Human Mig chemokine: biochemical and functional characterization

Mig is a chemokine of the CXC subfamily that was discovered by differential screening of a cDNA library prepared from lymphokine-activated macrophages. The mig gene is inducible in macrophages and in other cells in response to interferon (IFN)-gamma. We have transfected Chinese hamster ovary (CHO) cells with cDNA encoding human Mig and we have derived CHO cell lines from which we have purified recombinant human Mig (rHuMig). rHuMig induced the transient elevation of [Ca2+]i in human tumor-infiltrating T lymphocytes (TIL) and in cultured, activated human peripheral blood-derived lymphocytes. No responses were seen in human neutrophils, monocytes, or Epstein-Barr virus-transformed B lymphoblastoid cell lines. rHuMig was chemotactic for TIL by a modified Boyden chamber assay but rHuMig was not chemotactic for neutrophils or monocytes. The CHO cell lines, IFN-gamma-treated human peripheral-blood monocytes, and IFN-gamma-treated cells of the human monocytic cell line THP-1 all secreted multiple and identical HuMig species as revealed by SDS-PAGE. Using the CHO-derived rHuMig, we have shown that the species' heterogeneity is due to proteolytic cleavage at basic carboxy-terminal residues, and that the proteolysis occurs before and not after rHuMig secretion by the CHO cells. The major species of secreted rHuMig ranged from 78 to 103 amino acids in length, the latter corresponding to the full-length secreted protein predicted from the HuMig cDNA. Carboxy-terminal-truncated forms of rHuMig were of lower specific activity compared to full-length rHuMig in the calcium flux assay, and the truncated species did not block the activity of the full-length species. It is likely that HuMig plays a role in T cell trafficking and perhaps in other aspects of the physiology of activated T cells.     

APOE in non-Alzheimer amyloidoses: transmissible spongiform encephalopathies

We have identified a member of the VEGF family by computer-based homology searching and have designated it VEGF-D. VEGF-D is most closely related to VEGF-C by virtue of the presence of N- and C-terminal extensions that are not found in other VEGF family members. In adult human tissues, VEGF-D mRNA is most abundant in heart, lung, skeletal muscle, colon, and small intestine. Analyses of VEGF-D receptor specificity revealed that VEGF-D is a ligand for both VEGF receptors (VEGFRs) VEGFR-2 (Flk1) and VEGFR-3 (Flt4) and can activate these receptors. However. VEGF-D does not bind to VEGFR-1. Expression of a truncated derivative of VEGF-D demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGF-C. In addition, VEGF-D is a mitogen for endothelial cells. The structural and functional similarities between VEGF-D and VEGF-C define a subfamily of the VEGFs.     

The laboratory diagnosis of spring-summer infections in Yekaterinburg in the epidemic season for tick-borne encephalitis

The authors propose a comprehensive approach to laboratory diagnosis of seasonal transmissible infections, based on modern methods permitting etiological deciphering of disease. A universal diagnostic algorithm notably accelerated the laboratory diagnosis due to cutting the period between collection of material from a patient and consecutive screening for antibodies to agents of tick-borne encephalitis, Lyme disease, and California encephalitis.     

Capsule contraction after continuous curvilinear capsulorhexis

We report two cases of capsular bag contraction that occurred within 1 month after continuous curvilinear capsulorhexis, phacoemulsification, and intraocular lens implantation. Neither patient had a known risk for this complication. Both patients had a neodymium:YAG laser anterior capsulotomy, which disrupted the capsulorhexis margin and led to prompt capsular bag distension.     

Intrarenal nitric oxide activity and pressure natriuresis in anesthetized dogs

In the course of an ongoing cohort study on constitutional and occupational risk factors for the development of irritant hand dermatitis in hairdressing apprentices, an increased prevalence of irritant skin changes was noted in a subgroup examined during particularly cold winter months. Prompted by this observation, the importance of several meteorological factors (day means of temperature, relative and absolute humidity) was assessed in extensive statistical analyses based on data of 742 participants, supplemented by meteorological information obtained from the German Meteorological Service (DWD). There were significant associations of existing hand dermatitis with low temperature and low absolute humidity (Mann-Whitney U-test, P < 0.0001), but not with relative humidity (P = 0.38). Logistic regression analysis, including known determinants of irritant hand dermatitis in this setting, showed that low temperature and low relative humidity tended to be risk factors (OR = 1.66 and 1.57, respectively, for the lower quartiles, P = 0.07 in both cases), and confirmed that absolute humidity significantly influenced the occurrence of irritant hand dermatitis (OR = 2.06 for < 4.8 mg/L, P < 0.01). Thus, these environmental factors must be regarded as possible confounders in the analysis of future epidemiological studies on irritant hand dermatitis and should be considered in multifactorial analyses.     

Pathologic seminal vesicle invasion after radical prostatectomy for patients with prostate carcinoma: effect of early adjuvant radiation therapy on biochemical control

BACKGROUND: The authors evaluated the effect of postoperative radiation therapy on freedom from biochemical failure (bNED) in men with prostate carcinoma who had pathologic seminal vesicle invasion after radical prostatectomy and negative pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty-three men (13%) had pT3cN0 prostate carcinoma and were the subject of this analysis. Men in whom prostate specific antigen (PSA) could not be detected were deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate carcinoma, 18 had an elevated PSA immediately after surgery and received salvage radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3 months, PSA could not be detected in the other 35 men. Fifteen of those 35 men underwent early adjuvant RT, and the other 20 were observed for biochemical failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01). CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0 prostate carcinoma and no detectable PSA postoperatively reduces the likelihood of future biochemical failure. Men with pT3cN0 prostate carcinoma and a persistently elevated postoperative PSA level are less likely to benefit from RT and should be considered for systemic therapy.