T lymphocytes express either alpha beta or gamma delta T-cell receptor heterodimers. Most alpha beta T cells recognize antigenic peptides bound to major histocompatibility complex molecules but the antigen recognition and biological function of gamma delta T cells is unknown. A major human gamma delta T-cell subset expressing V gamma 2 and V delta 2 germline genes, but having diverse junctional sequences, is found in human mycobacterial lesions and responds in vitro to antigens of bacteria and parasites. In addition, certain haematopoietic tumour cells are specifically recognized and lysed by these T cells. V gamma 2V delta 2-bearing T cells were shown to recognize mycobacterial antigens that are protease resistant and phosphatase sensitive. Because of the difficulty in isolating natural antigens from mycobacterial culture filtrates or extracts, we synthesized a series of monoalkyl phosphates, and found that some, particularly monoethyl phosphate, could mimic the activity of mycobacterial antigens in stimulating these gamma delta T cells. Here we report the identification of natural antigens produced by mycobacteria recognized by human V gamma 2V delta 2-bearing T cells as isopentenyl pyrophosphate and related prenyl pyrophosphate derivatives, compounds involved in the synthesis of complex polyisoprenoid compounds in microbial and mammalian cells. Substitution of phosphate for the pyrophosphate moiety, or elimination of the double bond, greatly reduced antigenic activity of these compounds. These results provide formal evidence that, in contrast to recognition of major histocompatibility complex-bound peptide antigens by alpha beta T cells, human gamma delta T cells can recognize naturally occurring small non-peptidic antigens.

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Comorbid alcohol and substance use disorders occur commonly among patients with schizophrenia and contribute to the morbidity of schizophrenia. These comorbid disorders add greatly to the financial costs and emotional toll that schizophrenia places on patients, families and the entire mental health system. While the basis for the increased abuse of alcohol and other substances in patients with schizophrenia have been linked by some investigators to "self-medication" of negative symptoms of schizophrenia or extrapyramidal system effects of typical antipsychotics, we have presented a neurobiologic formulation suggesting that alcohol or other substances may transiently correct a dysfunction of the dopamine-mediated mesocorticolimbic pathways in patients with schizophrenia - pathways linked to brain reward circuits. This formulation further suggests that alcohol or other substances serve to transiently enhance the functioning of this circuit by improving the "signal detection" capability of the dopamine-rich mesocorticolimbic pathways. Treatment of comorbid substance use disorder in patients with schizophrenia involves careful use of psychosocial approaches aimed at fostering program participation and at enhancing the likelihood of abstinence. While the typical antipsychotics do not limit the comorbid substance use, and may actually worsen it, preliminary data suggest the novel antipsychotic clozapine may have the unusual ability to dramatically decrease alcohol and other substance use in patients with schizophrenia. It is not clear whether other novel antipsychotics share this ability of clozapine to limit alcohol and substance abuse. We have proposed that the effect of clozapine in this population may relate to its broad pharmacological effects, including its relatively weak blockade of the dopamine D2 receptor and its potent blockade of the serotonergic 5-HT2 receptor and the noradrenergic alpha 1 and alpha 2 receptors. Studies of other agents, employed in the pharmacotherapy of alcohol and substance use disorders without schizophrenia, are currently underway in patients with schizophrenia and comorbid disorders.

SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.

Gross excision of the tumor followed by radiotherapy is used for treatment of early breast cancer. Local recurrence after this form of treatment is uncommon except in patients with infiltrating ductal carcinoma whose excision specimens reveal an extensive intraductal component (EIC). It is unclear whether this observation is due to a qualitative difference in the response of tumors with EIC to radiation or to a quantitative difference in the tumor burden remaining after gross excision in patients with EIC. To address this question, the authors examined pathologic material in 71 patients with infiltrating ductal carcinoma treated with gross excision of the tumor and then selected for re-excision of the tumor site prior to radiotherapy because of the presence of either EIC in the primary excision specimen or microscopic tumor at or close to margins in the initial excision. Residual carcinoma was seen in 62% of all patients but was more frequent among the 25 patients with EIC than the 46 without (88% YS. 48%, P = 0.002). The nature of the residual tumor differed for patients with and without EIC in the primary excision specimen. Residual carcinoma in patients with EIC was often widespread and composed predominantly of intraductal carcinoma. In contrast, residual tumor in patients without EIC usually consisted of only scattered microscopic foci of infiltrating and/or intraductal carcinoma. The authors conclude that patients with EIC treated with gross excision of the tumor frequently have considerable residual intraductal carcinoma near the primary site. This finding may account for the increased risk of local recurrence observed in patients with EIC treated without re-excision of the tumor site before radiation therapy.

ocial work in the United States can trace its roots back to the religious institutions of the 19th century (Canda & Furman, 1999). It was from within these institutions that social workers found support and direction. In striving to become a profession the early 20th century, social work abandoned this source of support and direction when it shed its historic grounding in religion and spirituality

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