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Biomedical subjects

J Grosse

Publications and source records attributed to J Grosse.

At least 55 records · Page 3Linked to original sources
PubMed1995

Behavioural and cellular responses to light of the circadian system of tau mutant and wild-type Syrian hamsters.

The tau mutation shortens the free-running circadian period of the activity rhythm of the Syrian hamster from around 24 h in the wild-type, to 20 h in the homozygous mutant. The aim of this study was to examine the effects of light pulses on the activity rhythms and expression of c-fos in the suprachiasmatic nuclei of wild-type and mutant hamsters. This would make it possible to determine the relative durations of subjective day and night, and thereby characterize further the effect of the mutation upon the circadian cycle. Presentation of light pulses (15 min) to animals kept in dim red light for seven to 10 days induced phase-dependent shifts in the onset of activity. During subjective day (inactive phase) there was no effect of light upon the activity rhythm of either normal or mutant animals. Early in subjective night (i.e. after the start of the active phase), light pulses induced phase delays of approximately one circadian hour in both phenotypes. However, later in subjective night light pulses induced phase advances in activity rhythms. The magnitude of the advance phase shifts differed considerably between the two phenotypes, with the wild-types typically showing shifts of about one circadian hour, while the mutants showed much larger advances of up to 12 circadian hours. In both strains, advances were observed following light at circadian time 22 but not after light at circadian time 24. The relative duration of subjective night was therefore comparable in the mutants and wild-types i.e. around 11 circadian hours. In order to examine the light-induced expression of the immediate early gene c-fos at different circadian phases, animals received a second light pulse (15 min) or a control "dark pulse" at the same circadian time as they had received the first, but seven to 10 circadian days later. They were perfused 1 h after the start of the pulse and brains processed for the immunocytochemical detection of Fos, the protein product of c-fos. Animals receiving dark pulses showed minimal Fos immunoreactivity in the suprachiasmatic nucleus, regardless of the circadian time of presentation of the stimulus. During subjective day (circadian times 4-11), light induced very little Fos immunoreactivity. In contrast, light presented during subjective night (after circadian time 12) induced a dense pattern of Fos immunoreactivity in the ventrolateral, retino-recipient region of the suprachiasmatic nucleus of both wild-type and mutant animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Gonadal responses of the male tau mutant Syrian hamster to short-day-like programmed infusions of melatonin.

Changes in the duration of the nocturnal peak of the circadian rhythm of melatonin secretion by the pineal gland mediate pohotoperiodic control of reproductive cycles in mammals. The present study examined whether the tau mutation of the circadian clock of the Syrian hamster altered the ability of the animals to exhibit photoperiodic, gonadal responses to timed infusions of exogenous melatonin. Pinealectomized tau mutant and wild-type hamsters received s.c. infusions of vehicle or melatonin solution (50 ng/h) for either 8 h or 6.67 h (i.e., 83% of 8 h, a reduction by the same proportion as circadian period is shortened by the mutation, 20 h vs. 24 h) once every 20 h for 6 wk. Testicular weight and serum levels of LH and prolactin were measured to assess the effects of the infusions on the reproductive axis. Both genotypes exhibited significant gonadal regression to the 8 h and 6.67 h melatonin signals, versus saline controls, although in taus the magnitude of the response to 6.67 h melatonin was significantly greater and more consistent than in wild-types. Compared to saline-infused hamsters, animals that received infusions of melatonin of either duration showed significantly reduced serum levels of LH and prolactin. There was no significant difference between the two genotypes in the observed endocrine responses to melatonin infusions. These preliminary data demonstrate that tau mutant hamsters can respond to programmed systemic infusions of melatonin in a manner comparable to that observed in wild-type hamsters, and therefore, that the tau mutation of the circadian clock has not impaired the ability of the hamster to measure photoperiodic time, as represented by melatonin.

Animals↗
PubMed1995

Methohexital impairs osmoregulation. Studies in conscious and anesthetized volume-expanded dogs.

BACKGROUND: Anesthetic agents influence central regulations. This study investigated the effects of methohexital anesthesia on renal and hormonal responses to acute sodium and water loading in dogs in the absence of surgical stress. METHODS: Fourteen experiments (two in each dog) were performed in seven well-trained, chronically tracheotomized beagle dogs kept in highly standardized environmental and dietary conditions (2.5 mmol sodium and 91 ml water/kg body weight daily). Experiments lasted 3 h, while the dogs were conscious (7 experiments) or, after 1 h control, while they were anesthetized (7 experiments) with methohexital (initial dose 6.6 mg/kg body weight and maintenance infusion 0.34 mg.min-1.kg-1 body weight) over a period of 2 h. In both experiments, extracellular volume expansion was performed by intravenous infusion of a balanced isoosmolar electrolyte solution (0.5 ml.min-1.kg-1 body weight). Normal arterial blood gases were maintained by controlled mechanical ventilation. In another five dogs the same protocol was used, and vasopressin (0.05 mU.min-1.kg-1 body weight) was infused intravenously during methohexital anesthesia. RESULTS: Values are given as means. During methohexital anesthesia, mean arterial pressure decreased from 108 to 101 mmHg, and heart rate increased from 95 to 146 beats/min. Renal sodium excretion decreased; urine volume increased; and urine osmolarity decreased from 233 to 155 mosm/l, whereas plasma osmolarity increased from 301 to 312 mosm/l because of an increase in plasma sodium concentration from 148 to 154 mmol/l. Plasma renin activity, plasma aldosterone concentration, plasma atrial natriuretic peptide, and plasma antidiuretic hormone concentrations (range 1.8-2.8 pg/ml) did not change in either protocol. In the presence of exogenous vasopressin (antidiuretic hormone 3.3 pg/ml), water diuresis did not occur, and neither plasma osmolarity nor the plasma concentration of sodium changed. CONCLUSIONS: Methohexital may impair osmoregulation by inhibiting adequate pituitary antidiuretic hormone release in response to an osmotic challenge.

Aldosterone↗
PubMed1995

Lymphocyte-conditioned medium in combination with interleukin-2 effectively induces antitumour autoimmunity by adoptive transfer of short activated killer (SHAK) cells.

In this study, effective antitumour immunity was transferred by autologous short activated killer (SHAK) cells induced over four hours with lymphocyte conditioned medium (LCM) and recombinant interleukin-2 (rIL-2). Among eight patients with progressive metastatic renal cell carcinoma refractory to standard therapy, there were six objective tumour responses to SHAKs. Progression-free survival ranged from 0 to 8+ months, and overall survival ranged from 2 to 14+ months, with a median of 9+ months. Systemic toxicity of SHAKs was limited to flulike symptoms. Patient SHAKs provided a tumour-specific immunity, both cellular and humoral (expression and secretion of secondary cytokines, including IL-2, GM-CSF, INF-gamma and TNF-alpha), far superior to rIL-2 activated killer cells.

Adoptive Transfer↗
PubMed1994

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXIII: Influence of the oligoamine RE 1492 on the deformability of red blood cells.

The influence of the oligoamine RE 1492 on the deformability of Red Blood Cells (RBCs) was measured with the micropipette aspiration technique and the capillary rigidometer. The maximal cell flow resistance (MCFR) and the apparent elastic membrane shear modulus mu were increased by 45% at RE 1492 concentrations > 10 mumol/L. There was a decrease of the surface/volume ratio of 6% at RE 1492 concentrations of 25 mumol/L. The qualitative analysis of the polypeptide pattern of membranes and extracted membranes of human RBCs suggests that the reduction of deformability is due to an increased affinity of skeletal proteins to the cytosolic part of the membrane. RE 1492 caused a decrease of osmotic hemolysis by 80% at concentrations of 8 mumol/L.

Anticoagulants↗
PubMed1994

Soluble interleukin 2 receptors abrogate IL-2 induced activation of peripheral mononuclear cells.

Soluble interleukin 2 receptors (sIL-2R) exert a potential role in immunoregulation. We investigated the in vitro effects of sIL-2R on several interleukin 2 (IL-2)-dependent cellular events. Cytotoxicity of human rIL-2-stimulated PBMC against K562 and Daudi was correlated inversely to the concentration of sIL-2R in the culture medium during rIL-2 stimulation. sIL-2R concentrations higher than 4.0 pM produced a significant loss of cytotoxicity (P < 0.01). The effect of different sIL-2R concentrations added to cultured human PBMC on secondary sIL-2R production was tested by ELISA. Secondary sIL-2R production was abrogated by high initial sIL-2R dosages whereas low initial dosages were followed by a continuing production of secondary sIL-2R after five days of culture. Proliferation of the IL-2-dependent mouse cell line CTLL-2-was suppressed by sIL-2R added to the culture medium in a dose-dependent way. The neutralizing capacity of sIL-2R strongly depended on the initial number of CTLL set in per proliferation assay. In contrast, variation of rIL-2-concentration had no significant effect on reduction of proliferation by sIL-2R. Furthermore, preincubation of sIL-2R with rIL-2 did not enhance growth suppression. These last findings indicate that there is at least no functional interaction between sIL-2R and free IL-2, whereas an interaction of sIL-2R with the membrane-bound receptor for IL-2 seems possible.

Animals↗
PubMed1994

Induction of cytokines and cytotoxicity against tumor cells by Newcastle disease virus.

The use of NDV as biological adjuvant in vaccines against human cancer is still actual in several clinical treatment protocols. In this study, we have investigated in vitro-effects of Newcastle disease virus (NDV) strain 73-T on isolated mononuclear blood cells and cultured tumor cells. Cellular cytotoxicity of PBMC freshly isolated from healthy donors against tumor cells was enhanced significantly (p < 0.01) after coincubation of NDV with effector cells. NDV failed to enhance cytotoxicity of effector cells when PBMC were stimulated three days with 500 IU recombinant interleukin-2 (rIL-2) per ml prior to coincubation with the virus. No significant enhancement of cellular lysis was seen when only target cells were coincubated with NDV. As shown by depletion of various lymphocyte subsets, NK cells were the predominant mediator of lysis. Enhancement of cytotoxicity correlated with the induction of interferon-alpha (IFN-alpha) in PBMC by NDV. NDV also induced high amounts of tumor necrosis factor-alpha (TNF-alpha) in PBMC. Induction of interferon-gamma (IFN-gamma) was weak. A direct cytopathic effect (CPE) of NDV on different target cells was detected by colorimetric measurement of metabolic cell activity. The human tumor cell lines A-498, A-704, Caki-1, Caki-2, and K-562 and the fibroblast line MRC-5 showed progressive cellular destruction 48 h after infection with NDV, whereas PBMC and Daudi cells remained unaffected during the observation period. The nontransformed monkey kidney cell line CV-1 and the transformed monkey kidney cell line COS-1 were both lysed by NDV with marginal difference in time course of CPE. Our results indicate a reasonable potential of pleiotropic modifications of the immune response against tumors by NDV.

Adjuvants, Immunologic↗
PubMed1994

In vivo time and dose dependency of interleukin-6 secretion in response to low-dose subcutaneous recombinant interleukin-2.

Serum concentrations of Interleukin-6 (IL-6) were determined in renal cell carcinoma patients treated with low-dose subcutaneous human recombinant interleukin-2 (rIL-2). In all patients, administration of rIL-2 resulted in a significant increase in IL-6 serum levels to peak values within 4 to 6 hours as measured by enzyme-linked immunosorbent assays (ELISA). Repetitive administration of rIL-2 induced significantly lower IL-6 serum peaks when compared to the initial administration of rIL-2. Cumulative IL-6 release, as expressed by the area under the concentration curve (AUC), appeared to be independent of rIL-2 dose distribution (10 million IU rIL-2/m2 versus 20 million IU rIL-2/m2), and IL-6 serum peaks showed no direct dose dependency. Prior rIL-2 immunotherapy had no measurable effect on rIL-2 induced IL-6 release, while steroids resulted in a significant suppression of secondary IL-6 did not correlate with response to rIL-2 therapy or survival of rIL-2 treated renal cell carcinoma patients.

Aged↗
PubMed1993

Testicular regression in pinealectomized Syrian hamsters following infusions of melatonin delivered on non-circadian schedules.

The aims of this study were to validate the use of a timed infusion protocol for restoring physiologically appropriate rhythms of melatonin in the circulation of pinealectomized hamsters and, using such infusions, to compare the relative importance of the parameters of the nocturnal melatonin signal--frequency, phase, and duration of the interval between signals--in the photoperiodic control of testicular function in male Syrian hamsters. Hamsters were pinealectomized and fitted with a chronic s.c. cannula enabling them to receive timed infusions of melatonin (50 ng/h) or saline vehicle (50 microliters/h). In experiment 1, RIA of serum samples confirmed that s.c. infusions produced a pattern of melatonin in the blood equivalent in amplitude and duration to that observed previously in pineal-intact animals exposed to a short photoperiod. In experiment 2, we investigated the relative importance of the frequency of the melatonin signal and the duration of the interval between signals. Pinealectomized animals that received infusions of saline for 6 wk had large testes and high concentrations of LH in the serum. Animals that received a series of short-day-like infusions of melatonin of 14-h duration, separated by an interval of either 10 h or 6 h, underwent gonadal regression and had low serum concentrations of LH. Animals that received infusions of melatonin of 8-h duration, separated by intervals of 12 h, also exhibited full gonadal collapse. However, animals that received the same 8-h infusions separated by intervals of 8 h (i.e., once every 16 h) did not undergo gonadal regression and their circulating levels of LH remained high.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Non-photic phase shifting of the circadian activity rhythm of Syrian hamsters: the relative potency of arousal and melatonin.

This study investigated the relative potency of melatonin and arousal as Zeitgebers in the non-photic phase shifting of circadian rhythmicity in the adult Syrian hamster. Animals held under dim red light (DD) exhibited robust free-running rhythms of wheel-running activity. Melatonin (1 mg/kg) or ethanolic saline vehicle, delivered manually by subcutaneous injection after removing the animal from its cage, resulted in phase advances of the activity rhythm. This effect was phase dependent, injections at CT 8 and 10 being effective (CT 12 = anticipated activity onset), whereas injection at CT 2, 6, 14 and 20 did not cause a shift. There was no significant difference between the magnitude or timing of phase shifts in response to injections of saline or melatonin. To determine whether the observed shifts were related to arousal of the animals induced by handling, a second group held under DD were fitted with chronic s.c. cannulae so that melatonin solution or vehicle could be delivered remotely at projected CT 10. Neither solution had any effect upon the free-running rhythm. However, when these animals received manual s.c. injection of saline or melatonin solution, they exhibited phase advances similar to those observed in Expt. 1. These results fail to support the hypothesis that melatonin can exert a chemically specific, acute phase-shifting action in the adult Syrian hamster. They do, however, demonstrate the potent effect of arousing stimuli upon the circadian clock in this species.

Animals↗
PubMed1992

Pretreatment natural killer antigen density correlates to clinical response in tumor patients receiving long-term subcutaneous recombinant interleukin-2 and recombinant interferon-alpha.

We evaluated density of the natural killer (NK) cell-associated CD56 antigen on circulating NK cells of 47 patients with advanced renal cell carcinoma. Patients received a combination of low-dose subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as home therapy. Antigen density of CD56 before therapy was 2.2-fold higher (P < 0.005) in patients who subsequently achieved a complete or partial remission when compared with patients who presented with progressive disease on therapy. After a 6-week treatment cycle, NK cells of treatment responders expressed significantly (2.1-fold; P < 0.005) more CD56 antigens than NK cells in nonresponding patients. These results suggested a potential role of both pre- and posttreatment NK antigen density levels as a biologic correlate to treatment response.

Antigens, CD↗
PubMed1990

[A uterine rupture during peridural anesthesia].

A 31 years old multiparous woman was delivered by caesarean section at her first pregnancy. For her third, spontaneous, full-term labour an epidural analgesia was realized with 0.125% epinephrined bupivacaine and fentanyl (1 mg per kg). In spite of its initial efficacy, pains appeared only localized at the caesarean scar. An uterine rupture was suspected, due probably to the use of oxytocin. The operating room was immediately prepared for an emergency caesarean section. As none other pejorative clinical manifestation was present, vaginal delivery was pursued and an healthy boy was taken out after application of forceps. The uterine revision and the secondary laparotomy, performed under epidural anesthesia, confirmed an uterine break, not very wide. The end result was satisfactory both for the mother and the child. The use of epidural analgesia and oxytocin are discussed from the literature and the clinical facts. The absence of internal tocography is an arguable point in this case report.

Adult↗
PubMedDate not supplied

Immunocytochemical detection of P-glycoprotein: initial expression correlates with survival in renal cell carcinoma patients.

We evaluated 28 patients with advanced renal cell carcinoma for the initial expression of P-glycoprotein (MDR1 gene product) employing immunocytochemistry. Tumor specimens were obtained upon primary tumor nephrectomy. In all patients, progression-free survival time following nephrectomy was evaluated and correlated statistically with the staining results. Progression-free survival of patients with no or very few (< 1%) P-glycoprotein-positive tumor cells (n = 8, median survival 27.0 months) was significantly extended (p < 0.04) as compared to patients with 1% or more P-glycoprotein-positive tumor cells (n = 20, median survival 4.0 months). Correlations with histopathological tumor characteristics were insignificant. These results suggest a potential role for P-glycoprotein as a biologic parameter predictive of tumor progression in renal cell carcinoma patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Platelet endothelial cell adhesion molecule-1 (PECAM-1): a potential prognostic marker involved in leukocyte infiltration of renal cell carcinoma.

We investigated immunohistochemically the leukocyte infiltrate [CD3, CD4, CD8, CD11a, CD11b, CD14, CD56, VLA-4 and platelet endothelial cell adhesion molecule-1 (PECAM-1)] and the endothelial expression of cell adhesion molecules (PECAM-1, VCAM-1, ICAM-1 and ICAM-2) in 23 renal cell carcinoma tumor tissues. Tumors with a moderate or high density of PECAM-1 positive endothelia showed a stronger infiltration with PECAM-1-positive leukocytes as compared to tumors with a low density of positive endothelia (p<0.0085). Additionally, overall survival of patients who presented with tumors exhibiting a moderate or high density of PECAM-1 endothelia alone or in combination with a PECAM-1-positive infiltrate was extended (median survival: 23.5 months) as compared to patients without these tumor characteristics (median survival: 6.5 months). These results suggest an involvement of PECAM-1 in the process of leukocyte migration and a potential role as a prognostic marker in renal cell carcinoma.

Adult↗
PubMedDate not supplied

Altered expression of beta 1 integrins in renal carcinoma cell lines exposed to vinblastine.

BACKGROUND: Cellular expression of P-glycoprotein (P-gp) which mediates a well characterized mechanism of multidrug resistance (MDR) has been reported previously to be associated with an enhanced tumor dissemination. Since adhesion receptors of the beta 1 integrin family play a substantial role in tumor spread, we studied expression of VLA-1 to -6 in a total of four renal carcinoma cell (RCC) lines prior to and after induction of MDR via exposure to vinblastine. MATERIAL AND METHODS: Surface expression of P-gp and VLA-1 to -6 was determined immunocytochemically in untreated pre-established renal carcinoma cell lines (Caki-1, Caki-2, A498) and a cell line derived from a RCC patient who had received a vinblastine-containing therapy regimen prior to the resection of a local relapse of the tumor (EH). Resistant sublines were cultivated in the presence of 1 ng/ml and 10 ng/ml of vinblastine sulfate, respectively. RESULTS: In all cell lines examined, an increased number of P-gp expressing cells was observed upon exposure to vinblastine. Significant changes of beta 1 integrin expression were observed in three of four RCC cell lines. A de novo expression of VLA-1, VLA-2, and VLA-4 as detected by immunocytochemistry occurred in resistant Caki-1 cells. A498 cells showed an increasing number of VLA-2 positive cells in drug resistant sublines. In contrast, a decrease of VLA-2 and VLA-5 expression was found in EH cells, the only cell line exhibiting P-gp expression prior to vinblastine exposure. Caki-2 cells showed no significant changes of surface integrin expression upon treatment with vinblastine. CONCLUSIONS: Our results demonstrate that induction of drug resistance can be associated with substantial changes of the integrin phenotype in renal carcinoma cell lines. In our experiments, among all VLAs studied, VLA-2 was most frequently altered in expression by RCC cell lines. The significance of these observations for aberrant metastatic properties of multidrug resistant tumor cells will be the subject of further studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗