Beta glucuronidase short-term immunotherapy.
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Adult↗
Biomedical subjects
F Angelini
Publications and source records attributed to F Angelini.
Metachronous muscle metastases as a unique manifestation of colon cancer relapse.
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Adenocarcinoma↗
Regulation of androgen receptor mRNA expression in primary culture of Harderian gland cells: cross-talk between steroid hormones.
The androgen receptor (AR) must be considered a transcription factor belonging to the steroid-thyroid hormones receptor superfamily. Previous results gained from the Harderian gland, a tubulo-alveolar gland located in the orbital cavity of the golden hamster, indicate that Harderian gland cells express mRNAs encoding for androgen, glucocorticoid, thyroid hormone (T(3)), and estrogen receptors, respectively. Since in other systems, these receptors have been related to the expression of the androgen receptor, we have studied the regulation of AR expression in primary cultures of the male hamster Harderian gland. Our in vitro experiments show that androgen, and thyroid hormones increase the expression of AR. Retinoic acids also show a positive effect on AR expression, while exposure to glucocorticoid or estrogen blocks AR expression. Since these steroids differently modulate AR expression, our results must be considered in the context of multi-hormonal control of gene expression that could act through cross-talk between members of the steroid-thyroid hormones.
Animals↗
Restriction in T-cell receptor repertoire in a patient affected by trichothiodystrophy and CD4+ lymphopenia.
Molecular analysis of T-cell receptor (TCR) repertoire, by measuring the CDR3 heterogeneity length of beta-variable regions (spectratyping), is useful for acquiring novel information on the status of immune system in primary immunodeficiency. Here, we evaluate TCR repertoire in a child with trichothiodystrophy (TTD) and combined immunodeficiency (CID). Spectratyping revealed marked alterations of TCR repertoire distribution: 21 and 10 out of 27 TCR Vbeta (TCRBV) families and subfamilies were skewed in CD8+ and CD4+ subsets, respectively. These findings revealed, for the first time in a TTD patient with CID, a marked reduction in the TCR repertoire complexity, which may reflect alterations in the mechanisms regulating the generation and homeostasis of T cells.
ATP-Binding Cassette Transporters↗
Evidence of clonotypic pattern of T-cell repertoire in synovial fluid of children with juvenile rheumatoid arthritis at the onset of the disease.
Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site.
Antibodies, Monoclonal↗
Usefulness of CT scan, MRI and radiocholesterol scintigraphy for adrenal imaging in Cushing's syndrome.
The aim of this study was to evaluate the sensitivity and accuracy of computed tomography (CT) scanning, 75Se-selenomethyl-norcholesterol scintigraphy (SNS) and magnetic resonance imaging (MRI) in patients with Cushing's syndrome (CS) undergoing adrenalectomy. A series of 67 patients with CS due to benign adrenal disease was reviewed. There were 11 (16.4%) men and 56 (83.6%) women, with an overall median age of 44 years (range 19-69 years). Prior to surgery all patients underwent both CT and SNS, and 58 (86.6%) underwent adrenal MRI. Thirty-five (52.2%) of the patients (group A) had histologically confirmed unilateral adrenal involvement (33 patients with a solitary adrenocortical adenoma, and two with unilateral nodular cortical hyperplasia), while 32 (47.8%) of the patients (group B) had CS caused by bilateral adrenal involvement, including two patients with multinodular adrenal hyperplasia. The sensitivity, specificity and accuracy of adrenal imaging in group A were 97.1%, 100% and 98.5% for SNS, 94.3%, 68.7% (P<0.05, chi2 test) and 82.1% for CT scan, and 92.3%, 60.0% (P<0.05) and 64.3% (P<0.05) for MRI, respectively. In group B the sensitivity, specificity and accuracy were 100%, 97.2% and 98.5% for SNS, 64.5% (P<0.05), 97.2% and 82.1% for CT scan, and 60.0% (P<0.05), 92.3% and 35.7% (P<0.05) for MRI, respectively. In conclusion, SNS represents the most sensitive and specific adrenal imaging study and should be used in all patients with confirmed biochemical diagnosis of CS undergoing adrenalectomy. The sensitivity and specificity of CT scan and MRI are similar, but the latter shows a lower accuracy, especially in patients with bilateral adrenal involvement.
Adrenal Cortex Neoplasms↗
Fine-needle aspiration cytology of adrenal masses in noncancer patients: clinicoradiologic and histologic correlations in functioning and nonfunctioning tumors.
BACKGROUND: Image-guided, fine-needle aspiration (FNA) cytology is performed currently in patients with malignant disease who have suspected adrenal metastases. The objective of this study was to evaluate the usefulness and safety of FNA cytology in patients with incidental adrenal masses and functioning tumors. METHODS: Computed tomography (CT)-guided or ultrasound-guided aspirates using 21-23-gauge needles were performed successfully in 70 patients with functioning (n = 38 patients) and nonfunctioning (n = 32 patients) adrenal masses (median size, 4 cm; range, 3-12 cm) that were detected previously by CT scans. RESULTS: Definitive histology was available in 68 patients (97.1%), showing 53 benign tumors (77.9%), 11 primitive malignant tumors (16.2%), and 4 unsuspected adrenal metastases (5.9%) in patients with unknown primary tumors. In two patients with aspirate reports that ruled out malignancy, the mass was unchanged on CT scan follow-up; thus, they were considered benign lesions. The benign masses were significantly smaller (P < 0.01), although seven malignant tumors (46.7%) measured 3-4 cm in greatest dimension, and eight benign lesions (14.5%) measured 5-6 cm in greatest dimension. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 96.4%, 83.3%, 91.4%, and 90.0%, respectively, for CT scan and 93.3%, 100%, 100%, 98.2%, and 98.6%, respectively, for FNA cytology. The morbidity rate of image-guided FNA cytology was 4.3% (two patients with self-limited, asymptomatic pneumothorax and one patient with spontaneously resolved adrenal hematoma). CONCLUSIONS: Adrenal FNA cytology represents a safe and specific procedure for evaluating patients with adrenal masses measuring > 2 cm in greatest dimension. FNA is able to reveal malignancies and unsuspected pheochromocytomas and should be performed in all patients with adrenal tumors whenever requested for surgical planning.
Adolescent↗
Molecular analysis of arterial stenosis in rat carotids.
A new model of surgical injury for the induction and development of stenosis in common rat carotids is described. This model differs from balloon angioplasty or vein graft systems currently applied on animals to develop stenosis, since it involves the entire vessel wall layers and mimics the injury occurring during arterial grafts, endarterectomy or organ transplantation. At different times following arterial damage, the pattern of expression of genes already known to be involved in the proliferation, differentiation, and apoptosis of smooth muscle cells (c-myc, Angiotensin II receptor 1, Bcl-2 and Bax alpha), as well as of Rb and Rb2 genes, whose pattern of expression after arterial injury has not yet been reported, was analyzed by semi-quantitative reverse transcription-polymerase chain reaction technique. Histological and histochemical analysis on carotid sections shows the morphological changes which occurred 30 days after surgical injury in the vessel wall. Molecular and histological data demonstrate that this model of surgical injury induces neointimal proliferation in about 30% of rats. In about 70% of the remaining rats, it induces the processes responsible for negative remodelling, namely the significant accumulation of extracellular matrix and fibers and disorganization of arterial tunics. This model is therefore available for further studies on the expression of genes involved in the arterial stenotic process, as well as for testing drugs aimed at limiting this recurrent pathophysiological phenomenon.
Animals↗
Defective dendritic cell maturation in a child with nucleotide excision repair deficiency and CD4 lymphopenia.
We report a case of a combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD) characterized by an altered response to ultraviolet (UV) light due to a defect in the XPD gene. The XPD gene encodes a subunit of the transcription factor II H (TFIIH), a complex involved in nucleotide-excision repair (NER) and basal transcription. Our patient showed neurological and immune system abnormalities, including CD4 + lymphopenia never previously reported in TTD patients. In vitro immunological studies revealed a marked reduction in T-cell proliferation in response to mitogens and CD3 cross-linking which was partially recovered by the addition of anti-CD28 antibody or exogenous interleukin-2. The patient's T cells displayed alterations in T-cell receptor (TCR/CD3) proximal signalling characterized by marked reduction in Lck kinase activity coupled with a constitutive hyperactivation of Fyn kinase. Despite these alterations, normal levels of Lck and Fyn proteins were detected. The role of antigen-presenting cells (APCs) in the pathogenesis of the T-cell defect was investigated by analysing dendritic cells (DCs) generated from the patient's blood monocytes. In these cells, flow cytometry revealed significantly reduced expression of the CD86 co-stimulatory molecules and HLA glycoproteins. In addition, the patient's DCs showed a decreased ability to stimulate naive T lymphocytes. Overall, the results of our study suggest that a defective TFIIH complex might result in alterations in T cells and DC functions leading to a severe immunodeficiency.
CD4-Positive T-Lymphocytes↗
The moderating effect of aggressive problem behaviors in the generation of more positive attitudes toward nursing home residents.
This study examined the ability of a social history intervention to generate more positive attitudes toward nursing home patients, and to increase staff members' perceived rewards of care-giving. In contrast to prior studies, residents' problem behaviors were examined as potential moderators in the relationship. Forty-three staff members participated in an experimental, 3 (informational condition: social history, medical, control) x 2 (time: pre-test, post-test) within-subjects factorial design that employed newly admitted residents as target patients. Findings showed that the social history intervention alone did not generate more positive attitudes toward patients or greater rewards of care-giving. Although a larger proportion of target patients manifested other problem behaviors with greater frequently, only aggressive problem behavior was associated with more negative attitudes toward patients. A post-hoc analysis revealed that after statistically controlling for the impact of patients' aggressive behavior, the social history information appeared to allow staff members to maintain more neutral attitudes toward patients. Considerations for the use of social history information in long-term care settings are addressed.
Adult↗
Localization of FMRFamide-like immunoreactivity in the brain of the viviparous skink (Chalcides chalcides).
Neuroanatomical distribution of FMRFamide-like immunoreactivity was investigated in the brain and olfactory system of the viviparous skink, Chalcides chalcides. In the adult brain FMRFamide immunoreactive (ir) perikarya were observed in the diagonal band of Broca, medial septal nucleus, accumbens nucleus, bed nucleus of the anterior commissure, periventricular hypothalamic nucleus, lateral forebrain bundle, and lateral preoptic, subcommissural, suprachiasmatic and lateral hypothalamic areas. This pattern was seen in both male and female brains. Though all major brain areas showed FMRFamide-ir innervation, the densest ir fiber network was observed in the hypothalamus. During development, ir elements were observed for the first time in embryos at mid-pregnancy. FMRFamide perikarya were located along the ventral surface of the vomeronasal nerve, in the olfactory peduncle mediobasally, as well as in the anterior olfactory nucleus and olfactory tubercle. Furthermore, some ir neurons were observed in the rhombencephalic reticular substance; however, the ir fiber network was poorly developed. Later in development FMRFamide-ir neurons appeared also in the bed nucleus of the anterior commissure as well as the rhombencephalic nucleus of solitary tract and the dorsal motor nucleus of vagus nerve. In juveniles, the distribution profile of FMRFamide immunoreactivity was substantially similar to that of the adults, with a less widespread neuronal distribution and a more developed fiber network. Ontogenetic presence of FMRFamide immunoreactivity in the nasal area has been linked to the presence of a nervus terminalis in this reptile.
Animals↗
Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH.
OBJECTIVE: This study tested the hypothesis that administration of human recombinant thyroid-stimulating hormone (rhTSH: Thyrogen, thyrotropin alpha) could promote iodine-131 ((131)I) uptake in the therapy for metastatic or locally invasive differentiated thyroid cancer (DTC), obviating L-thyroxine suppressive therapy (L-T4) withdrawal and hypothyroidism in patients with advanced disease. METHODS: Twelve totally (or almost completely) thyroidectomized adults, nine of whom had received earlier therapy after L-T4 withdrawal, underwent (131)I treatment while euthyroid on L-T4, after rhTSH administration. Nine underwent diagnostic whole-body scanning (WBS) after two consecutive daily i.m. injections (0.9 mg) of rhTSH. They then received an identical second course of rhTSH to promote therapeutic (131)I uptake. Post-therapy WBS was performed one week later. Three patients received only rhTSH (131)I therapy. RESULTS: Administration of rhTSH promoted (131)I uptake in all patients, as demonstrated by post-therapy WBS. Administration of rhTSH also promoted a significant increase in serum thyroglobulin (Tg) concentrations. According to the most recent measurements, 3-12 months after therapy, serum Tg levels fell in four, and stabilized in two out of eleven patients. Upon additional rhTSH-WBS 8 months post-study, a reduction in one metastatic site was noted in one patient. The rhTSH was well tolerated, with mild, transient fever and/or nausea occurring in only a minority of patients. Individuals with bone metastases experienced degrees of peritumoral pain and swelling that were similar (though more short-lived) to those seen in the same or other patients after L-T4 withdrawal. CONCLUSIONS: Administration of rhTSH is a safe, successful tool for inducing (131)I uptake in local and metastatic DTC lesions, and avoids L-T4 withdrawal, preserving metabolic homeostasis and preventing the debilitating effects of hypothyroidism.
Aged↗
[New therapeutic options in the treatment of hepatocellular carcinoma].
Hepatocellular carcinoma (HCC) is the fourth cause of death for cancer, the first in northern Africa and is the eighth tumor for incidence in the world. Risk factors are: liver cirrhosis, HBV, HCV and natural toxins (i.e. aflatoxin). A screening program is feasible and based on serum alpha-fetoprotein dosage and periodic liver ultrasonography. Instrumental diagnosis is based on ultrasonography associated with angiography or spiral TC associated with systemic portography. The best therapy of HCC is based on a multimodal approach: surgery when feasible, associated with or in alternative to intratumoral ethanol injection (PEI), transcatheter arterial chemoembolization (TACE), chemotherapy and radiotherapy. These different therapeutical approaches are related to the liver extent of the disease and liver functioning. Poor results obtained with chemotherapy led to research different therapeutical approaches as hormonal substances, immune modulators or genetic modulators. Most patients present with advanced disease, and their survival rate decreases with the increase of liver cirrhosis concomitant with HCC. Better results should be obtained with the use of different therapeutical approaches as angiogenetic inhibitors, today only for experimental use at present.
Antineoplastic Agents↗
Identification of nine novel mutations in the Bruton's tyrosine kinase gene in X-linked agammaglobulinaemia patients.
Mutations in the Bruton's tyrosine kinase (BTK ) gene are responsible for X-linked Agammaglobulinemia (XLA), an immunodeficiency caused by a block in B cell differentiation. Non Isotopic RNAse Cleavage Assay (NIRCA), followed by sequencing was used to screen for BTK mutations in 11 Italian XLA patients. Nine novel mutations were identified: 6 missense (Y39S, L512P, L512Q, R544G, S578Y, E589K), one non-sense (Q260X), one frameshift (1599-1602del GCGC) and one in-frame insertion (2037-2038insTTTTAG), that represents the first case of premature stop codon introduction in the BTK coding frame. These data support the high molecular heterogeneity of BTK gene in XLA disease and provide new insight to the diagnosis and to the role of BTK domain in XLA and in B cell signal transduction and development. Hum Mutat 15:117, 2000.
Agammaglobulinaemia Tyrosine Kinase↗
The expression of androgen receptor messenger RNA is regulated by tri-iodothyronine in lizard testis.
The network of hormonal and non-hormonal signals required for testicular activity during the reproductive cycle of the seasonal breeding lizard, Podarcis sicula, are not yet well understood. Androgens are significantly involved in meiosis and spermiogenesis, and such an effect is mediated through their receptor (AR). Estrogens also affect the testicular activity down-regulating the expression of AR mRNA. Since over the last few years, extensive works have reported, in mammals, a clear influence of tri-iodothyronine (T(3)), the biologically active thyroid hormone, on Sertoli cell activities, we carried out a study to shead light on the effect/s exerted by T(3) in lizard testis. A thyroid hormone receptor mRNA (TR mRNA) has been found in the testis indicating that T(3) might be involved in the regulation of gonadal activity. In in vivo experiments, injection of T(3) to male lizards, captured during the recrudescence period (March) and maintained under experimental photothermal conditions (24 degrees C and 15 h daylight), increased the expression of AR mRNA. The in vitro results confirmed the stimulatory effect of T(3) on AR mRNA levels. Thus, in testosterone (T) exposed cells, the highest values of AR mRNA were observed in T(3)-primed animals, indicating that T and T(3) increase AR gene transcription independently. The present data suggest that, in lizards, the combined action of androgens, estrogen and T(3) might regulate testicular activity, modulating AR mRNA levels.
Actins↗
Advantages of combined technetium-99m-sestamibi scintigraphy and high-resolution ultrasonography in parathyroid localization: comparative study in 91 patients with primary hyperparathyroidism.
OBJECTIVE: To evaluate the usefulness of the combination of Tc-sestamibi/Tc-pertechnetate subtraction scintigraphy (SS) and high-resolution neck ultrasonography (US) in patients with primary hyperparathyroidism (pHPT) undergoing parathyroidectomy. DESIGN AND METHODS: Ninety-one patients with proved pHPT were studied, excluding patients with persistent or recurrent disease. There were 65 (71.4%) women and 26 (28.6%) men, with a median age of 59 years (range 18-78 years). All patients underwent both SS and US prior to surgery, and the results were compared with operative and histological findings. The intraoperative quick-parathyroid hormone assay was available for 52 (57.1%) patients. When multiglandular disease was found, both SS and US were considered truly positive only when at least two enlarged parathyroid (PT) glands had been localized. RESULTS: Eighty-three (91.2%) solitary PT adenomas and three (3.3%) carcinomas were found. Moreover, two (2.2%) patients had a double adenoma and three (3.3%) patients had diffuse PT hyperplasia. The overall sensitivity of combined SS+US was 94.5% (86.8% and 80.4% for SS and US respectively). There was a significant (P<0.05, Student's t-test) difference in size between the PT glands correctly identified and undetected by SS, whereas the site of the removed PT tumors significantly (P<0.05, Fisher exact test) influenced only the US sensitivity. CONCLUSIONS: When the preoperative localization of the PT glands is chosen, the combination of SS and US represents a reliable noninvasive localization technique and should be considered for use in each patient with pHPT undergoing surgery.
Adenoma↗
Detection of DNA in ancient bones using histochemical methods.
We describe histochemical techniques for detecting DNA within the osteocytic lacunae of ancient bones. The bones examined were fragments of femurs from two human individuals found in the Pompeian C. I. Polybius house and fragments of metacarpals from two horses (Equus sp.) found in the Pompeian "Casti Amanti" house. Both buildings were buried by the 79 A. D. Vesuvius eruption. Fragments of femurs from a modern horse, a modern swine and a modern amphibian also were studied as controls. Some bone sections were stained with two different DNA-specific fluorochromes, 4'-'6-diamidino-2-phenylindole (DAPI) and chromomycin A3 (CMA), while others were stained by the Feulgen reaction. All of the techniques gave a positive reaction within the osteocytic lacunae. Histological analysis of the undecalcified, ground and unstained sections agreed well with results of bone sections stained with either the fluorochromes or the Feulgen reaction. Bones showing good histology also were positive by our DNA-specific stain. Histochemical and histological analyses correlated well with the success of DNA extraction and amplification. Using conventional DNA-specific histochemical techniques in conjunction with histological analysis can be useful in the study of DNA extracted from ancient bone remains while reducing both the amount of time and cost.
Animals↗
Tumors of the parathyroid glands. Changes in clinical features and in noninvasive localization studies sensitivity.
Primary hyperparathyroidism is the most common cause of hypercalcemia and 80-85% of the patients have parathyroid tumors. The purpose of this retrospective review was to analyse whether differences exist between patients with parathyroid tumors treated in the 1980s and 1990s. Between 1980-1997, 253 patients underwent initial surgical neck exploration for hyperfunctioning parathyroid tumors. Renal (polyuria, nocturia, renal colic due to lithiasis), rheumatologic (bone and joint pain), neurological (fatigue, memory loss, depression) and gastrointestinal (dyspepsia, anorexia, nausea) symptoms were recorded and main biochemical parameters were measured. In all patients one or more preoperative localization procedures were carried out prior to successful parathyroidectomy, and the confirmation of imaging findings was obtained after surgery. The patients were divided in two groups. Group A: 121 (47.8%) patients who underwent surgery from 1980-1989; Group B: 132 (52.2%) patients in whom parathyroidectomy was performed from 1990-1997. There were no differences (p=NS) between the two groups in average age, preoperative serum creatinine and intact-PTH levels. Symptoms were most common in Group A, and pre-operative serum calcium levels were significantly lower in Group B. Ultrasonography (n=191) sensitivity did not improve significantly (82.8% vs 82.9%), but positive predictive value (PPV) was higher (89.8% vs 96.0%). CT-scan (n=73) sensitivity was 79.2% and 82.6%, and PPV was 95.0% and 100% in Groups A and B, respectively. 201Tl/99mTc subtraction scintigraphy (n=111, Group A) was 84.6% sensitive (PPV=92.6%) whereas 99mTc-sestamibi scanning (n=90, Group B) was 85.1% sensitive (PPV=96.1%). In conclusion, the clinical features of parathyroid tumors has changed in the nineties and increasing asymptomatic pHPT rate has been found. Although sensitivity and PPV of preoperative localization procedures has improved moderately, at present noninvasive techniques may offer excellent results and should be used in all patients with suspected parathyroid tumors.
Adult↗