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Biomedical subjects

A D'Agostino

Publications and source records attributed to A D'Agostino.

At least 19 recordsLinked to original sources

nef gene sequence variation among HIV-1-infected African children.

BACKGROUND: There are few data on African children infected with nonclade B HIV-1 in endemic settings, which limits generalizations about pathogenesis and progression. Genotypic and phenotypic variations in host immunogenetics and HIV-1 negative factor (nef) accessory protein may influence disease progression and have frequently been characterized in subjects infected with clade B HIV-1. METHODS: In this descriptive study, we report nef gene sequence variation and host genetic polymorphisms in 32 Kenyan children, including 12 slow progressors. RESULTS: Phylogenetic analysis identified HIV-1 clades A, C and D and a recombinant A/D subtype. Grossly defective nef genes or significant changes from relevant clade reference sequences were not identified in children with delayed disease progression. CONCLUSIONS: nef sequence variations may not be common in perinatally infected African children. Further studies are warranted in HIV-1-infected subjects in settings where infection is endemic.

Adolescent↗

Cervical anterior hyperostosis: a rare cause of dysphagia. Report of 3 cases.

Disorders of the cervical spine rarely cause dysphagia and/or dysphonia. Exuberant osteophytosis, secondary to diffuse idiopathic skeletal hyperostosis, also referred to as Forestier's disease, seems to be the predominant cause. Forestier's disease is a non inflammatory enthesopathy, of unknown etiology, ossifying the anterior longitudinal ligament of the spine, sparing the discs, and usually affecting older men. We describe the successful surgical treatment of 3 cases, over the course of 26 years, observed in our Neurosurgical Unit.

Adult↗

The relationship between expressed HIV/AIDS-related stigma and beliefs and knowledge about care and support of people living with AIDS in families caring for HIV-infected children in Kenya.

At the end of 2001, AIDS-related deaths had left an estimated 900,000 living orphans in Kenya (UNAIDS/WHO Epidemiology fact sheet, Kenya report, 2004). Many of those orphans are also HIV+. In Eastern Kenya, the Lea Toto Kangemi Outreach Program provides support to families caring for HIV+ children, many of whom are orphaned or soon to be orphaned. A major challenge for these families is the stigma attached to the family. In 2003, the Kangemi Program conducted a household survey of client families. We examined markers of expressed stigma and the association between expressed stigma and other demographic and belief/knowledge domains. The focus of the present study was the specific belief/knowledge domain surrounding care/support of HIV+ persons. Our goal was to explore this domain in the Kangemi families and to examine its relationship to expressed stigma. We created an AIDS-related stigma scale from selected items in the household survey and cross-tabulated stigma scores with care/support knowledge items. We found significant associations between less expressed stigma and greater care/support knowledge. Our results have implications for interventions that reduce expressed stigma and/or improve quality of care.

Adolescent↗

Theoretical models to evaluate hazard due to organochlorine compounds (OCs) in Mediterranean striped dolphin (Stenella coeruleoalba).

Many studies document the chemical stress related to organochlorine (OC) xenobiotics in Mediterranean cetaceans. The aim of this study was to establish a theoretical model to evaluate the hazard to Mediterranean striped dolphins (Stenella coeruleoalba) due to HCB, DDTs and PCB congeners. Differences in OC levels in blubber of stranded and free-ranging specimens enabled us to evaluate the hazard associated with different chlorinated xenobiotics, taking the live population as control sample, assumed to be in good health. For the most toxic compounds, with teratogenic, mutagenic, carcinogenic and endocrine disrupting capacity, we indicate levels beyond which there can be toxicological hazard for the striped dolphin. Using a mathematical formula derived from knowledge of the length and age of 62 stranded specimens, the age of dolphins was estimated and sexual maturity was identified at nine years. This evaluation was important for understanding differences in contaminant burden between males and females.

Age Factors↗

Maxillary post-traumatic outcome correction literature review and our experience. Part I: maxillary bone non-unions-"poor bone positioning".

Still today, there is no classification of non-unions in maxillofacial traumatology. There is a broad spectrum of definitions that simultaneously describe the pathological conditions and functional implications determined by the anatomical location of the fractures and the time factor. In this article the authors describe a literature review about bone non-union classification. Weber, in 1973, introduced the term "pseudo-arthrosis" to describe an altered process of bone healing characterised by the presence of fibrous tissue interposed between the fracture segments, that was lined with cartilaginous tissue and joined by a capsule; Spiessl, in 1988, used the term "non-union" to define any alteration of the bone healing process after a time period of more than 6 months from the initial traumatic event; Rosen, in 1990, proposed a new classification of the modes of altered bone healing in fractures, distinguishing 5 categories: delayed consolidation, non-union, non-union vascular, non union avascular, pseudoarthrosis. The authors also talk about "poor bone positioning". This factor describes the incorrect anatomical position of the bone fragments despite perfectly normal healing according to Gruss. In this article they also discuss about the treatment of non-unions and the treatment of occlusal alterations caused by poor post-traumatic bone positioning.

Bone Plates↗

Maxillary post-traumatic outcome correction. Literature review and personal experience. Part II: loss of maxillary substance (free grafts of autologous bone).

Loss of maxillary substance following trauma varies significantly in relation to the dimensions, site and type of tissue involved. Anatomical maxillary interruptions, loss of dental elements and consequent bone re-absorption give rise to altered chewing, swallowing and speech functions. Treatment of pathological conditions over the years has seen the development of surgical protocols designed to achieve simultaneous aesthetic and functional restoration of the stomatognatic apparatus. The advent of osteointegrated implantology and continual progress in pre-prosthesis surgical techniques have undoubtedly revolutionised established approaches to prosthetic rehabilitation by introducing the concept of supported implant prostheses. The implantation protocols used are a safe and reproducible treatment method suitable for adequate anchorage of such prosthetic implants; the application of such protocols in any case is subordinated to the presence of adequate morpho-volumetric bone at the skeletal bases. Depending on the entity of maxillary loss of substance, the reconstruction methods we propose, in agreement with numerous other authors, are based on the use of free and free-revascularised autologous bone grafts or, even more recently, the application of osteogenetic distraction techniques. The purpose of this article is to evaluate treatment of loss of maxillary substance following trauma by means of non-revascularised free flaps. The use of free grafts of autologous bone is elective in patients presenting bone deficits less than 6 cm with and/or without upkeep of maxillary and mandibular cortical bone continuity but without compromise to the integrity and trophism of the soft tissues.

Bone Transplantation↗

Cauda equina melanoma presenting with subarachnoid hemorrhage. A case report.

The case of a 57-year-old woman with a primary melanoma of the cauda equina is reported. The peculiarity of the case is the very rare clinical presentation mimicking a subarachnoid hemorrhage. The patient underwent surgical excision of the mass. The clinicopathological and neuroradiological features are summarized.

Cauda Equina↗

Inv dup del (1)(pter-->q44::q44-->q42:) with the classical phenotype of trisomy 1q42-qter.

We report on a girl with a trisomy 1q42-q44 due to an inverted duplication of this region, associated with a terminal deletion of the long arm of the rearranged chromosome 1. Both the large duplication (more than 30 cM) and the small deletion were detected by FISH. Complete karyotype was: (46,XX, inv dup(1)(q44q42).ish(dup del 1)(q44q42)(D1S446x2, D1S423x2, tel1q-). The phenotype of the patient is characterized by macrocephaly with prominent forehead, downslanting palpebral fissures, micrognathia, and psychomotor retardation. All these clinical features are the same as observed for the typical trisomy 1q42-qter syndrome. The phenotypic effects of the inversion and the terminal deletion of 1q in addition to the trisomy are discussed here.

Child↗

Identification and cellular localisation of voltage-operated calcium channels in immature rat testis.

Sertoli cells regulate the spermatogenic process mainly through the secretion of a complex fluid into the lumen of the seminiferous tubules behind the blood-testis barrier, containing many of the essential proteins necessary for maintenance and maturation of male germ cells. Thus, the study of Sertoli cell secretory processes is strictly correlated with the understanding of the regulatory mechanisms of spermatogenesis. In this work the authors have explored the voltage-sensitive calcium channel variety in the immature rat testis, their localisation and distribution within the seminiferous epithelium and peritubular and interstitial tissues as well as the possible role in the control of Sertoli cell secretion. The results reported in this paper, obtained by in situ hybridisation, immunohistology of rat testicular sections and Western blot analysis of Sertoli cell plasma membranes, show that mammalian Sertoli cells express mRNA encoding for several voltage-operated calcium channel subunits and express such proteins on their surface. Experiments performed on Sertoli cell monolayers cultured in the presence of specific toxins indicate that both N and P/Q-type Ca(2+) channels are involved in the regulation of protein secretion.

Animals↗

Highly stable oligomerization forms of HIV-1 Tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR.

The use of newly generated murine monoclonal antibodies directed against distinct epitopes of a functionally active, chemically synthesized HIV-1 Tat protein has permitted the identification of several molecular forms including monomers, dimers and trimers. Dimers and trimers are particularly stable and resistant to strong reducing conditions. Through epitope mapping it has been possible to demonstrate that the major immunodominant epitope is contained within the basic region of the Tat protein and is lost after oligomerization of the molecule. In contrast, N-terminal, C-terminal and conformation-dependent epitopes are still accessible to mAb specific recognition after Tat oligomerization. Moreover, by using a quantitative HIV-LTR transactivation assay depending upon exogenous Tat, we could extrapolate the amount of functional Tat produced by cell lines stably transfected with the viral transactivator. More importantly, we could show that only the monomeric form of exogenous Tat is the relevant functional form acting in cells harbouring the HIV-1 LTR promoter.

Alkylation↗

HIV-1 Tat mutants in the cysteine-rich region downregulate HLA class II expression in T lymphocytic and macrophage cell lines.

Human macrophage and T cell lines were stably transfected with HIV-1 wild-type Tat or Tat mutants in the cysteine-rich region displaying trans-dominant negative effects on HIV-1 life cycle. The expression of HLA class I and class II molecules was not affected by wild-type Tat. Tat mutants, instead, profoundly down-regulated in a dose-dependent fashion the expression of class II, but not of class I, in both cell types by acting at the transcriptional level. Down-regulation was manifested on constitutive and IFN-gamma-induced class II gene expression and did not correlate with reduced transcription of the AIR-1 gene product CIITA, the major transcriptional activator of class II genes, indicating that Tat mutants did not act by inhibiting AIR-1 gene expression. Class II down-modulation had important functional implications in macrophages, as both antigen processing and presenting capacity were inhibited. These results represent the first evidence that a modified HIV-1 Tat product can act as a potent immunosuppressor by inhibiting the HLA class II expression necessary for triggering both cellular and humoral responses against pathogens. The use of these HIV-1 Tat mutants also discloses new opportunities to investigate the molecular mechanisms underlying the coordinate HLA class II gene transcription.

Antigen Presentation↗

Immediate cell signal induced by laminin in rat sertoli cells.

Rat Sertoli cells in primary culture have been studied for their ability to respond to extracellular matrix macromolecules by increases of [Ca(2+)](i). We observed that cells seeded on glass coverslips, loaded with the intracellular Ca(2+) indicator fura-2, responded to laminin, but not to fibronectin, with an immediate [Ca(2+)](i) raise, with a peak followed by a prolonged plateau. [Ca(2+)](i) increases were dependent upon Ca(2+) influx across the plasma membrane and Ca(2+) release from intracellular Ca(2+) pools. Ca(2+) influx was inhibited by extracellular Ca(2+) removal by EGTA, and by treatment with La(3+), or with the L-type voltage operated Ca(2+) channel blocker, nifedipine. Ca(2+) release from intracellular Ca(2+) storing organelles, was inhibited by the microsomal Ca(2+)-ATPase blocker thapsigargin. Responses were mimicked by synthetic peptides carrying the Arg-Gly-Asp adhesion sequence, but not by the control Arg-Gly-Glu-containing peptide, in which aspartic acid was replaced by glutamic acid. Laminin-dependent [Ca(2+)](i) increases were down-regulated by the follicle-stimulating hormone. However, this occurred only when cells were not subjected to homotypic cell-cell contact, and responded to the hormone with a significant [Ca(2+)](i) elevation. These results indicate that laminin may regulate Sertoli cells by intracellular signals that perturb Ca(2+) homeostasis. This role may be related to an effect exerted by the seminiferous epithelium basement membrane on the regulation of spermatogenesis.

Animals↗

A veteran with acute mental changes years after combat.

A 49-year-old man presented with a five-week history of worsening confusion, agitation, and bizarre behavior. According to his mother and sister, who live with him, he had inexplicably jumped out of bed one day and complained of injuring his back. The pain apparently resolved within several days. Two weeks later, again just after awakening, he had experienced a period of confusion, lasting about 15 min. The latest episode occurred three days previously and included vivid hallucinations--at various times, he seemed to believe that he was talking to his brother on the telephone, drinking a glass of water, emptying the refrigerator, jumping into a foxhole, and stomping on rattlesnakes. He was disoriented to time as well as environment.

Antipsychotic Agents↗

An unusual manifestation of diabetes mellitus.

MEDICAL HISTORY: Type 2 diabetes mellitus for five years; unexplained 35-lb weight loss three years ago; Bell's palsy on right side many years ago. MEDICATIONS: Glipizide, 10 mg/day. FAMILY HISTORY: Father died of leukemia at age 65; mother has kidney stones; no diabetes or neuromuscular disease. SOCIAL HISTORY: Insurance salesman; heterosexual, promiscuous, uses condoms; smokes (25 pack years); does not drink. PHYSICAL EXAMINATION: Well-nourished, well developed, not in acute distress; had difficulty rising from a sitting position because of right lower extremity weakness. Blood pressure, 154/74; pulse, 88; temperature, 36.6 degrees C; respiratory rate, 16. Head, eyes, ears, nose, and throat: normal. Neck: normal. Heart: S4. Lungs: clear. Abdomen: mildly obese. Extremities: no cyanosis, clubbing, or edema; atrophy and weakness of right thigh and both calves; wide-based gait; able to walk on toes but not heels. Neurologic responses: cranial nerves intact; deep tendon reflexes, 1 + symmetrically; plantar reflexes, flexor bilaterally. Skin: macular rash in sun-exposed areas. LABORATORY FINDINGS: Hemoglobin, 13.2 gm/dL; mean corpuscular volume, 80 micron 3; white blood cell count, 7,200/mm3 (normal differential); platelet count, 137,000/mm3. Serum: electrolytes, normal; blood urea nitrogen, 18 mg/dL; creatinine, 0.8 mg/dL; glucose, 308 mg/dL; total protein, albumin, liver enzymes, and creatine kinase, normal. Urine: 1 + glucose. Venereal disease test: nonreactive; HIV test: negative. DIFFERENTIAL DIAGNOSIS: Dermatomyositis; heavy-metal poisoning; diabetic amyotrophy. HOSPITAL COURSE: The patient was given 50 mg/day of oral amitriptyline to alleviate the painful paresthesias and was switched to 20 U/day of subcutaneously injected neutral protamine Hagedorn (NPH) insulin to normalize the blood glucose level. Histologic studies of skin and muscle showed sun damage and neuropathic changes, respectively. There was no evidence of vasculitis. Screening for heavy-metal toxins produced negative results.

Diabetes Mellitus, Type 2↗

Prenatal findings in trisomy 16q of paternal origin.

A 34-year-old pregnant woman was referred at 30 weeks of gestation with suspected fetal congenital heart disease. On prenatal ultrasound the following anomalies were detected: intra-uterine growth retardation, micrognathia, coarctation of the aorta with ventricular and atrial septal defects, ambiguous external genitalia, and clinodactyly of one hand with adducted thumb. Prenatal karyotyping was offered but refused by the patient. The fetus was delivered by Caesarean section due to fetal distress at 36 weeks of gestation. The neonate, weighing 2150 g was transferred to the neonatal intensive care unit, where he died 10 days later. The karyotype from peripheral blood lymphocytes was 46,XY+der(20)t(16;20)(q12.1;p13)pat. The maternal karyotype was unremarkable, whereas the father had the translocation t(16;20)(q12.1;p13). Necropsy confirmed all the prenatal findings. These are discussed together with the implications of the chromosomal diagnosis and the pertinent literature is reviewed.

Abnormalities, Multiple↗

Distinct regulation of HLA class II and class I cell surface expression in the THP-1 macrophage cell line after bacterial phagocytosis.

Expression of HLA and CD1b molecules was investigated in the THP-1 macrophage cell line within 2 weeks following phagocytosis of mycobacteria or Escherichia coli. During the first 2-3 days, cell surface expression of HLA class II and CD1b was drastically down-modulated, whereas HLA class I expression was up-modulated. In the following days both HLA class II and CD1b expression first returned to normal, then increased and finally returned to normal with kinetics similar to that observed for the steadily increased HLA class I. The initial down-modulation of HLA class II and CD1b cell surface antigens was absolutely dependent on phagocytosis of bacteria. Further studies indicated that initial HLA class II cell surface down-modulation (1) was not due to reduced transcription or biosynthesis of mature HLA class II heterodimers, (2) was only partially, if at all, rescued by treatment with IFN-gamma, although both mRNA and corresponding intracellular proteins increased up to sixfold with respect to untreated cells, and (3) resulted in failure of THP-1 cells to process and present mycobacterial antigens to HLA-DR-restricted antigen-specific T cell lines. The existence of a transient block of transport of mature HLA class II heterodimers to the cell surface in the first days after phagocytosis of bacteria may have negative and positive consequences: it decreases APC function early but it may increase it later by favoring optimal loading of bacterial antigens in cellular compartments at high concentration of antigen-presenting molecules.

Antigen Presentation↗

The Chiari II malformation: lesions discovered within the fourth ventricle.

Structural lesions associated with the Chiari II malformation have been identified within the fourth ventricle in 8 patients. During the 42-month period encompassing the operations of the 7 patients treated surgically, only 9 other patients were explored without the discovery of some associated structural lesion. The patients ranged in age from 2 to 26 years. The following lesions were identified: glial or arachnoidal cysts (3 patients), glial or choroidal nodules (3 patients) and subependymoma (2 patients). These lesions were all situated in the roof of the fourth ventricle adjacent to or interspersed with the choroid plexus. Only the cystic lesions were identified by preoperative imaging. In only 1 case did the associated lesion, a 2-cm cyst, seem to contribute to the patient's clinical presentation. Structural lesions of the fourth ventricle associated with the Chiari II malformation are common in patients who are submitted to decompression. These lesions may be dysplasias of developmental origin, or they may be reactive lesions related to chronic compression and ischemia. They do not necessarily required biopsy or excision.

Adolescent↗