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J Szabo

Publications and source records attributed to J Szabo.

At least 73 records · Page 4Linked to original sources
PubMed1996

[A single positive prostatic biopsy out of six systematic biopsies is not correlated with the intracapsular nature of the tumor on an individual level].

OBJECTIVE: To evaluate whether or not a single positive prostatic biopsy out of six systematic ultrasound-guided biopsies, is reliably correlated manner with favourable histopathological features of the tumour on the radical prostatectomy (RP) specimen. MATERIALS AND METHODS: In a series of 158 patients undergoing RP for clinically localized prostatic cancer, 15.2% had only one positive biopsy out of 6 systematic biopsies. We compared the rates of capsular effraction (C+) and positive resection margins (RM+), assessed on the operative specimen, in this group of patients with a single positive biopsy (group 1) and in the group (group 2) diagnosed by more than one positive biopsy. The postoperative biological progression rate (P+), defined as an immediate or secondary postoperative elevation of PSA beyond 0.1 ng/ml by polyclonal assay, was also evaluated in the two groups. The Gleason score was evaluated and compared on biopsies and on RP specimens. RESULTS: 29.2 of cases were C+, 16.7% were RM+ and 26% were P+ in group 1, versus 70%, 46.5% and 49.5%, respectively, in group 2. All differences were statistically significant. All patients in group 1 with less than 10% of prostatic tissue invaded on the positive biopsy had stage P2, while all patients with 100% of the length of the biopsy invaded by tumour had stage P3. The Gleason score was accurately predicted by the positive biopsy in 39% of cases and was underestimated in 39% of cases. CONCLUSION: A single positive prostatic biopsy out of six systematic biopsies is a useful predictive factor of local extension, but, in the individual patient, does not guarantee favourable histopathological characteristics of the tumour, nor a favourable course of the disease.

Aged↗
PubMed1995

Genetic abnormalities in sporadic parathyroid adenomas: loss of heterozygosity for chromosome 3q markers flanking the calcium receptor locus.

Inactivating mutations of the parathyroid cell calcium receptor (CaR) gene cause one form of familial benign/hypocalciuric hypercalcemia, and in homozygous form, cause neonatal severe primary hyperparathyroidism with parathyroid hyperplasia. Thus, we postulated that partial or total loss of CaR function might contribute to calcium insensitivity or even stimulate cell proliferation in sporadic parathyroid adenomas (PAds). To examine this possibility, we sought loss of heterozygosity (LOH) for markers flanking the CaR locus (3cen-3q21) in 35 PAds. We used 16 highly-polymorphic PCR-based markers in paired normal and tumor DNA, extracted from slices of archived surgical specimens. Nineteen to 24 of the DNA pairs were informative with at least one marker. In two informative pairs, we found LOH for markers D3S1303, D3S1267, or D3S1269, which are tightly-linked with and flank the CaR locus. In one tumor, deletion mapping confined the lost area between D3S1271 and D3S1238 (41.7 centimorgans, cM). In the other tumor, LOH spanned most of chromosome 3, ranging at least from D3S1307 to D3S1311 (271.4 cM). LOH was confirmed by repetition of the experiments and quantified by phosphorimaging. Thus, we found LOH encompassing the CaR locus in approximately 10% of sporadic PAds. These data are consistent with the hypothesis that loss of CaR function may occur in PAds, with functional consequences for calcium sensitivity and cell proliferation.

Adenoma↗
PubMed1993

Effect of nutrients on plasma corticosteroid concentration in cold-stressed rats.

Little is known about the mechanisms as to how nutrients affect plasma corticosteroids in cold-stressed and starved animals. Therefore, cold-stressed rats (maintained at 7 degrees C) were fasted (control) or fed a balanced diet (casein 20 wt%, fat 5 wt%, starch 70 wt% and vitamin-mineral premix 5 wt%) or the following dietary nutrients for 72 h: casein, lard, starch, glycerol, stearic acid, leucine or glutamic acid. The animals were then killed and plasma corticosteroid concentrations (PCC) were determined. PCC were significantly reduced (p < 0.05) in cold-stressed animals fed a balanced diet (16.95 micrograms/100 ml plasma) compared to the fasted cold-stressed controls (FCSC) (24.16 micrograms/100 ml plasma). Additionally, corticosteroid concentrations (micrograms/100 ml plasma) of animals fed the following specific nutrients were also significantly lower than the FCSC values: starch (15.53), lard (12.01), stearic acid (12.74), glycerol (13.32) and leucine (16.03). Casein and glutamic acid did not significantly alter plasma corticosteroid levels relative to the FCSC concentration. It is concluded that certain specific building blocks of nutrient classes, i.e. stearic acid or glycerol, can alter PCC to the same extent as the parent compound (lard), however the individual components of casein, a complex nutrient, i.e. leucine, a ketogenic amino acid, versus glutamic acid, a glycogenic amino acid, may elicit a different PCC effect.

Adrenal Cortex Hormones↗
PubMed1993

Do heat shock proteins play a role in Graves' disease? Heat shock protein-specific T-cells from Graves' disease thyroids do not recognize thyroid epithelial cells.

Thyroid-derived T-cells from patients with Graves' disease were analyzed for their reactivity to recombinant heat shock proteins (hsp) and autologous thyroid epithelial cells (TEC). Five of six uncloned T-cell lines responded to stimulation with recombinant mycobacterial 71-kilodalton (kDa) hsp and cross-reacted with the corresponding amoebial and human proteins. Only one line reacted with recombinant 65-kDa hsp. Thyroid-derived T-cell lines also showed a proliferative response to TEC, which could be increased in four of the lines, when hsp expression was induced in thyroid cells by heat stress before the initiation of coculture. Clonal specificity analysis of thyroid-derived T-cell clones, however, demonstrated that distinct T-cells were responsible for the recognition of recombinant hsp and TEC. None of the clones responsive to recombinant hsp recognized TEC, whereas TEC-responsive clones did not react with recombinant hsp. Interestingly, the response of the majority of TEC-reactive clones could be dramatically increased when heat-shocked TEC were used as stimulator cells. These results suggest that T-cells specific for hsp of the 70- or 60-kDa families do not recognize TEC in the autoimmune thyroid gland. Heat shock-inducible proteins may, however, still play a role in the autoimmune process by facilitating the presentation of thyroid-specific autoantigen(s) to autoreactive T-cells.

Adult↗
PubMed1993

[Surgical cure of anomalies of the pyelo-ureteral junction with posterior vertical lumbar excision: report of 25 cases].

Posterior vertical lumbar (PVL) incision does not involve any muscle or nerve section. It is minimally painful, does not give rise to incisional hernias and reduces the hospital stay. Pyeloplasty for cure of the ureteropelvic junction (UPJ) is a good indication, as this incision provides access to the renal pelvis without renal mobilisation and without interference by the vascular pedicle and allows a more superficial operative field. This retrospective study is based on 25 PVL incisions performed between 1979 and 1992 in 24 patients (15 females and 6 males with a mean age of 31.8 years) on the left kidney in 11 cases, right kidney in 12 cases and bilaterally in 1 case. No intraoperative complications were observed. The anastomosis was stented with a Gil-Vernet ureteronephrostomy tube for an average of eight days in every case. Early complications (< or = 1 month) consisted of six cases of fever, one wound abscess and one urinary fistula. Normal feeding was always rapidly restored. Long-term follow-up did not reveal any incisional hernias, but two cases of recurrence (8%), two cases of stones and one case (4%) of refractory neuralgia (> or = 6 months) in the territory of the ilioinguinal nerve. In this indication, there is no gain in terms of hospital stay due to the need to maintain the ureteronephrostomy tube for at least five days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Human IL-3 induction of c-jun in normal monocytes is independent of tyrosine kinase and involves protein kinase C.

We have used normal human monocytes as a model system to begin elucidating the signal transduction mechanism associated with the IL-3R. Normal human monocytes deprived of human serum and CSF become quiescent in vitro. Stimulation of these cells with rIL-3 induces expression of the c-jun protooncogene, as detected by Northern blotting of total monocyte RNA. This protooncogene is also induced in these cells by phorbol ester through direct stimulation of protein kinase C. Concentrations of the protein kinase C inhibitor I-(5-isoquindinyl-sulfonyl)-2 methylpiperazine (H-7) between 30 and 100 microM (5-20 x Ki) inhibit this induction by phorbol ester. The same concentration-range of H-7 completely inhibited the induction of c-jun by human IL-3. A structural analog of H-7 designated HA-1004 preferentially inhibits cyclic nucleotide-dependent protein kinase rather that protein kinase C. HA-1004 at 5 to 20 x Ki did not inhibit IL-3-induced c-jun mRNA accumulation. Further 30 microM genistein that is an effective inhibitor of cellular tyrosine kinases did not inhibit IL-3-induced c-jun expression. Immunoprecipitation of lysates from [32P]orthophosphate labeled cells with antiphosphotyrosine polyclonal antibody showed that IL-3-stimulated phosphorylation of a 70-kDa protein and a 110-kDa protein on tyrosine, and that these protein phosphorylations were completely inhibited by 30 microM genistein. As further confirmation that IL-3 is stimulating protein kinase C in human monocytes we have found that IL-3 stimulates phosphorylation of the unique protein kinase C substrate myristoylated alanine-rich C kinase substrate in these cells. It is therefore likely that the interaction of IL-3 with its receptor generates diacylglycerol and stimulates the Ca2+/phospholipid-dependent protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Sera but not immunoglobulins of ophthalmic Graves' patients stimulate human embryonal fibroblasts' biosynthetic activity in culture.

The retroocular connective tissue changes in the ophthalmopathy of Graves' disease are known, however, the mechanism which leads to the increase in fibroblast number and activity is poorly understood. Using human embryonal fibroblast monolayers, fibroblast biosynthetic activity in the presence of sera, immunoglobulin deprived sera or immunoglobulins of Graves' patients with and without ophthalmopathy has been measured. Both sera and immunoglobulin deprived sera of the ophthalmic Graves' patients caused a marked increase of protein synthesis and a moderate increase of the sulphated glycosaminoglycan synthesis of fibroblasts. The same stimulatory effect was not found when immunoglobulin in fetal calf serum was used instead of sera, though anti-fibroblast IgG-s were present both in the sera and separated immunoglobulin fractions, as it has been demonstrated in an ELISA system. We conclude that the sera of ophthalmic Graves' patients contains a factor which stimulates human embryonal fibroblasts' biosynthetic activity in culture; this factor is not an immunoglobulin. The system described here seems to be suitable for studying the accompanying connective tissue changes in Graves' disease.

Cells, Cultured↗
PubMed1991

Metabolism of narasin in chickens and Japanese quail.

Thirty mature chicken hens and 60 mature Japanese quail hens were used to compare pathways of narasin excretion. Carbon-14-labeled narasin was injected into chickens (.7 microCi) and quail (.113 microCi) via cardiac puncture. Blood, sampled at varying times thereafter, and eggs and excreta collected daily for 28 days, were analyzed for 14C. Groups of six chickens and 12 quail were killed prior to [14C]narasin injection and on Days 1, 7, 14, and 28 postinjection to obtain tissue samples for 14C analysis. Blood rapidly cleared the label in both species. Less than 1% of the dose of [14C]narasin remained in blood plasma after 3 h postinjection in both chickens and quail. Label excretion peaked on Day 1 in both species, and most of the 14C was cleared via the excreta (76.7 and 93.6% of the dose for quail and chickens, respectively). Label appeared in the excreta more rapidly and cleared more quickly in quail than in chickens. After 24 h, 68 and 49% of the dose of [14C]narasin appeared in the excreta of quail and chickens, respectively. More label was recovered in the eggs of quail (4.18% of the dose) than in the eggs of chickens (1.32% of the dose). Liver, heart, fat, and ovarian tissues contained traces of radioactivity 1 day postinjection in both species. Muscle and kidney did not contain detectable amounts of label. By Day 7, all tissue had cleared 14C beyond detectable limits. The results indicate that chickens and quail metabolize [14C]narasin via similar pathways and that excretion in quail may be more rapid than in chickens.

Adipose Tissue↗
PubMed1990

Lymphangioscintigraphy in AIDS-associated Kaposi sarcoma.

Kaposi sarcoma, a common opportunistic neoplasm complicating AIDS, is thought to arise from the vasculature and possibly from lymphatic endothelium. To evaluate the nature and extent of lymphatic involvement in AIDS-associated Kaposi sarcoma, we used an improved technique of whole-body lymphangioscintigraphy. Six human-immunodeficiency-virus-seropositive men (40-51 years old) with AIDS and extensive Kaposi sarcoma had bilateral foot and/or hand intradermal injection of 0.05 ml of 99mTc-labeled human serum albumin (500 microCi, 18.5 MBq). After sequential whole-body scanning with a digital gamma camera, the findings were interpreted by comparing them with findings from similar studies in 30 other patients without AIDS or Kaposi sarcoma (26 with primary or secondary lymphedema and four with normal extremities). Unlike in normal limbs, where lymphangioscintigraphy displayed early lymphatic truncal and regional nodal filling with radionuclide, in patients with Kaposi sarcoma, lymphangioscintigraphy disclosed a variety of abnormal patterns with some features distinct and others resembling lymphatic dysplasia as seen in primary and secondary lymphedema. These included focal accumulation of tracer within lymphatic channels in the distribution of cutaneous Kaposi lesions; delayed tracer transport with absent, faint, or intense regional lymph nodal uptake; and retarded or impeded lymphatic drainage with tracer intensification in the region of Kaposi sarcoma plaques. The impaired lymphatic drainage and nodal dysfunction seen on scintigrams in patients with AIDS-associated Kaposi sarcoma suggest a close connection between the lymphatic system and this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Alteration of lymphocyte reactivity in pregnant women treated with the progesterone receptor inhibitor ZK 98734.

Thirteen women during the 5th and 6th weeks of gestation were treated with a progesterone receptor blocker (ZK 98734) for pregnancy termination. Five patients received 100 mg/day of the compound, and eight patients received 50 mg/day for 4 days. Daily blood samples were obtained during the treatment period as well as on days 8 and 15 after the beginning of drug administration, and cytotoxic activity, progesterone sensitivity, and progesterone binding capacity of the lymphocytes were determined. Determination of SP-1 concentrations monitored the saturation state of trophoblastic progesterone receptors. High and low responders to the progesterone antagonist were identified. Lymphocytes of high responders treated with the 100 mg/day dose demonstrated a rapid increase of cytotoxicity, with a concomitant fall in progesterone sensitivity and progesterone binding capacity. Vaginal bleeding began as early as the 2nd day of treatment, and pregnancy was terminated by the 8th day of the treatment. Low responders receiving 100 mg/day demonstrated similar but attenuated changes. Low responders did not bleed during the first 4 days of treatment, and termination of pregnancy occurred later compared to high responders. Lymphocytes of high responders treated with 50 mg/day behaved similarly to those obtained from the low responders treated with 100 mg/day, and abortion was not completed before the 25th day after the beginning of the treatment. Lymphocytes function of low responders treated with 50 mg/day did not change significantly, the SP-1 concentration did not decline, and pregnancies continued. We conclude that a difference in sensitivity to the progesterone receptor blocker explains the selective block at trophoblastic binding sites only and the inability to block those in the lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents↗
PubMed1989

Detection of cells producing anti-idiotypic antibody to thyroid stimulating hormone-reactive antibodies.

BALB/c mice were immunized either with bovine (b) or human (h) thyroid stimulating hormone (TSH) or with one of several mouse monoclonal anti-hTSH antibodies. The binding of biotinylated mouse monoclonal anti-hTSH to sections of spleen, kidney, liver and lung was assessed with fluorescein isothiocyanate labelled avidin. Clusters of cells in the spleens of mice immunized with bTSH bound the labelled monoclonal anti-TSH. We suggest that these cells synthesized auto-anti-idiotypic antibodies to anti-TSH.

Animals↗
PubMed1989

Effect of malabsorption syndrome on pancreatic function in broilers.

The effect of "malabsorption syndrome" on pancreatic function was studied in newly hatched broiler chicks orally inoculated during the first few hours of life with intestinal homogenates from birds with naturally occurring malabsorption syndrome. The control groups were treated with saline. Tissue samples were collected at 0, 2, 4, 6, 9, 13, 17, and 29 days of age from both groups. The BW of inoculated birds decreased significantly relative to that of controls as early as 9 days of age. Pancreatic amylase activity was significantly greater than that in controls by 2 days. Protease activity of inoculated birds increased significantly over that in controls on the 2nd day and decreased significantly on the 6th and 9th days. Reoviruses were detected in the fecal samples of inoculated birds on the 2nd and 3rd days and did not appear in control samples. Reoviruses were also isolated from the pancreatic tissue of two inoculated birds on the 3rd day. Symptoms characteristic of malabsorption syndrome may be elicited by maldigestion; in the present study, this probably resulted from reduced digestive enzyme production of the pancreas. Similarities of changes in plasma triiodothyronine and pancreatic protease levels suggested a possible relationship between thyroid and pancreatic dysfunction in the condition of the malabsorption syndrome.

Amylases↗
PubMed1988

New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice.

"Reverse" analogues (RAD's) of actinomycin D (AMD) and their antitumor activity against mouse and human colon tumor cells are reported. RAD's are tetracyclic, and they have an oxazole ring fused on the tricyclic phenoxazine chromophore of AMD. The oxazole ring in RAD is substituted at the C-2 carbon with either a CH3 (in RAD I), a C6H5 (in RAD II), or a CH2CONH(CH2)4NH2 (in RAD III) group. In tumor cells and rat hepatic microsomes, RAD's are metabolized to a tricyclic "symmetrical" analogue of AMD (SAD) with the loss of the oxazole ring and its substituents. RAD and SAD are very active in priming superoxides in the presence of microsomal enzymes as well as in inhibiting the synthesis of DNA and the growth of human colon tumor HT-29 cells in vitro. RAD III and SAD efficiently cleave closed circular plasmid pBR322 DNA like the antitumor agent bleomycin. In addition to their strong inhibitory activity against P388 and B16 tumors in vitro and in vivo, RAD III and SAD demonstrate high levels of activity against primary C26 and advanced C38 colon tumors in mice and against a xenograft of human colon adenocarcinoma CX-1 in athymic mice. In all these biological activities, the analogues demonstrate superiority to AMD in several experimental tumors. Also, the analogues, in contrast to AMD, show reduced toxicity in tumor-free mice, which is possibly due to the metabolic deactivation of SAD in host organs.

Animals↗
PubMed1988

Comparative drug depletion in domestic animals and birds.

Decoquinate (Rhone-Poulenc Inc) and Narasin (Eli Lilly and Co) were selected as model drugs for a comparison of metabolism between major (cattle and chickens) and minor (sheep and quail) species. Decoquinate has been studied in all four species. Narasin studies are in progress in chickens and quail. More than 96% of injected 14C-decoquinate (DQ) was eliminated from blood of all species within 1 hr. Disappearance of the remaining 1 to 4% from blood was rapid for all species. Half-times for DQ appearance in excreta were all less than one day. Cumulative excretion of DQ in eggs of chickens and quail was about 1% for both species. Disappearance of DQ from tissues was essentially complete in 14 days. More than 80% of injected 14C-narasin was eliminated from blood within 1/2 hr. Disappearance of the remainder was rapid for both chickens and quail.

Animals↗