established by using in situ fluorescence mapping with a recombinant lambda-Zap phage containing the full cDNA coding sequence. The study showed that the human tissue transglutaminase gene is localized on chromosome 20 and, more precisely, within the band 20q12. To date, this is the third member of the transglutaminase gene family to be mapped. Human factor XIIIa (plasma transglutaminase), human keratinocyte transglutaminase (type I), and human tissue transglutaminase (type II) genes, although codifying for homologous enzymes, are localized on three different chromosomes.

Penile metastases from bladder cancer are unusual. A case of a man, 50 years old, with undifferentiated bladder carcinoma submitted to radical cystoprostatectomy and ileal conduit is presented. Twelve months after the primary diagnosis the patient presented metastases of the penis.

We present data collected among men attending a free call service on information on erectile dysfunction (ED) activated in Italy during the period 1997-1999. Their attitudes towards discussion with their partner and physician about the condition are considered. Each subject, was asked if he was affected by ED (defined as inability to achieve and maintain an erection sufficient for satisfactory sexual performance). In the case of a positive answer, the subject was asked if he had ever discussed his condition with partner or a physician. A total of 12 761 subjects with ED called the service: 7265 (56.9%) reported to have discussed their condition with their partner. The proportion tended to increase with duration of ED, being 47.9% in subjects reporting ED lasting6 months and 59.9% in those reporting ED lasting3 y (w(2)(1) trend0.05). Likewise, the proportion of subjects reporting to have discussed ED with a physician was 50.3% (6416 subjects), being 33.6% in subjects with ED lasting6 months and 57.9% of those with ED lasting3 y (w(2)(1) trend, P0.01).

Erectile dysfunction is one of the factors influencing negatively the quality of life of patients in hemodialytic treatment. The international literature shows that erectile dysfunction is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialytic treatment. Fertility, libido and erectile dysfunction, suffer progressive worsening with time, in spite of hemodialysis. The availability of a drug like Sildenafil can improve the quality of life of the patient and give him a normal sexual activity.Twenty patients between 29 and 51 years, were selected; 2 of these had been subjected to renal transplant, with a dialytic treatment time varying from 3 to 13 years. Before the treatment all the patients have been subjected to an andrological screening (testosterone, prolactin, penile color Doppler ultrasound) and proposed the IIEF test. Therapeutic strategy included the assumption of the drug in the days in which the patients were not subjected to dialysis, with an interval from 1 to 3 weeks between assumption and another. The dose was 25-50 mg. At the end of three months of therapy the patients were again subjected to the IIEF test.All patients reported an improvement in sexual activity and sexual desire with very good repercussions on general and psychophysical conditions.The results demonstrate at least that Sildenafil is also effective in uremic patients in dialytic treatment or after renal transplant and that it can therefore resolve one of the main problems for the normal development of the life of such patients.

A review has been made on the role of nitric oxide in the physiology and pathophysiology of penis, bladder, prostate and the nervous structures involved in the urinary control. NO is an essential mediator in penile erection and his action can be modulated by sildenafil. Nitric oxide could be involved in bladder detrusor relaxation and in the development of interstitial cystitis. Little is known about the role of nitric oxide in the physiology and pathophysiology of the prostate: this molecule is released by the epithelial and stromal cells of the prostate, and by the prostatic nerves. Actually some studies hypothesize a role played by nitric oxide in benign prostatic hyperplasia development.

A study of antibody levels (in saliva and blood) against common vaccine antigens was performed in a population of 32 children suffering from recurrent upper respiratory tract infections (URTI). None of the patients had primary or secondary immunodeficiency syndromes or other known predisposing factors for respiratory diseases. Titres of the isotype-specific antibodies immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) against two vaccine antigens--poliovirus type 3 (P3) and tetanus toxoid (TT), a viral antigen and a bacterial antigen, respectively--were measured in unstimulated saliva and serum, both in patients and in 24 healthy children (controls), by using a standard enzyme-linked immunosorbent assay (ELISA). In addition, levels of total IgA and avidity of IgA antibodies to both P3 and TT in saliva were evaluated. No difference was found between patients and controls as to levels of total IgA, or specific IgA and IgM antibodies against both P3 and TT in saliva. Furthermore, the avidity of salivary IgA antibodies against the two antigens did not differ between the two populations. However, the average concentrations of saliva-specific IgG antibodies to both the viral and the bacterial antigen were significantly lower (p0.01 for P3 and p0.05 for TT, respectively) in saliva of children with recurrent URTI, whereas no difference was found in serum for any immunoglobulin isotype determined compared with healthy individuals. The results of the present study provide suggestive evidence for the existence of subtle IgG-restricted defects in antibody responses at the mucosal level, but not at the serum level, in some children with undue susceptibility to URTI.

The ability of several cereal proteins to act as substrates for transglutaminase purified from guinea pig liver was investigated. Among the various dietary proteins tested, wheat glutelins and gliadins, as well as purified A-gliadin, were found to be the most effective acyl donor substrates for transglutaminase. In particular, these proteins seemed to be able to produce not only γ(glutamyl) spermidine adducts but also polymeric complexes, probably through intermolecular e(γ-glutamyl)lysine crosslinks. In the case of A-gliadin, the single lysyl residue occurring in the amino acid sequence (Lys-186) is supposed to act as acyl acceptor site. The peptic-tryptic fragments of gliadins and prolamines of different origin behaved as transglutaminase substrates similarly to native gliadin, mostly in giving rise to large Mr polymers. These results are consistent with the hypothesis that animal transglutaminase may be involved in the metabolism of cereal dietary proteins, or of their peptide fragments, when present either in the intestinal lumen or in the mucosal cells.

Proteins and peptides responsible for the celiac small intestinal lesion inhibit both the enterocyte recovery of in vitro cultured flat celiac mucosa and the in vitro development of fetal rat intestine, They also agglutinate K 562 (S) cells. Using these three in vitro systems (cultured human celiac and rat fetal intestine and cell agglutination), it is shown that several small-molecular-weight amines, mostly the polyamines spermidine and spermine, prevent and reverse K 562 (S) cell agglutination induced by gliadin peptides, whereas they do not prevent cell agglutination induced by concanavalin A and wheat germ agglutinine Some of these amines also protected in vitro developing fetal rat intestine and fiat celiac mucosa from the damaging effect of gliadin peptides. This protective effect may be related to the trophic activity exerted by amines on the intestine and/or the effect of amines on the functions of intestinal brush border or intracellular membranes involved in the intestinal handling of gliadins.

One of the major proteins secreted from the rat seminal vesicle epithelium, namely SV-IV, was shown to act in vitro as acyl donor and acceptor substrate for transglutaminase from both guinea pig liver and rat anterior prostate secretory fluid. Electrophoretic and chromatographic experiments indicated that the enzyme catalyzed the formation of multiple modified forms of SV-IV. In the absence of small Mr amines, transglutaminase was able to produce at least six different molecular forms of the protein, hall of which possessed an Mr higher than that of native SV-IV. These findings suggested that a variable number of intermolecular, and perhaps intramolecular, crosslinks were formed between one or both glutamine residues and one or more lysine residues occurring in the SV-IV polypeptide chain. In addition, at least three modified forms of the protein were produced by transglutaminase in the presence of high concentrations of spermidine, thus indicating the formation of different (-glutamyl)polyamine derivatives of SV-IV. Rabbit uteroglobin and rat anterior prostate secretory protein(s) were also shown to be able to covalently bind spermidine in the presence of the enzyme. The possible biological significance of transglutaminase-mediated modifications of SV-IV, as well as of other proteins occurring in the mammal seminal fluid, are discussed.

We report the results of a biological and molecular study carried out on 11 Italian families, with a total of 111 individuals in which adult dominant polycystic kidney disease segregates. A restriction fragment length polymorphism analysis was performed. Two families have shown a genetic heterogeneity even if not phenotypically different from the other ones: they resulted unlinked to 16p markers. A prenatal diagnosis has been performed in a family of the linked type.

Genetic defects of the CD95 (Fas/Apo-1) receptor/ligand system, has recently been involved in the development of human and murine autoimmunity. We investigated whether a deregulation of the ;tissue' transglutaminase (tTG), a multifunctional enzyme which is part of the molecular program of apoptosis, may act as a cofactor in the development of autoimmunity. We found that MRLlpr/lpr, which are characterized by a defect in the CD95 receptor and suffer of a severe systemic lupus erythematosus-like disease, produce large amounts of circulating tTG autoantibodies. This phenomenon is paralleled by an abnormal accumulation of an inactive enzyme protein in the accessory cells of lymphoid organs. To investigate the molecular mechanisms by which tTG inhibition may contribute to the development of autoimmunity we generated a cell culture model system consisting of L929 cells stably transfected with a full length tTG cDNA. When L929 cells were killed by Tumor Necrosis Factor alpha (TNFalpha) a pronounced release of DNA and Lactate Dehydrogenase (LDH) was observed. Overexpression of tTG in these cells largely prevented the leakage of macromolecules determined by TNFalpha treatment, an effect which is abolished by inactivating the enzyme cross-linking activity by a synthetic inhibitor. These in vitro observations provided the basis to explain the increased levels of plasmatic LDH we detected in MRLlpr/lpr mice. These data suggest that lack of an active tTG may represent a cofactor in the development of autoimmunity.

Sexually transmitted diseases (STDs) may recognize multiple etiological agents. Among them, Chlamydia trachomatis (Ct) and herpes simplex virus type 2 (HSV-2) cause symptomatic, subclinical and asymptomatic infections of the urogenital tract which can lead to serious sequelae. In the present study the coinfection and superinfection by Ct and HSV-2 in epithelial cultured cells from human cervix (HeLa 229) are described. A double infection, followed by the intracellular synthesis of chlamydial and viral antigens, was established. Both synergistic and interfering phenomena were recorded: viral antigen synthesis resulted increased whereas Ct inclusion bodies were produced to a lower extent.

Human immunodeficiency virus envelope glycoprotein gp120, but not its precursor gp160, covalently incorporates both spermidine and glycine ethyl ester in the presence of Ca2+ and transglutaminase purified from guinea pig liver. The examined ability to act as enzyme substrate of various glutamine-containing gp120 fragments, including the principal neutralizing determinant, the CD4 binding domain, and the sequence 254-274, suggested to be involved in post-binding events and in virus entry in the host cell, indicated the glutamine-265 as possible reactive acyl donor site of the protein.

Proteins and peptides responsible for the celiac small intestinal lesion inhibit both the enterocyte recovery of in vitro cultured flat celiac mucosa and the in vitro development of fetal rat intestine. They also agglutinate K 562 (S) cells. Using these three in vitro systems (cultured human celiac and rat fetal intestine and cell agglutination), it is shown that several small-molecular-weight amines, mostly the polyamines spermidine and spermine, prevent and reverse K 562 (S) cell agglutination induced by gliadin peptides, whereas they do not prevent cell agglutination induced by concanavalin A and wheat germ agglutinin. Some of these amines also protected in vitro developing fetal rat intestine and flat celiac mucosa from the damaging effect of gliadin peptides. This protective effect may be related to the trophic activity exerted by amines on the intestine and/or the effect of amines on the functions of intestinal brush border or intracellular membranes involved in the intestinal handling of gliadins.

One of the major proteins secreted from the rat seminal vesicle epithelium, namely SV-IV, was shown to act in vitro as acyl donor and acceptor substrate for transglutaminase from both guinea pig liver and rat anterior prostate secretory fluid. Electrophoretic and chromatographic experiments indicated that the enzyme catalyzed the formation of multiple modified forms of SV-IV. In the absence of small Mr amines, transglutaminase was able to produce at least six different molecular forms of the protein, half of which possessed an Mr higher than that of native SV-IV. These findings suggested that a variable number of intermolecular, and perhaps intramolecular, crosslinks were formed between one or both glutamine residues and one or more lysine residues occurring in the SV-IV polypeptide chain. In addition, at least three modified forms of the protein were produced by transglutaminase in the presence of high concentrations of spermidine, thus indicating the formation of different (gamma-glutamyl)polyamine derivatives of SV-IV. Rabbit uteroglobin and rat anterior prostate secretory protein(s) were also shown to be able to covalently bind spermidine in the presence of the enzyme. The possible biological significance of transglutaminase-mediated modifications of SV-IV, as well as of other proteins occurring in the mammal seminal fluid, are discussed.

Two transglutaminase-mediated modifications of the rat epididymal spermatozoon surface were demonstrated in vitro. Transglutaminase was effective in promoting the binding of spermidine to the sperm. Moreover, the enzyme, by reacting with one of the major proteins secreted by the rat seminal vesicle epithelium, produced a modified form of the protein with a higher molecular weight and the capability of binding to the sperm cells. A specific physiological role for the enzyme, bringing about modifications of the rat sperm surface in the seminal fluid environment, is suggested.

Forty subjects to whom artificial ventilation was applied before death because of respiratory failure, mainly due to cerebral contusions, were examined. The presence of characteristic pulmonary lesions was confirmed. Moreover, the demonstration of membranaceous PAS- (periodic acid- Schiff)-positive material in the lumen of glomerular capsules, and of PAS-positive granules in hepatic, tubular and myocardial cells, together with the interstitial oedema of all the organs and the reticuloendothelial reaction, indicates that pulmonary alterations can be considered only a part of a general disease due to oxygen toxicity.

Swiss male albino mice were treated subcutaneously with the main cannabinoids (CBN, CBD, delta9-THC) at the dosage of 1 mg/kg per day for 30 days, and with the crude resin. At the end of the treatment, after supramaximal stimulation of the sciatic nerve, a significant decrease of both maximal twitch and tetanus tensions was observed in delta9-THC-treated animals; CBD and resin treatment produced some decrease in active tension, while CBN treatment induced an enhancement of the contractile strength. Histology showed lesions interpretable as due to muscular dystrophy. Analysis of protein and hydroxyproline muscular content showed a marked reduction in protein in all treated animals, with a corresponding high increase in hydroxyproline content.

Tissue transglutaminase (tTgase) is a GTP-binding Ca(2+)-dependent enzyme which catalyses the post-translational modification of proteins via epsilon(gamma-glutamyl) lysine bridges. Recent evidence suggests that the GTP-binding activity of tTgase may be important in intracellular signaling thus explaining some of the diverse suggested roles for the enzyme. In the following work a malignant hamster fibrosarcoma (Met B) has been stably transfected with both the full length tTgase cDNA (wild type) and a mutant form of the cDNA whereby the active site cysteine (Cys 277) has been replaced by serine. Expression of this mutant cDNA leads to a protein with GTP binding activity which is deficient of protein crosslinking activity. When synchronised into S-phase and allowed to progress through the cell cycle tTgase transfected clones (both mutant and wild type), when compared to transfected controls, show a delayed progression from S-phase to G2/M when analysed by flow cytometry which appears to be elicited by the G-protein activity of the tTgase.

Binding sites for [14C]spermine have been identified in rat brain cortex subcellular fractions. The binding, characterized by using synaptosomal membranes, is specific for spermine. It was not detected below 20 degrees C and increased about three/four-fold with a temperature rise of 10 degrees C. Binding occurred only in the presence of -SH reducing agents. It was completely suppressed by metal chelating agents, and was stimulated about four-fold by 1-5 x 10(-5) M Fe2+. Smaller increases were observed in the presence of Mn2+, Ni2+, Ca2+, Mg2+, and Zn2+; in contrast, millimolar concentrations of most divalent cations inhibited the binding differently (Mn2+ = Ni2+ = Zn2+ = Co2+ much greater than Mg2+ greater than Ca2+). Bound radioactive spermine was not displaced by the addition of high concentrations of unlabelled polyamine or chelating agents, nor by precipitation and washing of the membranes with 10 percent trichloroacetic acid, or by boiling of the precipitate in the presence of 1.0 percent SDS and 10 percent beta-mercaptoethanol. The trichloroacetic acid precipitate showed two radioactive bands, corresponding to low Mr (less than 8,000) components, after SDS-polyacrylamide gel electrophoresis and fluorography. The Fe2+-stimulated [14C]spermine binding was neither influenced by a previous heating of the membranes at 100 degrees C for 30 min nor by trypsin or pronase digestion, whereas the heat-treatment increased the binding occurring in the absence of Fe2+ by about two fold. A non-enzymatic formation of a spermine-metal complex tightly bound to some membrane peptide(s) is suggested.

Both alpha- and beta-endorphin were shown to incorporate radioactive polyamines during incubation in the presence of purified transglutaminase and Ca2+, spermine acting as the best acyl acceptor substrate. The endorphin labelling is dependent on the time of exposure to the enzyme and on the substrate concentration. In the absence of acyl acceptor polyamines, isotopically labelled beta-endorphin gives rise to high molecular weight radioactive polymer(s). Moreover, when different proteins acting as transglutaminase substrates are added, beta-endorphin produces heterologous structures. These data indicate that the glutamine-71 of the beta-lipotropin chain, contained in both alpha- and beta-endorphin, functions as acyl donor substrate for the enzyme and that at least one beta-endorphin lysyl residue can serve as acyl acceptor.

Since a specific inhibition of cerebral spermidine (Spd) synthase activity by alicyclic amines was preliminarily observed in vitro, we examined the in vivo inhibitory effectiveness of dicyclohexylamine (DCHA) on Spd biosynthesis in 21-day-old rat brain. For this purpose a previously reported HPLC procedure (Porta et al., 1981a) was modified to analyze the cerebral levels of DCHA at the time of polyamine determinations. The intraperitoneally injected DCHA was shown to cross the blood-brain barrier easily, reaching high levels in the cerebral tissue (approximately 750 nmol/g brain) within 1 h of its administration. The effect of the drug on the polyamine metabolism resulted in a significant depletion of Spd biosynthesis from the sixth hour after the treatment and in an earlier and prolonged increase of the putrescine (Pt) steady-state levels. Conversely, the spermine (Spm) endogenous pools remained unchanged throughout the 24-h post-DCHA period. Moreover, following the intracerebral administration of [1,4-14C]Pt, significantly lower specific radioactivity (s.r.a.) values for labeled Pt and Spd were recorded in the brains of DCHA-treated animals. Conversely, after intracerebral [14C]Spd injection, the s.r.a. of newly formed [14C]Spm remained unchanged, confirming the specificity of the DCHA effect on the Spd biosynthesis.

Recent progress in ABO typing of body fluids and stains have been obtained by highly sensitive methods such as Inhibition of Hemagglutination on Microtiter Plates (HIM) by using monoclonal antibodies (Fiori, 1985), enzyme-immunoassays (EΙA) as the ELISA procedures (Inoue and Okada, 1978; Fletcher 1984; Bolton and Thorpe, 1986; Mudd 1986; Mukoyama and Sakai 1986; Takatori and Tsutsubuchi 1986), and EIA-like Mixed Agglutination on Solid Phase (MASP; Fiori and Chiarotti, 1 985, Silvestri et al. 1981).

Three groups of subjects (I with infections of the lower urinary ways; II with chronic pyelonephritis; III healthy controls) were treated with pipemidic acid for 10 consecutive days and the behaviour of their urinary NAG and AAP was studied. It was discovered that the healthy group and the patients with infections of the lower urinary ways showed no significant variations in the urinary activity of the two enzymes following the administration of pipemidic acid. However there was a distinct reduction in both enzymes in patients with chronic pyelonephritis who presented demonstrable bacterial sensitivity to the drug. Apart from the fact that it produces no nephrotoxic effects at least in the doses used and for the treatment period adopted, the drug is therefore considered to reduce renal inflammation that is beneficial to individuals with chronic interstitial nephropathy.

A simple empirical method based on linear relation-ships between certain types of enzymuria (NAG, LDH, GRS, Isoenzymes I and V of total dehydrogenase lactate) has been used in a series of 80 patients presenting chronic nephropathy [40 interstitial nephropathy (IN) and 40 glomerulonephritis (GN)]. Diagnosis made on the basis of the results obtained in each case was identical to that based on clinical findings (in the absence of enzymuria determinations). This method, if confirmed on a larger number of statistically significant data, might be useful to obtain a differential diagnosis between I.N. and G.N. only assaying these few enzymurias. Prefixed relationships could be employed on a larger group of patients with other diseases studied for comparative purposes. Furthermore, this method appears to be fast and unexpensive.

Lymphocytes are unique cells evolved to guard, in collaboration with other accessory cells (such as macrophages), the selfness of vertebrate organisms against the invasiveness of alien elements or macromolecules. Recognition of intruders is obtained either by cell-cell or cell-molecule interactions, in which sophisticated biochemical machineries, endowed in the lymphocyte plasma membrane, are set in action as important parts of defence mechanisms used by singles to defend their own individualities. As a consequence of the activity of all these surface molecular devices, a metabolic turmoil is triggered in these cells. Numerous intra- and extra-cellular biochemical signals are released, bringing about in a short time marked modifications of a number of important metabolic pathways such as those related to: 1) energy production; 2) control of electrolyte traffic in the cell; 3) transcription and translation of specific messenger RNA; 4) biosynthesis of tRNA and rRNA; 5) control of DNA replication and cell division1–10.

However adequately treated, surface carcinomas of the bladder recur sooner or later with infiltration found in about 10% of cases. Any development that may offer therapeutic progress and reduce the incidence of recurrences is therefore of primary importance. Two homogeneous groups of patients were selected for the present study: 35 were given Adriamycin and 25 Mitomycin C. In evaluating results, the incidence of recurrences in relation to the primary neoplasia and the existence of single or multiple tumors was analysed. It is concluded that Mitomycin C in association with either T.U.R. or T.V.R. is a particularly useful and indubitably effective form of topical chemotherapy in cases of single or multiple primary neoplasias.