Biomedical subjects

M Girardi

Publications and source records attributed to M Girardi.

18 recordsLinked to original sources

PubMed2001

Regulation of cutaneous malignancy by gammadelta T cells.

The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

Amino Acid Sequence↗

PubMed2001

Predicting fall risks in an elderly population: computer dynamic posturography versus electronystagmography test results.

OBJECTIVES/HYPOTHESIS: Falls are the leading cause of morbidity and mortality for persons aged 65 years and older, with more than 2 million people falling and sustaining serious injury annually. This study compared computer dynamic posturography (CDP) and electronystagmography (ENG) results as predictors of falls. STUDY DESIGN: Retrospective. METHODS: Thirty-three patients over the age of 65 years who presented to a balance disorders and falls prevention clinic were used for this study (22 women and 11 men, with an average age of 78.0 y and a mean fall rate of 3.5 times). All had experienced at least one fall in the year before visiting the clinic and were tested with both CDP and ENG. The CDP results were divided into subcategories (sensory organization testing and limits of stability); ENG results were divided into four categories (ocular motor, rotational chair, positional, and caloric studies). RESULTS: Test findings were classified as normal or abnormal based on age-matched normative data. Of the patients in the study, 27.3% were normal for one type of testing and abnormal for the other. Twenty-six patients (78.8%) had abnormal results on CDP, and 20 individuals (60.6%) showed ENG abnormalities (42.4% for ocular motor, 28.6% for positional, 13.6% for caloric, and 11.2% for rotational chair studies). The limits of stability category was significant in predicting multiple falls. CONCLUSION: For this population, CDP was determined to be a more sensitive test for identifying patients who have fallen, with limits of stability testing the most significant part of the CDP battery; for ENG studies, the best falls indicator was the ocular motor battery.

Accidental Falls↗

PubMed2001

The clonotypic T cell receptor is a source of tumor-associated antigens in cutaneous T cell lymphoma.

To develop cancer vaccines for the treatment of cutaneous T cell lymphoma (CTCL), immunogenic peptides were identified by two approaches. First, through the use of "reverse immunology" the peptide sequence of the idiotypic region of the beta chain of the T cell receptor (TCR) was determined and a series of overlapping peptides synthesized and tested for CD8 T cell recognition. In two patients, the idiotypic CDR3 region provided immunogenic epitopes that were recognized in a class I-restricted fashion by autologous CD8 T cell lines. In a second strategy, peptides were isolated directly from class I MHC molecules on the CTCL surface and sequenced. A peptide with partial homology to sequences contained in the conserved variable portion of the clonotypic TCR beta chain was recognized as immunogenic by autologous CD8 T cells. Therefore, both approaches demonstrated that the clonotypic TCR in CTCL is a source of immunogenic tumor epitopes. To confirm that recognition of TCR-derived sequences provides immunoprotection against tumor growth, a murine model of T cell lymphoma was studied. The immunogenicity of a thymoma, which lacks cell surface TCR expression, was enhanced by transfection of the beta chain of the TCR. The studies reviewed in this paper demonstrate that the TCR can serve as one source for immunogenic tumor peptides in T cell lymphoma in vitro and in vivo. Presentation of TCR epitopes on dendritic cells that express high levels of MHC, costimulatory, and adhesion molecules may provide an effective means for immunization against T cell malignancy.

Amino Acid Sequence↗

PubMed2001

Extracorporeal photochemoimmunotherapy in cutaneous T cell lymphomas.

Extracorporeal photochemotherapy (ECP), or photopheresis, is a widely used treatment for cutaneous T cell lymphoma (CTCL) and other T cell-mediated disorders, having been administered in more than 150 centers worldwide more than 200,000 times. Consistent with the theme of this conference--that is, highlighting the potentially most productive investigative avenues for unraveling the mysteries of CTCL in the next decade--ECP has been futuristic since its inception in the early 1980s. In 1988, the treatment was the first FDA-approved selective immunotherapy for any type of cancer. Yet, the mechanism by which it could suppress a clone of CTCL cells or inactivate multiple autoreactive T cell clones in graft-versus-host disease (GVHD) or allograft rejection remained obscure until quite recently. In fact, the scientific principles necessary to begin to comprehend the basis of ECP's efficacy were not available when the treatment was first introduced in 1982. In the intervening years, necessary detailed knowledge of the structure and function of the clonotypic T cell receptors, of class I major histocompatibility complex (MHC) presentation of tumor antigens, of CTCL tumor-specific antigens, of dendritic antigen presenting cell (DC) biology, and of 8-methoxypsoralen immunopharmacology has been attained. Although much remains to be learned, we now appreciate that ECP simultaneously and efficiently induces both apoptosis of disease-causing T cells and conversion of monocytes to functional DCs. By processing and presenting the unique antigenic determinants of pathogenic T cell clones, the DCs can either initiate a clinically relevant anti-CTCL cytotoxic response or suppress the activity of autoreactive T cell clones. This paper will review clinical trials of ECP in CTCL and evolving scientific understanding of ECP's mechanism in the context of exciting future directions.

Antigen Presentation↗

PubMed2000

Cutaneous T-cell lymphoma and cutaneous graft-versus-host disease. Two indications for photopheresis in dermatology.

Dermatologists are frequently involved in the management of cutaneous T-cell lymphoma (CTCL) and graft-versus-host disease (GVHD). The similarities of these two entities are reviewed in the context of clinical and histologic findings, pathogenesis, and therapy. Photopheresis therapy (extracorporeal photochemotherapy) is used in the treatment of both entities, and the mechanisms underlying the responses represent yet another striking similarity of these two crippling dermatologic diseases.

Graft vs Host Disease↗

PubMed2000

Spin-1 aggregation model in one dimension

We studied a simple model of aggregation in one dimension that resembles the self-assembly of amphiphiles in an aqueous solution. We mapped the water and amphiphilic molecules by Ising spin variables for S=1. The zero component of spin represents the water molecules, while the remaining components (+/-1) account for the amphiphilic molecules. We defined an aggregate in one dimension by a set of spin components (+/-1) placed between two zero spin components. There is no difference between up and down components of the spins inside the aggregates. In this way what really matters is the square of the spin component. The grand-canonical partition function and the probability of formation of different aggregate sizes were calculated by the transfer matrix method. We have shown that for any value of the chemical potential and temperature, the system does not exhibit the typical aggregate size distribution which is observed in micellar solutions at low concentrations. The distribution curve for the aggregate size does not show the minimum and the maximum as a function of the concentration which is the signature of the appearance of micelles. We can say that this one-dimensional model does not present any phase transition nor a transition from the micellar to nonmicellar state.

Journal Article↗

PubMed2000

Postirradiation morphea of the breast presentation of two cases and review of the literature.

The advent of radiation therapy as a common modality in the treatment and palliation of breast cancer has led to the observation of morphea developing months to years after supervoltage radiation therapy, in and around the site of treatment. We report 2 new cases of morphea at the site of previous supervoltage radiation therapy for breast cancer. The time period between irradiation and onset of morphea in our 2 patients were an atypically long 6.5 years and 32 years, the latter being the longest reported such interval. With conservative treatment, the inflammatory component of the lesions resolved over an approximately 1-year period, leaving residual sclerosis. These patients are compared to those previously reported in the medical literature so as to summarize the range of clinical presentation and course. Recognition of postirradiation morphea is important in distinguishing it from infectious cellulitis, recurrent carcinoma, metastatic carcinoma or development of a second primary carcinoma.

Adult↗

PubMed2000

Cutaneous T-cell lymphoma: pathogenesis and treatment.

Cutaneous T-cell lymphoma (CTCL) is a malignancy of a distinctive subset of T-helper cells designated "cutaneous T cells" because of their central role in the normal functioning of the skin immune system. Guided by selective adhesion molecules, activated/memory T cells of the skin immune system normally circulate among the skin, lymph nodes, and peripheral blood. Thus, a better understanding of the skin immune system, which normally functions to provide immunosurveillance against cutaneous pathogens and other insults, has led to a better understanding of the clinical spectrum, pathogenesis, staging, and management of CTCL. This article describes the major subtypes of CTCL and provides an update on the pathogenesis and treatment of this lymphoma.

Forecasting↗

PubMed1999

Extracorporeal photochemotherapy in human and murine graft-versus-host disease.

Extracorporeal photochemotherapy (ECP) is an immunotherapy that has found a role in the therapy of cutaneous T cell lymphoma, a disease of mature activated T cells. Graft-versus-host disease (GVHD) is also mediated by activated T cells, and thus often responds to therapies that target T cells. Murine models for both GVHD and ECP can be combined to study the impact of this immunotherapy on GVHD. In this paper we present a patient with GVHD who demonstrated a beneficial therapeutic response to treatment with ECP. The findings of this case are compared with the observations from a murine model for GVHD-ECP. The potential mechanisms of ECP in the treatment of GVHD are discussed. along with the similarities observed with ECP in the treatment of other conditions.

Acute Disease↗

PubMed1999

Balance and aging.

OBJECTIVES/HYPOTHESIS: To provide a basic science and clinical review of normal balance changes with age, and to provide a current review for the evaluation and treatment of elderly patients with balance disorders. As we age, we lose balance function through loss of sensory elements, the ability to integrate information and issue motor commands, and because we lose musculoskeletal function. Diseases common in aging populations lead to further deterioration in balance function in some patients. Treatment of balance dysfunction in aging populations is based on the knowledge of normal aging processes and on an evaluation of the individual's balance loss and remaining balance elements. Prevention and rehabilitation play a major role in treatment; medical and surgical therapy also have a place. STUDY DESIGN AND METHODS: Review of literature, personal research and observations. RESULTS AND CONCLUSIONS: Although older patients may be subject to most of the common balance disorders of younger patients, they have more problems with chronic disequilibrium and falls. Prevention and rehabilitation play an important role in treating these patients.

Accidental Falls↗

PubMed1999

Subcutaneous Fusarium foot abscess in a renal transplant patient.

Fusarium species are ubiquitous plant and grain phytopathogens that rarely cause opportunistic infections in immunocompromised patients. While disseminated Fusarium infections are almost always fatal, localized infections may be responsive to a combination of systemic antibiotic therapy and surgical debridement. We present a diabetic renal transplant patient who developed a foot abscess due to Fusarium solani. Infection persisted despite aggressive surgical debridement and a 3-month course of intravenous liposomal amphotericin B.

Abscess↗

PubMed1998

Vestibular rehabilitation therapy for the patient with dizziness and balance disorders.

Vestibular disorders and balance dysfunctions affect a significant number of patients seeking treatment from otolaryngologists. Vestibular Rehabilitation Therapy (VRT) has been shown to be a highly efficacious treatment modality for a majority of individuals with vestibular or central balance system disorders, or a combined etiology. Assessment methods, treatment paradigms, and recommendations for referral are presented.

Adaptation, Physiological↗

PubMed1996

Vestibular deficits in deaf children.

Considerable knowledge has been accumulated regarding acquired and congenital deafness in children. However, despite the intimate relationship between the auditory and vestibular systems, data are limited regarding the status of the balance system in these children. Using a test population of 15 children, aged 8 to 17 years, we performed electronystagmography testing. The test battery consisted of the eye-tracking (gaze nystagmus, spontaneous nystagmus, saccade, horizontal pursuit and optokinetic) tests, positional/positioning (Dix-Hallpike and supine) tests, and rotational chair tests. With age-matched controls, five children were tested in each of the following three categories: normal hearing, hereditary deafness, and acquired deafness. The children in the hereditary deafness category were congenitally deaf and had a family history of deafness. Those subjects in the acquired deafness category had hearing loss before the age of 2 years, after meningitis. Analysis of variance demonstrated significant differences between the two deaf groups and the control subjects in the gaze nystagmus test, saccade latencies, horizontal pursuit phase, and Dix-Hallpike and supine positionally provoked nystagmus. Also, significant differences were found in rotational chair gain and phase between the deaf and normal-hearing children. The children with acquired deafness exhibited the most profound results. In addition, there were significant differences in rotational chair gain between the acquired and congenitally deaf children. No differences were noted in horizontal pursuit gains, saccade accuracies, or saccade asymmetries. These preliminary data demonstrate that the etiologic factors responsible for congenital and acquired deafness in children may indeed affect the balance system as well. These findings of possible balance disorders in conjunction with the profound hearing loss in this patient population will have prognostic implications in the future evaluation, treatment, and rehabilitation of these patients.

Adolescent↗

PubMed1996

Management of benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is one of the most common balance disorders of the peripheral vestibular system. Diagnosis is made from patient history and the manifestation of specific symptoms. Treatment differs for the individual patient and may include pharmacological, surgical, dietary, and/or therapeutic modalities. Various versions of Modified Liberatory Maneuvers (MLM), and other, similar rehabilitation therapy treatments have been shown to be very effective in the management of the BPPV patient.

Diagnosis, Differential↗

PubMed1995

Alpha beta and gamma delta T cells can share a late common precursor.

BACKGROUND: The subdivision of T cells into alpha beta and gamma delta subtypes is conserved throughout vertebrate development. The respective alpha beta and gamma delta T-cell receptors (TCRs) are encoded by somatically rearranged genes. There has been broad speculation as to whether an individual thymocyte can become either a gamma delta T cell or an alpha beta T cell as a result of stochastic gene rearrangement processes, or whether the two types of T cell are derived from separate lineages. Many of the experimental findings are apparently conflicting, however, and the issue--a basic one in immunology and development--remains unresolved. RESULTS: To address this issue, we have used the recently developed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, which allows us to examine quantitatively the status of TCR gamma and delta genes in postnatal alpha beta T cells and their progenitors. Interestingly, such cells are depleted of productively rearranged delta and gamma genes, which can encode delta and gamma TCR polypeptide chains. However, in mice that can rearrange TCR delta gene segments, but in which the TCR delta gene is non-functional in other respects, no such depletion of productive rearrangements is seen. CONCLUSION: The quantitative data that we have obtained fulfill the predictions of the stochastic hypothesis: that is, a progenitor T cell first attempts to become a gamma delta T cell and, if unsuccessful, then attempts to become an alpha beta T cell. Thus, alpha beta and gamma delta T cells can derive from a common precursor thymocyte. In the simplest case, therefore, lineage-determining factors are the successful rearrangement of both gamma and delta genes before TCR alpha gene rearrangements occur, which lead to deletion of the TCR delta locus and thereby preclude further gamma delta T-cell differentiation. In contrast, successful rearrangement of the TCR beta locus remains compatible with cells becoming either gamma delta or alpha beta T cells.

Animals↗

PubMed1995

Specific suppression of lupus-like graft-versus-host disease using extracorporeal photochemical attenuation of effector lymphocytes.

(C57BL/6 x DBA/2)F1 (B6D2F1) mice inoculated with parental DBA/2 (D2) splenocytes develop chronic stimulatory graft-versus-host reaction with many of the clinical manifestations of systemic lupus erythematosus. This investigation tested the ability of 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light-treated D2 cells, primed to contain an expanded population of T cells specific for B6D2F1 major histocompatability complex antigens, to treat and/or prevent such systemic lupus erythematosus-like disease. 8-MOP/UVA-treated cells from B6D2F1-primed D2 donors were inoculated into B6D2F1 recipients weekly six to ten times, either before or after initiating graft-versus-host disease with normal D2 cells. A third group of B6D2F1 recipients were vaccinated weekly six times before disease initiation using 8-MOP/UVA-attenuated, B6D2F1-primed D2 cells that had been secondarily stimulated and expanded in vitro in the presence of irradiated B6D2F1 targets and interleukin-2. Control B6D2F1 mice were vaccinated with 8-MOP/UVA-treated D2 cells stimulated in vitro and/or in vivo with (C3H/HeJ x DBA/2)F1 cells. Only mice vaccinated with 8-MOP/UVA-attenuated D2-anti-B6D2F1 cells that were secondarily stimulated and expanded in vitro exhibited differences from controls when measured by the clinical parameters of ascites formation, and mean survival (p < 0.025). These groups also differed significantly in mean antinuclear antibody titer measured 14 weeks after disease initiation (p < 0.05). At 28 weeks, histologic evidence of systemic lupus erythematosus-like kidney disease was found only in the control group. These results indicate that photochemically attenuated D2-anti-B6D2F1 cells primed in vivo and secondarily stimulated and expanded in vitro are capable of vaccinating recipients against progression of graft-versus-host reaction-initiated systemic lupus erythematosus-like disease.

Animals↗

PubMed1976

[Evaluation of hemolysis in 308 patients with valve prostheses. Practical value and causes of errors].

A study of haemolysis in 308 patients with prosthetic valves, making up a total of 364 prostheses, showed that the most practical test for screening patients is the level of the LDH 1 isoenzyme alpha-HBDH. After analysis of the lowest levels for each type of prosthesis currently in use, an acceptable average level for each is proposed. If the level of LDH 1 exceeds the limits of confidence, a complication must be excluded; this may be silent, and the most important is a dehiscence but a thrombosis or a deep haematoma must also be excluded. A periodic check on the enzyme levels should form part of the routine follow-up of these patients.

Aortic Valve↗

PubMedDate not supplied

Familial multiple basaloid follicular hamartomas: A report of two affected sisters.

Basaloid follicular hamartoma (BFH) is one of several benign skin tumors that may occur in multiple and solitary forms. While the histologic findings of BFH may be observed in a variety of clinical settings, familial multiple BFH represents a distinct clinical entity characterized by tiny flesh-colored papules scattered predominantly over the face. We present two sisters with this rare condition and review the clinical and histologic differential diagnosis of familial multiple BFH.

Child↗