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J M Blom

Publications and source records attributed to J M Blom.

17 recordsLinked to original sources

Modulation of glutamate receptors in response to the novel antipsychotic olanzapine in rats.

BACKGROUND: A disturbance in glutamate neurotransmission has been hypothesized in schizophrenia. Hence, the beneficial effects of pharmacological treatment may be related to adaptive changes taking place in this neurotransmitter system. METHODS: In this study, we investigated the modulation of ionotropic and metabotropic glutamate receptors in the rat brain following acute or chronic exposure to the novel antipsychotic olanzapine. RESULTS: In accordance with the clear distinction between classical and atypical drugs, olanzapine did not alter glutamate receptor expression in striatum. Chronic, not acute, exposure to olanzapine was capable of up-regulating hippocampal mRNA levels for GluR-B and GluR-C, two alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-forming subunits. This effect could be relevant for the improvement of schizophrenic alterations, which are thought to depend on dysfunction of the glutamatergic transmission within the hippocampal formation. We also found that the expression of group II glutamate metabotropic receptors was up-regulated in the frontal cortex after chronic exposure to clozapine, and to a lesser extent olanzapine, but not with haloperidol. CONCLUSIONS: The adaptive mechanisms taking place in glutamatergic transmission might prove useful in ameliorating some of the dysfunction observed in the brain of schizophrenic patients.

Animals↗

Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate).

The interplay between dopamine and glutamate appears to be relevant in the etiopathology of schizophrenia. Although currently used antipsychotics do not interact with glutamatergic receptors, previous results have demonstrated that the expression profile of ionotropic glutamate receptors can be regulated by drugs such as haloperidol or clozapine. In the present investigation, the mRNA levels for NMDA and AMPA receptor subunits were measured after chronic treatment with the novel antipsychotic agent Seroquel (quetiapine fumarate, quetiapine) as compared to haloperidol and clozapine. Similarly to the prototype atypical clozapine, quetiapine reduced the mRNA expression for NR-1 and NR-2C, two NMDA forming subunits, in the nucleus accumbens. Furthermore, quetiapine, but not haloperidol or clozapine, increased the hippocampal expression for the AMPA subunits GluR-B and GluR-C. The differences between classical and atypical antipsychotics, as well as among the novel agents, might be relevant for specific aspects of their therapeutic activity and could provide valuable information for the role of glutamate in specific symptoms of schizophrenia.

Animals↗

Adrenalectomy reduces FGF-1 and FGF-2 gene expression in specific rat brain regions and differently affects their induction by seizures.

We have previously reported that limbic seizures regulate the gene expression of fibroblast growth factor-2 (basic, FGF-2) according to a specific spatio-temporal pattern. In the present paper we have investigated the role of adrenal hormones on seizure-induced elevation of fibroblast growth factor-1 (acidic, FGF-1) and FGF-2 gene expression. Adrenalectomy reduces FGF-2 mRNA expression in specific brain regions, such as frontal cortex, hippocampus and striatum, whereas FGF-1 mRNA levels were decreased only in the frontal cortex. The injection of kainic acid in adrenalectomized rats produced a widespread increase of FGF-2 mRNA with a pattern similar to sham animals as indicated by in situ hybridization. In contrast, although kainate-induced elevation of FGF-1 mRNA in the hippocampus was not influenced by adrenalectomy, its induction in frontal cortex was prevented by this surgery procedure. Taken together, these data indicate that adrenal hormones play a role in the regulation of the gene expression for fibroblast growth factors, but different mechanisms are operative in their induction following seizure activity.

Adrenal Glands↗

Photoperiodic effects on steroid negative feedback in female prairie voles (Microtus ochrogaster).

Breeding in prairie voles is mainly restricted to the autumn and winter of most years. The organization of estrus in female prairie voles is unusual because behavioral estrus is induced by chemosensory stimuli from the urine of adult conspecific males. Isolated females exhibit undetectable levels of estradiol and never display estrous behavior, yet exposure to male urine causes a cascade of endocrine changes that evoke estrogen secretion from the ovaries and estrous behavior within 24 hr. In the prairie vole, the extreme dependence of estrus on chemosensory stimuli raises the possibility that their ovaries may be less prominent in the regulation of gonadotropin secretion than in species with more endogenously organized estrous cycles. The present study examined the contribution of the ovaries in luteinizing hormone (LH) regulation in prairie voles. Females were maintained for 9 weeks in either long (LD 16:8) or short (LD 8:16) photoperiodic conditions, a blood sample was obtained, and then animals were either ovariectomized or received a sham procedure. Another blood sample was obtained a week later and assayed for serum LH. Blood serum LH levels were significantly reduced in short-day voles, compared to long-day animals. After ovariectomy both long-day and short-day voles exhibited equivalent elevations in LH levels. This study provides evidence that photoperiod is measured in female voles and the ovaries appear to produce sufficient steroids to suppress LH release.

Animals↗

Influence of photoperiod, green food, and water availability on reproduction in male California mice (Peromyscus californicus).

California mice (Peromyscus californicus) breed primarily during the winter rainy season and generally terminate breeding during the dry summer months. This pattern of reproduction could be regulated by day length, availability of green vegetation, or water availability. The effects of photoperiod and green vegetation on reproduction were examined in Experiment 1 by housing adult male P. californicus either in long (LD 14:10) or short (LD 8:16) photoperiods for 10 weeks with ad lib food and water availability. A subset of animals in each photoperiod treatment group also received supplements of fresh spinach thrice weekly. The effects of water availability were examined in Experiment 2 by housing adult males in long day length conditions for 10 weeks with ad lib or restricted (50% of ad lib) water availability. Neither photoperiod nor availability of green plant food significantly affected reproductive function in male California mice, although animals in long days with green food supplements displayed elevation of some reproductive organ masses. Short days did not suppress plasma LH or prolactin levels. Male P. californicus provide extensive care of the young during the short days of winter. The absence of photoperiod-induced changes in prolactin levels is consistent with the observation that elevated plasma prolactin titers are associated with male parental care in this species. In contrast, water restriction (simulated summer drought) reduced reproductive organ masses, as well as plasma levels of prolactin, and may act as an environmental cue to terminate breeding. Thus, water availability may regulate breeding in this species independently of photoperiod and food availability.

Animal Feed↗

Day length affects immune cell numbers in deer mice: interactions with age, sex, and prenatal photoperiod.

The extent to which day length affects immune function was examined in the present study. Three goals were pursued: 1) to confirm and extend the observation that the immune systems of adult deer mice (Peromyscus maniculatus) are responsive to changes in photoperiod, 2) to examine the development of the photoperiod-associated changes in immune function, and 3) to discover whether photoperiodic information transmitted to the young during gestation influences immune function. In experiment 1, adult mice housed in short days had higher white blood cell and lymphocyte numbers than their long-day cohorts. Red blood cell and differential cell counts did not differ between long- and short-day animals. No sex differences were observed in the pattern of immune responses to photoperiod. The effect of photoperiod on immune cells in prepubertal animals was examined in experiment 2; a similar pattern of results was obtained as that for experiment 1, suggesting that the photoperiodic effect on the immune system is not mediated by sex steroid hormones. Prenatal and postnatal photoperiodic effects on immune cells were examined in experiment 3; pups gestated in one day length were cross-fostered to mothers in the same day length conditions or to mothers maintained in the alternative day length. The results of experiment 3 suggested that photoperiodic information transmitted from the mother to the young in utero subsequently affected immune systems of the pups. Animals gestated in short day lengths displayed higher immune status throughout life than mice gestated in long days. These results are discussed from an adaptive functional perspective.

Aging↗

Photoperiodic effects on tumor development and immune function.

Seasonal changes in adaptations associated with winter coping strategies have been frequently studied. Central among the suite of energy-saving, winter-coping strategies is the suspension of reproductive activities. The inhibition of reproduction by nontropical rodents is mediated by daylength changes. Although balanced annual energy budgets are critical, survival and subsequent reproductive success also require avoiding predators, illness, and early death. Because the stressors of winter could lead to suppressed immune function, we hypothesized that animals should have evolved survival strategies involving immunoenhancement. Short daylengths provide a predictive cue to individuals that could be used to enhance immune function in advance of stress-induced immunosuppression. In Experiment 1, adult female deer mice (Peromyscus maniculatus) were housed in either long (LD 16:8) or short (LD 8:16) days for 8 weeks, then injected with the chemical carcinogen 9,10-dimethyl-1,2-benzanthracene (DMBA) dissolved in dimethyl sulfoxide (DMSO) or with the DMSO vehicle alone. Animals were evaluated weekly for 8 weeks after injection. None of the animals treated with DMSO developed tumors in any of the experiments. Nearly 90% of the long-day deer mice injected with DMBA developed squamous cell carcinoma. None of the short-day deer mice injected with DMBA developed tumors. Small lesions developed at the site of injection; short-day females had less severe lesions and healed faster than long-day females. Immunoglobulin G (IgG) response to i.p. injection of sheep red blood cells (SRBC) did not differ photoperiodic conditions. The role of estrogens in the photoperiodic responses was evaluated in Experiment 2: Ovariectomized or sham-ovariectomized deer mice received estradiol benzoate replacement therapy or a control procedure in long daylengths for 8 weeks prior to injection of DMBA or DMSO, then were monitored for 8 additional weeks. Females treated with DMBA developed tumors at the same rate, regardless of estrogen manipulation. Estrogen did not affect healing rates. In Experiment 3, female deer mice were injected with a slurry of microspheres that either contained bromocriptine or were empty. Suppression of prolactin with bromocriptine resulted in a decrease of tumor incidence from 55.6% to 24% in long-day females 8 weeks after injection with DMBA. Healing rates were not affected by prolactin manipulations. Silastic capsules that were filled with either melatonin or cholesterol were implanted into long-day female deer mice in Experiment 4; 8 weeks later, females received an injection of either DMBA or DMSO, then were monitored for 8 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

Photoperiod influences the critical caloric intake necessary to maintain reproduction among male deer mice (Peromyscus maniculatus).

The concept of critical day length is well established among rodents; reproductive function is maintained when day lengths are greater than some specific threshold. In addition to day length cues, seasonal breeding in deer mice can also be regulated by food availability. The caloric threshold necessary to support reproduction remains unspecified for seasonally breeding rodents. The present study examined the interaction between photoperiod and food availability on reproductive function in adult male deer mice (Peromyscus maniculatus). A critical caloric intake profile was constructed in long (16L:8D) and short (8L:16D) photoperiods; groups of deer mice in both photoperiods either received food ad libitum or 90, 80, or 70% of their individual ad libitum food intake for 10 wk. At autopsy, paired testes, epididymides, and seminal vesicles were removed and weighed. Body mass, total body fat, and total body water contents were also obtained. Short, as compared to long, day lengths inhibited the reproductive systems of male deer mice. However, food consumption interacted with photoperiod to affect reproductive function. Significant reductions in reproductive organ size as well as spermatogenic activity were observed among short-day mice after a 10% reduction in ad libitum food intake. Long-day animals required a 20% reduction in caloric intake to depress reproductive function. Body mass and total body water content were generally unaffected by either photoperiod or food consumption. Total body fat content was reduced in short- as compared to long-day mice. Individual reproductive responsiveness to short days increased as food availability decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lymphography in the diagnosis of non-seminoma tumours of the testis.

In a series of 86 lymphograms correlated to histological findings after retroperitoneal lymph node dissection or to laparotomy findings, reliability proved to be 78%. The reliability of lymphograms evaluated as positive was 88%, while that of negative lymphograms was 74%. Retroperitoneal lymph node metastases were detected with the aid of lymphography in 58% of the patients. It was impossible to establish a node size above which metastases could be demonstrated with certainty by lymphography.

Humans↗

Lipogranulomatosis of the mesentery.

This paper describes a 21-year-old man with lipogranulomatosis of the mesentery. This condition is characterized by a non-specific inflammatory process of the adipose tissue in the radix mesenterii. So far as could be established, this is the first patient in whom vascular anomalies and displacement of lymphatic vessels and lymph nodes have been described. However, these changes are hardly specific so that definite conformation of the diagnosis must be obtained by a biopsy. The aetiology is unknown. There is no established therapy for this benign, self-limiting disease.

Adult↗

Lesions of the trochlea tali. Osteochondral fractures and osteochondritis dissecans of the trochlea tali.

Osteochondral fracture of the trochlea tali, which can result in osteochondritis dissecans of this trochlea, is often not recognized as such and therefore not adequately treated. The nonrecognition is mainly due to the fact that the fracture can either remain asymptomatic or produce symptoms of inversion-distortion; to a lesser degree it is also due to the fact that the lesion is not identified in the radiograph. In view of these facts it would seem necessary in all cases of distorsion to make an X-ray examination of the ankle, ascertaining that the trochlea tali is adequately visualized. Unless the symptoms abate within a week, radiological examination should be repeated. The same applies to patients whose initial recovery is followed by a relapse of symptoms. Surgical treatment of choice for osteochondral fractures. The symptomatology and therapeutic results in 46 osteochondral fractures studied were in agreement with data from the literature. Therapeutic results can be improved by earlier diagnosis and more adequate treatment of the condition.

Fractures, Bone↗

Learned immunosuppression is associated with an increased risk of chemically-induced tumors.

Based on the hypothesis that certain aspects of the CNS and immune system interact and that altered immune function affects carcinogenesis, an animal model was developed to examine the effects of learned immunosuppression on the development of a chemically induced tumor. In two experiments, we evaluated whether mice, for which immunosuppression was associated with a neutral (conditioned) stimulus, would exhibit an increased susceptibility to tumor development upon reexposure to the conditioned stimulus, as compared to nonconditioned and control animals. A taste aversion conditioning paradigm, based on classical conditioning techniques, was employed to suppress immune function using the cytotoxic and immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus and consequently increase the risk of chemically induced tumorigenesis. CY (100 mg/kg, intraperitoneal) was paired with saccharin in the drinking water (0.1%) of adult female mice (CF-1). Conditioned mice were exposed to saccharin twice in the absence of CY, on days 4 and 7 after the first exposure (day 1). All mice were injected with the chemical carcinogen 9,10-dimethylbenzanthracene (DMBA, 50 mg/kg, subcutaneous) on day 4 of conditioning. Two subsequent exposures to saccharin alone substantially increased the risk of developing DMBA-induced tumors (ranging from 83-91%), as compared to control animals (36%) that had not received this pairing. Mice that received all agents (i.e., CY, DMBA, and saccharin) in a slightly different order did not display elevated tumor incidence. Three separate exposures to CY also significantly increased the number of animals developing tumors in response to the carcinogen (75%). Mice were observed for at least 8 weeks after conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗