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Biomedical subjects

K Lapis

Publications and source records attributed to K Lapis.

At least 19 recordsLinked to original sources

Testing the efficacy of fermented wheat germ extract against Mycoplasma gallisepticum infection of chickens.

The effect of fermented wheat germ extract (FWGE, Immunovet-HBM) was studied in chickens challenged with Mycoplasma gallisepticum. Ninety M. gallisepticum- and M. synoviae-free 3-wk-old chickens were exposed to aerosol infection of M. gallisepticum. One group (30 birds) was treated with FWGE, a second group with tiamulin, and a third group was untreated. The fourth group was exposed to PBS aerosol as a negative control. On d 9, all chickens were slaughtered and examined for the presence of gross and histological lesions, the presence of the challenge strain in the organs and specific antibodies in the serum. Body weight gains and feed conversion rates were recorded. In the groups treated with FWGE and with tiamulin, the chickens remained clinically healthy: their BW gains were 441.7 g and 446.8 g, respectively. Feed conversion ratios were 1.72 and 1.71 for FWGE- and tiamulin-treated birds, respectively. Control birds had BW gain of 480.8 g, and feed conversion ratio of 1.78. The numbers of birds with gross lesions (15 and 11, respectively) and lesion scores (25 and 25, respectively) of the FWGE- and tiamulin-treated groups were significantly lower than in the infected untreated group (25 birds, lesion score of 190). No mycoplasma was reisolated from brain, liver, spleen, heart, or kidneys of the FWGE-treated birds, and the number of mycoplasma isolations from the respiratory tract samples was less frequent (10) than from the infected untreated group (64). In addition, 35 samples from other internal organs were also positive. Twenty percent of the birds treated with FWGE showed serological response with a 5.0% reaction score, whereas in the infected untreated group, 83.3% of birds were reactors, with a 62.5% reaction score.

Animals↗

A medical nutriment has supportive value in the treatment of colorectal cancer.

MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.

Adult↗

Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats.

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).

Animals↗

Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells.

The fermented wheat germ extract with standardized benzoquinone composition has potent tumor propagation inhibitory properties. The authors show that this extract induces profound metabolic changes in cultured MIA pancreatic adenocarcinoma cells when the [1,2-13C2]glucose isotope is used as the single tracer with biologic gas chromatography-mass spectrometry. MIA cells treated with 0.1, 1, and 10 mg/mL wheat germ extract showed a dose-dependent decrease in cell glucose consumption. uptake of isotope into ribosomal RNA (2.4%, 9.4%, and 28.0%), and release of 13CO2. Conversely, direct glucose oxidation and ribose recycling in the pentose cycle showed a dose-dependent increase of 1.2%, 20.7%, and 93.4%. The newly synthesized fraction of cell palmitate and the 13C enrichment of acetyl units were also significantly increased with all doses of wheat germ extract. The fermented wheat germ extract controls tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation-related and cell differentiation-related macromolecules. Wheat germ extract treatment is likely associated with the phosphorylation and transcriptional regulation of metabolic enzymes that are involved in glucose carbon redistribution between cell proliferation-related structural and functional macromolecules (RNA, DNA) and the direct oxidative degradation of glucose, which have devastating consequences for the proliferation and survival of pancreatic adenocarcinoma cells in culture.

Adenocarcinoma↗

Effect of MSC on the immune response of mice.

The supposed immunostimulatory actions of MSC, a new fermented wheat germ extract standardized to its benzoquinone composition (trade name: AVEMAR) were studied examining blastic transformation of peripheral blood lymphocytes of mice treated with MSC. It was found that MSC significantly increased the degree of blastic transformation caused by Concanavalin A. Using the B10LP to C57Bl skin graft system, MSC (0.03 and 3.0 g kg(-1) applied orally) acted in favour of restoring the immune function. On the other hand, 2,6-dimethoxy-p-benzoquinone (DMBQ), applied in equivalent doses (0.012 and 1.2 mg kg(-l)), did not shorten the rejection time of skin grafts. The immune restoring effect, as well as the blastic transformation enhancing potential of MSC may be exploited in various cases of decreased immune response.

Adjuvants, Immunologic↗

MSC, a new benzoquinone-containing natural product with antimetastatic effect.

An orally applicable fermentation product of wheat germ containing 0.04% substituted benzoquinone (MSC) has been invented by Hungarian chemists under the trade name of AVEMAR. Oral administration (3 g/kg body weight) of MSC enhances blastic transformation of splenic lymphocytes in mice. The same treatment shortens the survival time of skin grafts in a co-isogenic mouse skin transplantation model, pointing to the immune-reconstructive effect of MSC. A highly significant antimetastatic effect of MSC has been observed in three metastasis models (3LL-HH, B16, HCR-25). The antimetastatic effect of MSC--besides the immune-reconstitution--may also be due to its cell adhesion inhibitory, cell proliferation inhibitory, apoptosis enhancing, and antioxidant characteristics, also observed in our in vitro experiments. It is even more noteworthy that combined treatment with MSC and one of the following antineoplastic agents (5-FU and DTIC)--both in wide use in every day clinical practice--exhibited a significantly enhanced antimetastatic effect in appropriate metastasis models (established from C38 mouse colon carcinoma and B16 mouse melanoma respectively) as compared to the effect elicited by any component of these therapeutic compositions (MSC + 5-FU and MSC + DTIC) administered alone. The results show that the fermented wheat germ extract (MSC) has more than an additive effect and synergistically enhanced the metastasis inhibitory effect of both antineoplastic agents studied till now. It is also worthy of mention that the synchronous treatment with MSC profoundly decreased the toxic side effects of the applied antineoplastic agents (decreased weight loss etc). Based on the biological effects of MSC--shown to be non-toxic by subacute toxicology studies--this product may be used as an adjuvant in the therapy of malignant neoplasia and other diseases caused by or following immune-deficiency.

Animals↗

Relationship between the survival and the clinicopathological parameters of the patients with tumors in the pancreatic head region.

Retrospective study was performed to assess the possible prognostic factors for survival in patients after radical surgery with carcinoma of the pancreatic head region. Twenty-nine patients underwent pancreaticoduodenectomy for cancers of the pancreatic head (n = 22) and the papilla of Vater (n = 7). Using flow cytometry, authors measured the nuclear DNA content of tumor cells. DNA ploidy status was evaluated from paraffin-embedded tumor tissues. Fourteen DNA diploid and eight DNA-aneuploid pancreatic carcinomas occurred. Six DNA diploid and one DNA-aneuploid tumors were diagnosed in the group of papilla of Vater. Mean survival of patients with the carcinoma of pancreatic head was 9.3 months. Survival of the patients with the cancer of papilla of Vater was 20.5 months. The mean survival was 10 months in case of DNA-diploid pancreatic carcinoma, and it was 8 months in case of DNA-aneuploid cancer. The survival of the patients with DNA* diploid Vater papilla tumor was 17 months, and it was 40 months with the DNA-aneuploid cancer. The mean proliferative index (PI) of DNA-diploid pancreatic cancers was 9.7%, whereas that of the DNA-aneuploid cases was 13.3%. The mean PI of DNA-diploid tumors of papilla of Vater was 7.5% and that of the DNA aneuploid cases was 28%. There was no significant correlation between the PI and the survival. DNA-ploidy status and PI had no significant effect on the survival in patients with carcinoma of the pancreatic head region.

Adult↗

[A new benzoquinone-containing antimetastatic product].

An orally applicable fermentation product of wheat germ containing 0.04% substituted benzoquinone (MSC) was invented by Hungarian chemists under the trade--name of AVEMAR. The following biological effects of this product were observed. Oral administration (3 g/kg body weight) of MSC enhances blastic transformation of splenic lymphocytes of mice. The same treatment shortens the survival time of skin grafts in co-isogenic mouse skin transplantation model, which points to immune-reconstructive effect of MSC. Highly significant anti-metastatic effect of MSC was observed in three metastasis models (3LL-HH, B16, HCR-25). The antimetastatic activity of MSC--besides the immune reconstitution--may also due to the cell-adhesion inhibitory, cell proliferation inhibitory, apoptosis-enhancing and antioxidant effects, which were also observed in our in vitro experiments. Based on the biological effects of MSC--which is non-toxic, according to subacute toxicology studies--this product may be used as an adjuvant in the therapy of malignant neoplasia and other diseases caused by or following immunedeprivation.

Administration, Oral↗

Experimental and human liver fibrogenesis.

In this work, we provide an overview of our results obtained by studying the role of transforming growth factor beta1 and proteoglycans in liver fibrogenesis. It has been found that transforming growth factor beta1 is one of the most important stimulators of extracellular matrix synthesis in the liver. In chronic liver injury, desmin-positive non-parenchymal liver cells expressed transforming growth factor beta1. The extracellular localization of the growth factor correlated well with types I, III and IV procollagen-alpha, which were detected in the fibrous septa of chronically injured livers. A similar distribution pattern was observed in human specimens. To identify the role of transforming growth factor beta1 in liver extracellular matrix protein synthesis, transforming growth factor beta1-positive transgenic mice were generated. Animals expressing the growth factor in their liver showed spontaneous liver fibrosis. Proteoglycans also participate in fibrogenesis. The majority of liver-specific heparan sulfate proteoglycans, such as syndecan-1 and fibroglycan, are produced by hepatocytes. The extracellular matrix proteoglycans decorin and perlecan are synthesized by non-parenchymal liver cells. The amount of the latter is very low in normal liver, but increases dramatically in liver fibrosis. The effect of regulatory factors on liver proteoglycans seems to be cell type-specific. In contrast to previous observations, elevated amounts of decorin did not inhibit the action of transforming growth factor beta1 in the liver.

Animals↗

Human and experimental hepatocarcinogenesis.

Human liver cancer is increasing worldwide, including in Hungary. The detection of liver tumors in premalignant or early malignant states is essential for successful treatment. MC-29 virus-induced chicken hepatoma and rodent, fish and monkey models for chemical hepatocarcinogenesis were studied and compared to humans. Changes in phenotypic enzyme alterations and in the expression of certain oncogens and growth factors characterize the experimentally induced hepatomas, and might also be characteristic of human premalignant and malignant focal liver lesions. Fish hepatocarcinogenesis is useful for studying compounds in environmental pollution. Increased expression of transforming growth factor á can be observed both in experimental and human liver tumors. Increased tumor incidence was detected in transgene mice containing both transforming growth factor alpha and c-myc genes. Animal models of hepatocarcinogenesis help to understand the development of liver tumors. Methods applied in studies using those models are useful in the study of premalignant and malignant human liver lesions.

Animals↗

Role of sinusoidal heparan sulfate proteoglycan in liver metastasis formation.

Previous studies have indicated that the predominant sites of tumor cell extravasation in the liver are the sinusoidal vessels, where tumor cells contact the sinusoidal endothelium and the subendothelial extracellular matrix containing the basic components of the basement membrane. We studied the role of sinusoidal extracellular matrix in metastatsis formation by 3LL-HH murine tumor cells selected for their preferential liver colonization. 3LL-HH tumor cells did not efficiently adhere to cryosections of the liver, but they recognized the sinusoids and vessel walls. Pre-treatment of the mice with polyclonal anti-basement membrane antibodies [anti-laminin, anti-fibronectin and anti-heparan sulfate proteoglycan (HSPG)] significantly modulated the organ distribution of tumor cell colonies following intracardial injection: all 3 antibodies inhibited kidney colonization; anti-laminin and anti-fibronectin antibodies inhibited lung colonization; and only anti-HSPG antibody inhibited liver colonization. In several organs such as the heart, stomach, pancreas and bladder, anti-basement membrane antibody treatment did not alter the process of colonization. Immunofluorescence studies showed that anti-HSPG antibody recognized the basement membranes of sinusoids and blood vessels. Our data suggest a specific involvement of sinusoidal HSPG in the liver colonization of 3LL-HH cells.

Animals↗

Studies on the proliferative activity of diethylnitrosamine-induced hepatocellular carcinomas in monkeys.

In this study, synthetic phase fractions (SPFs) determined by flow cytometry and AgNOR counts were analysed in benign liver lesions (regenerative nodules and adenomas), hepatocellular carcinomas (HCCs), and lung metastases of a monkey hepatocarcinogenesis model to find out if AgNOR counts and SPFs can discriminate between malignant and non-malignant liver lesions. The average per cent SPF values and the AgNOR counts were significantly (P = 0.001) increased in regenerative liver nodules (5.30 per cent; 4.96), adenomas (5.34 per cent; 3.46) and well-differentiated HCCs (6.75 per cent; 4.47), compared with the untreated control livers (3.18 per cent; 0.98), but the differences between these three groups were not significant. In the poorly differentiated HCC group, however, the average SPF value (9.60 per cent) and AgNOR count (7.14) were significantly higher than in any of the other liver lesions examined. A significant correlation was found between the SPF values and AgNOR counts on the one hand, and differentiation and cytological grade of the HCC samples on the other. The results of this study show that the SPF values and AgNOR counts are not reliable in differentiating between regenerating liver nodules, adenomas, and experimental well-differentiated HCCs. The SPF value, however, may serve as a prognostic factor in HCC, since it was found to be significantly higher in HCCs with lung metastasis than in those without.

Adenoma↗

Effect of the DNA ploidity on survival in patients with carcinoma of papilla of Vater.

The authors investigated the possible prognostic factors for survival after pancreaticoduodenectomy for carcinoma of papilla of Vater. From 1984 to 1995, 8 patients underwent radical surgical intervention for tumor of papilla of Vater. The mean age of the patients was 58 years. Three of them were over 60 years. In one case Whipple procedure was performed, and pylorus-preserving pancreaticoduodenectomy was carried out in 7 patients. Using flow cytometry, the authors measured the nuclear DNA content of tumor cells. DNA ploidity status was evaluated from paraffin-embedded tumor tissues. Perioperative mortality occurred in one patient. Reoperation was performed on 2 patients, because of presence of anastomotic leakage. Survival was 50% at 1 year, 37.5% at 3 years, and 25% at 5 years. Tumor size (> 2 cm) was not negative prognostic factors for survival. The mean survival of patients with diploid cancer (n:6) was 17 months, and the mean survival of patients with aneuploid carcinoma (n:2) was 56 months. The proliferative index of the diploid carcinomas ranged from 3% to 11%. The proliferative index of the aneuploid tumors ranged from 17% to 28%. In conclusion, tumor size (> 2 cm), DNA ploidity status and proliferative index were not significantly negative prognostic factors for survival in patients with tumor of papilla of Vater.

Age Factors↗

[Pulmonary tuberculosis revealed by lupus vulgaris].

The incidence of pulmonary tuberculosis in Hungary had been significantly decreased until the 1980s and its common cutaneous manifestation was found to be extremely rare. During the past years an increasing number of reports were dealing the novel increasing incidence of tuberculosis, mostly on homeless and immunocompromized persons. The present report dealt with a pulmonary tuberculotic patient on whom severe cutaneous TBC manifestations (lupus vulgaris) that was heralded the underlying systemic tuberculotic disease.

Humans↗

[Experiences with a new vacuum-accelerated microwave histoprocessor].

Methods of microwave and vacuum accelerated fixation, dehydration and paraffin embedding are described. They can be carried out in a new type of vacuum and temperature stabilizable microwave histoprocessor: MFX-800. The whole histoprocessing lasts 3.5-5.5 hours depending on the thickness of the tissue blocks. Preserved structural detail, intensive staining and good antigen preservation were achieved with various tissues. This new histoprocessing facility can be highly recommended for pathology laboratories interested in speeding up the processing procedure, as well as in immunohistochemistry.

Equipment Design↗

Working experience with a new vacuum-accelerated microwave histoprocessor.

Methods of microwave and vacuum-accelerated fixation, dehydration, and paraffin embedding are described, using a new type of vacuum and temperature stabilizable microwave histoprocessor: MFX-800. The whole histoprocessing cycle lasts 3.5-5.5 h, depending on the thickness of the tissue blocks. Well-preserved structural detail, intense staining, and good antigen preservation were achieved with various tissues. This new histoprocessing facility is recommended for routine pathology laboratories in speeding up their processing procedures.

Decalcification Technique↗

The antimetabolite Tiazofurin (TR) inhibits glycoconjugate biosynthesis and invasiveness of tumour cells.

We investigated the effect of Tiazofurin (TR-2-beta-D-furanosylthiazole-4-carbamide) on tumour cell invasion using metastatic 3LL-HH murine lung carcinoma and HT168-M1 human melanoma as experimental models. TR pretreatment of 3LL-HH cells, in a dose range of 15-60 microM, caused inhibition of cell proliferation, adhesion to plastic and extracellular matrix proteins. The TR-induced altered matrix interactions of 3LL-HH cells were reflected in decreased migration through matrix-covered filters. Analysis of the expression of certain invasion markers indicated that TR suppressed the expression of alpha v beta 3 integrin and MMP2 metalloproteinase. Biochemical studies indicated that 24 h 60 microM TR treatment of 3LL-HH cells inhibited glycosylation of a wide range of glycoproteins with the most pronounced effect on proteoglycans. TR pretreatment of 3LL-HH tumour cells resulted in the loss of lung colonisation potential in vivo. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of 3LL-HH murine carcinoma. TR treatment also induced inhibition of integrin and MMP2 expression, migration and liver colonisation of the human melanoma HT168-M1 cell line. Since the TR concentration which inhibited various cellular functions was much lower for cell adhesion and lung colonisation than for cell proliferation, we suggest that the predominant effect of TR is the inhibition of metastasis in these model systems. We also suggest that both the effect of TR on tumour cell proliferation and on extracellular matrix interaction contribute to its remarkable antimetastatic potential in vivo.

Amino Acid Sequence↗

Accuracy of admission and clinical diagnosis of tumours as revealed by 2000 autopsies.

Admission, clinical and autopsy diagnoses of tumour were computed in 2000 consecutive cases, aged 30-80 years, using data collected in two university pathology departments in Budapest, Hungary. Based on diagnosis of tumour, regardless of site, as the underlying cause of death false-negative rates were 37.4% at admission and 8.8% clinically. Corresponding false-positive rates were 8.4 and 9.1%. General practitioners who correctly diagnosed a tumour as the cause of the terminal illness identified the primary site wrongly in 20.6% (90/436) of cases. Hospital clinicians did so in 20.4% (130/636) of cases. Overall, of site-specific tumours considered as the underlying cause of death at autopsy, 27.4% were incorrectly diagnosed clinically and 50.4% at admission. Diagnostic errors were particularly common for tumours of the lung, liver, ovary and gall bladder. Graduate and postgraduate education, planning of the health care system and quality of cancer care may benefit from statistical data derived from autopsy diagnoses.

Adult↗