Typology of Ohio, USA, tree farmers based upon forestry outreach needs.

This study differentiated groups of Ohio tree farmers through multivariate clustering of their perceived needs for forest management outreach. Tree farmers were surveyed via a mailed questionnaire. Respondents were asked to rate, on a 1-7 scale, their informational needs for 26 outreach topics, which were reduced to six factors. Based on these factors, three clusters were identified-holistic managers, environmental stewards, and pragmatic tree farmers. Cluster assignment of individuals was dependent upon a tree farmer's age, acreage owned, and number of years enrolled in the American Tree Farm System. Holistic managers showed a greater interest in the outreach topics while pragmatic tree farmers displayed an overall lesser interest. Across clusters, print media and in-person workshops were preferred over emails and webinars for receiving forest management information. In-person workshops should be no more than 1 day events, held on a weekday, during the daytime, at a cost not exceeding $35. Programming related to environmental influences, which included managing for forest insects and diseases, was concluded to have the greater potential to impact clientele among all outreach factors due to the information being applicable across demographics and/or management objectives.

Implementation of a Problem-Based Presentation Format to Improve Residents' Ambulatory Patient Presentations.

Background: The format for residents to present hospitalized patients to teaching faculty is well defined; however, guidance for presenting in clinic is not uniform. Objective: We report the development, implementation, and evaluation of a new standardized format for presenting in clinic: the Problem-Based Presentation (PBP). Methods: After a needs assessment, we implemented the format at the teaching clinics of our internal medicine residency program. We surveyed participants on innovation outcomes, feasibility, and acceptability (pre-post design; 2019-2020; 5-point scale). Residents' primary outcomes were confidence in presentation content and presentation order, presentation efficiency, and presentation organization. Faculty were asked about the primary outcomes of resident presentation efficiency, presentation organization, and satisfaction with resident presentations. Results: Participants were 111 residents and 22 faculty (pre-intervention) and 110 residents and 20 faculty (post-intervention). Residents' confidence in knowing what the attending physician wants to hear in an outpatient presentation, confidence in what order to present the information, and how organized they felt when presenting in clinic improved (all P<.001; absolute increase of the top 2 ratings of 25%, 28%, and 31%, respectively). Residents' perceived education in their outpatient clinic also improved (P=.002; absolute increase of the top 2 ratings of 19%). Faculty were more satisfied with the structured presentations (P=.008; absolute increase of the top 2 ratings of 27%). Conclusions: Implementation of a new format for presenting in clinic was associated with increased resident confidence in presentation content, order of items, overall organization, and a perceived increase in the frequency of teaching points reviewed by attending physicians.

Cirrhosis: diagnosis, management, and prevention.

Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mortality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians share responsibility with specialists in managing the most common complications of the disease, screening for hepatocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every six to 12 months. Causes of hepatic encephalopathy include constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and noncompliance with medical therapy. These should be sought and managed before instituting the use of lactulose or rifaximin, which is aimed at reducing serum ammonia levels. Ascites should be treated initially with salt restriction and diuresis. Patients with acute episodes of gastrointestinal bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours. Physicians should also be vigilant for spontaneous bacterial peritonitis. Treating alcohol abuse, screening for viral hepatitis, and controlling risk factors for nonalcoholic fatty liver disease are mechanisms by which the primary care physician can reduce the incidence of cirrhosis.

Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts.

The role of HLA-DR+ cells in NK activity against CMV-infected FS4 foreskin fibroblasts and K562 erythroleukemia cells was examined. When nonadherent PBMC were depleted of either HLA-DR+ or Leu-11b+ cells by treatment with mAbs plus C, NK activity against CMV-FS4 target cells was markedly reduced. In contrast, depletion of HLA-DR+ cells had no effect on NK activity against K562 target cells. When HLA-DR-depleted cells were added to Leu-11b-depleted cells, NK activity against CMV-FS4 was restored. Negative selection experiments indicated that the HLA-DR+ cells contributing to NK activity against CMV-FS4 are not B or T cells, while negative and positive selection experiments excluded a role for monocytes. Experiments in which HLA-DR- and Leu-11b- cells were mixed in varying proportions indicated that NK(CMV-FS4) is mediated by Leu-11b+ cells, while HLA-DR+ cells provide an accessory function. Irradiation (50 GY) abolished the NK effector function of Leu-11b+ cells, but not the accessory function of HLA-DR+ cells. The NK activity against CMV-FS4 of HLA-DR- cells was restored by the addition of rIFN-alpha or of cell-free supernatants generated by coculturing PBMC or Leu-11b- cells with CMV-FS4. The ability of these supernatants to restore NK activity of HLA-DR- cells was completely abrogated by the addition of neutralizing amounts of antibody to IFN-alpha. In related experiments, neutralization of IFN-alpha in NK assays had little or no effect on NK activity against CMV-FS4, suggesting that the accessory function of HLA-DR+ cells might be mediated by alternative mechanisms in addition to the secretion of extracellular IFN-alpha.

Impaired interleukin 12 production in human immunodeficiency virus-infected patients.

Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.

Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients.

Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a heterodimeric lymphokine produced by B cells that has multiple effects on T and NK cell functions. NKSF at concentrations as low as 0.4 pM enhances the spontaneous cytotoxic activity of peripheral blood lymphocytes (PBL) against a variety of tumor-derived target cell lines and virus-infected target cells. The combined treatment of PBL with NKSF and IL-2 results in a less than additive enhancement of cytotoxicity. NKSF enhances the cytotoxic activity of spontaneously cytotoxic CD16+CD5- NK cells and does not confer cytotoxic activity to CD16-CD5+ T cells. PBL from patients infected with human immunodeficiency virus (HIV) have significantly lower cytotoxic activity against tumor-derived target cells and virus-infected target cells than PBL from control healthy donors. Treatment of PBL from HIV-infected patients with NKSF and/or IL-2 results in an increase of NK cell cytotoxicity against both types of target cells to levels similar to or higher than those of untreated PBL from healthy donors. PBL from HIV-infected patients produce interferon gamma in response to NKSF and/or IL-2, although at levels 5- or 10-fold lower than those produced by PBL from healthy donors. The multiple biological effects of NKSF, its activity at very low molar concentrations, and its ability to synergize with other physiological stimuli suggest that NKSF/IL-12 is a lymphokine likely to have physiological importance and considerable therapeutic potential.

Effects of Water Temperature Under Projected Climate Change on the Development and Survival of Enallagma civile (Odonata: Coenagrionidae).

Current climate projections for the Great Plains of North America indicate markedly increased air temperatures by the end of the current century. Because the Great Plains contains >80,000 intermittent wetlands that serve as irreplaceable wildlife habitat, this projected warming may have profound effects throughout a continental-scale trophic network. However, little research has been done to determine how projected warming may affect the growth, development, or survival of even common species in this region. We conducted laboratory warming experiments, using an abundant amphibious predatory insect, Enallagma civile (Hagen, 1861), as a model organism, to determine whether projected warming may affect development or survival. Eggs were collected and reared under four water temperature regimes representing current (26°C) and projected future conditions (32, 38, and 41°C). Nymph body size after each molt, development rate, and deaths were recorded. Elevated water temperatures were found to significantly affect the survivorship of E. civile eggs and nymphs as well as adult body size at emergence: an increase in temperature incurred a decrease in survival and size. Nymphs in the two hotter treatments were smaller and had low survivorship whereas individuals in the cooler temperatures generally survived to adulthood and were larger. Nymphs reared at 32°C experienced accelerated ontogenetic development compared with the other temperatures, going from egg to adult in 26 d. Projected elevated temperatures may, thus, be both advantageous and detrimental, causing concern for aquatic invertebrates in this region in the future.

Immunology of herpes simplex virus infection: relevance to herpes simplex virus vaccines and cervical cancer.

The immunology of herpes simplex infections has been reviewed, particularly in relation to potential herpes simplex virus (HSV) vaccines, and to the association between HSV and cervical cancer. Relevant data from humans, experimental animals, and in vitro systems implicate both specific immune mechanisms and nonspecific factors in the course of HSV infections. There appear to be complex interactions between the various populations of mononuclear cells, marcrophages, and lymphokines or other humoral factors. It is not yet possible, however, to pinpoint the crucial factors determining the different manifestations of the viral infection (primary infection, endogenous recurrence, or exogenous reinfection) in the various human hosts, although genetic factors may be important. While numerous animal models of HSV infection are available for the evaluation of HSV vaccines, models of HSV-induced cervical cancer require further exploration.

Immunology Update: Biologics.

Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material. The fused gene is inserted into a tissue culture that produces the gene product (ie, a chimeric monoclonal antibody). Biologics are used to manage many conditions, including malignant and nonmalignant conditions. They are widely used in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include erythropoietin for renal failure-associated anemia and the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients with persistently elevated low-density lipoprotein levels despite statin treatment who are at high risk of cardiovascular events.

Immunology Update: Long-Term Care of Solid Organ Transplant Recipients.

Nearly 31,000 US patients received solid organ transplants in 2015 and the number is increasing. Care of transplant recipients includes management of a variety of common posttransplantation issues. Skin cancers are common because of immunosuppression and require skin examinations at intervals. Patients should be educated about the need to report new skin lesions. The rates of other cancers also are increased, including cancers of the head and neck, lung, esophagus, cervix, and urinary tract. Osteoporosis is common in transplant recipients; monitoring and early therapy are important. Patients should not smoke, and vaccinations should be current except for live-virus vaccines, which are contraindicated in patients with immunosuppression. Family physicians should be familiar with the posttransplantation immunosuppression drugs their patients are taking and know their adverse effects and drug interactions. For example, calcineurin inhibitors (eg, cyclosporine, tacrolimus) can impair renal function and increase rates of hypertension and myocardial ischemia. They also interact with statins, macrolide antibiotics, diltiazem, and other drugs. Interval laboratory testing is required to monitor the health of the transplanted organ (eg, renal function tests for kidney transplants, transaminases for liver transplants). Finally, clinicians should remain alert for development of opportunistic infection.

Immunology Update: Primary Immunodeficiency Diseases.

There are 264 primary immunodeficiencies (PIDs), most of which are rare. They are caused by complement deficiencies, defects in phagocyte function, impaired T-cell function, and/or impaired B-cell function with antibody deficiencies. Most patients with PIDs will present, at varying ages, with frequent infections. These infections can be common respiratory tract infections such as otitis media or pneumonia, or they can be unusual bacterial, fungal, or parasitic infections. Neonatal screening for severe combined immunodeficiency syndrome, one of the most common and serious PIDs, is now performed in most US states, but many PIDs manifest and are detected after birth. Clinicians should be alert for PIDs when patients have unusual or frequent infection and perform a diagnostic evaluation. After ruling out HIV and hepatitis C infection, the next step is to obtain a complete blood count, immunodeficiency panel, and immunoglobulin and complement levels. If results are abnormal, or if a PID is suspected clinically but the diagnosis is not clear, prompt referral to an appropriate subspecialist is indicated. Some PIDs can be managed with stem cell transplantation, and transplantation before the first serious infection is associated with better outcomes. In addition, antimicrobial prophylaxis is indicated for many PIDs patients to prevent opportunistic infections.

Immunology Update: New Vaccines.

A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States.

Thrombolysis and Q wave versus non-Q wave first acute myocardial infarction: a GUSTO-I substudy. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries Investigators.

OBJECTIVES: We assessed the outcomes of patients with a first myocardial infarction with ST segment elevation, with and without the development of abnormal Q waves after thrombolysis. BACKGROUND: Prethrombolytic era studies report conflicting short-versus long-term mortality in the overall non-Q wave population, probably related to its heterogeneity. METHODS: Patients with no electrocardiographic (ECG) confounding factors or evidence of previous infarction were included. Q wave infarction was defined as a Q wave duration > or = 30 ms in lead aVF; R wave > or = 40 ms in lead V1; any Q wave or R wave < or = 10 ms and < or = 0.1 mV in lead V2; or Q wave > or = 40 ms in at least two of the following leads: I, aVL, V4, V5 or V6. In-hospital clinical events and mortality at 30 days and 1 year were assessed. RESULTS: No Q waves developed in 4,601 (21.3%) of the 21,570 patients. This group comprised more women and had a lower Killip class, lower weight and less anterior baseline ST elevation. The non-Q wave group had less in-hospital cardiogenic shock (2.1% vs. 3.3%, p < 0.0001), less heart failure (8.5% vs. 13.9%, p < 0.0001) and a trend toward less stroke (0.7% vs. 1.0%, p = 0.07) but an increased use of angioplasty (28% vs. 24%, p = 0.0001). The unadjusted mortality rate in the non-Q wave group was lower at 30 days (0.9% vs. 1.8%, p = 0.0001) and 1 year (2.7% vs. 4.2%, p = 0.0001), as was the adjusted 30-day mortality rate (4.8% vs. 5.3%, p < 0.0001). CONCLUSIONS: Patients with no ECG confounding factors or evidence of previous infarction who do not develop Q waves after thrombolysis have a better 30-day and 1-year prognosis than patients with a Q wave infarction.

Use of colloidal silica (Sepracell-MN) for enrichment of dendritic cells from human peripheral blood: comparison with other methods.

Three methods are described for enrichment of dendritic cells from human peripheral blood. In method 1, mononuclear cells were incubated in plastic tissue culture flasks for two h. Nonadherent cells were removed. Adherent cells were washed to remove floating cells and incubated for 14 h at 37 degrees C in 5% CO2. Carbonyl iron was added, and the flasks were incubated for another 2 h. Nonadherent cells were subjected to centrifugation over metrizamide gradient. Phagocytic cells containing ingested carbonyl iron, small lymphocytes, and free carbonyl iron particles passed through the metrizamide, while the interface cell population was enriched for dendritic cells. The purity and yield of enriched dendritic cells were 52.8% and 0.05%, respectively. In method 2, adherent mononuclear cells were cultured overnight, and the released cells (released adherent cells) were centrifuged over metrizamide to separate low-density cells. Monocytes from this low-density cell population were removed by panning over human gamma globulin-coated plastic Petri dishes. In this method the average purity and yield of DC were 63.8% and 0.1%, respectively. In method 3, released adherent cells were treated with anti-CD5 and anti-CD14 monoclonal antibodies plus baby rabbit complement for 15 min, washed, and centrifuged with colloidal silica (Sepracell-MN). Centrifugation with Sepracell-MN was repeated three times. Low-density cells were panned twice over human gamma globulin-coated plastic Petri dishes. Nonadherent cells were highly enriched for DC. Contamination of T cells, B cells, and NK cells was undetectable by flow cytofluorometry. Contamination of monocytes was less than 2%. This method provided greater than 85.0% purity and 0.4% yield. This method (method 3) combines adherence, complement-dependent lysis, centrifugation with colloidal silica, and panning and provides the best yield and purity; it is therefore recommended for optimal purification of DC.

Mycobacterium avium intracellulare complex infection in HIV-infected children.

OBJECTIVE: To describe the incidence of, and risk factors for, Mycobacterium avium intracellulare complex (MAC) infection in HIV-infected children. SETTING: University-affiliated children's hospital. DESIGN AND METHODS: The medical records of 70 HIV-infected infants and children were reviewed retrospectively. RESULTS: Seven children (10% of the HIV-infected patients; 18% of those with AIDS) developed disseminated MAC (dMAC). An additional seven children had gastrointestinal colonization with MAC. Risk of dMAC was associated with increasing age, decreasing CD4 cell count, and (possibly) long-term steroid therapy. CONCLUSIONS: HIV-infected children are at risk of developing dMAC. Children older than 60 months and those with a CD4 cell count < 100 x 10(6)/l are most at risk.

Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.

The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t1/2) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (Cmax/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.

In vitro and in vivo responses of cytomegalovirus to acyclovir.

Laboratory strains and fresh isolates of human cytomegalovirus (HCMV) were tested for sensitivity to acyclovir. Fifty percent inhibition was achieved at about 10 micrograms/ml, but 25 to 100 micrograms/ml was necessary for 90 percent or greater inhibition. Acyclovir was administered intravenously to four patients with congenital cytomegalovirus (CMV) infection. There was only a temporary diminution of virus titer in the urine and no obvious clinical improvement. One child experienced hematuria. Pharmacokinetic studies showed a large volume of distribution and slow excretion of acyclovir with a half-life of approximately three hours.

CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors.

We have previously shown that using agonist affinity at recombinant receptors selectively expressed in clonal cells as the dependent variable in three-dimensional quantitative structure-activity relationship studies (3D-QSAR) presents a unique opportunity for accuracy and precision in measurement. Thus, a comparison of affinity's structural determinants for a set of compounds at two different recombinant dopamine receptors represents an attainable goal for 3D-QSAR. A molecular database of bound conformations of 16 structurally diverse agonists was established by alignment with a high-affinity template compound for the D1 receptor, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-1H-benzazepin. A second molecular database of the bound conformations of the same compounds was established against a second template for the D2 receptor, bromocriptine. These aligned structures suggested three-point pharmacophore maps (one cationic nitrogen and two electronegative centers) for the two dopamine receptors, which differed primarily in the height of the nitrogen above the plane of the catechol ring and in the nature of the hydrogen-bonding region. The ln(1/KL) values for the low-affinity agonist binding conformation at recombinant D1 and D2 dopamine receptors stably expressed in C6 glioma cells were used as the target property for the CoMFA (comparative molecular field analysis) of the 16 aligned structures. The resulting CoMFA models yielded cross-validated R2 (q2) values (standard error of prediction) of 0. 879 (1.471, with five principal components) and 0.834 (1.652, with five principal components) for D1 and D2 affinity, respectively. The simple R2 values (standard error of the estimate) were 0.994 (0.323) and 0.999 (0.116), respectively, for D1 and D2 receptor. F values were 341 and 2465 for D1 and D2 models, respectively, with 5 and 10 df. The predictive utility of the CoMFA model was evaluated at both receptors using the dopamine agonists, apomorphine and 7-OH-DPAT. Predictions of KL were accurate at both receptors. Flexible 3D searches of several chemical databases (NCI, MDDR, CMC, ACD, and Maybridge) were done using basic pharmacophore models at each receptor to determine the similarity of hit lists between the two models. The D1 and D2 models yielded different lists of lead compounds. Several of the lead compounds closely resembled high-affinity training set compounds. Finally, homology modeling of agonist binding to the D2 receptor revealed some consistencies and inconsistencies with the CoMFA-derived D2 model and provided a possible rationale for features of the D2 CoMFA contour map. Together these results suggest that CoMFA-homology based models may provide useful insights concerning differential agonist-receptor interactions at related receptors. The results also suggest that comparisons of CoMFA models for two structurally related receptors may be a fruitful approach for differential QSAR.

Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines.

The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor, we have identified a number of compounds which are the most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT2C receptor model and our proposed binding mode for this class of ligands within that model.

Natural killing of cytomegalovirus-infected targets in renal transplant recipients.

The ability of peripheral blood mononuclear cells of renal transplant recipients to lyse cytomegalovirus (CMV) infected fibroblasts was determined in an 18-hr 51Cr release assay. Natural killing (NK) against CMV-infected targets was generally depressed for the first two years after transplantation. In three individuals who developed CMV disease after transplantation, NK activity against CMV-infected and uninfected targets rose to high levels following reductions in immunosuppressive therapy and in temporal association with resolution of disease.