Elevated plasma levels of C-reactive protein have been found in the majority of patients with unstable angina. The evidence of elevated levels of acute-phase proteins in unstable angina is in line ...with a growing body of evidence that suggests that inflammation plays a role in this syndrome and is an indirect sign of increased production of interleukin-6, which is the major determinant of acute-phase-protein production by the liver. However, in unstable angina, there is no direct proof of the role played by interleukin-6.
We measured levels of interleukin-6 in 38 patients with unstable angina at the time of their admission to the coronary care unit and in 29 patients with stable angina. In the same groups of patients, we also measured C-reactive protein. Interleukin-6 (undetectable, ie, < 3 pg/mL, in healthy volunteers) was detectable in 23 (61%) of 38 patients with unstable angina but in only 6 (21%) of 29 with stable angina (P < .01). Median interleukin-6 levels were 5.25 pg/mL (range, 0 to 90 pg/mL) in patients with unstable angina but were below the detection limit of the assay in patients with stable angina (range, 0 to 7 pg/mL). A significant correlation was observed between interleukin-6 and C-reactive protein levels (r = .4, P = .013).
Our study demonstrates that raised levels of interleukin-6 are common in unstable angina, correlate with C-reactive protein, and are associated with prognosis, thus confirming the importance of the cytokine pathway for the production by the liver of acute-phase proteins and strengthening the importance of inflammation in this syndrome. Further studies are required to elucidate better the role of interleukins in unstable angina.
COVID-19, the disease caused by the SARS-CoV-2 virus, is highly contagious. The persistence of the virus after infected individuals die remains unclear. This article reports the findings taken from ...postmortem nasopharyngeal swabs performed to investigate the presence of SARS-CoV-2 in the corpses transferred to the Genoa District Mortuary from the outset of the Italian lockdown (March 9) to the end of the first emergency phase (July 13). One hundred and eighty swabs were carried out: 13 corpses resulted positive for the virus, with the diagnosis being reached only after death. Seven were male and 6 female with an average age of 73.5 years old. The most frequent comorbidities recorded were arterial hypertension, diabetes, Alzheimer's, and pulmonary disease. In two cases, the swab tested positive at a distance of 125 h and 165 h from actual death. The nasopharyngeal swab results a useful way to screen corpses for COVID-19 and to handle bodies in Legal Medicine Centers where safe autoptic rooms are not available. Swabs are also a means of safeguarding forensic pathologists, identifying the presence of breeding grounds in the community and providing information for the Public Prosecutor's Office in legal cases. They are able to produce reliable results up to at least 7 days following death, provided that the corpse is correctly preserved.
Optimally effective antitumor therapies would not only activate immune effector cells but also engage them at the tumor. Folate conjugated to immunoglobulin (F-IgG) could direct innate immune cells ...with Fc receptors to folate receptor-expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR)-overexpressing cancer cell line, as determined by flow cytometry. Recognition of F-IgG by natural killer (NK) cell Fc receptors led to phosphorylation of the ERK transcription factor and increased NK cell expression of CD69. Lysis of KB tumor cells by NK cells increased by about 5-fold after treatment with F-IgG, an effect synergistically enhanced by treatment with IL2, IL12, IL15, or IL21 (P< 0.001). F-IgG also enhanced the lysis of chronic lymphocytic leukemia cells by autologous NK cells. NK cells significantly increased production of IFNγ, MIP-1α, and RANTES in response to F-IgG-coated KB target cells in the presence of the NK cell-activating cytokine IL12, and these coculture supernatants induced significant T-cell chemotaxis (P< 0.001). F-IgG-coated targets also stimulated FcR-mediated monocyte effector functions. Studies in a murine leukemia model confirmed the intratumoral localization and antitumor activity of F-IgG, as well as enhancement of its effects by IL12 (P =0.05). The antitumor effect of this combination was dependent on NK cells and led to decreased tumor cell proliferation in vivo Thus, F-IgG can induce an immune response against FR-positive tumor cells that is mediated by NK cells and can be augmented by cytokine therapy.
Purpose: Expression of the FHIT protein is lost or reduced in most solid tumors and a significant fraction of hematopoietic malignancies.
Adenovirus 5 (Ad5) virus or adeno-associated viral vectors ...have been used to study the tumor suppressor function of FHIT in
solid tumors, but these tools have not been effective in leukemias. We have generated a chimeric FHIT -containing adenovirus composed of Ad5 and the group B adenovirus called F35 with which we have been able to efficiently infect
hematopoietic cells.
Experimental Design: Infection efficiency of Ad5/F35- FHIT and Ad5/F35- GFP viruses was tested in leukemia cell lines that lacked FHIT expression, and biological effects of successful infection were
assessed. An acute myelogenous leukemia, a chronic myelogenous leukemia, and four acute lymphoblastic leukemia human cell
lines were examined as well as two EBV-transformed B lymphoblastoid cell lines that expressed endogenous FHIT.
Results: Two of four acute lymphoblastic leukemia cell lines, Jurkat and MV4;11, which were efficiently infected with Ad5/F35- FHIT , underwent growth suppression and massive induction of apoptosis without apparent activation of caspase-8 or caspase-2 and
late activation of caspase-3. Treatment of infected cells with caspase-9 and caspase-3 inhibitors partially blocked FHIT-induced
apoptosis. The two remaining infected acute lymphoblastic leukemia cell lines, Molt-3 and RS4;11, were apparently unaffected.
Restoration of FHIT expression in the chronic myelogenous leukemia K562 cell line and the acute myelogenous leukemia KG1a
cell line also induced apoptosis but at later time points than seen in the acute lymphoblastic leukemia Jurkat and MV4;11
cell lines. I.v. injection of Ad5/F35- FHIT -infected Jurkat cells resulted in abrogation of tumorigenicity in the NOD/SCID xenogeneic engraftment model.
Conclusion: FHIT restoration in some FHIT-deficient leukemia cells induces both antiproliferative and proapoptotic effects involving the intrinsic
caspase apoptotic pathway.
Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable ...angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B).
Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001).
Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.
The epidemiology of HBV-associated hepatitis has changed in recent years, especially after the introduction of anti-HBV vaccination, with a consequent decrease in the incidence of HDV-associated ...hepatitis. However, HDV remains of concern in non-vaccinated people and in immigrants. The aim of this retrospective survey has been to assess prevalence and clinical characteristics of HDV infection in Liguria, a region in Northern Italy, in both HIV-positive and negative patients.
During the year 2010, 641 patients chronically infected with HBV entered an observational study of HBV infection conducted in eight tertiary care centres belonging to the 'Ligurian HBV Study Group'.
Of 641 patients, 454 (70.8%) were evaluated for HDV serology and 26 (5.7%) were found positive. Among them, 16 were also HIV-positive and 10 were not. Of the 428 HDV-negative patients, only 313 were tested for HIV and 33 (10.5%) were positive. At the time point of study entry there was no age difference between HIV-positive or negative patients, but HIV-positive patients were 10 years younger than HIV-negative (mean age 34.25 ±6.16 versus 41.50 ±8.89 years; P=0.021) at the time point of their first visit in each centre and they were also more frequently intravenous drug users (P=0.009). Despite a similar rate of cirrhosis in the two groups, no HIV-positive patient received an HDV-active therapy (that is, interferon), versus 4 of 10 HIV-negative patients (P=0.014).
HDV infection is still a problem in patients not covered by HBV vaccination. Both HDV and HIV testing were frequently overlooked in our setting.
Recent studies on autoptic findings have underlined the complexity of perioral muscles; the discovery of a fourth band of buccinator muscle and the effects it can have on teeth, alveolar bone, and ...oral mucosa during growth has stressed the importance of muscular influence on the genesis of and therapy for basal class II dentofacial alterations. Frederick proposed a surgical marginal myotomy to elongate the buccinator bundle together with inferior vestibuloplasty to unload the jaw from the overcontraction of the muscle and to reduce the inferior lip hypotone. In our investigation, we have applied this technique on a group of 50 patients with basal class II defect selected according to our protocol before functional or fixed orthodontics, and we have recorded and compared cephalometric measurements and clinical facial profile changes 12 (T1) and 24 (T2) months after the end of therapy to a control group with the same defect treated only with orthodontic functional devices. We obtained improvement of cephalometric parameters in 80% of patients who underwent surgery and orthodontics, and in only 50% of patients who underwent only orthodontics. Results suggest that neutralizing buccinator and mental muscles pressure on the jaw during growth can help the clinician dealing with II basal malocclusion therapy and relapse.
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