Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF-α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow-up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF-α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF-α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow-up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.     

Delay of cranial bone regeneration by CO2 and Nd-YAG laser application: an experimental study related to craniosynostosis

In this study we have investigated the negative influence of CO₂ and Nd-YAG laser irradiation on rapid cranial regeneration and whether it has any use in certain types of craniosynostosis. Twenty-two newborn rats were used in the study. Both CO₂ and Nd-YAG laser irradiation, which was applied to free bony edges after, suturectomies, resulted in a significant decrease in skull regeneration. Histopathological examinations revealed severe degeneration caused by both types of laser energies.     

RELATIONSHIP OF HLA-DR EXPRESSION WITH REJECTION AND MONONUCLEAR CELL INFILTRATION IN RENAL ALLOGRAFT BIOPSIES

DNA methods have resulted in improved renal allograft survival rates in cadaveric renal transplantation. This paper describes the impact of DNA typing by PCR-SSP on a living-related renal transplant (LRRT) programme. It evaluates error rates in serology, acute rejections, graft function and survival rates between the two typing methods. Serological typing was carried out on CTS 120 antisera Class 1, 60 antisera Class 2, 72 antisera Terasaki Class 1 and 72 antisera Class 2 antigens. Low-resolution PCR-SSP typing was carried out by 24 primers for HLA-A, 48 for HLA-B and 24 for HLA-DR. Of the 585 transplants: 159 (Group I) were serology based; 172 were serology and PCR-SSP based for HLA-DR (Group II); and 254 were serology and PCR-SSP based for HLA-A and -B, and only PCR-SSP based for HLA-DR (Group III). Error rates in serology compared with PCR-SSP were 24% for HLA-A, 16% for HLA-B and 35% for HLA-DR. Acute rejections were 39%, 30% 26% in Groups I, II and III, respectively ( P= 0.02). Graft function of serum creatinine <1.5 mg/dl at 1 year was found in 26% of the Group I patients compared with 48% of those in Group III ( P <0.0001). One- and 3-year graft survival was 93% and 87% for Group II compared with 81% and 69% for Group I, respectively ( P= 0.0001). Matching by this combination of serology and PCR-SSP is not only economical for a developing country but also improves graft survival by 12% and 18% at 1 and 3 years, respectively.     

Identification of two different mutations in the PDS gene in an inbred family with Pendred syndrome

Recently the gene responsible for Pendred syndrome (PDS) was isolated and several mutations in the PDS gene have been identified in Pendred patients. Here we report the occurrence of two different PDS mutations in an extended inbred Turkish family. The majority of patients in this family are homozygous for a splice site mutation (1143-2A-->G) affecting the 3' splice site consensus sequence of intron 7. However, two affected sibs with non-consanguineous parents are compound heterozygotes for the splice site mutation and a missense mutation (1558T-->G), substituting an evolutionarily conserved amino acid. The latter mutation has been found previously in two Pendred families originating from The Netherlands, indicating that the 1558T-->G mutation may be a common mutation.     

Antibody spectrum against the viral transactivator protein in patients with human immunodeficiency virus type 1 infection and Kaposi's sarcoma

We analyzed patterns of antibody response to recombinant transactivator protein (human Immunodeficiency virus type 1 [HIV-1] tat) in serum samples from HIV-1-negative subjects (n = 60), HIV-1-infected asymptomatic patients (n = 20), HIV-1-infected patients with Kaposi's sarcoma (n = 25), and patients with Kaposi's sarcoma without HIV-1 infection. None of the healthy subjects possessed anti-tat immunoglobulin G (IgG) in their serum. All asymptomatic patients with HIV-1 infection were anti-tat IgG-positive. Epitope mapping revealed that these sera had anti-tat IgG to all the functional domains of tat protein. Histochemical studies on lymph nodes from five asymptomatic HIV-1-infected patients showed that, in all cases, tat-positive cells were present within the germinal center at the stage of follicular fragmentation containing immunoblasts and small lymphocytes. Of the 25 HIV-1-infected patients with Kaposi's sarcoma, 4 were anti-tat IgG-positive; however, the epitope analysis revealed that IgG to functional domains of tat protein--in particular to transactivating response element (TAR)-binding site--were absent. All patients with Kaposi's sarcoma without HIV-1 infection were anti-tat IgG-negative. Presence or absence of anti-tat IgG and a prevalence of different antibody profiles in different groups of patients indicated the pathophysiologic role of tat protein. Thus, a passive immunization with anti-tat IgG could be a useful strategy to influence the pathophysiologic state of the disease.     

Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides

We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by tat protein, the functional protein of the transactivator gene. We selected the target sequence localized near the 5 end of the tat mRNA. The following conclusions can be drawn from the data presented here: a) Antisense oligonucleotides modified by conjugation of cholesterol at the 3 end have a severalfold higher inhibitory response, b) inhibitory response is dependent on the mode of introducing oligonucleotides, and c) the inhibition by antisense oligonucleotides is sequence specific and directed towards the targeted region. This approach could be useful for targeting functional regions of regulatory gene products and designing gene-targeted inhibitors of virus replication.Dedicated to Professor Klaus Ring on his 60th birthday.     

Skin flap survival after superficial and deep partial-thickness burn injury

Whether a flap can be raised successfully in a body region that has been subjected to burn injury remains an issue. The aim of this study was to investigate the survival of skin flaps that were elevated after superficial and deep partial-thickness burn injury in a rat model. Sixty-five rats were divided into five groups: Group 1 (N = 15) was the control group, group 2 (N = 10) included rats with superficial partial-thickness burns that had flaps elevated on day 0, group 3 (N = 15) was comprised up of rats with superficial partial-thickness burns that had flaps elevated on day 4, group 4 (N = 10) included rats with deep partial-thickness burns that had flaps elevated on day 0, and group 5 (N = 15) was comprised of rats with deep partial-thickness burns that had flaps elevated on day 4. Caudally based dorsal flaps consisting of skin and panniculus carnosus were elevated in all groups, and the amount of surviving tissue on each flap was quantified. The surviving areas of flaps elevated on postburn days 0 and 4 in superficial partial-thickness burn zones (groups 2 and 3) were larger than those of flaps that were elevated on postburn days 0 and 4 in deep partial-thickness burn zones (groups 4 and 5). The surviving portions of flaps that were elevated on day 4 in superficial partial-thickness burn zones (group 3) were similar to the surviving areas of flaps in the control group (group 1), and were larger than those of all other groups (groups 2, 4, and 5). In this rat model, flaps were elevated in superficial dermal burn zones with successful outcomes. However, raising flaps in deep dermal burn zones was not a reliable method.