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Biomedical subjects

C Farina

Publications and source records attributed to C Farina.

At least 37 records · Page 2Linked to original sources

Urinary detection of Streptococcus pneumoniae antigen for diagnosis of pneumonia.

Streptococcus pneumoniae is one of most common causes of community-acquired pneumonia. We evaluated a newly available rapid immunochromatographic test to detect S. pneumoniae in urine samples verifying its importance in the diagnosis of pneumococcal pneumonia. Our data, obtained from 104 patients with community-acquired pneumonia, show that Now S. pneumoniae Urinary Test is characterized by a sensitivity value of 77.7%, a specifity of 98.8%: positive and negative predictive values are 93.3% and 95.5%, respectively. In conclusion, Now S. pneumoniae Urinary Test should be a useful test to establish the etiology of community-acquired pneumonia.

Adult↗

[Antiestrogen therapy in the treatment of breast neoplasms].

During recent years the development of hormone therapy for the treatment breast neoplasms has seen, in addition to classic aspecific antiestrogens (AE) like tamoxifen (TAM) and to a lesser extent toremifen, a major development of new molecules divided into two groups: the first is the so-called selective estrogen receptor modulators (SERMs), the most important of which is Raloxifen, which mediate estrogen-agonist effects in some tissues and estrogen-antagonist effects in others; the second group includes the aromatase inhibitors (AI), important enzymes for peripheral estrogen conversion. Some studies compare or associate classic AE with the new SERMs and AI, both in adjuvant therapy and in treatment for advanced forms. Other trials assess the anti-osteoporotic activity of some SERMs which present concomitant inhibitory activity on the breast and endometrium.

Adult↗

Stepwise modulation of neurokinin-3 and neurokinin-2 receptor affinity and selectivity in quinoline tachykinin receptor antagonists.

A stepwise chemical modification from human neurokinin-3 receptor (hNK-3R)-selective antagonists to potent and combined hNK-3R and hNK-2R antagonists using the same 2-phenylquinoline template is described. Docking studies with 3-D models of the hNK-3 and hNK-2 receptors were used to drive the chemical design and speed up the identification of potent and combined antagonsits at both receptors. (S)-(+)-N-(1-Cyclohexylethyl)-3-[(4-morpholin-4-yl)piperidin-1-yl]methyl-2-phenylquinoline-4-carboxamide (compound 25, SB-400238: hNK-3R binding affinity, K(i) = 0.8 nM; hNK-2R binding affinity, K(i) = 0.8 nM) emerged as the best example in this approach. Further studies led to the identification of (S)-(+)-N-(1,2,2-trimethylpropyl)-3-[(4-piperidin-1-yl)piperidin-1-yl]methyl-2-phenylquinoline-4-carboxamide (compound 28, SB-414240: hNK-3R binding affinity, K(i) = 193 nM; hNK-2R binding affinity, K(i) = 1.0 nM) as the first hNK-2R-selective antagonist belonging to the 2-phenylquinoline chemical class. Since some members of this chemical series showed a significant binding affinity for the human mu-opioid receptor (hMOR), docking studies were also conducted on a 3-D model of the hMOR, resulting in the identification of a viable chemical strategy to avoid any significant micro-opioid component. Compounds 25 and 28 are therefore suitable pharmacological tools in the tachykinin area to elucidate further the pathophysiological role of NK-3 and NK-2 receptors and the therapeutic potential of selective NK-2 (28) or combined NK-3 and NK-2 (25) receptor antagonists.

Amino Acid Sequence↗

Mouse DREAM/calsenilin/KChIP3: gene structure, coding potential, and expression.

Ca2+-binding proteins containing EF-hands are important constituents of intracellular signaling pathways. Recently, three new members of the Neuronal Calcium Sensor subgroup have been cloned in humans. Calsenilin interacts with presenilins, DREAM is a calcium-regulated transcriptional repressor and KChIP3 binds and modulates A-type potassium channels. Here we describe the mouse full-length cDNA and the genomic locus, demonstrating that the three proteins are encoded by the same unique gene. Various mechanisms contribute to the coding potential of this locus. These include alternate translation starts in the first exon and alternative splicing yielding transcripts lacking the EF-hand domains. In situ hybridization, RT-PCR, and Northern blotting reveal nervous system-restricted expression largely coinciding with the distribution of the Kv4.2 alpha-subunit of potassium channels. The presence of transcripts in early embryonic stages suggests roles for the protein also during development.

Alternative Splicing↗

Serum allopregnanolone in women with postpartum "blues".

OBJECTIVE: To relate serum allopregnanolone and progesterone levels postpartum to maternity "blues." METHODS: Forty primiparous, healthy, married women (24-39 years of age; at least 13 years of education) who delivered healthy neonates in the Department of Obstetrics at the University of Pavia entered the present study. Blood samples were drawn at 8:30 AM on postpartum day 3 for measurements of serum allopregnanolone, progesterone, cortisol, prolactin, and estradiol. On the same day, every woman was interviewed using the Hamilton Rating Scale for Depression for psychometric testing and completed a self-administered version of the Stein Questionnaire for symptoms of the "blues." RESULTS: Eighteen of 40 women (45%) experienced maternity "blues" (12 who delivered vaginally and six who delivered by cesarean). Serum allopregnanolone levels were significantly lower in those women experiencing postpartum "blues" with respect to euthymic women (1.1 +/- 0.4 versus 2.3 +/- 1.0 nmol/L; P <.001), whereas progesterone levels did not differ significantly (11.6 +/- 5.6 versus 19.1 +/- 15.6 nmol/L; P >.058). Allopregnanolone and progesterone levels correlated significantly in euthymic women (r =.648; P =.001) but not in those with postpartum "blues" (r =.317; P =.199). There was a significant negative correlation between the Hamilton score and levels of serum allopregnanolone (r = -.62; P =.001) and progesterone (r = -.36; P =.024). CONCLUSION: Serum allopregnanolone levels were detectable postpartum and were significantly decreased in women with maternity "blues."

Adult↗

Report of human nocardiosis in Italy between 1993 and 1997.

During a 5-year period, from 1993 to 1997, nocardial infection was diagnosed in 26 patients admitted to hospitals in 11 cities in Italy. Pathogens were identified as Nocardia asteroides in 18 cases, as N. farcinica in five cases, as N. nova in two and as N. brasiliensis in one case. All cases were difficult to diagnose, as usually it happens with this disease: physicians have to be alert to suspect nocardial infection so that appropriate therapy can be early given. This is the second retrospective report on Nocardia spp. infection conducted in Italy, suggesting the utility to organise a permanent network for a national survey system for nocardiosis.

Drug Resistance, Microbial↗

Treatment of pulmonary nocardiosis in heart-transplant patients: importance of susceptibility studies.

Pulmonary nocardiosis is an infrequent but insidious disease in transplant patients. It has occurred in our centre in 3 out of 233 heart-transplant recipients since 1988. Common clinical features were mild symptoms and a severe nodular lung involvement. Early diagnosis was based upon cultures of bronchoalveolar lavage or fine-needle aspirate specimens of the lung lesions. Susceptibility studies and tests of antibiotic synergism guided the therapy. Two patients were treated with a combination of piperacillin-tazobactam and ciprofloxacin, and one with imipenem and amikacin, for 3-4 wk followed by a 3-month course of trimethoprim-sulphamethoxazole. The nocardial disease was successfully treated in the 3 patients; however, one died of subsequent invasive pulmonary aspergillosis. In the absence of consensus on the length of therapy, this experience suggests that a synergistic combination of a beta-lactam/beta-lactamase inhibitor with ciprofloxacin or amikacin followed by a short course of trimethoprim-sulphamethoxazole may be effective in eradicating nocardial disease and may reduce the need for long-term treatment.

Adult↗

Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-gamma response in blood cells.

Copolymer-1 (Copaxone or COP) inhibits experimental allergic encephalomyelitis and has beneficial effects in multiple sclerosis. There is presently no practical in vitro assay for monitoring the immunological effects of COP. We used an automated, computer-assisted enzyme-linked immunoadsorbent spot assay for detecting COP-induced interferon-gamma (IFN-gamma)- and interleukin-4 (IL-4)-producing cells and a standard proliferation assay to assess the immunological response to COP in peripheral blood mononuclear cells from 20 healthy donors, 20 untreated multiple sclerosis patients and 20 COP-treated multiple sclerosis patients. Compared with untreated and healthy controls, COP-treated patients showed (i) a significant reduction of COP-induced proliferation; (ii) a positive IL-4 Elispot response mediated predominantly by CD4 cells after stimulation with a wide range of COP concentrations; and (iii) an elevated IFN-gamma response partially mediated by CD8 cells after stimulation with high COP concentrations. All three effects were COP-specific as they were not observed with the control antigens, tuberculin-purified protein or tetanus toxoid. The COP-induced changes were consistent over time and allowed correct identification of COP-treated and untreated donors in most cases. We propose that these criteria may be helpful to monitor the immunological response to COP in future clinical trials.

Adult↗

Lactobacillus casei subsp. rhamnosus sepsis in a patient with ulcerative colitis.

Lactobacillus species are part of normal gastrointestinal flora and are an uncommon cause of bacteremia. Lactobacillus casei subsp. rhamnosus was repeatedly isolated in the blood cultures of a 43-year-old woman with ulcerative colitis. Lactobacillus spp. could be considered a potential opportunistic pathogen whenever there is disruption of the physiologic architecture of the intestinal mucosa, such as in abdominal surgery, endoscopic procedures, or enteric pathologies. Clinicians and clinical microbiologists need to be aware of this infective complication in patients with ulcerative colitis.

Adult↗

Performance assessment of new multiplex probe assay for identification of mycobacteria.

A new DNA probe assay (INNO LiPA Mycobacteria; Innogenetics, Ghent, Belgium) for the simultaneous identification, by means of reverse hybridization and line-probe technology, of Mycobacterium tuberculosis complex, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium gordonae, the species of the Mycobacterium avium complex (MAC), Mycobacterium scrofulaceum, and Mycobacterium chelonae was evaluated on a panel of 238 strains including, besides representatives of all the taxa identifiable by the system, a number of other mycobacteria, some of which are known to be problematic with the only other commercial DNA probe system (AccuProbe; Gen-Probe, San Diego, Calif.), and two nocardiae. The new kit, which includes a control probe reacting with the whole genus Mycobacterium, correctly identified 99.6% of the strains tested; the one discrepancy, which remained unresolved, concerned an isolate identified as MAC intermediate by INNO LiPA Mycobacteria and as Mycobacterium intracellulare by AccuProbe. In five cases, because of an imperfect checking of hybridization temperature, a very slight, nonspecific, line was visible which was no longer evident when the test was repeated. Two strains whose DNA failed amplification at the first attempt were regularly identified when the test was repeated. Interestingly, the novel kit dodged all the pitfalls presented by the strains giving anomalous reactions with AccuProbe. A unique feature of INNO LiPA Mycobacteria is its ability to recognize different subgroups within the species M. kansasii and M. chelonae, while the declared overlapping reactivity of probe 4 with some M. kansasii and Mycobacterium gastri organisms and of probe 9 with MAC, Mycobacterium haemophilum, and Mycobacterium malmoense, may furnish a useful aid for their identification. The turnaround time of the method is approximately 6 h, including a preliminary PCR amplification.

Animals↗

Discovery of a novel antitumor benzolactone enamide class that selectively inhibits mammalian vacuolar-type (H+)-atpases.

A series of naturally occurring compounds reported recently by multiple laboratories defines a new small-molecule class sharing a unique benzolactone enamide core structure and diverse biological actions, including inhibition of growth of tumor cells and oncogene-transformed cell lines. Here we show that representative members of this class, including salicylihalamide A, lobatamides A-F, and oximidines I and II inhibit mammalian vacuolar-type (H+)-ATPases (V-ATPases) with unprecedented selectivity. Data derived from the NCI 60-cell antitumor screen critically predicted the V-ATPase molecular target, while specific biochemical assays provided confirmation and further illumination. The compounds potently blocked representative V-ATPases from human kidney, liver, and osteoclastic giant-cell tumor of bone but were essentially inactive against V-ATPases of Neurospora crassa and Saccharomyces cerevisiae and other membrane ATPases. Essential regulation of pH in cytoplasmic, intraorganellar, and local extracellular spaces is provided by V-ATPases, which are ubiquitously distributed among eukaryotic cells and tissues. The most potent and selective V-ATPase inhibitors heretofore known were the bafilomycins and concanamycins, which do not discriminate between mammalian and nonmammalian V-ATPases. Numerous physiological processes are mediated by V-ATPases, and aberrant V-ATPase functions are implicated in many different human diseases. Previous efforts to develop therapeutic pharmacological modulators of V-ATPases have been frustrated by a lack of synthetically tractable and biologically selective leads. Therefore, availability of the unique benzolactone enamide inhibitor class may enable further elucidation of functional and architectural features of mammalian versus nonmammalian V-ATPase isoforms and provide new opportunities for targeting V-ATPase-mediated processes implicated in diverse pathophysiological phenomena, including cancer.

Animals↗

[Nocardia and human nocardiosis].

Nocardia spp. are pathogens commonly found in soil worldwide, and they cause mostly opportunistic infections in humans and animals, complicating both immunodepressive states and primary diseases. Nocardiosis is difficult to proper microbiological and clinical diagnosis because of its non-specific symptoms, which manifest as the cutaneous and sub-cutaneous infections, lung symptoms and the dissemination through the bloodstream to other organs. General characteristics of Nocardia, human nocardiosis as well as the microbiological diagnostics routine and treatment are discussed.

Aminoglycosides↗

Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients.

BACKGROUND: Fungal infections (FI) after solid organ transplantation (Tx) remain a major cause of morbidity and mortality. Aspergillus and Candida account for more than 80% of FI. METHODS: One thousand nine hundred and sixty-three patients undergoing thoracic organ Tx [1,852 heart and 111 lung (35 heart-lung Tx, 30 double-lung Tx, 46 single-lung Tx)] in 12 Italian Centers between November 1985 and January 1997 were included in the study. RESULTS: Fifty-one patients (41 heart Tx - 2.2%; 9 heart-lung Tx - 25.7%; 1 single-lung Tx - 2.2%) developed 53 invasive FI at a median of 58 days (range 6-2479) after Tx. Aspergillosis was the most frequent FI in our series accounting for 64.1% (34/53) of all FI [A fumigatus, n=29 (85.3%); A nidulans, n=2 (5.9%); A niger, n=2 (5.9%); A terreus, n=1 (2.9%)]; 30 (88.2%) patients developed invasive lung aspergillosis, 2 (5.9%) a tracheobronchitis, 1 (2.9%) a skin infection, and 1 (2.9%) a sternal wound infection. Twelve patients (22.6%) developed candidiasis [C albicans, n=8 (66.6%); C krusei, n=1 (8.3%); C glabrata, n=1 (8.3%); C parapsilosis, n=1 (8.3%); C sake, n=1 (8.3%)]. There were seven episodes (58.3%) of candidemia, two (16.7%) esophagitis, two (16.7%) gastritis, and one (8.3%) tracheobronchitis. Mortality was 29.4% for patients developing aspergillosis and 33.3% for those experiencing candidiasis. Furthermore, four patients developed the following: one C neoformans meningitis, one Sporothrix cyanescens pneumonia, one Rhizopus spp. tracheobronchitis, and one Trichosporon beigelii disseminated infection. Three additional patients were diagnosed affected by deep mould infection by histology alone. CONCLUSIONS: Deep-seated FI were relatively rare in our series, although their mortality rate is still very high.

Adult↗

Multiple sclerosis: comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells.

Copolymer 1 (COP), a standardized mixture of synthetic polypeptides consisting of l-glutamic acid, l-lysine, l-alanine, and l-tyrosine, has beneficial effects in multiple sclerosis and experimental autoimmune encephalomyelitis. We selected a panel of 721 COP-reactive T cell lines (TCL) from the blood of COP-treated and untreated multiple sclerosis patients and from healthy donors by using the split-well cloning technique. All TCL selected with COP proliferated in response to COP but not to myelin basic protein (MBP). Conversely, 31 control TCL selected with MBP proliferated in response to MBP but not to COP. We used intracellular double-immunofluorescence flow cytometry for quantitative analysis of cytokine production (IL-4, IFN-gamma) by the TCL. The majority of the COP-reactive TCL from untreated multiple sclerosis patients and normal donors predominantly produced IFN-gamma and, accordingly, were classified as T helper 1 cells (TH1). In contrast, the majority of the COP-reactive TCL from COP-treated patients predominantly (but not exclusively) produced IL-4-i.e., were TH2 (P < 0.05 as assessed by using a suitable preference intensity index). Longitudinal analyses revealed that the cytokine profile of COP-reactive TCL tends to shift from TH1 to TH2 during treatment. Interestingly, although there was no proliferative cross-reaction, about 10% of the COP-reactive TCL responded to MBP by secretion of small amounts of IL-4 or IFN-gamma, depending on the cytokine profile of the TCL. These results are consistent with a protective effect of COP-reactive TH2 cells. It is hypothesized that these cells are activated by COP in the periphery, migrate into the central nervous system, and produce immunomodulatory cytokines after local recognition of MBP.

Adolescent↗

Fatal disseminated Nocardia farcinica infection in a renal transplant recipient.

Six years after a renal cadaver transplant, a 20-year-old girl developed multiple painful cutaneous abscesses and bilateral pneumonia secondary to Nocardia farcinica infection. Despite broad in vitro sensitivity to several antibiotic agents and aggressive medical treatment, the patient failed to respond and died after 10 weeks of therapy. We conclude that Nocardia farcinica is a very aggressive organism in immunocompromised patients and is often resistant to antimicrobial agents.

Adult↗