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Purpose: To report our personal experience with the locoregional treatment of breast cancer., Material and Methods: Eighteen patients aged 33-67 years (mean: 54 years) were treated with 31 sessions of intra-arterial antiblastic infusion, 5 of them for neoadjuvant purposes (Group 1), 5 for palliation in unresectable tumors (Group 2) and 8 for cutaneous recurrences after mastectomy (Group 3)., Results: 2/5 CR and 3/5 PR were obtained in Group 1; 2/5 lesions were made resectable and 3/5 RP obtained in stage III or unresectable lesions (Group 2). Finally, 3/8 CR, 3/8 PR, 1/8 SD and 1/8 PD were observed in Group 3. An objective response according to WHO criteria was demonstrated in 15/18 cases (88%). We had no post-treatment hematologic complications, but one patient presented focal subcutaneous sclerosis and one cutaneous necrosis., Conclusions: The morphological efficacy of intraarterial antiblastic infusion in our series was similar to that of other series. No definitive conclusions can be drawn yet about clinical results and long-term survival. This poorly invasive and low risk procedure, which should be combined with other treatments, permits to reduce the extent of surgery and to treat skin recurrences.

Background: Urinary tract infections (UTI) are a common usual pathological event. They relapse often due to the periurethral colonization of microorganisms from the intestinal bacterial flora. They also constitute an important and considerable social and clinical problem. The absence of inducing organic conditions or an infective focus at the base of the pathogenetic mechanism suggests the existence of alterations of the immune response of the subject., Materials and Methods: In this work we wanted to verify if, in those subjects with relapsing UTI (more than four events every year) cure with "biological" response modifiers, particularly "thymopentin", meaningfully reduced the number of events., Results: The results obtained confirm that for those cases in which the chemo-antibiotic therapy did not have the expected results, it is rational to support it with an immune-modulating drug (thymopentin). In fact the post-therapy reduction of UTI observed during two years of follow-up is statistically significant when compared to the average of UTI before therapy., Conclusions: The "cost-benefits" analysis should prove to be a saving in favour of the use of thymopentin, taking into consideration the reduction of chemo-antibiotics consumption and the lower number of working hours lost every year.

Purpose: We report four cases of advanced malignant cancer of the gallbladder treated with hypoxic hepatic perfusion., Material and Methods: Hypoxic hepatic perfusion is currently used to treat diffuse hepatic metastases: the common hepatic artery is occluded with a balloon catheter and then a large amount of antiblastic solution is infused into the liver. Hypoxia and slow flow increase the effect of the drug on neoplastic tissue. Two sessions were performed in three patients with an interval ranging 2-4 months, while one patient underwent a single session. The drug was Mitomycin C, whose dose ranged 20-40 mg (mean: 30 mg). Blood filtration was performed after one of the six procedures only and can be considered unnecessary., Results: Acute gastric bleeding appeared in a patient after the embolization of the right gastric artery with bucrylate during the first session performed to avoid drug reflux into gastric wall arteries. No other technical or clinical complications occurred. An objective morphological response (tumor necrosis or reduction in size > 50%) was observed in all patients after the first session. CT findings were stable in two of three patients submitted to a second session, while local progression was observed in the other patient. Complete clinical response was achieved in all symptomatic patients. No WHO toxicity was observed., Discussion and Conclusions: The rate of positive morphological and/or clinical responses after hypoxic perfusion was very high in our experience, even though our series was small. Recurrences were found in two patients some months later, which suggests the need of long-term follow-up. Hypoxic perfusion can be nevertheless considered as a new and interesting therapeutic approach for advanced malignant gallbladder cancer, with a strong short-term effect on the lesion and good results on clinical symptoms.

Purpose: We report the morphological and clinical results in a series of patients with advanced thoracopulmonary, abdominal, pelvic and lower limb tumors treated with stop-flow perfusion (SFP)., Material and Methods: We performed 77 SFPs with the percutaneous angiographic technique in 55 patients (25 women and 30 men; mean age: 53 years). Eighteen thoracic perfusions with aortocaval block (ASI) were performed in 11 patients, 33 abdominal hypoxic perfusions (HAP) in 26 patients, 17 hypoxic pelvic perfusion (HPP) in 11 patients and 9 hypoxic lower limb perfusions (HILP) in 7 patients. 42/77 procedures were followed by hemofiltration., Results: No technical complications were observed. Twenty-eight patients in our series are still alive (mean follow-up: 14 months) and 23 have died (mean survival: 8 months), 20/23 of them (87%) for disease progression. Three of 77 patients (3.8%) died within 7 days of the procedure (2 AS, 1 HAP). At CT or MR follow-up, responses > 50% were observed in 56% of the procedures and clinical CR was achieved in 53/77 patients (69%). In the subgroups classified by procedure, positive responses were observed in 56, 48, 59 and 78%, respectively for ASI, HAP, HPP and HLP. Clinical CR was observed in 67, 67, 71 and 78%, respectively. The death rate for disease progression relative to the overall death rate was 100, 86, 75 and 100%. Hematologic toxicity according to WHO criteria (mean: 2) was observed in 77% of the whole of procedures (59/77). Statistical analysis showed no relationship between morphological responses and type of antiblastic drug or previous antiblastic treatments., Conclusions: SF procedures permit the effective control of many advanced tumors which cannot be treated otherwise, with a high rate of positive morphological and of complete clinical responses. The best results were obtained in hypoxic perfusion of the lower limb. The results were not correlated with previous antiblastic treatments. However, the high rate of sequels and the low hematologic tolerance of those procedures must be emphasized.

Patients and Methods: 27 patients (14 men and 13 women aged 35 to 71 years; average: 59 years), with 3-11 months' follow-up (average: 5 months) were treated for hepatic metastases (17/22 from colorectal, 10/22 from other primary tumors) with hypoxic locoregional hepatic perfusion. Sixteen of 22 patients had been pretreated with resection, systemic chemotherapy or freeflow locoregional infusion. Our protocol consists in blocking arterial flow with an occlusion balloon catheter inflated in the hepatic artery; the main catheter channel is connected with a pump system and 250-300 ml saline with 30-40 mg Mitomycin C are perfused in the arterial hepatic system. Embolization with a gelatin sponge is performed after the end of perfusion., Results: 19/27 patients are still alive, and 8/27 are dead but death was caused by the progression of intrahepatic disease in only 2/27 (7%). Iatrogenic lesions of the arterial wall were shown at follow-up DSA in 15/22 patients (56%). Thirteen CR (48%) and 9 PR (33%) were demonstrated at CT follow-up, amounting to 81% of objective responses. Follow-up showed a clinical CR in 12/18 symptomatic patients (66%). No case of hematologic toxicity was observed. Mean CEA values changed from 129 to 10.60. Twelve of 27 patients exhibited mild posttreatment sequels, none of them lasting longer than three days; ischemic cholecystitis was seen in 3/15 cases (14%)., Conclusions: The occlusion catheters on the market are not optimal for this procedure; the axillary percutaneous approach is advantageous. CR rate was very high in our series but the objective response rate doses do not differ from those in the series with free-flow procedures. The highest CR rate was observed in untreated patients and in hypervascularized lesions; the rate of clinical sequels was low, clinical CR rates were high and there was no hematologic toxicity. This well-tolerated procedure provides good local disease control, but the high rate of deaths from extrahepatic progression suggests that systemic chemotherapy and long-step intraarterial perfusion be combined.

The puborectalis syndrome is a defecation disorder supported by the nonrelaxation of puborectalis sling with consequent dyschezia. We report on a series of 98 patients submitted to clinical examination, defecography, anorectal manometry, electromyography and intestinal transit time studies. Puborectalis anatomy and physiology are briefly reviewed. The main symptoms of puborectalis syndrome in our patients were incomplete defecation (89%) and intermittent evacuation (63%); 28% of patients turned to finger defecation. In all patients, defecography showed an abnormal increase in puborectalis impression on the posterior anorectal wall, reduced anorectal angle opening under straining (mean value: 113 degrees) and prolonged expulsion time with barium pooling in the ampulla (mean evacuation time: 38 seconds). Such anorectal abnormalities as rectal mucosal prolapse (47 cases) and anterior rectocele (36 cases) were also associated. In 33 of 98 patients (34% of cases), sling assessment by bidigital palpation at preliminary clinical examination revealed puborectalis hypertonia, which was later confirmed at defecography. Manometry was not specific for the diagnosis of puborectalis syndrome, detecting increased external anal sphincter pressure under straining in 24 of 35 patients (68.8%). Puborectalis activity was increased under straining in 16 subjects submitted to electromyography. Intestinal transit time studies showed a typical expulsion delay and radiopaque marker pooling in the ampulla in 18 of 23 patients (78.2%). In our experience, defecography is a useful, simple and noninvasive method for the accurate diagnosis of the puborectalis syndrome.

The authors introduce a new technique for performing aortic stop-flow infusion (ASI) or hypoxic abdominal perfusion (HAP) to treat advanced thoracoabdominal tumors, via an angiographic percutaneous approach. To date, the maneuver has always been performed with surgical exposure of vascular sites in the groins. The materials available on the market were initially used and then dedicated materials have been developed, such as 11-F vascular sheaths, 8-F catheters, latex balloons with maximum phi's of 4 cm and maximum capacity of 70 ml. We performed 72 maneuvers in 56 patients during 22 months. No technical or instrumental complications occurred and all treatments were successful. Three patients (6%) died within 12 hours, two because of ARDS following thoracic perfusion and one for acute renal failure and disseminated intravascular coagulation following abdominal perfusion. The percutaneous approach provides the same mechanical-occlusive efficacy for aortocaval occlusion and therefore the same therapeutic results as surgery, but it has fewer risks of technical complications and no technical failures. Moreover, this technique is more repeatable and less expensive than surgery and its hospital stay and recovery time are shorter. To conclude, the ASI/HAP procedure is an interesting therapeutic chance in otherwise untreatable advanced cancer patients offering several prospects of technical and pharmacologic development to further increase its efficacy.

Defecography (DG) is a useful method to detect many morpho-functional deformities of anus and rectum and pelvic floor. We report on a clinical and radiologic study of 165 patients (36 men and 129 women) suffering from defecation disorders and rectal muscosal prolapse (RMP). All the patients had been submitted to clinical examination, endoscopy and double contrast enema to rule out organic colorectal conditions. DG was performed with a dedicated conmode and high-density barium and videorecorded on VHS cassettes to assess the dynamics of evacuation phases and to reduce exposure doses. DG showed single RMP in 28% of cases and multiple RMP in 72% of cases; the condition was isolated in 22% of cases, while in 88% of cases it was associated with other anorectal dysfunctions, such as rectocele (65%), perineal descent syndrome (PDS) (15%), puborectal muscle syndrome (14%) and intussusception (8%). RMP appeared at DG as a wall defect bulging into rectal lumen, which was more evident under straining and during barium evacuation. In 12 patients with multiple RMP, dynamic CT of the pelvis was carried out to study the whole pelvic floor and in 5 cases it showed levator ani diastasis. Fifty-eight patients were submitted to surgery by elastic binding of RMP; DG follow-up showed RMP remission in 47 patients, single RMP relapse in 3 patients and multiple RMP relapse in 3 patients. One patient with PDS and intussusception was submitted to rectopexy and mucosectom.

In the past years Moraxella (Branhamella) catarrhalis has finally gained respect as a pathogen thanks to the many reports of its causal role. The intent of this review is to provide a critical evaluation of the intent of this review is to provide a critical evaluation of the microbiological features (taxonomy, diagnosis, virulence, epidemiology and drug resistance), clinical diseases and therapy of this microorganism

This paper explores the means by which lighter safety regulations alter the precautionary behavior of 200 subjects in a field test of cigarette lighters with a child-resistant feature. The new lighter design leads respondents to believe the lighters are safer, but there is no clear-cut evidence that the effect on perceived risk levels is excessive. Using the estimated relationship between cigarette lighter risk perceptions and a variety of measures of precautions, this paper provides explicit estimates of the effect of regulations on precautionary behavior and on lighter safety. On balance, the child-resistant feature will reduce fire-related injuries by much more than any diminished precaution taking.

Several lines of evidence suggest that nitric oxide (NO), generated through nitric oxide synthase (NOS) by cleavage of terminal guanidino nitrogen from L-arginine, mediates tumor cell killing by mononuclear phagocytes. Natural killer (NK) cells are cytotoxic effector cells that lyse a variety of tumor and virus-infected cells in a MHC-unrestricted manner. NK cells cultured with interleukin 2 proliferate and acquire the ability to lyse a wide range of targets, including NK-resistant tumor cells (LAK activity). The present study was designed to investigate whether a NOS pathway exists in fresh or IL-2-activated NK cells and to assess the importance of NO synthesis in their activation and cytotoxic functions. NKR-P1 triggering, which is known to induce NK cell activation and mediate reverse ADCC, was able to induce arginine metabolism with consequent increase of nitrite and citrulline levels. Moreover, stimulated NO synthesis leads to guanylate cyclase activity with consequent cGMP generation. We also report that cytotoxic activities of fresh or IL-2-activated NK cells appear to be dependent on arginine levels in medium. Tumoricidal activity of both these effector cells, assessed against YAC-1 and P815 target cells, respectively, was indeed significantly reduced when cytotoxic assays were performed in arginine-free medium or in the presence of the L-arginine analog L-N-monomethyl-arginine, which inhibits nitroxide formation from L-arginine. Normal levels of cytotoxic activities could be restored by addition of exogenous L-arginine. NO generation by NK and LAK cells, determined as nitrite, citrulline, and cGMP synthesis, correlated well with their cytotoxic activities. Moreover, NOS activity gradually increased during the LAK generation and correlated well with the increasing capability of IL-2-activated NK cells to lyse NK-resistant targets, such as P815.

The SCID-hu mouse, a severe combined immunodeficient mouse transplanted with human hematopoietic cells, has been proposed as an experimental model for HIV-1 infection. However, like other animal models for infectious diseases, the SCID-hu mouse should provide the replication of the experimental agent without conferring any alteration during growth in the host. In this study using Southern blot hybridization, in situ hybridization and PCR analysis we demonstrate the presence of specific murine retroviral sequences in human cells recovered from the in vivo passages in SCID mice. Since the acquisition of endogenous retrovirus by human cells was demonstrated after their growth in nude mice, the data reported here extend this observation to the SCID model.

Videoproctography has proved to be a useful diagnostic technique to investigate anorectal disorders; it can provide morphological and functional information which no other diagnostic method yields. From a series of 898 videoproctographs, the findings of 117 patients with rectal intussusception were retrospectively reviewed. The most common symptoms were an incomplete emptying feeling (93% of cases), obstructed defecation (78%), and a feeling of upright rectal weighting (71%). Of the three known types of rectal intussusception, the most common type was distal intussusception (44%), followed by the rectoanal type (38%) and finally by the proximal type (19%). The three types of intussusception were frequently (42%) associated with other disorders of rectal ampulla and especially with rectocele (15%), mucosal prolapse (8%), and descending perineum syndrome (12%); they had different clinical correlations and proctographic patterns and could be recognized in different defecation phases. In our personal experience, proctography with videorecording was a useful diagnostic tool in the dynamic assessment of this morphofunctional disorder which represents one of its major indications.

We tested whether inhibition of carnitine acyl-transferase-1 (CAT-1) during coronary artery occlusion can limit infarct size (IS) by suppressing accumulation of long-chain acylcarnitines (LCAs), potentially cytotoxic intermediates of fatty acid metabolism. The CAT-1 inhibitor 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) was administered to dogs before 90-min occlusion and 4-h reperfusion of the left anterior descending or left circumflex coronary artery (LAD, LCX). Dogs in the LAD occlusion series received 7.5 (n = 5) or 15 (n = 2) mg/kg POCA intravenously (i.v.); dogs in the LCX occlusion series received 15 mg/kg i.v. (n = 7); an equal number were treated with drug vehicle. Biopsies were obtained for determination of myocardial LCAs. The region at risk and IS were delineated by dye injection and tetrazolium staining. In vehicle-treated dogs, myocardial LCAs (in picomoles per milligram of wet weight +/- SEM) increased from 11 +/- 3 to a peak of 75 +/- 24 during LAD occlusion and from 32 +/- 10 to 192 +/- 55 during LCX occlusion. In POCA-treated dogs LCAs increased from 12 +/- 2 to only 33 +/- 13 pmol/mg wet weight during LAD occlusion (p < 0.05 vs. vehicle) and did not increase significantly during LCX occlusion; 22 +/- 8 to 27 +/- 5 pmol/mg wet weight (p < 0.005 vs. vehicle). LCX occlusion resulted in larger areas at risk and larger infarcts (as a percentage of left ventricle) than did LAD occlusion. IS as a percentage of the region at risk did not differ significantly among the experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute otitis media (AOM) is an infection frequently found in children, but tends to be less frequent with age and its frequency in adults is only about 1%. The etiology of AOM in children is prevalently bacterial; numerous studies have shown the most common etiological agents. But the etiology in adults has not been well studied. The authors examined 40 cases of AOM in adults, the pathologic material was obtained by needle aspiration; in 32 samples there was bacterial growth. In the majority of the cases (94%) the bacteria isolated were the same as those found in children: S. pneumoniae, H. influenzae and B. catarrhalis; much rarer were S. pyogenes and S. aureus. On the potential beta-lactamase producing strains, this activity was measured. From our findings we believe that there is the necessity to have a rational antibiotic therapy (due to the difficulty in obtaining pathologic material) with active drugs for the probable etiological agents of AOM.

The immune response to viral infections is a combination of many events: viral antigen presentation to the immune system, proliferation of specific lymphocytes, cytokine intervention. This review describes the virus-cell relationship contributing to the latency state in viral infections (especially in AIDS) and cytokine network, its importance in the pathogenesis of viral diseases and its therapeutic potential.

A new, orally active de-N-acetylated lysoglycosphingolipid (WILD20) was evaluated as antiinflammatory agent using a model of chemically-induced inflammatory bowel disease (IBD) in the rat to mimic human ulcerative colitis and Chron's disease. IBD was induced by hapten trinitrobenzenesulphonic acid (TNB). WILD20, orally administered as preventive or curative, was demonstrated to be efficacious at daily dosages of 0.1-1 mg/kg for 4-5 days. Damage scores, body weight, spleen weight, colonic tissular levels of LTB4, myeloperoxidase (MPO) and malondialdehyde (MDA) are influenced and brought into parameters of normality. Histological observation demonstrated quicker healing, better repair, reduced inflammation, and poor eosinophil degranulation. The mechanisms underlying WILD20 antiinflammatory effects were investigated: whereas WILD20 fails to show a direct effect on PKC, it reduces PKC translocation to the membrane; cellular PLA2 was consequently greatly reduced through this mechanism and thought to be responsible for WILD20 efficacy towards chemically-induced IBD.

Gal beta 1-->3GalN beta 1-->4Gal(3<--2 alpha Neu)beta 1-->4Glc beta-->1Sph (WILD20), a new glycosphingolipid, a breakdown product of the monosialoganglioside GM1 obtained through alkaline hydrolysis, shows dose-dependent platelet anti-aggregating properties in vitro and in vivo. This effect is agonist- and species-independent. The family of lysosphingolipids, to which the compound belongs, is present in platelets particularly after thrombin treatment. WILD20 antiplatelet effect is due to the interference with ADP or thrombin-induced aggregation, probably via phospholipase A2 (PLA2) blockade; the substance is also effective when arachidonic acid is used as an agonist. Serotonin blood levels are also reduced. The substance, orally active at dosages of 0.1-0.01 mg/kg as antiplatelets agent, prolonged bleeding time without interfering with the coagulative or fibrinolytic processes.

We have identified 18 cases of functional pouch of the posterior rectal wall visualized by defecography. In the absence of previous evidence in the literature, we named this anomaly "posterior rectocele" and studied it from the clinical, radiologic, and endoscopic points of view.

The authors report 10 cases of gastrointestinal bleeding angiodysplasia (4 male and 6 female). The surgical treatment was normally provided and the main clinical features, were observed by radiological, endoscopic and pathological findings. Angiodysplasia was observed in the colon (4 cases), in the small intestine (3 cases) and in the stomach (3 cases). Common symptoms (bleeding and sideropenic anaemia), where possible associated with endoscopic and angiographic study, permitted to determine diagnosis and lesion's extension. Pathological findings showed that vascular dilatation wasn't present only in the mucosa and in the submucosa, as in the amartomatous congenital forms, but was present in all intestinal wall, as in the secondary forms, more frequent.

The present study examined the protective effect of IFN-alpha against mouse cytomegalovirus (MCMV) infection in embryo fibroblasts (MEF) of genetically resistant (C3H/HeJ) and susceptible (C57BL/6) mouse strains. At a M.O.I. of 1 IFN-alpha was protective in C3H/HeJ-MEF but not in C57BL/6-MEF. Dot-blot analysis during MCMV replication in C3H/HeJ-MEF showed that IFN-alpha pretreatment reduced the steady state level of immediate early and late mRNAs but partially reduced early gene expression.

Activation of 202 and (2'-5')(A)n synthetase genes after injection of interferon (IFN)-inducing, double-stranded, poly rI:rC was compared in various mouse strains. The 202 mRNA level increased 4.5- to 10-fold in DBA/2, BALB/c, and C3H/HeJ mice, whereas in C57BL/6 mice it rose only to about that in untreated DBA/2, BALB/c, and C3H/HeJ mice. To determine whether this low level was due to a reduced transcription rate, a nuclear "run-on" assay was performed with NIH 3T3 cells or BLK cells derived from C57BL/6 mice. IFN-alpha increased the 202 mRNA transcription severalfold in NIH 3T3 cells only, and that of a (2'-5')(A)n synthetase gene in both cell lines. The possibility that an alteration in transacting factors could be responsible for this difference was examined. For this purpose the 5' terminal flanking region (called the b segment, about 0.8 kb) of the 202 gene was linked to a heterologous reporter gene--chloramphenicolacetyl-transferase (CAT) and transfected into normal or transformed NIH 3T3 cells and into various C57BL/6-derived cell lines. IFN-alpha induced strong CAT activity in transfected normal or transformed NIH 3T3 cells, but a much lower activity in those from C57BL/6 mice. The b segment contains an IFN-responsive element (ISRE) (35 bp) homologous to that present in several other IFN-inducible genes. Three tandem copies of the 202 ISRE were linked to an enhancerless SV40 early promoter driving an influenza virus hemagglutinin (HA) cDNA segment. No increase in HA mRNA expression was detected in the transfected BLK cell line derived from C57BL/6 mice following IFN treatment, whereas in the NIH 3T3 cell line, the IFN treatment resulted in a 2.5-fold increase. These and other results suggest that C57BL/6 mice and cell lines derived from them might carry defective transacting factors impairing the ability of IFN-alpha to activate the 202 gene without impairing its ability to activate a (2'-5')(A)n synthetase gene.

MuIFN-gamma receptor cDNA has been stably transfected in the human WISH cell line. A stable transfectant, denominated WISH-C2, expressed 46;000 receptors/cell whose affinity was similar to that observed on murine cells (Kd = 2.6 x 10(-9) M). When WISH-C2 cells were treated with Hu- or MuIFN-gamma, antiviral and antiproliferative activities were observed with HuIFN-gamma only. These findings suggest that other species-specific components associated to the binding site are required for the signal transduction. To overcome the complexity of measuring biological functions that very likely involve more than one regulatory and structural gene, we set up for the first time a system where a reporter gene driven by a murine promoter was used to directly evaluate the interaction of MuIFN-gamma receptor with an inducible promoter through the missing transducer factor.

Bacteria were the first living beings to appear on our planet: the most ancient fossils available, all of them were procaryotic microorganisms, developed 4, 5 billion years ago. The paleomicrobiological studies made on that kind of fossils, which are by now several hundreds in each continent, proved bacteria to have constantly evolved and to have originated the modern Eubacteria as well as the Archebacteria and the Cianobacteria. These last appeared about 2 billion years ago and, having acquired the oxygen-type photosynthesis, have caused the formation of a large amount of organic material, afterwards used by the younger organisms, and have modified the atmosphere introducing oxygen in it and conditioning in this way the other living being's evolution. From Bacteriaceae and Cyanobacteria derive the eucaryotic microorganisms (algae, fungi, protozoa, mould) and, little by little, all the other organisms both vegetable and animal subjected to the evolutionary pressures. Nevertheless bacteria undergo more frequently than all the others the evolution law because of their short reproductive time; this is the reason why bacteria are favourite compared with the other organisms. In fact each species is subjected to a genetic mutation every 10(5)/10(6) generations: in the vegetables and animals the consequences of a genetic mutation will be evident after millennia whereas in the bacteria the mutation happens in a short time. We ourselves have witnessed the revolution which took place in the bacteria populations during the last half century when numerous antibiotic-resistant strains appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Dihydroxybenzoic acid (DHBA) derivatives of acetylsalicylic acid (ASA) are formed in vivo by the action of the hydroxyl radical (OH.). In order to evaluate the possible formation of OH(.) in acute myocardial infarction (AMI) in man, 9 consecutive patients with a first episode of AMI (8 males, 1 female, mean age 50.3 years), treated with rt-PA, and 8 healthy volunteers (7 males, 1 female, mean age 29.8 years) were studied. All subjects received 100 mg ASA p.o. daily; venous blood samples were taken 30 min after the first dose (time 0) and then at 3-, 6-, 12-, 24- and 48 h and 5 days. Serum was analyzed by HPLC and electrochemical detection for 2,3- and 2,5-DHBA contents. 2,3-DHBA was present in all subjects with AMI and undetectable in healthy volunteers at all time points studied. Serum levels of 2,5-DHBA did not show statistically significant differences between AMI patients and healthy volunteers. These data support the hypothesis that hydroxyl radicals are formed during AMI in man.

The authors report eight cases of rectocele in male subjects studied with defecography and computed tomography. The pocket is located between the prostatic apex and the urogenital diaphragm. The abnormality has clinical significance.

We analyzed the effects of synthetic dsRNA (poly rI:rC) treatment on the expression in vivo of two interferon (IFN)-inducible genes. DBA/2 mice were injected i.p. with poly rI:rC and its effect on the levels of the following mRNAs was determined; 202, 2'-5' oligoadenylate synthetase (2-5A synthetase) and beta-actin. After poly rI:rC treatment the levels of the 202 and 2-5A synthetase mRNAs in the spleen and in bone marrow peaked between 12 and 24 h and decreased thereafter, whereas beta-actin levels remained unchained unchanged. Pretreatment of DBA/2 mice with sheep anti-murine IFN-alpha/beta antibodies before rI:rC injection strongly diminished the induction of 202 mRNA indicating that IFN-alpha/beta mediated this induction.

When treated with IFN-alpha, NIH-3T3 cells express after a few hours high levels of the mouse 202 gene mRNA. This activation takes place at the transcriptional level as shown by nuclear "run on" assay. For this purpose a fragment of 806 base-pairs (the b fragment), spanning the 5'-flanking region of the 202 gene, was linked to the reporter CAT gene and transiently transfected into mouse NIH 3T3. The data suggest that the b fragment is sufficient to confer transcriptional inducibility upon IFN stimulation and can account in large part for the response of the 202 gene. Binding assays, using a 40-bp probe derived from the IFN-stimulated response element (ISRE) comprised in the b fragment, demonstrated the presence of two DNA-binding proteins. One of these, defined as complex A, was inducible upon IFN treatment, whereas the other, defined as complex B, was constitutively present regardless of IFN treatment. The IFN-alpha-induced complex A appears to have the necessary characteristics to be the transcriptional activator of the 202 gene: it requires the same nucleotides for binding as are required for IFN-dependent gene activation and is dependent on IFN-alpha treatment.

The 40-kDa 2'-5'-oligoadenylate [(2'-5') (A)n] synthetase isoenzyme was proven to be a mediator of the inhibition of encephalomyocarditis virus (EMCV) replication by interferon (IFN). When activated by double-stranded RNA, this enzyme converts ATP into 2'-5'-oligoadenylate [(2'-5') (A)n], and (2'-5') (A)n was found to accumulate in IFN-treated, EMCV-infected cells. The only known function of (2'-5') (A)n is the activation of RNase L, a latent RNase, and this was also implicated in the inhibition of EMCV replication. Intermediates or side products in EMCV RNA replication, presumed to be partially double stranded, were shown to activate (2'-5') (A)n synthetase in vitro. These findings served as the basis of the long-standing hypothesis that the activator of (2'-5') (A)n synthetase in IFN-treated, EMCV-infected cells is the viral RNA. To test this hypothesis, we have generated a polyclonal rabbit antiserum to the human 40-kDa (2'-5') (A)n synthetase. The antiserum immunoprecipitated, from IFN-treated HeLa cells that had been infected with EMCV, the 40-kDa (2'-5') (A)n synthetase protein in complex with both strands of EMCV RNA. The immunoprecipitate was active in (2'-5') (A)n synthesis even without addition of double-stranded RNA, whereas the immunoprecipitate from IFN-treated, uninfected cells was not. These and other results demonstrate that in IFN-treated, EMCV-infected cells, viral RNA is bound to the (2'-5') (A)n synthetase and suggest that the agent activating the (2'-5') (A)n synthetase is the bound viral RNA.

Twenty patients with recurrent, inoperable head and neck squamous cell carcinoma received perilymphatic injections of natural interleukin-2 (nIL-2) for 10 days. Ten patients received 200 units (U) of nIL-2; five 1,000 U; and five 5,000 U. Irrespective of the location of the recurrence, the injections were always performed 1.5 cm below the insertion of the sternocleidomastoid muscle on the mastoid. When the ipsilateral lymphatic chain was still present, they were performed on the same side as the tumor site, whereas when it had been stripped as a result of previous surgery, they were contralateral. Patients who had undergone bilateral neck dissection were injected on the tumor side. Whenever possible, the treatment was repeated after 45-day intervals. In 13 patients (65%) with bilateral or contralateral lymph nodes, complete or partial disappearance of the lesion was observed. Despite these marked responses, the tumor always relapsed, and subsequent IL-2 courses were poorly effective. There were no systemic disturbances during or after treatment, but only moderate local swelling and pain.

We have examined the effects of synthetic dsRNA (poly rI:rC) treatment or of immunization with irradiated allogeneic cells on the expression in vivo of several interferon (IFN)-inducible genes. For this purpose, DBA/2 mice were injected i.p. once with poly rI:rC, or once and then again 3 weeks later, with irradiated C3H/He spleen cells and the effect of these treatments on the levels of the following mRNAs was determined: 202, 2',5'-oligoadenylate synthetase (2-5A synthetase), class I and class II major histocompatibility antigens, and beta-actin. After poly rl:rC treatment, the levels of the 202 and 2-5A synthetase mRNAs in the spleen and in the bone marrow peaked between 12 and 24 h and decreased thereafter. The class I mRNA levels started to increase at 12 h, peaked at 24 h, and declined thereafter. No increase in class II mRNA expression was observed after poly rl:rC injection, whereas beta-actin levels remained unchanged. Pretreatment of DBA/2 mice with sheep anti-murine IFN-alpha/beta antibodies before poly rI:rC injection strongly diminished the induction of 202 mRNA, indicating that IFN-alpha/beta mediated this induction. When irradiated C3H/He spleen cells were injected into DBA/2 mice, the class I and class II mRNAs in the spleen, but not in the bone marrow, started to increase at 12 h, peaked between 48 and 96 h, and decreased thereafter. No increase in the levels of 202 and 2-5A synthetase mRNAs was detected, whereas beta-actin levels remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular oncogenes may acquire transforming properties and take part in induction or progression of tumors. In the present study we have examined the expression of c-met, c-ras and c-myc in some head and neck carcinomas. In 3 tumors we have found an elevated expression of the c-met oncoprotein, in 2 tumours of the c-myc one. These data suggest that oncogenes could participate in the development of some head and neck cancers.

In this study we have evaluated the effects of an antibiotic, such as cefonicid, on some immune reactivities in vitro. The following immune parameters have been analyzed: i) interferon-gamma and interleukin-2 production and ii) lymphocyte proliferation following mitogen stimulation in the presence of cefonicid concentrations ranging from 50 to 500 microg/ml. No. decrease in lymphokine production in the presence of cefonicid concentrations up to 250 microg/ml was observed between untreated or antibiotic-treated lymphocyte cultures. When lymphocyte proliferation upon Con A stimulation, as evaluated by 3H-dHtd incorporation, was measured in the presence of cefonicid, no differences were observed with untreated controls. These results demonstrate that the in vitro interaction of cefonicid with the immune system does not lead to a decrease of the immune response.

The division of T cells into distinct subsets (Th-1 and Th-2), based upon cytokine production, is a major advance in understanding the immune reactivities particularly those associated with allergy. This report summarizes some of the highlights on pathogenesis of allergic rhinitis. Th-2 cells, driven by IL-4, play an important role in allergic reactions inducing IgE switching in B cells and proliferation of mastocytes. In addition, by interaction with IL-5, Th-2 lymphocytes promotes eosinophil growth. By contrast, Th-1 cells antagonize Th-2 activity by IFN-gamma production. Finally IL-10, produced by Th-2, blocks the effects of the cytokines elaborated by Th-1. Recent results of this rapidly expanding area of research provide the background for this review. The intricate connections between Th-1, Th-2, the endothelial cells of the nose vessels and stromal cells are discussed.

Clinical, immunological, immunophenotypical, pathological and molecular biological studies were performed on tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LN-ly) of 8 patients with squamous cell carcinoma of the oral cavity and oropharynx treated with 10 daily locoregional injections of low doses of IL-2 before surgery. No complications were seen during or after surgery. In 3 cases the LN-ly showed a moderate LAK activity, higher in the LN-ly omolateral to the tumor and near the IL-2 injection site; in 2 of these 3 patients a good LAK activity was induced after 6-day culture with IL-2. The LN-ly derived from nodes next to the tumor showed a decreased NK activity and proliferative ability both in basal conditions and after in vitro lymphokine challenging. LN-ly of 2 IL-2 treated patients showed high levels of mRNA encoding for IL-2-R, while it was absent in 2 untreated cases. Immunophenotypical studies on TIL showed statistically improved levels of CD25+ and LAK1+ cells in treated cases. Clusters of CD11c+ (macrophages) cells were seen close to the neoplastic sheets.

The goal of antimicrobial therapy is to eliminate invading bacteria both in the extracellular and intracellular environment. Thus, recent work has focused on the ability of various antibiotics to enter phagocytic cells and kill intracellular pathogens, since bacteria which survive within phagocytes may often produce prolonged or recurrent infections. In the last ten years the antibiotic modulation of phagocytic cell functions has become the subject of our major investigational activity. Taking into account that entry of antibiotics into phagocytes is necessary for activity against intracellular organisms, we examined the uptake of 11 radiolabelled antibiotics by macrophages. Penicillins and cephalosporins were taken up poorly by phagocytes. Teicoplanin was efficiently concentrated by macrophages, achieving intracellular concentrations higher than those in the surrounding extracellular medium. Roxithromycin was more markedly accumulated within phagocytes than was erythromycin, depending upon an active transport mechanism. Antitubercular drugs were concentrated approximately twofold in the macrophages. Besides, since antibiotics that act on phagocytosed bacteria have clinical advantages, we evaluated the direct action of the above mentioned drugs on the macrophage, by determining their interference with its functions or their potentiation of both phagocytosis and killing of bacteria.

Results are reported concerning the extraction and purification of gangliosides present in CER cells, a cell line which is highly suitable for the cultivation in vitro of rabies virus. By means of thin layer chromatography it has been possible to demonstrate that the CER cell ganglioside pattern is composed mainly of monosialo and disialogangliosides.

The protective effect of IFN alpha/beta or IFN-gamma against MCMV infection in mouse embryo fibroblasts (MEF) of genetically resistant and susceptible strains have been examined. For this purpose, MEF derived from Balb/c, C3H, DBA2, C57BL6 mouse strains were used. Cells were pretreated for 24 hrs with either IFN alpha/beta or IFN-gamma and subsequently infected with MCMV at different M.O.I. No difference in susceptibility to MCMV was observed between untreated Balb/c, C3H, C57 and DBA2-MEF when infected at a M.O.I. of 5 whereas at a M.O.I. of 1 or 0.5 untreated DBA2-MEF displayed the highest susceptibility to viral infection. Pretreatment of MEF with IFN alpha/beta showed that the degree of protection to MCMV was dependent on the M.O.I. used. At a M.O.I. of 5, IFN alpha/beta did not inhibit viral replication in any MEF tested, whereas at a M.O.I. of 1 or 0.5 was protective in C3H-MEF and to a lesser extent in Balb/c-MEF. No protection was observed in DBA2 and C57-MEF. Different results were observed when MEF were pretreated with IFN-gamma. C57-MEF were protected when infected at a M.O.I. of 5 or 1; no protection was observed at a M.O.I. of 0.5. Balb/c-MEF were protected only at a M.O.I. of 1. No protection was observed in C3H and DBA2-MEF.

We have examined the mechanisms by which interferon (IFN)-gamma and IFN-alpha regulate the expression of 2'-5'-oligoadenylate synthetase (2-5A synthetase) and class I major histocompatibility complex antigens in murine T cells and in cell types of other histological origin. When treated with IFN-alpha both fibroblasts and T cell lines displayed a marked increase of the 2-5A synthetase activity and of the corresponding mRNA. The augmentation of the enzyme activity in T cells was induced by IFN-alpha at the transcriptional level, as determined by nuclear run-on analysis. In contrast IFN-gamma was capable of increasing 2-5A synthetase activity only in fibroblasts, but not in T cells. Nuclear run-on assays revealed that the 2-5A synthetase gene in T cells is not transcriptionally activated by IFN-gamma. After IFN-alpha and -gamma treatment we also observed a significant increase in class I gene expression in fibroblasts and T cell lines as measured both on the cell surface and by cytoplasmic RNA accumulation. In the case of the T cell line, DO1110, the observed increase in the steady-state levels of class I transcripts was a consequence of a high rate of H-2 gene transcription as demonstrated by run-on analysis. However, the molecular mechanisms involved in this IFN-dependent H-2 gene transcriptional activation are different between IFN-alpha and IFN-gamma. When the T cell lines DO1110, L12-R4 and EL4 were transfected with a plasmid containing a reporter gene (chloramphenicol acetyltransferase) under the control of a regulatory IFN-responsive DNA element of 237 bp or 1.4 kb, IFN-alpha was able to activate the transcription of these constructs. In contrast, IFN-gamma did not recognize the IFN-responsive element which, by itself, activated transcription of the reporter gene in response to IFN-gamma in other cellular types of non-T cell origin. Therefore, in the T cell lines examined, IFN-gamma increases the H-2 gene expression by acting on DNA elements located upstream of the regulatory segment used in this study or downstream of the cap site. This suggests a possible cell specificity in the activation of an IFN-responsive element, that in turn may regulate the IFN-inducible gene expression in a cell-specific fashion. Thus, the differential biological activities of IFN-gamma on T cells could be generated by a differential gene activation at the transcriptional level.

Having outlined the important role played by zinc in the human metabolism and the alteration which may occur as a result of a zinc deficit, the paper reports a study of 50 patients affected by irritable bowel syndrome. Two subgroups have been identified (Ac and Ad), characterised by reduced blood zinc [correction of zinchemia] and increased fecal excretion of zinc. This finding suggests that the syndrome has a multifactorial pathogenesis and that over time it may follow a different pattern in the different subgroups.

We describe the immunomodulatory activity of GM-1/P a processed form of GM-1 (monosialoganglioside) extracted from ox brain, purified and physically modified. We examined the effect of in vivo and in vitro treatment of GM-1/P on natural (NK) activity and its ability to induce the production of interleukin-2 (IL-2) in the mouse. In vivo treatment with GM-1/P (1 mg/Kg, i.v., day-1) resulted in a marked increase and in a change of distribution of NK activity, which was associated with lower density Percoll fractions. Marked increase was already observed at 18 hrs and then declined by day 4. In vitro treatment with GM-1/P (2 micrograms/ml) enhanced NK activity of B6 spleen cells, already after 6 hours of incubation, remaining at plateau levels within 18 hours. A role of IL-2 in this enhancement was suggested by the ability of an anti-IL-2 rabbit antiserum to abolish in vitro increased cytotoxicity. The presence of IL-2 in the supernatants of splenocytes from GM-1/P (1mg/Kg, i.v., ,day-1) treated mice stimulated with Con A or Con A plus TPA for 48 hrs was evaluated by proliferation of an IL-2 dependent CTLL cell line. GM-1/P by itself was unable to stimulate IL-2 production; however it markedly increased IL-2 production induced by Con A or Con A plus TPA.

In this study we investigated the ability of GM-1/P, a calcium mediated processed form of monosialoganglioside GM-1, of in vivo augmenting mouse T and B-lymphocyte blastogenesis induced by mitogens. We have also determined its effect on IL-2 responsiveness by analyzing the induction of the expression of IL-2 receptor (IL-2r) on mouse spleen cells. Lymphocyte blastogenesis was evaluated by 3H-TdR incorporation of spleen cells from untreated or GM-1/P (1mg/Kg, i.v., day-1) treated mice cultured in the presence of T (PHA, ConA) B (LPS) cell specific mitogens. The stimulatory effects appeared to be due to a direct action on T and B lymphocytes, since proliferative response was not abolished by removal of macrophages. Splenocytes from GM-1/P treated mice showed increased proliferation in response to various concentrations of HrIL-2; moreover under these conditions an increased generation of LAK activity was found. A direct evidence for enhanced expression of IL-2r was obtained by immunofluorescence and FACS analysis using a monoclonal antibody (PC.61) directed against the p55 subunit of murine IL-2r. 29% PC.61+ cells were found in IL-2 cultures from treated spleen cells.

Host-parasite interactions were studied by several researchers in these last years, both to better understand some parasite diseases and to identify new targets and strategies for the control of these infections. In this paper some of the most important recognition's mechanisms demonstrated between specific parasite structures and host cell receptors are reported, and particularly those concerning protozoa Leishmania, Plasmodium, Entamoeba, Giardia and Pneumocystis.