K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men.

Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactory amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT----GAT transition, four had GGT----GTT transversions, and one had both GGT----GAT and GGT----GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.     

Antisocial personality disorder, HIV risk behavior and retention in methadone maintenance therapy

In a sample of 55 consecutive methadone maintenance admissions to our clinic, 42% were diagnosed with antisocial personality disorder (ASPD) using the National Institute of Mental Health Diagnostic Interview Schedule NIMH DIS. Individuals with ASPD exhibited greater risk for HIV infection as defined by more sexual contacts, needle use and equipment sharing. Data at 1 year follow-up were obtained on this group of patients. The objective was to compare the ASPD and non-ASPD groups with regards to demographics, drug abuse history, outcome and retention in treatment. There were no significant differences between the groups on any demographic or treatment outcome variables. Survival analysis indicated that there were no group differences in treatment retention. In conclusion, although there were no differences in treatment outcome between ASPD and non-ASPD groups it is possible that ASPD patients who drop out of treatment will be at higher risk for contracting and spreading HIV within the IV drug using population. These data also suggest that in this population the diagnosis of ASPD using primarily behavioral traits as measured in the NIMH-DIS-III, has little utility in predicting treatment outcome.     

Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen cells to secrete prostaglandin E2, and indomethacin upregulates immune functions.

Incubation of microorganisms with macrophages enhances the production of prostaglandin E2 (PGE2). Previous research had indicated that macrophages from syphilitic rabbits suppressed spleen cell synthesis of interleukin-2 (IL-2); this suppressive activity was reversed by indomethacin. Experiments were designed to further characterize the involvement of prostaglandins in immune processing. When Treponema pallidum was incubated with unfractionated spleen preparations, PGE2 production was accelerated, and within 24 h, pharmacologic concentrations of the prostaglandin were detected. When cytochalasin B was used to block phagocytosis, decreased levels of PGE2 were apparent. Commercial preparations of PGE2, in the range generated by macrophage-treponeme interaction, inhibited concanavalin A-induced IL-2 secretion by splenic cells. T. pallidum stimulated IL-1 production by adherent cells, and indomethacin markedly enhanced this effect. In vivo, indomethacin upregulated immune function. Two groups of rabbits were infected, and one was given daily injections of indomethacin for 18 days. Both groups were treated with penicillin to terminate infections. One week later, rabbits were challenged with viable organisms to determine their immune status. The indomethacin-treated group was more resistant to reinfection. In further research, indomethacin enhanced the immunogenicity of vaccine preparations containing heat-killed T. pallidum. Results are discussed in terms of the role of PGE2 as it impinges on immune functions involving macrophage activation (IL-1 production) and T lymphocyte activation (IL-2 production).     

Brain and tissue levels of mercury after chronic methylmercury exposure in the monkey

Estimated half-lives of mercury following methylmercury exposure in humans are 52-93 d for whole body and 49-164 d for blood. In its most recent 1980 review, the World Health Organization concluded that there was no evidence to suggest that brain half-life differed from whole-body half-life. In the present study, female monkeys (Macaca fascicularis) were dosed for at least 1.7 yr with 10, 25, or 50 micrograms/kg.d of mercury as methylmercuric chloride. Dosing was discontinued, and blood half-life was determined to be about 14 d. Approximately 230 d after cessation of dosing, monkeys were sacrificed and organ and regional brain total mercury levels determined. One monkey that died while still being dosed had brain mercury levels three times higher than levels in blood. Theoretical calculations were performed assuming steady-state brain:blood ratios of 3, 5, or 10. Brain mercury levels were at least three orders of magnitude higher than those predicted by assuming the half-life in brain to be the same as that in blood. Estimated half-lives in brain were between 56 (brain:blood ratio of 3) and 38 (brain:blood ratio of 10) d. In addition, there was a dose-dependent difference in half-lives for some brain regions. These data clearly indicate that brain half-life is considerably longer than blood half-life in the monkey under conditions of chronic dosing.     

Models of adult day care: findings from a national survey

We examined a nationally representative sample of 60 adult day care centers to describe the state of this evolving care modality after a decade's growth. Results indicate that day care centers can be categorized into three models of care, each of which serves a distinctive subpopulation. Model appropriateness was tested with analysis of variance of differences in participant characteristics. Services, staffing, costs, and other program features are contrasted among the three models.     

Basic surgical techniques and variations of endoscopic sinus surgery

This article gives complete information on the care of the endoscopic sinus surgery patient. Indications and preoperative evaluations necessary for endoscopic sinus surgery are described. The technique of functional endoscopic sinus surgery is covered in detail. Postoperative care and complications are also described. Various procedures for patients with extensive or unusual disease are discussed.     

Picture naming in early sequential bilinguals: a 1-year follow-up.

In a previous study, a cross-sectional approach was used to investigate developmental changes in basic-level lexical production and cognitive processing in early sequential bilinguals, exploring the effects of age and years of experience during single-language (Spanish or English) and mixed-language (alternating between Spanish and English) picture naming (K. Kohnert, E. Bates, & A. E. Hernandez, 1999). The current study reports on the performance, 1 year later, of a subgroup of these original study participants (n = 28; mean age = 10.2 years) on the same experimental task. Overall, from Time 1 to Time 2 testing, gains were greater in English than in Spanish and in the high-competition mixed-language processing condition than in the single-language processing condition. These results reinforce previous findings of a shift toward greater strength in L2 with increasing age (and years of language experience), as well as the primary role of cognitive development in control of the dual-language system. In addition, examination of individual performance revealed a complex non-monotonic pattern of L1-L2 change across time within an overall pattern of increasing speed, accuracy, and control of the dual-lexical system.     

Neuropeptide modulation of muscarinic receptors and function in cerebral cortex of young and senescent rats.

The possible influence of several neuropeptides on muscarinic receptor binding and function in fronto-parietal cortex of young and senescent Fischer 344 rats was examined. Low concentrations (100 nM) of cholecystokinin, neurotensin and vasoactive intestinal polypeptide (VIP), added in vitro, enhanced carbachol-stimulated phosphoinositide metabolism in cortical miniprisms from both young and senescent rats, while somatostatin was ineffective. Interestingly, the VIP receptor antagonist [d-parachloro-Phe6,Leu17[VIP shifted the dose-response curve for carbachol significantly to the right, indicating inhibition of phosphoinositide hydrolysis. No direct actions of neuropeptides on the number or affinity of [3H]l-quinuclidinyl benzilate binding sites nor on agonist conformation states of the muscarinic receptor were noted in cortex from young animals. The neuropeptide modulation of phosphoinositide metabolism was selective for muscarinic systems, as norepinephrine-stimulated phosphoinositide hydrolysis was not altered. Pretreatment with hemicholinium-3, an inhibitor of high-affinity choline uptake, did not prevent the neuropeptide effects, indicating the interaction was probably postsynaptic. It is possible that pharmacologic manipulation of peptidergic processes could improve cholinergic neurotransmission in brain.