Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

Cultural values and happiness: an East-West dialogue.

Happiness as a state of mind may be universal, but its meaning is complex and ambiguous. The authors directly examined the relationships between cultural values and experiences of happiness in 2 samples, by using a measurement of values derived from Chinese culture and a measurement of subjective well-being balanced for sources of happiness salient in both the East and the West. The participants were university students-439 from an Eastern culture (Taiwan) and 344 from a Western culture (the United Kingdom). Although general patterns were similar in the 2 samples, the relationships between values and happiness were stronger in the Taiwanese sample than in the British sample. The values social integration and human-heartedness had culture-dependent effects on happiness, whereas the value Confucian work dynamism had a culture-general effect on happiness.

Establishment and characterization of NS3 protein-specific T-cell clones from a patient with chronic hepatitis C.

Our previous study showed dominant proliferative response of peripheral mononuclear cells to hepatitis C virus (HCV) nonstructural (NS-3) (T9, from aa 1188 to 1493) in chronically infected patients. Six T9-specific T-cell clones derived in an HCV patient were established and studied for the antigen specificity and the ability of augmentation of in vitro antibody production. All these cloned T-cell lines responded exclusively to T9 antigen and could help autologous B cells in producing anti-T9 antibody in vitro. Cytokine mRNAs of these T cells was detected by polymerase chain reaction and predominant IL-2 and IFN-gamma production was noted. In addition, further elucidation of T-cell antigenic determinant and MHC restriction suggested that these T-cell clones recognized at least two different T-cell antigenic determinants within the NS-3 region in an HLA DQ2-restricted manner. We believe characterization of HCV-specific T-cell responses, especially T-cell epitope mapping and cytokine production pattern, may shed light on further understanding the pathogenic mechanism and designing therapy for HCV infection.

Attitudes of Asian and American graduate nursing students towards death and dying.

This study compared the difference in attitudes towards death and dying between 17 Asian and 11 American graduate nursing students. Asian and American students did not significantly differ in attitudes related to fear of death, of self, or others, but Asian students were significantly more afraid than American students of their own process of dying. Asian students were more averse than American students to interacting and discussing death with dying patients. Talking about death with dying patients was the most difficult aspect of care for both groups. However, Asian students gained more personal satisfaction than American students in caring for dying patients. The findings provoke discussion regarding differences in nursing practice by Asian and American graduate nursing students.

Changes of protein kinase C subspecies in staphylococcal enterotoxin-B-induced thymocyte apoptosis.

Our previous studies demonstrated that intravenous administration of staphylococcal enterotoxin B (SEB) to BALB/c mice resulted in thymocyte apoptosis. In the present study, we evaluated the role of protein kinase C (PKC) in thymocyte apoptosis induced by SEB. Our results showed that the level of protein phosphorylation in the thymocytes was reduced after the in vivo SEB treatment for 24 h. The activity of classical PKC subspecies was decreased in both cytosolic and membrane fractions of thymocytes following SEB administration. The lowest level of PKC activity was reached by 24 and 48 h, then was recovered gradually after 72 h. Furthermore, the mRNA expression of PKC-beta and, to a much less extent, PKC-alpha, but not PKC-sigma, in thymocytes was reduced by SEB. The decrease of mRNA level of PKC-beta showed good correlation with the pattern of PKC activity. These results provide direct evidence showing the changes in PKC subspecies mRNA expression during the process of apoptosis.

Immunostimulation by Alsophila spinulosa extract fraction VII of both humoral and cellular immune responses.

Alsophila spinulosa (Cyatheaceae) has been used in Asia as a herbal medicine. In this study, the immunomodulatory effects of Alsophila spinulosa dried stems water extract fraction VII (AS-VII) were studied in vitro using an animal model. The results showed that AS-VII stimulated splenocyte proliferation in both BALB/c and C3H/HeJ mice. By cell fractionation analysis, the results showed that the mitogenic effect of AS-VII was predominantly on B cell population. The antibody response was also augmented by AS-VII in BALB/c and C3H/HeJ mice. The augmentation of immune responses in C3H/HeJ, the lipopolysaccharide (LPS)-hyporesponsive mouse strain, indicated that the activity was not simply due to the LPS contamination which may be present in AS-VII preparation. Furthermore, AS-VII caused an increase in cytotoxic T cell activity in a mixed lymphocyte reaction culture. These data indicate that AS-VII possesses the capability of augmenting both humoral and cellular immune responses.

Judging interevent relations: from cause to effect and from effect to cause.

Stimulus competition was studied in college students' correlational judgments in a medical decision-making setting. In accord with prior findings, subjects making cause-to-effect (predictive) judgments discounted a stimulus event that was moderately correlated with a target event when rival stimuli were more highly correlated with the effect. However, subjects making effect-to-cause (diagnostic) judgments were not at all disposed to discount a stimulus event which was moderately correlated with a target event when rival stimuli were more highly correlated with the cause. The theoretical implications of these results are considered in connection with associative and mentalistic models of causal attribution.

The effects of glaucoma medications on Tenon's capsule and conjunctiva in the rabbit.

Glaucoma filtering surgery fails most frequently due to fibrosis at the episcleral-conjunctival/Tenon's capsule interface. Sherwood et al have suggested that chronic topical antiglaucoma medications increase conjunctival inflammatory cells, which could increase the likelihood of fibrosis and subsequent bleb failure. In a pilot study in a rabbit model, we placed timolol, pilocarpine, and epinephrine, or a combination of all three, in one eye of 24 animals twice daily for 7 months. The fellow eye received distilled water. Microscopic examination revealed no statistically significant change in the number of acute or chronic inflammatory cells, fibroblasts, or goblet cells in the treated as compared with the control eyes. A longer duration of drug administration, or drug administration followed by surgical intervention, may be required to produce an effect on the conjunctiva and Tenon's capsule, if such an effect exists.

Contributions of specific cell information to judgments of interevent contingency.

College students considered the possible effect of an experimental drug on a skin rash. The information came from a 2 x 2 contingency table involving receipt or nonreceipt of the drug and improvement or nonimprovement of the rash: Cell A = receipt-improvement; Cell B = receipt-nonimprovement; Cell C = nonreceipt-improvement; Cell D = nonreceipt-nonimprovement. Without numerical information. Ss judged cells to be ordered A greater than B greater than C greater than D. The same order held when the contribution of each cell was derived from the contingency judgments of other subjects given numerical information. No such consistency was seen when one group of Ss made both judgments: whether individual Ss equally or unequally assessed the importance of the four cells, their contingency estimates showed cell use to be ordered A greater than B greater than C greater than D. These findings may result from strong biases that Ss harbor in processing contingency information.

The effects of exercise on intraocular pressure in pigmentary glaucoma patients.

Previous studies of normal volunteers and open-angle glaucoma patients have shown that exercise temporarily lowers intraocular pressure. However, two case reports have described pigmentary dispersion syndrome patients who developed symptomatic increased intraocular pressure after exercise. We evaluated the intraocular pressure response to exercise in ten pigmentary glaucoma patients. An exercise protocol was designed to increase the likelihood of lens zonule-iris pigment epithelium contact. Intraocular pressure measurements during the first two hours after exercise showed no statistically significant elevation of mean intraocular pressure. The pressure rose 6 mm Hg and 7 mm Hg respectively at 15 minutes in two eyes, but returned to baseline by 30 minutes. Our results suggest that exercise may not significantly increase the clinical intraocular pressure in pigmentary glaucoma patients.

Anterior chamber depth following filtration surgery.

We measured the anterior chamber depth in 20 consecutive phakic glaucoma patients undergoing thermal sclerostomy (n = 12) or trabeculectomy (n = 8). Using the Haag-Streit pachymeter, measurements were taken preoperatively and at postoperative days 1, 2, 3, 6, 15, and 42. In all eyes, shallowing of the anterior chamber was observed following surgery. It was greatest by postoperative day 2 or 3, with maximum mean decreases from preoperative anterior chamber depths of 70.9% for thermal sclerostomy and 54.0% for trabeculectomy. In 18 patients, the anterior chamber depth gradually deepened over the course of postoperative days 4 through 15, so that by 15 days after surgery, the average anterior chamber depth was 87.6% of the preoperative level. In two patients who ultimately required surgical reformation on their anterior chamber, however, only a minimal deepening occurred over this interval. At 15 days after surgery, the average anterior chamber of these two patients was significantly more shallow (37.5% of the preoperative anterior chamber depth, p = 0.003) than the mean of the other 18 patients (87.6% of the preoperative anterior chamber depth). These observations suggest that if the anterior chamber has not reformed by postoperative day 15, spontaneous reformation of the anterior chamber is unlikely and surgical intervention may be required.

Clinical comparison of the Oculab Tono-Pen to the Goldmann applanation tonometer.

The Oculab Tono-Pen tonometer was compared with the Goldmann applanation tonometer through studies on 197 eyes of 103 patients with glaucoma or ocular hypertension to evaluate the reliability of the Tono-Pen in determining intraocular pressure (IOP). Patients were randomized into four groups and all applanations were done by the same investigator. The Tono-Pen initially used (Tono-Pen #1) failed to calibrate after being used on 77 eyes. Tono-Pen #2 was then obtained and tested. Each Tono-Pen showed high correlation with the Goldmann readings (r greater than or equal to 0.86 in both eyes). The overall sensitivity of the Tono-Pen in detecting IOPs of 21 mmHg or higher (as measured by the Goldmann instrument) was 62.1% in right eyes, 72.4% in left eyes, with corresponding specificities of 92.6% in the right and 97.1% in the left. Given the substantial increase in sensitivity noted with Tono-Pen #2, the Tono-Pen appears adequate for screening programs where an IOP of 21 mmHg or above is considered abnormal; however, at higher IOPs (greater than or equal to 30 mmHg) the Tono-Pens tended to underestimate Goldmann IOPs. At low IOPs (less than or equal to 9 mmHg) the Tono-Pens tended to overestimate the IOPs. Perhaps with further modifications of the instrument, it could be used for clinical diagnosis and management of glaucoma patients.

A review (1970-1980) of 28 presumptive cases of syphilitic uveitis.

We classified 1.1% of our uveitis cases from 1970 to 1980 as presumably caused by syphilis. We did not initially suspect syphilis in most of these 28 patients. None of the women and only half of the men had reactive VDRL tests. If the fluorescent-treponemal-antibody absorption test had not been used, three-fourths of these would have gone undiagnosed.