Accumulation of CD5<Superscript>+</Superscript>CD19<Superscript>+</Superscript> B lymphocytes expressing PD-1 and PD-1L in hypertrophied pharyngeal tonsils

Programmed death-1 (PD-1) is one of the most important inhibitory co-receptors expressed predominantly on activated T and B lymphocytes whose expression could be sustained by permanent antigenic stimulation accompanying chronic or recurrent tonsillitis. The expression of PD-1 and PD-1L was analyzed using flow cytometry on hypertrophied tonsils collected from 57 children. We observed high expression of PD-1 and PD-1L on certain lymphocytes subpopulations of hypertrophied tonsils; among T cells, the expression of PD-1 on protein level was higher on CD4⁺ cells (70.3 %) than on CD8⁺ cells (35 %). Interestingly, a limited expression of PD-1 was observed on CD19⁺ B lymphocytes (6.5 %), while CD5⁺CD19⁺ B cells overexpressed PD-1 (52.5 %). Moreover, the expression of PD-1L was also higher on CD5⁺CD19⁺ B cells (16.5 %) than on CD19⁺ B cells (3.5 %) and on CD4⁺ T cells (20 %) than on CD8⁺ T cells (10 %). PD-1 and PD-1L expressions correlated only on CD5⁺CD19⁺ cells. In conclusion, high expression of PD-1 and PD-1L on T and B cells could represent hallmark of immune system adaptation to chronic antigenic exposition in patients with tonsillitis.     

The variability of clinical presentation of chronic obstructive pulmonary disease in patients with hereditary alpha-1 antitrypsin deficiency

Four patients with alpha-1 antitrypsin (alpha-1 AT) deficiency are presented: one woman with severe (phenotype PiZ) and 3 men with moderate (phenotype PiMZ) deficiency of alpha-1 AT. The variability of clinical presentation of hereditary emphysema is described. In all patients tobacco smoking history, spirometric and 6-minutes walking tests as well as HRCT of the lung were performed and compared. The influence of smoking on the functional status is underlined.     

Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer

The RAD51 protein and its paralog, XRCC3, play an important role in the repair of DNA double-strand breaks (DSBs) by homologous recombination. Since DSBs may contribute to the pathogenesis of breast cancer and variability in DNA repair genes may be linked with some cancers, we performed a case-control study (135 cases and 175 controls) to check the association between the genotypes of the Thr241Met polymorphism of the XRCC3 gene and the 135G>C polymorphism of the RAD51 gene and breast cancer occurrence and progression. Genotypes were determined in peripheral blood lymphocytes by RFLP-PCR. We did not find any association between either polymorphism singly and breast cancer occurrence. Both polymorphisms were not related to tumor size, estrogen and progesterone receptors status, cancer type and grade. However, the Thr241Met genotype of the XRCC3 polymorphism slightly increased the risk of local metastasis in breast cancer patients (OR 2.56, 95% CI 1.27-5.17). The combined Thr241Met/135G>C genotype decreased the risk of breast cancer occurrence (OR 0.22, 95% CI 0.08-0.59). Our results suggest that the variability of the DNA homologous recombination repair genes RAD51 and XRCC3 may play a role in breast cancer occurrence and progression, but this role may be underlined by a mutual interaction between these genes.     

Maturational changes in connexin 43 expression in the seminiferous tubules may depend on thyroid hormone action

Introduction

Connexin 43 (Cx43) mediates the effect of thyroid hormone on Sertoli cell maturation in vitro. We investigated the influence of triiodothyronine (T3) administration on Cx43 expression in relation to the progress in seminiferous tubule maturation.

Material and methods

Male rats were daily injected with 100 µg T3/kg body weight from birth until postnatal day (pnd) 5 (transient treatment – tT3) or until pnd 15 (continuous treatment – cT3) or solvent – control (C). On pnd 16 serum hormone levels, body and testes weight, seminiferous tubule morphometry, Cx43 immunostaining and germ cell degeneration were investigated. Cx43 expression was also assessed in six 50-day-old adult untreated rats.

Result

tT3 increased 2.6-fold serum level of T3, testes weight, and seminiferous tubule diameter, and induced maturation-like dislocation of Cx43 expression from the apical to the peripheral region of Sertoli cell cytoplasm. In addition, incidence of Cx43-positive tubules declined from 86% in C to 46% after tT3, being similar to the adult value (30% of tubules Cx43-positive). In turn, cT3 increased serum T3 level 12-fold, and decreased body weight. Seminiferous tubules became shortened and distended, Sertoli cell cytoplasm vacuolated, Cx43 expression had minimal intensity and germ cell degeneration increased.

Conclusions

Cx43 might intermediate a short and transient stimulatory effect of T3 on seminiferous tubule maturation that disappeared together with exposure to the toxic effect of a continuously high level of the hormone.     

Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients

Introduction

Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are autosomal dominant, multisystem disorders, considered the most common dystrophies in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP genes, respectively.

De novo minimal change disease associated with reversible post-transplant nephrotic syndrome. A report of five cases and review of literature

Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be related to a large variety of glomerular lesions. In some of these cases, the transplant biopsy showed no significant glomerular changes and the NS was reversible, but the primary renal disease was not minimal change disease (MCD), suggesting that MCD may develop de novo in renal transplant setting. Knowledge of this entity, however, is limited. Among 67 cases of post-transplant NS encountered in a 12-yr period, five were found to be associated with de novo MCD. A critical review of the literature revealed nine additional cases of de novo MCD. The data from these 14 cases show that patients with de novo MCD had a large variety of primary renal diseases but MCD or focal segmental glomerulosclerosis was not among them. Eight of the 14 transplanted kidneys (60%) were from living related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3-76 g/d) developed immediately or shortly after transplantation (within 4 months for all reported cases, except for one at 24 months). The serum creatinine when NS was first diagnosed was normal or mildly elevated, but acute renal failure occurred in three patients. On biopsy, the glomeruli were normal or, more frequently, displayed mild, focal segmental mesangial sclerosis, hypercellularity, deposition of IgM/C3, or accumulation of mononuclear inflammatory cells in some glomerular capillaries. The tubulointerstitial compartment was normal in cases with normal renal function; displayed mild acute and/or chronic rejection that correlated with a mildly elevated serum creatinine; or showed acute changes including acute rejection, acute tubular necrosis, or acute cyclosporin A toxicity, which accounted for both acute renal failure at presentation and its subsequent reversibility. Under various treatments, including increased steroids, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers, sustained remission of NS was achieved in 13 cases, within a year (0.5-12 months) in 10 and later (24, 34 and 98 months, respectively) in three. In the remaining case, the patient died of septic shock 2 months after transplantation. After remission of the NS, the grafts functioned well without or with minimal proteinuria for several years. De novo MCD has characteristic clinical and pathologic features. It represents an important but hitherto underemphasized cause of post-transplant NS, which is potentially reversible and does not adversely affect the renal transplants.     

The endothelin-1 level in blood serum of patients with primary open angle glaucoma abd its influence on the static perimetry abd Gdx changes

PURPOSE: The aim of the work was to define the relationships between the endothelin-1 level in blood serum of glaucoma patients concerning the visual field defects and the number of nerve fibers. MATERIAL AND METHODS: 24 women and 14 men, aged 38-74 year (mean 53.4 year) with primary open angle glaucoma, without any systemic diseases. The control group consisted of 20 healthy women and men, aged 34-70 year (mean 52.6 year). The endothelin-1 level was tested with the enzymo-immunologic method from the blood serum. The visual field defects were examined with the Humphrey static perimetry. The nerve fibers were analyzed with the Gdx apparatus. RESULTS: Mean value of ET-1 in blood serum were similar in both examined groups, it was 0.51 in group of glaucoma patients and 0.54(fmol/l) in the control group. There were no significant correlations between ET-1 level, static perimetry, GDx parameters and age in the group of patients with POAG. The statistics significances were stated for ET-1 level and MD-parameter in static perimetry (p < 0.03) and ET-1 level with The Number--the GDx parameter (p < 0.03). CONCLUSION: There was no significant level of ET-1 in blood serum in group of patients with POAG. There have not been stated any relationships between the static perimetry and GDx changes in patients with POAG to endothelin-1 level in blood serum. It is the preliminary communication.     

Measurements in the peripheral retina using LDF and laser interferometry are mainly influenced by the choroidal circulation

PURPOSE: Two laser based methods for the assessment of ocular hemodynamics in humans have been investigated: laser Doppler flowmetry (LDF) and laser interferometric measurement of fundus pulsation amplitude (FPA). When the laser with either of the two methods is focused onto the fovea it is obvious that only choroidal blood flow contributes to the signals. When the laser is, however, directed to other parts of the retina the situation is more complex. Whereas the retina shows a pronounced vasoconstrictor response to systemic hyperoxia the effect in the choroid is small. We therefore investigated the effect of 100% O2 breathing on results as obtained with the above mentioned techniques at different fundus locations. METHODS: Twelve healthy subjects were included. Four 15-minutes 100% O2 breathing periods were scheduled for each subject. During two of these breathing periods LDF was performed at the fovea (ChBFf) and at a fundus location approximately 7.5 degrees nasally to the fovea (ChBFp), respectively. During the other two periods FPA was assessed at the same fundus locations (FPAf, FPAp). RESULTS: ChBFf tended to decrease during 100% oxygen breathing (6 +/- 4%), but this effect was not significant. The decrease in ChBFp (10 +/- 4%), was comparable. FPAf (10 +/- 2%; P < 0.001) and FPAp (13 +/- 2%; P < 0.001) decreased significantly during systemic hyperoxia, but again there was no difference in the response obtained at the two fundus locations. CONCLUSION: When LDF and FPA are applied at the peripheral retina the obtained signal is mainly influenced by the choroidal circulation.     

Tuberculosis of the central nervous system: case reports

Tuberculosis of the central nervous system possess a serious clinical and radiological problem, since early treatment of this condition is crucial for the patient's life, and tuberculous process in the CNS may mimic many other pathologies. In this paper three cases of tuberculous process difficult to diagnose are presented. In all the cases early treatment could be started due to MRI findings suggesting tuberculous etiology. The authors emphasize the importance of presumptive radiological diagnosis in reducing the morbidity and mortality rates due to CNS tuberculosis.     

Neuroimaging in a chronic demyelination process following tick-borne encephalomyelitis

We present a case of a 17-year-old female patient with a tick-borne neuroinfection. Tick-borne encephalitis is a viral disease of the CNS. Tick-borne encephalitis is usually of diphasic type, with partial epileptic seizures. No such symptoms were observed in this case. Since areas of demyelination could be seen on CT and MRI scans, immunological etiology should be taken into consideration. The correct diagnosis was established on the basis of serological examination and neuroimaging findings.