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Biomedical subjects

M Bak

Publications and source records attributed to M Bak.

At least 37 records · Page 2Linked to original sources

Delayed neutropenic enterocolitis in a 12-year-old girl treated with total colectomy and J-pouch reservoir.

Neutropenic enterocolitis (NE) is a clinicopathologic condition characterized by bowel wall inflammation, which can proceed to necrosis and perforation. It is mostly seen in neutropenic patients with leukemia who undergo induction treatment with chemotherapy. Most often the cecum is involved. The authors present a 12-year-old girl with acute lymphocytic leukemia who, under maintenance therapy, experienced NE. The disease was localized to the left side of colon, and even the rectum was involved, which is an unusual localization of the disease. An ileoanal anastomosis with a J-pouch was done in a second operation with a good outcome.

Antineoplastic Agents↗

Screening for human papillomavirus infection in asymptomatic women in Hungary.

BACKGROUND: A multicentre epidemiological survey was carried out in order to determine the prevalence of, and risk factors for, persistent cervical human papillomavirus (HPV) infection in women in Hungary. METHODS AND RESULTS: A total of 728 women were examined for the prevalence of HPV. The estimated overall rate of HPV infection was 17%. In univariate analysis the strongest predictors were young age (< or =24 years), unmarried family status, smoking, a pathological Papanicolaou (Pap) smear, having a condyloma and previous gynaecological cancer in the family (age and marital status being the most important predictors). In multiple regression analysis, young age (< or =24 years)(odds ratio = 1.86, 95% confidence interval = 1.19-2.90, P < 0.01), smoking (1.78, 1.17-2.71, P < 0.05), an abnormal Pap smear (6.92, 2.68-17.84, P < 0.001), having a condyloma (4.22, 1.42-12.58, P < 0.01) and living in a region where the unemployment rate is relatively high (1.56, 1.24-2.82, P < 0.01) were associated risk factors for HPV infection. CONCLUSIONS: The prevalence of HPV infection in young women in Hungary is high. Screening for HPV is suggested only in women with an unfavourable gynaecological history who are < or =24 years old.

Adult↗

Effects of the somatostatin analogue octreotide on renal function in conscious diabetic rats.

BACKGROUND: Studies performed during the last decade have indicated that growth hormone (GH) and insulin-like growth factors (IGFs) may mediate the early renal changes in diabetes mellitus, i.e. hypertrophy and hyperfiltration. This and other observations have led to the suggestion that GH/IGF inhibitors, such as long-acting somatostatin analogue (e.g. octreotide and lanreotide), may be useful in order to inhibit or prevent development of long-term diabetic complications. METHODS: The present study examined the acute and chronic effects of octreotide on renal function following induction of streptozotocin (STZ)-diabetes in rats. The studies were carried out in conscious, non-fasted diabetic animals. RESULTS: Chronic administration of octreotide for 7 days, from onset of diabetes, prevented the decrease of effective renal vascular resistance (ERVR), and the increases in filtration fraction (FF), glomerular filtration rate (GFR), and absolute proximal tubular fluid reabsorption (APR) induced by diabetes. The renal hypertrophy was only partially prevented. In the acute study, similar changes were observed in effective renal plasma flow (ERPF) and ERVR but FF increased and GFR remained unaltered. CONCLUSIONS: Chronic but not acute treatment with octreotide prevented the renal hyperfiltration caused by diabetes. This effect is most likely due to an increase in afferent arteriolar resistance.

Animals↗

Three-year results of the first educational and early detection program for testicular cancer in Hungary.

OBJECTIVE: To determine whether a testicular self-examination-based early-detection program may help in the early diagnosis of testicular cancer. METHODS: Advertisements were placed in the media describing the early signs of testicular cancer, the risk factors, the correct method of self-examination and the importance of early detection. Between April 1995 and April 1998, 5,056 men underwent physical and ultrasound examination of the testicles, and in case of suspicious findings tumor markers were checked. RESULTS: Testicular tumors were found in 1.28% of the men with symptoms. No tumors were found in men without symptoms or in men with pain, sensitivity to palpation, or complaints unrelated to the testicle. Of those with a palpable lump or swollen testicle, 4.5 and 3.9% were found to have a tumor. In total, 28 testicular cancers (15 seminomas and 13 nonseminomas) in 26 volunteers and 4 benign tumors were detected. The occurrence of cancer was most frequent in the age group of 15--40 years (1.6%). CONCLUSION: The rate of cancer detection and the detected seminoma rate in the program are not sufficient to justify a widespread early detection program for testicular cancer (examination of men who reveal testicular abnormalities by self-examination) despite the increased tumor incidence. Early diagnosis should be based on an educational program for the population at risk, the training of staff engaged in the health care of the young, and the use of early ultrasound examination in men with palpable lumps and swollen testicles, especially in young men.

Adolescent↗

The human hedgehog-interacting protein gene: structure and chromosome mapping to 4q31.21-->q31.3.

Hedgehog-interacting protein (Hhip) is a novel regulatory component in the vertebrate hedgehog-signalling pathway. The murine Hhip encodes a type I TM protein that attenuates hedgehog signalling by binding all three mammalian hedgehog proteins. Here we describe the cloning and characterisation of the homologous human hedgehog-interacting protein gene (HHIP). HHIP comprises 13 exons and spans >91kb encoding a protein of 700 aa which shares 94% sequence iden- tity with mouse Hhip. HHIP maps to chromosome 4q31.21--> q31.3. Additionally, we have mapped murine Hhip to chromosome 8.

Animals↗

Transforming growth factor-beta2 antibody attenuates fibrosis in the experimental diabetic rat kidney.

Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases co-ordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-152) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P<0.05, n=24, by ANOVA). In the anti-TGF-beta2-treated diabetic rats, kidney weights and UAE levels were decreased when compared with those in placebo-treated diabetics. Western blotting for the procollagen-I C-propeptide in kidney cortices showed a significant increase in levels in placebo-treated diabetic rats compared with non-diabetic controls over the 14 day diabetic period, indicating initiation of fibrogenesis. By contrast, in anti-TGF-beta2-treated diabetic rats, levels of the propeptide remained at non-diabetic levels. In summary, a significant suppression of kidney fibrosis was seen in anti-TGF-beta2-treated diabetic rats, compared with placebo-treated diabetic rats. We conclude that systemic delivery of CAT-152, a neutralising anti-TGF-beta2 antibody, during the acute stages of diabetic nephropathy reduces the rate of pathogenic fibrosis in the kidney.

Albuminuria↗

Colloidal calcium phosphates in casein micelles studied by slow-speed-spinning 31P magic angle spinning solid-state nuclear magnetic resonance.

The composition of bovine casein micelles was analyzed by 31P magic angle spinning solid-state nuclear magnetic resonance spectroscopy. By looking at isotropic and anisotropic 31P chemical shift parameters, resonance line shapes, the combination of single-pulse and 1H to 31P cross-polarization spectra, and comparison with spectra for various model compounds combined with multiple-component simulation and iterative fitting procedures, we were able to identify and quantify a variety of inorganic and organic phosphates in the micelles. These include phosphates from mobile and immobile inorganic hydroxyapatite-type phosphates as well as phosphates from kappa-casein and the Ca2+-binding phosphoserines from alphas1-, alphas2-, and beta-casein. This information is discussed in relation to previous knowledge and various models for the colloid formation.

Animals↗

[Bilateral germ cell testicular tumors]

PURPOSE: To study the clinical characteristics of bilateral testicular tumors in the cisplatin era. PATIENTS AND METHODS: Between November 1988 and November 1998 2386 testicular cancer patients were treated in our Department and 72 bilateral germ cell testicular cancer patients were retrospectively explored (3%). The incidence, the clinical and histological characteristics and, in the case of asynchronous tumor, the interval between the two tumors were analyzed. RESULTS: During the 10 years 19 synchronous (26.4%) and 53 asynchronous bilateral germ cell testicular cancers (73.6%) were treated. The incidence of bilateral synchronous seminoma was 68.4%. Among the asynchronous tumors 9 concordant seminomas and 9 concordant nonseminomas were detected. In the first, second and third 5-year follow-up period 39.6, 30.2, and 28.2% of asynchronous tumors were diagnosed. The incidence of seminoma after the first castration in the 5, 10 and 15 years was 19, 37.5, and 60%, respectively. The overall survival rates of synchronous and asynchronous testicular cancer were 84 and 93%. In cases of asynchronous tumor the prevalence of stage I cancer was significantly greater in a regularly controlled population (p=0.014) than in the not regularly followed population, but the survival rate was good in both groups. Nonseminoma showed up earlier as first and second tumor than seminoma (p=0.05, p=0.045). The interval between the two asynchronous tumors was shorter in the case of nonseminoma than in the case of seminoma (p=0.002). CONCLUSION: The prognosis of bilateral germ cell testicular cancer is good because of the high incidence rate of seminoma and the effective treatment. With regular follow-up the early diagnosis of second testicular tumors is probable. The interval between the tumors depends on the patients' age and the histology of the second tumor, in the case of seminoma it is longer. The effect of the previous treatment on the incidence of seminoma and the interval between the two asynchronous tumors requires further investigations.

Journal Article↗

[Retrospective evaluation of surgically treated cases of non-palpable breast tumor].

Between 10.01.1997 and 09.30.1999 authors performed operations on 78 patients who had nonpalpable breast tumors. If mammography was considered abnormal during breast screening program patients were recalled. Besides clinical investigation complimentary mammograms were performed. After sonogram, and if needed, aspiration biopsy cytology (ABC) if necessary core biopsy (CB) was the next investigation. 79 operations were performed on 78 patients (one was patient had synchronous breast tumor). The mean age of the patients was 56.3 years. If the radiological investigations (R4-R5) and/or the ABC (C4-C5) or CB suggested malignancy operation was performed. Mammography suggested malignancy in 60.75% of the patients, it was suggested by ABC in 30.18%, and by CB in 55.5%. The nonpalpable tumor, suspected to be malignant was marked with a wire loop and was excised under anesthesia along with the affected breast sector. The excision and tissue-border around the tumor was checked by specimen mammography performed during the narcosis. No cryohistology was performed. After the specimen mammography, the wound was closed. The final histology of the operations showed malignancy in 40.5%. In their retrospective study the authors evaluated the complete sensitivity and the positive predictive value (PPV) of the preoperative investigations regarding the final histology. They analyse the value of preoperative mammogram, the ABC and CB in malignant and in benign cases. Early diagnosis and surgical treatment is expected to improve significantly the survival of patients with breast cancer. Reduction in the number of unnecessary operations can be expected from increasing the accuracy of radiological and cytological investigations and the adequate usage of core biopsy.

Biopsy, Needle↗

SIMPSON: a general simulation program for solid-state NMR spectroscopy.

A computer program for fast and accurate numerical simulation of solid-state NMR experiments is described. The program is designed to emulate a NMR spectrometer by letting the user specify high-level NMR concepts such as spin systems, nuclear spin interactions, RF irradiation, free precession, phase cycling, coherence-order filtering, and implicit/explicit acquisition. These elements are implemented using the Tcl scripting language to ensure a minimum of programming overhead and direct interpretation without the need for compilation, while maintaining the flexibility of a full-featured programming language. Basically, there are no intrinsic limitations to the number of spins, types of interactions, sample conditions (static or spinning, powders, uniaxially oriented molecules, single crystals, or solutions), and the complexity or number of spectral dimensions for the pulse sequence. The applicability ranges from simple 1D experiments to advanced multiple-pulse and multiple-dimensional experiments, series of simulations, parameter scans, complex data manipulation/visualization, and iterative fitting of simulated to experimental spectra. A major effort has been devoted to optimizing the computation speed using state-of-the-art algorithms for the time-consuming parts of the calculations implemented in the core of the program using the C programming language. Modification and maintenance of the program are facilitated by releasing the program as open source software (General Public License) currently at http://nmr.imsb.au.dk. The general features of the program are demonstrated by numerical simulations of various aspects for REDOR, rotational resonance, DRAMA, DRAWS, HORROR, C7, TEDOR, POST-C7, CW decoupling, TPPM, F-SLG, SLF, SEMA-CP, PISEMA, RFDR, QCPMG-MAS, and MQ-MAS experiments.

Algorithms↗

The structure of the membrane-binding 38 C-terminal residues from bovine PP3 determined by liquid- and solid-state NMR spectroscopy.

The secondary structure and membrane-associated conformation of a synthetic peptide corresponding to the putative membrane-binding C-terminal 38 residues of the bovine milk component PP3 was determined using 1H NMR in methanol, CD in methanol and SDS micelles, and 15N solid-state NMR in planar phospholipid bilayers. The solution NMR and CD spectra reveal that the PP3 peptide in methanol and SDS predominantly adopts an alpha-helical conformation extending over its entire length with a potential bend around residue 19. 15N solid-state NMR of two PP3 peptides 15N-labelled at the Gly7 and Ala32 positions, respectively, and dissolved in dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol phospholipid bilayers shows that the peptide is associated to the membrane surface with the amphipathic helix axis oriented parallel to the bilayer surface.

Amino Acid Sequence↗

Vascular grading of angiogenesis: prognostic significance in breast cancer.

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P < 0.0001), node-negative patients (P < 0.0001) and node-positive patients (P < 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P < 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer.

Adult↗

Sentinel node localization in breast cancer patients using intradermal dye injection.

In a series of 161 consecutive breast cancer operations, intradermal injection of Patent Blue was used to localize the sentinel node (SN). The surgical localization rate was 60%. Including the blue lymph nodes found by the pathologist, localization rate was 70%. After the first 103 operations, the surgical procedure was changed, resulting in a localization rate of 83%. Ten surgeons participated, but only one had previous experience with SN dissection. The others experienced a steep learning curve. Metastasis was found in 42 of 97 SNs (43%). In 15 cases (36%) metastasis was recognized only after step-sectioning and immunohistochemical staining for cytokeratin. In one case a benign epithelial inclusion was found. The sentinel node was false negative in 9.1% of cases. The consensus from the literature is that the best results are achieved using a combination of dye and isotopic techniques.

Adult↗

Solid-state 13 C and 31 P NMR analysis of urinary stones.

PURPOSE: We investigated the applicability of solid-state nuclear magnetic resonance (NMR) spectroscopy to obtain information about the structure and composition of renal calculi. MATERIALS AND METHODS: Various types urinary and bladder stones as well as a variety of presumed constituents were investigated using 13C and 31P magic-angle spinning (MAS) solid-state NMR. Different experimental methods were applied to differentiate resonances from crystalline/amorphous (immobile/mobile) as well as protonated/non-protonated moieties. The NMR spectra were analyzed using multiple-component numerical simulations and iterative fitting to identify and quantify the major amorphous or crystalline organic and inorganic components. RESULTS: By comparison of the NMR spectra for the various renal calculi with those obtained under similar conditions for various presumed components, it is demonstrated possible to unambiguously distinguish and quantify the major amorphous or crystalline organic and inorganic components. The components are identified in terms of their isotropic and anisotropic chemical shielding parameters, protonation or proximity of protons, and the degree of crystallinity/mobility. For the calculi investigated we have detected and quantified calcium oxalate, uric acid, struvite, and calcium phosphates that closely resemble brushite and calcium hydroxyapatite. CONCLUSIONS: Using 13C and 31P MAS NMR spectroscopy we have been able to account for 60 to 85% (by weight) of the constituents in the calculi investigated. The ability to identify and quantify both crystalline and amorphous components makes solid-state NMR an interesting new method for the compositional analysis of renal calculi.

Calcium Oxalate↗

The prognostic value of angiogenesis by Chalkley counting in a confirmatory study design on 836 breast cancer patients.

This study addresses the prognostic value of estimating angiogenesis by Chalkley counting in breast cancer. A population-based group consisting of 836 patients with operated primary, unilateral invasive breast carcinomas was included from a predefined region and period of time. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. The Chalkley count was obtained by a 25-point grid within three, subjectively selected, vascular tumor areas of highest microvessel density. The Chalkley count was analyzed in three categories using predefined Chalkley cutoff points at five and seven. There were significant correlations between high Chalkley counts and axillary lymph node metastasis, large tumor size, high histological malignancy grade, and histological type. A high Chalkley count showed lower probabilities of recurrence-free survival (P < 0.0001) and overall survival (P < 0.0001). In the Cox multivariate analysis, the hazard ratio (and 95% confidence interval) showed that the increased risk to die were: 1.55 (1.19-2.03) with Chalkley counts between 5 and 7; 2.26 (1.72-2.98) with counts > or =7 compared with counts < or =5; and 1.46 (1.14-1.87) with counts > or =7 compared with counts between 5-7. The study confirmed that estimation of angiogenesis by Chalkley counting had independent prognostic value in breast cancer patients. The Chalkley count could be useful to stratify node-negative patients for adjuvant treatment.

Adenocarcinoma↗

[The clinical value of mdm-2 (proto-oncogene) expression in testicular cancer, Correlation with tumor progression].

To determine whether mdm-2 protein level is aberrant in germ cell testicular tumors (GCTT) and if so, what is the relationship between mdm-2 overexpression and other disease parameter including histologic subtypes, p53 status, metastatic potential, and clinical stage, 81 testicular germ-cell tumors were screened for their mdm-2 expression at the protein levels using immunohistochemistry (IHC) and Western blot (WB) analysis. Overall, in this study 45 (55.6%) tumors showed positive mdm-2 nuclear immunoreactivity. The incidence of mdm-2 immunostaining was significantly higher (p = 0.0007) in non-seminomas (NSGCT) than in seminomas (S). The frequency of positive tumor was higher in tumors from metastatic patients than in tumors of patients free from metastasis (p = 0.011). Mdm-2 expression was detected significantly more frequently in tumors of advanced stages, i.e. II/B, II/C, and III versus tumors of early stages (I and II/A) (p = 0.0098). A significant difference could be established between the three stages of disease and the expression of mdm-2 (chi 2 = 0.0386), namely the incidence of mdm-2 expression increased with an advanced stage. Using Western blotting 22 (68.8%) out of 32 tumors overexpressed the mdm-2 oncoprotein of 90 kd (p90). Mdm-2 expression as detected by immunostaining may provide a reliable prognostic tool to subgroup of patients with more aggressive GCTT.

Blotting, Western↗

[Sentinel node--malignant melanoma and primary breast cancer. The significance of sentinel node in the treatment of malignant melanoma and primary breast cancer].

Dissection of regional lymph nodes plays an important role in surgical treatment of melanoma and breast cancer. However, the dissection of regional nodes is connected with a high morbidity and dissection in the 50-75% of the patients, who have no regional metastases, represents an overtreatment. No diagnostic procedures are available which could select patients who should have a regional lymph node dissection. The sentinel node (SN) is the first node in the lymphatic basin that drains the primary tumour. SN can be localized by means of dye or isotope or a combination. SN can be localized in melanoma or breast cancer patients in 98% of the operations. In 0-1% (melanoma) or 0-5% (breast cancer) SN was false negative. In some melanoma centers SN technique is an established routine. If the SN is normal, no regional lymph node dissection is needed. In breast cancer technical improvements must be achieved before SN examination can be used routinely. Future studies must clarify if examination of SN could have clinical significance in other malignant tumour diseases.

Axilla↗

[Detection of human papillomavirus infection by the nucleic acid hybridization method (a multicenter study)].

The human papillomaviruses (HPV) are regarded as one of the important agents of cervical carcinoma. A multicentre study was organized to determine the prevalence of HPV in the fertile female population in Hungary. Parallel with the clinical sample collection, a questionnaire interview was performed to acquire data on the life style, socioeconomic status, sexual practice, etc. 1200 women were examined colposcopically and cervix samples were collected for cytology and the detection of HPV DNA. 17.4% of the samples were HPV-infected. 3.9% of the patients had acquired low-risk, and 10.1% 10.2% high-risk HPV types; 3.4% of the women were at the same time infected with both low-risk and high-risk HPV types. Simultaneously performance of cytology and the HPV hybrid capture assay contribute to recognise and treat the precancerous status and risk factors.

Adolescent↗