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Biomedical subjects

R Koren

Publications and source records attributed to R Koren.

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

Evaluation of mucinous metaplasia of the prostate gland by mucin histochemistry.

OBJECTIVE: To evaluate the presence of mucinous metaplasia in normal and benign hyperplastic prostates, using stains for neutral and acidic mucins. PATIENTS, MATERIALS AND METHODS: Normal prostate glands were removed during the post-mortem examination of 11 consecutive subjects (median age 45 years, range 17-79) who had died accidentally. Specimens were also obtained from 10 patients (median age 70.2, range 61-82) undergoing suprapubic prostatectomy for prostatic hyperplasia. The specimens were examined histologically; sections were stained using the periodic acid-Schiff (PAS) method for neutral mucins and the alcian blue (AB) method at pH 2.5 for acidic mucins. The positive sections were also immunostained for high molecular weight cytokeratin (KER), and prostate-specific antigen (PSA) using the strept-avidin-biotin (SAB) method. RESULTS: Mucinous metaplasia was found in six of the normal prostates and in three of the hyperplastic glands. Usually, the cells were tall columnar, containing both AB- and PAS-positive material. The cells were negative both for PSA and KER. Mucinous metaplasia affected all ages, including a 17-year-old, and mostly involved the inferior periurethral area. CONCLUSION: Benign mucinous metaplasia was more frequent than previously appreciated, involved all ages, was mainly periurethral and did not correlate with the usual distribution of adenocarcinoma of the prostate.

Adenocarcinoma, Mucinous↗
PubMed1996

Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report.

A new vaccine against hepatitis B virus (HBV) infection, produced in mammalian Chinese hamster ovary (CHO) cells, contains the small(s), middle (Pre S2) and large (Pre S1) surface proteins of HBV. Three injections of a 5-micrograms or 10-micrograms dose were administered intramuscularly (i.m.) at 0, 1 and 6 months to a group of 105 young adults, who were monitored for a period of 6 months after the third injection. Seroconversion rates were 100% after the second injection of the 5-micrograms or 10-micrograms dose. Geometric mean titres of HBsAb at 1 month after the third injection were 12,156 mIU ml-1 and 13,482 mIU ml-1 in those receiving the 5-micrograms and 10-micrograms dose respectively. The vaccine was well tolerated with no significant adverse events. These preliminary results suggest that the Pre S-s recombinant vaccine, produced in mammalian cells, is highly immunogenic, leading to 100% seroconversion in the population tested after injection of only two doses of 5 micrograms.

Adolescent↗
PubMed1996

Correlation between tumour and serum beta 2m expression in patients with breast cancer.

HLA class I antigens are composed of a major histocompatibility complex (MHC) encoded heavy chain that is associated non-covalently with a light chain beta-2 microglobulin (beta-2m). When the HLA complex is metabolized, beta-2m is shed into the serum. A large variety of human and experimental tumours have altered MHC class I expression. In a previous study we observed elevated mean beta-2m serum levels in breast cancer patients, as compared to controls. To study the relationship between tumour expression and serum levels, we examined 54 patients with breast cancer. Tumour beta-2m was determined by immunohistochemistry and serum levels by the ELISA technique. Of the 54 patients, 38 had low and 16 had high beta-2m expression on the tumour. There was a significant correlation between tumour beta-2m and serum beta-2m levels (P = 0.02), with patients whose tumours expressed high beta-2m having high serum beta-2m levels. There was an inverse correlation between tumour grade and tumour beta-2m expression which approached statistical significance (P = 0.06). These findings suggest that in a substantial number of patients the high serum levels derive from shedding of beta-2m from tumour cells. These levels may have implications for tumour growth and metastases due to influences on immunological responses.

Adult↗
PubMed1996

1,25-dihydroxyvitamin D3 increases the sensitivity of human renal carcinoma cells to tumor necrosis factor alpha but not to interferon alpha or lymphokine-activated killer cells.

Renal cell carcinoma is a chemotherapy-resistant tumor which is relatively responsive to immunotherapy. Immunotherapeutic regimes employ interferons or interleukin 2 with or without lymphokine-activated killer cells. Secondary cytokines, induced by interleukin 2 or interferon, may have an important impact on their anti-neoplastic activity. Notable among them is tumor necrosis factor (TNF alpha). We assessed the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the susceptibility of the human renal cell carcinoma cell line SK-RC-29 to the cytotoxic and cytostatic actions of TNF alpha, interferon alpha and lymphokine-activated killer cells. Using uptake of the vital dye neutral red as an indicator of viable cell number, we found that addition of 1,25(OH)2D3 (100 nM) to TNF alpha (30 ng/ml)-treated cultures resulted in a 2.6 +/- 0.2-fold (mean +/- S.E.) increase in the cytotoxic effect of the cytokine. The potentiating effect of 1,25(OH)2D3 was dose-dependent, and significant at concentrations equal to or higher than 10 nM. Another dihydroxylated vitamin D metabolite, 24,25(OH)2D3, had no effect on TNF alpha action. The cytotoxic effect of TNF alpha increased whereas the potentiation by 1,25(OH)2D3 decreased with cell density in culture. 1,25(OH)2D3, in contrast to its potentiating effect on TNF alpha action, did not modulate the cytostatic effect of interferon alpha or the susceptibility of SK-RC-29 to killing by lymphokine-activated killer cells. The findings reported here may explain some of the in vivo anti-tumor activity of 1,25(OH)2D3 and provide a rationale for the employment of active vitamin D analogs during immune anti-cancer therapy.

Calcitriol↗
PubMed1996

Sodium hyaluronate as a tool in strabismus surgery in rabbits.

BACKGROUND AND OBJECTIVE: The authors tested whether coating tissue with sodium hyaluronate (Na-HA) reduced postoperative adhesions and accelerated the healing process in strabismus surgery. MATERIALS AND METHODS: The surgical technique was tested during recession and resection operations performed on 30 rabbits and was compared with the use of NaCl 0.9%. Clinical, biomicroscopic examinations were performed on postoperative days 1, 2, 7, and 30 and histopathologic examinations were performed on postoperative days 2, 7, and 30. RESULTS: Clinically, there were no statistically significant differences between the study group and the control group. Also, there were no statistically significant differences between the two groups for most of the histopathologic criteria; however, new vessel formation was smaller with Na-HA than without it. Statistical significance was defined as P < .05. CONCLUSION: The authors found no significant positive effect of Na-HA on postoperative healing in rabbits.

Animals↗
PubMed1996

Healing of the esophageal suture line: does it differ from the rest of the alimentary tract?

We investigated the healing pattern of the esophageal suture line in rats. Fifty male wistar rats were divided into experimental (n = 40) and control (n = 10) groups. The rats in the experimental group underwent esophogostomy at the abdominal esophagus, which was immediately sutured, and sacrificed 2, 4, 7 and 14 days later. Esophageal bursting pressure and hydroxyproline content were determined in both groups. The measured bursting pressures in the experimental group on days 2, 4, 7 and 14 were (mean +/- SD) 78 +/- 35, 95 +/- 12, 1,163 +/- 98 and 1,224 +/- 22 cm H2O, respectively, and 1,308 +/- 87 cm H2O in the control group (P <0.05 vs. all the experimental group values). The hydroxyproline content in the experimental group on days 2, 4, 7 and 14 were 13.9 +/- 2.1, 12.53 +/- 2.68, 15.6 +/- 0.85 and 17.75 +/- 5.65 microg/mg, respectively, and 27.88 +/- 2.5 microg/mg in the control group (P <0.05 vs. all the experimental group values). We conclude that the esophagus demonstrates the same healing pattern as the rest of the alimentary tract, but its healing seems to occur at a slower pace.

Animals↗
PubMed1996

Late solitary pancreatic metastasis from renal cell carcinoma.

A 76-year-old woman was admitted for a pancreatic mass. Twenty-one years previously she had undergone a left nephrectomy for renal cell carcinoma. A computerized tomography-guided needle biopsy of the pancreatic mass raised the suspicion of metastatic renal cell carcinoma. Final pathologic examination of the resected mass after distal subtotal pancreatectomy confirmed the preoperative diagnosis of metastatic renal cell carcinoma.

Aged↗
PubMed1995

Acid mucin and high molecular weight cytokeratin in prostatic lesions: evaluation of a combined histochemical and immunohistochemical stain.

OBJECTIVE: To evaluate the presence of acid mucins and high molecular weight cytokeratin (KER) in prostatic lesions using a combined histochemical and immunohistochemical stain consisting of Alcian blue at pH 2.5(AB) with a strept-avidin-biotin complex (SAB) staining for KER (SAB-KER). MATERIALS AND METHODS: Sections were obtained from archival paraffin blocks which included 20 cases of prostatic carcinoma, 30 cases of benign hyperplasia, and five cases of basal cell hyperplasia. Sections were stained for mucosubstances using the AB stain, for KER using SAB-KER and by both AB and SAB-KER, the combined stain (CS). RESULTS: With the CS stain KER, which is present in the prostatic basal cells, was not detected in malignant glands and in 60% of these cases intraluminal blue-stained acidic mucin was seen. On the other hand, all benign hyperplastic prostatic glands were devoid of intraluminal acidic mucin and showed staining for KER of their basal cells. Areas of basal cell hyperplasia were strongly positive for KER and intraluminal acidic mucin was seen in one case. Each of the stains separately gave similar results to the CS method but the contrast between the areas of carcinoma and hyperplasia was accentuated by the CS, and small foci of carcinoma were easily detected. CONCLUSION: The combined AB+SAB-KER stain is quicker to perform and allows the simultaneous appraisal of acid mucin and KER.

Avidin↗
PubMed1994

1,25-Dihydroxyvitamin D3 potentiates the cytotoxic effect of TNF on human breast cancer cells.

We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the cytotoxic action of TNF on MCF-7 human breast cancer cells and on adult bovine aortic endothelial cells. 1,25(OH)2D3 increased the effect of TNF on MCF-7 cells but not on endothelial cells over a wide TNF concentration range. At a suboptimal concentration (1 ng/ml) the potentiation was twofold. The effect of 1,25(OH)2D3 was specific, dose-dependent and apparent at a physiological concentration (0.1 nM) of the hormone. The potentiating effect of 1,25(OH)2D3 on TNF action was abolished by cycloheximide indicating that their interaction requires protein synthesis. Addition of 1,25(OH)2D3 13 h after TNF in a 28-h assay was sufficient to induce its full potentiating effect indicating that the hormone modulates a late event in the cytokine's action. These data suggest that some of the in vivo antitumor effects of 1,25(OH)2D3 may be due to an increase in the anticancer activity of the immune system.

Animals↗
PubMed1994

Age as a determinant of the impact of growth hormone therapy on predicted adult height.

OBJECTIVE: Final adult height is determined by both childhood and pubertal growth. The later is a function of growth velocity and bone maturation, and both are regulated by growth hormone. In a study of the safety and efficacy of GH therapy, we analysed the impact of age on bone maturation and predicted adult height. PATIENTS AND METHODS: The subjects were 65 male patients with GH deficiency, as diagnosed by pharmacological or physiological tests, who participated in a multicentre trial and completed 3 years of hGH therapy. The age range at initiation of therapy was 3.1-15.7 years. Subcutaneous injections of hGH were given in a dose of 0.3 mg/kg/week, in thrice-weekly doses. Calculation of the adult height prediction was performed on annual growth parameters using the Bailey-Pinneau, TW-II and Roche methods. RESULTS: The rate of pubertal advancement correlated positively with the child's age at initiation of therapy. The bone age advanced in positive correlation with chronological age, and by the end of 3 years of hGH therapy the delta-bone age/delta-chronological age ratio increased to 1.5 for children with an age at start of therapy of 10.7 years. During the adolescent years, the predicted gained height over 3 years of therapy declined, in correlation with age, and became negative at a therapy-initiation age of 12.9 years. CONCLUSIONS: In a retrospective analysis of a group of children with heterogeneous GH secretory ability, GH induced acceleration of growth, around the age of normal puberty, advanced the age of pubertal onset and accelerated pubertal progression which, in turn, expedited bone maturation and thereby restricted predicted adult height gain from hGH therapy.

Adolescent↗
PubMed1994

1,25-Dihydroxyvitamin D3 increases the cellular content of the calcium-activated neutral protease mu-calpain in renal cell carcinoma.

mu-Calpain is a calcium-dependent neutral thiol protease activated by micromolar concentrations of calcium. mu-Calpain is implicated in various cellular functions regulated by calcium including exocytosis, cell fusion, apoptosis and control of cell proliferation. We studied the effect of 1,25-(OH)2D3 on mu-calpain levels in the human renal cell carcinoma line SK-RC-29 using monoclonal antibodies to the 80 kDa subunit of mu-calpain. Exposure of low density cultures (15000 cells/cm2) to 1,25-(OH)2D3 (100nM) for 48 hours resulted in 1.5-3 fold increase of mu-calpain cell content. The effect was not observed in higher density cultures (40000 cells/cm2). mu-Calpain content of high density cultures was higher than that of low density cultures and similar to that in low density cultures treated by 1,25-(OH)2D3. The cellular content of two other calcium binding proteins, annexin II and annexin VI was not affected by the hormone. 1,25-(OH)2D3 did not affect cell number or viability therefore its effect on mu-calpain is not secondary to changes in cell density. The effect of 1,25-(OH)2D3 was dose-dependent apparent already at 1nM and was not observed with 24,25-(OH)2D3. Increase in mu-calpain content may underlie some of the actions of 1,25-(OH)2D3 on classical and non classical target cells.

Calcitriol↗
PubMed1994

Effect of long-term growth hormone therapy on bone age and pubertal maturation in boys with and without classic growth hormone deficiency.

We evaluated the effect of growth hormone (GH) therapy on bone age, pubertal maturation and predicted adult height in two groups of boys treated for 4 years: 40 growth hormone-deficient boys who had growth hormone response to provocative stimulation < 10 micrograms/L (GHD group) and 43 boys whose stimulated growth hormone > or = 10 micrograms/L (group with neurosecretory dysfunction (NSD)). All patients had a subnormal integrated concentration of growth hormone < or = 3.2 micrograms/L, height < -2 SD, growth velocity < 4.5 cm/yr, and bone age < or = -2 SD for chronologic age. Patients were treated with recombinant growth hormone, 0.1 mg/kg per dose given three times a week. The pretreatment height SD of the GHD group (-3.6 +/- 1.0) was less than that of the NSD group (-2.7 +/- 0.7; p < 0.001). After 4 years of therapy, both groups had catch-up growth (GHD group to -2.0 +/- 1.3 height SD (n = 35), and NSD group to -1.4 +/- 0.7 height SD (n = 32)); the rate of height SD gain was better in patients with GHD (p < 0.01). The response to growth hormone was inversely related to pretreatment chronologic age (p < 0.001). The Tanner-Whitehouse II predicted adult height improved for both groups: +9.3 +/- 7.7 cm in the GHD group, giving an adult height SD of -0.9 +/- 1.0, and +5.4 +/- 5.5 cm in patients with NSD, for an adult height SD if -0.8 +/- 0.7. Testosterone levels became higher in the NSD group after 2 years and remained higher at year 4. We conclude that patients respond favorably to growth hormone therapy and in a manner similar to patients with GHD. Initiation of therapy at a younger age gives a greater improvement in gained height and predicted adult height.

Age Determination by Skeleton↗
PubMed1993

Foreign body granulomatous inflammation increases the sensitivity of splenocytes to immunomodulation by 1,25-dihydroxyvitamin D3.

1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, partially inhibits antigen and mitogen-driven lymphocyte stimulation. We studied the effect of granulomatous inflammation on the sensitivity of lymphocytes to 1,25-dihydroxyvitamin D3 in vitro, measuring the inhibitory effect of 1,25-dihydroxyvitamin D3 on mitogenesis of splenocytes of mice with chronic inflammation induced by subcutaneous injection of talc. Systemic manifestations of the local inflammation included loss in body weight, splenomegaly, enhanced DNA synthesis by freshly isolated splenocytes and enhanced prostaglandin secretion by activated splenocytes. Splenocytes from animals with local inflammation were more susceptible to inhibition by 1,25-dihydroxyvitamin D3, but not by prostaglandin E2. This increased sensitivity to 1,25-dihydroxyvitamin D3 was abolished by blocking prostaglandin synthesis in splenocyte cultures with indomethacin and was restored by adding prostaglandin E2. This effect cannot be attributed to enhanced prostaglandin synthesis in the presence of 1,25-dihydroxyvitamin D3, but is probably due to a qualitative change in the response of splenocytes from inflamed animals to the combined action of 1,25-dihydroxyvitamin D3 and prostaglandin E2.

Adjuvants, Immunologic↗
PubMed1993

1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer cells.

The effect of 1,25-dihydroxyvitamin D3 on lymphokine-activated killer (LAK) cells activity was studied. Treatment of LAK cells with 1,25-dihydroxyvitamin D3 for 24 h increased their cytotoxic activity without affecting cell proliferation. This effect was dose-dependent, detectable already at 10(-11) M attaining 44 +/- 7% increase at 10(-8) M. 1,25-dihydroxyvitamin D3 increased LAK cell content of the cytotoxic granule granzyme A by 21%. Secretion of granzyme A by LAK cells was triggered by 12-O-tetradecanoylphorbol 13-acetate and the calcium ionophore A23187. 1,25-dihydroxyvitamin D3 decreased the lag preceding secretion, increased the rate constant of exocytosis and the fraction of granzyme A cell content secreted. The potentiation of exocytosis was more pronounced at suboptimal calcium ionophore concentration suggesting that 1,25-dihydroxyvitamin D3 affects a calcium-dependent process. Since exocytosis of cytotoxic granules is a pivotal event in the killing of tumor cells by LAK cells, it is plausible that the enhancement of this process underlies the stimulation of LAK cell cytotoxic activity by 1,25-dihydroxyvitamin D3.

Analysis of Variance↗
PubMed1992

Stimulatory and inhibitory effects of 1,25-dihydroxyvitamin D3 on thymocyte mitogenesis induced by phorbol ester and calcium ionophore.

UNLABELLED: Mouse medullary thymocytes have specific receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The mitogenic stimulation of these cells by phytohemagglutinin in the presence or absence of the phorbol ester TPA is inhibited by 1,25(OH)2D3. The calcium ionophore A23187 did not reverse the inhibition by 1,25(OH)2D3 of phytohemagglutinin. Stimulation of thymocytes with either TPA or A23187 alone did not result in proliferation. Co-stimulation of the thymocytes with TPA and A23187 induces cell proliferation. 1,25(OH)2D3 markedly enhanced the TPA and A23187-induced cell proliferation even when added 4 h after the initiation of the culture. In contrast, DNA synthesis by thymocytes incubated for 4 h in the presence of TPA and A23187 and then cultured in medium containing 1,25(OH)2D3 but in the absence of both TPA and A23187, was inhibited by 1,25(OH)2D3. The extent of inhibition was comparable to the inhibition of lectin-induced stimulation by the hormone. Using monoclonal antibodies to neutralize IL-2 and block IL-2 receptors we showed that 1,25(OH)2D3 enhanced the IL-2-independent component of the A23187- and TPA-induced mitogenesis. IN CONCLUSION: (1) The nature and presence of the mitogenic signal determines whether 1,25(OH)2D3 enhances or inhibits thymocyte stimulation. (2) Both stimulatory and inhibitory actions of 1,25(OH)2D3 seem to take place at points distal to the initial increase in intracellular calcium or activation of protein kinase C.

Calcimycin↗
PubMed1992

Responsiveness to 1,25-dihydroxyvitamin D3 is reduced in lymphocytes from osteoporotic women.

The purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25(OH)2D3 on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins. A group of 39 postmenopausal women, at least 10 years after the menopause, participated in the study. Osteoporosis, defined as the presence of at least one nontraumatic vertebral crush fracture, was diagnosed in 19 subjects. Mitogenesis of PBM cells stimulated by phytohemagglutinin and cultured for 72 h in the presence or absence of 1,25-(OH)2D3 (0.03-1 nmol/liter) was assessed by [3H]thymidine incorporation during a 4 h pulse. The maximal inhibitory effect of 1,25-(OH)2D3 at saturating concentration (1 nM/liter) was 74.6 +/- 2.8% (mean +/- SEM) for normal compared to 65.3 +/- 2.9% for osteoporotic women (P = 0.015). The geometric mean of the ED50 values of 1,25-(OH)2D3 was 60% higher in the osteoporotic than in the normal group (P = 0.035). Our data are consistent with the notion that reduced responsiveness of target organs to 1,25-(OH)2D3 is associated with osteoporosis.

Aged↗