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Biomedical subjects

M Bak

Publications and source records attributed to M Bak.

At least 73 records · Page 4Linked to original sources

[Chronic pancreatitis and upper gastrointestinal hemorrhage].

A 46 year-old woman with a history of chronic pancreatitis, upper epigastric pain and upper gastrointestinal bleeding of obscure origin is presented. A haemoductal pancreatitis was the source of bleeding due to erosion of the splenic artery with bleeding into a pancreatic pseudocyst communicating with the pancreatic duct. This case was special, because there was no aneurysmal dilatation of the splenic artery. This rare entity must always be considered in the diagnosis of gastrointestinal haemorrhage of obscure origin. The appropriate investigation to confirm the diagnosis is visceral angiography, if necessary followed by CT-scan of the abdomen.

Chronic Disease↗

[Multidrug resistance of testicular cancers. (Detection of P-glycoprotein and MDR1 gene expression and their clinical connection)].

The most frequently reported alteration of multidrug-resistant cells is overexpression of a 170 kD glycoprotein (P-glycoprotein or P-170) encoding by the MDR1 gene family. Expression of the multidrug-resistance gene product P-glycoprotein was screened in 55 untreated human germ cell testicular tumors using monoclonal antibody (C219) and immunoenzyme staining. In samples out of 17 seminomatous germ cell testicular tumors (SGCT) 2 seminomas, and out of 38 non-seminomatous tumors (NSGCT) 20 carcinomas (15 teratomas, 4 embryonal carcinomas, 1 with Yolk sac differentiation and 1 embryonal rhabdomyosarcoma) showed high expression of P-glycoprotein. NSGCT-s, which are more refractory than seminomas to anticancer chemotherapy, frequently expressed P-glycoprotein. These immunohistochemically detected elevated P-170 expressions were correlated by the overexpression of MDR1 mRNA gene sequences. A relationship between clinical resistance and P-glycoprotein expression seems thus to exist in 4 teratomas 3 embryonal carcinomas, and 1 seminomas. A significant correlation (p < 0.02) between P-170 expression and clinical drug resistance in stage II-III germ cell testicular tumors could be demonstrated. The results suggest that a multidrug resistant phenotype may also occur and P-glycoprotein might contribute to drug resistance in testicular tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Widening of mediastinal shadow in a 10-year old girl with allergic alveolitis].

The case of a 10 year old girl widening of mediastinal shadow in X-ray examination is presented. Allergic pulmonary alveolitis as a primary disease was found. The broadening of the mediastinal shadow depended on lymphadenopathy in the course of associated mycoplasma infection and vasculature pattern.

Alveolitis, Extrinsic Allergic↗

Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells.

Cultured P388/VCR mouse lymphoma cells resistant to vincristine (VCR) and to 5-bromodeoxyuridine (BUdR) and deficient in thymidine kinase (TK-) were fused with P388/DAG cells resistant to 1.2:5,6-dianhydrogalactitol (DAG), an anticancer alkylating agent, and to 6-thioguanine (6-TG) and deficient in hypoxanthine phosphoribosyl-transferase (HPRT-). The hybrid cells expressed multidrug resistance (MDR), i.e., resistance to VCR and cross-resistance to Adriamycin (ADM) and actinomycin D (Act. D), in a dominant manner. The presence of glycoprotein p170, the MDR gene product, was detected in the hybrid cells. Resistance to DAG was also expressed dominantly, whereas cross-resistance to dibromodulcitol (DBD), a chemically related anticancer drug, was slight.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Thoracic surgery of testicular cancer patients.

Between 1 January 1980 and 31 December 1991 the authors treated 1450 patients with malignant testicular tumours. Out of them, in 42 patients aged 18-43 years with stage III non-seminoma germ cell testicular cancer, thoracic surgical interventions took place on 44 occasions since the combined cytostatic treatment did not result in a sufficient regression, or disease progression occurred. In one case the lesion was inoperable. In 43 cases successful resection was performed. In 27 cases unilateral, in two cases bilateral thoracotomy and in 15 cases median sternotomy took place. Solitary lesions were found in 26 and multiple ones in 18 cases, respectively. Two patients died in the direct postoperative phase. Forty patients were followed up for 4 to 130 months. Due to disease progression four and seven patients were lost within 12 and 12-24 months, respectively. Currently, 31 patients are alive 4 to 130 months following surgery (29 of them tumour-free, two with tumour). Based on adequate indications the thoracic surgery is justified both from diagnostic and therapeutic points of view. The metastasectomy might offer an advance in the management of these patients.

Adolescent↗

Effects of angiotensin-converting enzyme inhibition on renal adaptations to acute furosemide administration in conscious rats.

During administration of loop diuretics the initial volume depletion activates Na-conserving mechanisms, which reduces glomerular filtration rate (GFR) and stimulates renal tubular reabsorption of Na and water. By i.v. infusion of the angiotensin-converting enzyme inhibitor enalaprilat (100 micrograms bolus; 100 micrograms/h) we examined the role of angiotensin II for the compensatory renal responses occurring during furosemide administration in conscious rats. To evaluate the significance of hydration for the compensatory renal effects of angiotensin II, experiments were performed in groups of rats with or without i.v. replacement of urinary volume losses. Furosemide was administered i.v. (6 mg/kg/h) for 3 1/2 hr. Furosemide infusion produced a short-lasting increase in urine flow rate, Na, Li and K excretion after which the renal excretion rates returned toward pretreatment levels, along with significant reductions in effective renal plasma flow and GFR and increases in effective filtration fraction and effective renal vascular resistance. Sustained increases in urine flow and urinary excretion rates of Na, Li and K were observed in absence of changes in GFR in rats given furosemide with volume replacement. Enalaprilat did not alter the tubular response to furosemide during either euvolemia or volume depletion. However, enalaprilat attenuated the furosemide-induced increases in effective filtration fraction and effective renal vascular resistance. It is concluded that angiotensin II is not essential for the compensatory response of decreased GFR and increased tubular Na reabsorption. However, angiotensin II is an important mediator of renal vasoconstriction during furosemide infusion.

Absorption↗

Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM.

Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM.

Aging↗

Incidence of insulin-dependent diabetes mellitus in Warsaw, Poland, in children and young adults, 1983-1988.

The 5-year results of the incidence study of insulin-dependent diabetes mellitus (IDDM) in children (0-14 years) and young adults (15-29 years) which began in Warsaw on 1 July 1983 are presented. The overall number of new IDDM patients aged 0-29 registered in Warsaw during 5 years was 165. The average incidence rates in the age groups 0-14 and 15-29 were respectively 5.2 and 6.5 per 100,000 population in males and 4.5 and 4.4 in females. The highest incidence was observed in the age groups 25-29, 10-14 and 15-19 in males, and 5-9 and 25-29 in females. More patients reported the onset of their first symptoms in autumn and winter than in spring and summer. The IDDM incidence rates in Warsaw appear to be lower than those in some other countries for which data on IDDM at ages 0-29 years are available.

Adolescent↗

[Prevalence of gallbladder lithiasis in a Uruguayan population].

Ultrasound examinations were carried out in 693 volunteers from the health care personnel of the Hospital de Clinicas of Montevideo, with the aim of studying the prevalence of gallbladder gallstones in Uruguay, the proportion of symptomatic and asymptomatic people and its association to some definite risk factors. The prevalence found was 10.4%, which, according to the sample's size, is representative of the general population with a confidence of 99%. Sixty five per cent of gallstones carriers were asymptomatic. A statistically significant association with the following factors was found: people between 31 and 50 years old, slight obesity, and, for women, to have children. A marked tendency with the following factors was found, though it was not statistically significant: female sex, and a familiar history of mother carrying gallstones. Considering all these factors as a whole, the probability of having gallstones reached 19%. Results are discussed and compared with those of foreign publications. It is concluded that uruguayan people with more possibilities of having gallstones are: women between 31 and 50 years old, obese, with children, and whose mother has or had the same disease.

Adolescent↗

[Multidrug resistance of malignant tumors].

The development of resistance to chemotherapy is a major problem in the treatment of malignant tumors. Clinically, this is characterized by short periods of remission and failure to respond to subsequent therapy. Multidrug-resistance or pleiotropic resistance describes the simultaneous expression of cellular resistance to a vide range of structurally unrelated drugs (e.g. alkaloids, anthracyclines, antibiotics, etc.). The most frequently reported alteration of multidrug-resistant cells is the overexpression of a 170 kD glycoprotein (P--170 or P-glycoprotein) encoding by the MDR gene family. A great deal of evidence has suggested that the P-glycoprotein is, in fact, an energy-dependent drug efflux pump. Pharmacological overcome of MDR may indicate to circumvent clinically observed drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations.

Esophageal squamous cell carcinoma (ESC) samples from patients residing in Uruguay and in Normandy, France, where alcoholic beverages and tobacco smoke are major risk factors, were analyzed for point mutations in the p53 tumor suppressor gene. Among 34 tumors (15 from Normandy and 19 from Uruguay) 15 point mutations in the p53 gene that result in amino acid substitutions or chain termination were identified by polymerase chain reaction amplification of exons 5-8 and direct DNA sequencing. Base substitutions in ESC from these high-incidence areas are dispersed over the midregion of the p53 gene. There are differences between ESC and other types of gastrointestinal cancer in the nature of frequent base substitutions. CpG to TpG transitions were far less prevalent in these ESC than in colorectal tumors, whereas G to T transversions, rarely found in colon cancers, were found in one-fourth of the ESC samples. Base substitutions at A:T pairs constitute an important fraction of ESC p53 mutations, in contrast to mutation patterns in most other types of solid tumors. In contrast to the frequent mutation of the p53 gene in these samples, no mutations in the H-, K-, or N-ras genes were found in 16 tumors from Uruguay by direct sequencing of exons in which transforming mutations are known to occur. A previous study on ras mutations in ESC from France was also negative (M. C. Hollstein et al., Cancer Res., 48: 5119-5123, 1988). The role of distinct etiological factors in generating these differences and the potential for linking patient exposure histories with patterns of p53 mutations in high risk populations are considered.

Adult↗

Chromosome number distribution and cellular DNA content in colorectal adenomas from polyposis and nonpolyposis patients.

Ploidy analyses of colorectal adenomas were performed by combined flow cytometric DNA analysis of unfixed isolated nuclei and direct chromosome preparation after Colcemid incubation for 9-20 hours. Ten of 18 adenomas from nonpolyposis patients and 4 of 13 adenomas from patients with familial adenomatous polyposis yielded a mean of 25 countable metaphases (range 7-44) per tumor. Of 343 metaphases, only 38% had 46 chromosomes, and 62% were nondiploid. All but one adenoma had diploid or peridiploid modes in the range of 46-50 chromosomes. One adenoma was hyperploid, with a mode of 74 chromosomes and a correspondingly increased nuclear DNA content. In another two adenomas, the DNA analyses showed small hyperploid populations constituting 6% and 2% of the cells. The most striking difference between the DNA analyses and chromosome number distributions was that 13% of all metaphases were hyperploid with chromosome numbers outside the perimodal range but, except in one adenoma, without indication in the DNA histogram of corresponding hyperploid cell populations. We propose that these aberrant metaphases indicate an early acquired genetic instability of the neoplastic epithelium, which may be instrumental in generation of hyperploid, invasive clones, which constitute most colorectal carcinomas.

Adenoma↗

Amiloride-sensitive lithium reabsorption during doxazosin-induced blood pressure reduction in rats.

1. The effects of acute systemic alpha 1-adrenoceptor blockade by doxazosin on glomerular filtration rate, urine flow, sodium clearance and lithium clearance were investigated in acutely prepared conscious rats. 2. Clearance experiments were performed during water diuresis (20 mmol/l NaCl and 110 mmol/l glucose, 3 ml/h). After a control period, animals were randomized to one of the following treatments: time-control (n = 9), doxazosin (50 micrograms primer, 30 micrograms h-1 kg-1) (n = 10), amiloride (1 mg primer; 2.4 mg h-1 kg-1) (n = 10) and doxazosin plus amiloride (n = 9). 3. Doxazosin reduced the mean arterial blood pressure from 125 to 108 mmHg; this was associated with transient reductions in glomerular filtration rate, urine flow and lithium clearance. After the transient antidiuresis, the sodium excretion rate remained reduced in doxazosin-infused animals. Amiloride increased the sodium excretion rate without having effects on other variables. When doxazosin was given together with amiloride, the reduction in lithium clearance observed during the transient reduction in glomerular filtration rate and urine flow, was partly abolished. Thus the fractional lithium excretion was transiently increased in rats given doxazosin plus amiloride (from 29 to 40%), whereas in rats given doxazosin alone a non-significant reduction was observed (from 28 to 25%). The dissociation between lithium clearance and fractional lithium excretion in the two doxazosin-infused groups was only significant during the transient reduction in glomerular filtration rate and urine flow. 4. The results provide evidence for an amiloride-sensitive lithium reabsorption during acute systemic alpha 1-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Suitability of tritiated inulin for determination of glomerular filtration rate.

Purity of different batches of [3H]inulin delivered from leading manufacturers was elevated with a chromatographic method (Sephadex G-25 column) that allowed simultaneous analysis of cold inulin, [3H]inulin, and [14C]inulin in the same run. Among four batches of [3H]inulin received within 5 mo, two were found relatively pure, whereas two were partly decomposed to lower-molecular-weight fragments. The chromatographic profile of pure isotopes was not significantly affected by redistribution and freeze drying, nor by subsequent storage in the freeze-dried state at -20 degrees C for up to 5 mo, nor by incubation in aqueous solution at 37 degrees C for 24 h. Three batches of [3H]inulin with different grades of decomposition (noninulin percentages 13%, 38%, and 61%, respectively) were selected for clearance experiments and infused simultaneously with cold and undecomposed [14C]inulin to conscious rats. [14C]inulin had a significantly higher clearance than cold inulin (+7.6 +/- 0.6%) and relatively pure [3H]inulin (+12.4 +/- 0.4%). Decomposed [3H]inulin isotopes progressively underestimated clearance of cold inulin to an extent related to the degree of decomposition. Thus at the end of the 5-h clearance experiment, ratios between clearance of tracer and of cold inulin were 0.92, 0.71, and 0.60 for the three 3H isotopes, respectively. This study indicates that [3H]inulin delivered from leading manufacturers may be decomposed to an extent that invalidates its use as a marker for glomerular filtration rate (GFR). It is thus necessary to check the purity routinely before use. Within the same rat, clearance of undecomposed [3H]inulin and [14C]inulin may differ by 12%, and for this reason they should not be used interchangeably as GFR markers.

Animals↗

Observer reproducibility in grading dysplasia in colorectal adenomas: comparison between two different grading systems.

The two most well known and well defined grading systems for dysplasia in colorectal adenomas were compared with regard to reproducibility. The Konishi-Morson system (KMS) operates with several histological and cytological variables and grades of mild, moderate, and severe dysplasia. The Kozuka system is based on the extent of nuclear pseudostratification and also has three grades of dysplasia (III-V). As the group of severe dysplasia is very large in this system, it was extended with two higher grades, similarly based on individual histological criteria, known hereafter as the extended Kozuka system (EKS). Fifty six adenomas were graded by two observers, each observer grading twice according to the KMS criteria and twice according to EKS criteria. Intraobserver reproducibility was excellent for the KMS and moderate for the EKS, but this was not significant. The overall interobserver reproducibility was similar (moderate) for the KMS and for the EKS. Kappa values for interobserver reproducibility on individual categories were excellent for severe dysplasia according to the KMS, but low for all other categories in both systems. By simplifying both systems into two groups a high reproducibility can be obtained, but this implies that all the original grades (III-V) for the EKS must be grouped together. It is therefore recommended that a simplified KMS is used for further studies on the biological importance of dysplasia and for comparison between histological changes and other markers for colorectal neoplasia.

Adenoma↗

P-170 glycoprotein, glutathione and associated enzymes in relation to chemoresistance of primary human renal cell carcinomas.

High intrinsic chemoresistance contributes to the dismal outcome of patients with disseminated renal cell carcinoma (RCC). In experimental cell lines, two defined defence mechanisms, P-170 glycoprotein and glutathione metabolism, have been established in multidrug resistance, a cross-resistance to cytotoxic compounds without functional or structural similarities. In 21 primary human RCCs, P-170 expression was examined, glutathione content and activities of related enzymes determined and the results were correlated to the degree of in vitro chemoresistance. P-170 was found in 10 of 17 resistant tumors but in none of the sensitive cases. The glutathione content was significantly higher and the related enzyme distinctively enhanced in resistant RCCs. Both mechanisms occurred independently and may well explain the multidrug resistance of RCC. Therefore, reversal of one or both systems may have a clinical impact on the chemotherapy of RCCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗