Fungal Planet description sheets: 154-213.

Novel species of microfungi described in the present study include the following from South Africa: Camarosporium aloes, Phaeococcomyces aloes and Phoma aloes from Aloe, C. psoraleae, Diaporthe psoraleae and D. psoraleae-pinnatae from Psoralea, Colletotrichum euphorbiae from Euphorbia, Coniothyrium prosopidis and Peyronellaea prosopidis from Prosopis, Diaporthe cassines from Cassine, D. diospyricola from Diospyros, Diaporthe maytenicola from Maytenus, Harknessia proteae from Protea, Neofusicoccum ursorum and N. cryptoaustrale from Eucalyptus, Ochrocladosporium adansoniae from Adansonia, Pilidium pseudoconcavum from Greyia radlkoferi, Stagonospora pseudopaludosa from Phragmites and Toxicocladosporium ficiniae from Ficinia. Several species were also described from Thailand, namely: Chaetopsina pini and C. pinicola from Pinus spp., Myrmecridium thailandicum from reed litter, Passalora pseudotithoniae from Tithonia, Pallidocercospora ventilago from Ventilago, Pyricularia bothriochloae from Bothriochloa and Sphaerulina rhododendricola from Rhododendron. Novelties from Spain include Cladophialophora multiseptata, Knufia tsunedae and Pleuroascus rectipilus from soil and Cyphellophora catalaunica from river sediments. Species from the USA include Bipolaris drechsleri from Microstegium, Calonectria blephiliae from Blephilia, Kellermania macrospora (epitype) and K. pseudoyuccigena from Yucca. Three new species are described from Mexico, namely Neophaeosphaeria agaves and K. agaves from Agave and Phytophthora ipomoeae from Ipomoea. Other African species include Calonectria mossambicensis from Eucalyptus (Mozambique), Harzia cameroonensis from an unknown creeper (Cameroon), Mastigosporella anisophylleae from Anisophyllea (Zambia) and Teratosphaeria terminaliae from Terminalia (Zimbabwe). Species from Europe include Auxarthron longisporum from forest soil (Portugal), Discosia pseudoartocreas from Tilia (Austria), Paraconiothyrium polonense and P. lycopodinum from Lycopodium (Poland) and Stachybotrys oleronensis from Iris (France). Two species of Chrysosporium are described from Antarctica, namely C. magnasporum and C. oceanitesii. Finally, Licea xanthospora is described from Australia, Hypochnicium huinayensis from Chile and Custingophora blanchettei from Uruguay. Novel genera of Ascomycetes include Neomycosphaerella from Pseudopentameris macrantha (South Africa), and Paramycosphaerella from Brachystegia sp. (Zimbabwe). Novel hyphomycete genera include Pseudocatenomycopsis from Rothmannia (Zambia), Neopseudocercospora from Terminalia (Zambia) and Neodeightoniella from Phragmites (South Africa), while Dimorphiopsis from Brachystegia (Zambia) represents a novel coelomycetous genus. Furthermore, Alanphillipsia is introduced as a new genus in the Botryosphaeriaceae with four species, A. aloes, A. aloeigena and A. aloetica from Aloe spp. and A. euphorbiae from Euphorbia sp. (South Africa). A new combination is also proposed for Brachysporium torulosum (Deightoniella black tip of banana) as Corynespora torulosa. Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Discriminative stimulus effects of delta 9-tetrahydrocannabinol and delta 9-11-tetrahydrocannabinol in rats and rhesus monkeys.

Previous reports have suggested that delta 9-11-tetrahydrocannabinol (delta 9-11-THC), an exocyclic analog of delta 9-tetrahydrocannabinol (delta 9-THC), may have weak agonist effects as well as antagonistic properties. The purpose of the present study was to examine the effects of delta 9-11-THC in substitution and antagonism tests in rats and in rhesus monkeys trained to discriminate delta 9-THC from vehicle in two-lever drug-discrimination procedures. The substitution studies showed that delta 9-11-THC generalizes from the training dose of delta 9-THC in rats and in monkeys, although it was less potent in both species. The magnitude of the potency difference was greater in monkeys than in rats. When administered immediately following injection with the training dose of delta 9-THC, delta 9-11-THC failed to block the delta 9-THC cue in rats and showed a lack of dose-responsive inhibition in monkeys. These results suggest that delta 9-11-THC is devoid of antagonistic properties in the drug discrimination paradigm.

Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats.

CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in a number of studies as a radioligand for the cannabinoid receptor. This compound shares behavioral and biochemical properties with naturally occurring cannabinoids such as delta 9-THC. The purpose of the present study was 3-fold: to establish the ability of CP 55,940 to serve as a discriminative stimulus, to determine whether this discriminative stimulus is identical to that of delta 9-THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A, would antagonize the discriminative stimulus effects of CP 55,940. Rats were trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever operant conditioning chambers. CP 55,940 produced dose-dependent generalization from the training dose in dose-effect determinations conducted before and after testing with other drugs. The effects of the training dose of CP 55,940 were dose-dependently antagonized by co-administration of SR141716A. Results of substitution tests showed that delta 9-THC, WIN 55,212-2, and cannabinol substituted completely for CP 55,940 in a dose-dependent manner; however, CP 55,940 was approx 10-fold more potent than any of the other drugs in producing CP 55,940-like discriminative stimulus effects. Several drugs with CNS depressant properties (phencyclidine, haloperidol and diazepam) failed to produce reliable substitution for CP 55,940. These results demonstrate that CP 55,940 has discriminative stimulus effects and that it shares these effects with structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of stimulation and blockade of dopamine receptor subtypes on the discriminative stimulus properties of cocaine.

The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate cocaine from saline. In substitution tests, the stimulus effects of 10 mg/kg of this substance generalized to d-amphetamine (0.25-1.0 mg/kg) and the selective D2 against LY-171555 (0.05-0.25 mg/kg) but not to the D1 agonist SKF-38393 (5.0-15.0 mg/kg); in combination tests, the D1 antagonist Sch-23390 (0.0625-0.5 mg/kg) significantly blocked, and the D2 antagonist spiperone (0.25-0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D1 or D2 receptor activation; for example, the stimulus properties of this substance might involve both D1 and D2 receptor activation.

Pharmacological specificity of delta 9-tetrahydrocannabinol discrimination in rats.

While many previous studies have shown that a variety of cannabinoids substitute and cross-substitute for delta 9-tetrahydrocannabinol (THC) in drug discrimination procedures, few have systematically examined potential THC-like effects of non-cannabinoid compounds. The purpose of the present study was to delineate further the pharmacological specificity of THC discrimination. Rats were trained to discriminate THC (3.0 mg/kg) from vehicle. Following determination of a dose-effect curve with THC, substitution tests with selected compounds from a variety of pharmacological classes, including l-phenylisopropyl adenosine, dizocilpine, dextromethorphan, clozapine, buspirone, MDL 72222, muscimol, midazolam and chlordiazepoxide, were performed. Whereas THC produced full dose-dependent substitution, substitution tests with non-cannabinoid drugs resulted in less than chance (50%) levels of responding on the THC-appropriate lever, with the exception of (+)-MDMA (2.5 mg/kg, 50%) and diazepam (3.0 mg/kg, 67%). These results are consistent with those of previous studies and suggest that the discriminative stimulus effects of THC exhibit pharmacological specificity.

Clozapine blocks disruptive and discriminative stimulus effects of quipazine.

Clozapine was tested in two serotonin-dependent behavioral measures. One group of rats was trained to discriminate the serotonin agonist, quipazine, from saline in a two-lever operant choice task. Pretreatment with clozapine completely blocked the discrimination of quipazine. Another group of rats was trained to bar press for milk on a variable interval schedule of reinforcement. Quipazine decreased the response rate in these animals and pretreatment with clozapine completely reversed this effect. Thus, clozapine acted as a serotonin antagonist in both measures of serotonin function.

Pharmacological evaluation of dimethylheptyl analogs of delta 9-THC: reassessment of the putative three-point cannabinoid-receptor interaction.

The basic premise underlying the cannabinoid pharmacophore is that at least three functional groups are involved in the interaction between the ligand and the receptor and that these functional groups in delta 9-THC comprise (a) C11, (b) the phenolic hydroxyl, and (c) the side chain. In order to assess the relative importance of the C11 position and the side chain, a series of C11 substituted analogs were prepared which contained a dimethylheptyl side chain. Consistent with previous studies, incorporation of a dimethylheptyl side chain dramatically enhanced both pharmacological potency in mice and receptor affinity. Incorporation of a hydroxy at C11 along with this branched side chain resulted in an extremely potent cannabinoid with ED50S of 0.01, 0.04, 0.16 and 0.04 mumol/kg in depression of spontaneous activity, reduction in body temperature, antinociception, and immobility, respectively. This compound was also very potent as a discriminative stimulus in a drug discrimination procedure and exhibited an extended duration of action. Its high affinity for the cannabinoid receptor (Ki = 400 pM) was consistent with this pharmacological potency. Incorporation of an oxo rather than a hydroxy reduced potency somewhat, although this analog was much more potent than delta 9-THC in most behavioral assays. The most striking observation was that incorporation of a carboxylic acid to form 11-nor-delta 9-THC-DMH-9-carboxylic acid did not eliminate pharmacological activity. This analog was as potent as delta 9-THC. The improbability that all three of the functional groups are interacting in a similar fashion with the receptor provides further support that the C11 position is not an essential requirement for activity. On the other hand, it is possible that substituents in the C9 region are interacting somewhere within or near the same site, but differently.

Tolerance to the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol.

Although tolerance to a variety of behavioral and physiological effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has been demonstrated, previous studies have reported that tolerance to the discriminative stimulus effects of Delta(9)-THC does not develop when discrimination training is continued during repeated administration. The present study investigated development of tolerance to the discriminative stimulus effects of Delta(9)-THC under conditions of supplemental administration during suspended training. Rats, trained to discriminate Delta(9)-THC (3mg/kg) from vehicle in a two-lever drug discrimination procedure, under a fixed-ratio 10 schedule of food reinforcement, were tested with cumulative doses of Delta(9)-THC before and after repeated administration of vehicle and of high doses of Delta(9)-THC. Following suspended training with repeated vehicle injection, the Delta(9)-THC dose-effect curve for percentage of drug lever responding showed little change from the prevehicle curve. After supplemental administration of Delta(9)-THC, the degree of rightward shift in the post-THC dose-effect curve was 40-fold. Recovery to pre-THC levels of percentage of drug lever responding was observed during a second post-THC dose-effect curve administered 23 days later. The large reversible shift in the dose-effect curve following supplemental administration of Delta(9)-THC suggests that tolerance developed to the discriminative stimulus effects of Delta(9)-THC under suspended training conditions.

Anabolic steroids and craniofacial growth in the rat.

Anabolic steroids are misused by adolescents as well as adults to increase muscle and improve appearance and athletic performance. Since these substances strongly enhance protein synthesis, it was speculated that craniofacial changes in bone size and, perhaps, skeletodental relationships might also occur. Eighty rat pups were divided into three groups: (1) sham-treated controls, (2) a low-dose group (1 mg/kg/wk nandrolone phenpropionate), and (3) a high-dose group (10 mg/kg/wk). The high-dose regimen more closely mimics dosages used by abusers. Steroid therapy significantly increased all measures of the craniofacial complex (k = 20)--on the order of 3.5%-except some precocious calvarial dimensions. Importantly, significant alterations also occurred in facial morphology. The low-dose group exhibited proportionate increases in most craniofacial dimensions, but the high-dose produced overt shape changes, notably a maxillomandibular, anteroposterior jaw discrepancy due to maxillary excess. In sum, this anabolic steroid significantly altered facial growth in this animal model; by extension, steroid abuse by adolescent humans may produce discernible changes in their craniofacial complexes.

Heparin-induced white clot syndrome.

Heparin-induced thrombocytopenia and thrombosis (white clot syndrome) is a devastating clinical problem as illustrated by the case presented. A high index of suspicion is required to make the diagnosis. Management included discontinuing heparin and administering alternative forms of anticoagulation. Surgery on both the arterial and venous systems may be required. Fibrinolytic therapy as well as antiplatelet therapy may at times be necessary. The mortality rate is high and prevention is of key importance.

Anabolic steroid abuse and tooth size-arch dimensions in the rat.

Anabolic steroids are misused by adolescents and adults to increase muscle mass and improve appearance and athletic performance. Since anabolics strongly enhance protein synthesis, it was speculated that alterations in tooth size and arch length could occur. This study quantified the effects of the anabolic steroid nandrolone phenpropionate on these parameters in a rat model. The steroid significantly increased mandibular arch length. No difference in mesiodistal dimensions of the molars occurred. In consequence, the increased arch dimensions combined with unaltered tooth size may result in dental spacing and/or other malocclusions.

Stimulus properties of dopaminergic drugs: comparisons involving selective agonists and antagonists.

Rats were trained to discriminate the putatively selective dopamine (DA) receptor agonists SKF 38393 (10 mg/kg) or Ly 171555 (0.025 mg/kg) from saline in a two-lever situation involving fixed-ratio (FR 20), extinction schedules of water reinforcement. During substitution tests, no dose of any compound [apomorphine, Ly 171555, lisuride, LSD, amphetamine, cocaine, (-) 3-PPP, or SKF 82526] mimicked SKF 38393, the effects of which were blocked by the D1 antagonist Sch 23390 but not by haloperidol. Postsynaptic and DA "autoreceptor" agonists [apomorphine, (-) 3-PPP], as well as dopaminergic ergot derivatives (bromocriptine, lergotrile, lisuride) and Sch 23390, substituted for Ly 171555, a partial ergoline which has behavioral effects that are blocked by haloperidol and molindone, but not by either Sch 23390 or serotonin (5-HT) antagonists (ketanserin, pizotifen). Amphetamine and cocaine did not substitute for either SKF 38393 or Ly 171555. These results suggest that the stimulus properties of a variety of neuropharmacologically important and clinically useful compounds are transduced at (pre- or postsynaptic) D2 receptors. However, this conclusion must be tempered by evidence that actions at D1 and D2 receptors may not be entirely independent. The behavioral effects of abused psychomotor stimulants probably involve mechanisms other than "direct" agonist activity at either D1 or D2 receptors.

A comparison of the discriminative stimulus properties of delta 9-tetrahydrocannabinol and CP 55,940 in rats and rhesus monkeys.

CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3- hydroxypropyl)cyclohexanol] is a potent bicyclic analog of delta 9-tetrahydrocannabinol (THC) which has been used as a probe for a cannabinoid recognition site in neural tissue. In the present study, CP 55,490 was evaluated for delta 9-THC-like effects in rats and rhesus monkeys trained to discriminate delta 9-THC from vehicle. Rats trained to discriminate delta 9-THC (3.0 mg/kg i.p.) from vehicle were tested with various doses of delta 9-THC and CP 55,940 at both 30 and 90 min postinjection. Catalepsy was measured immediately after these operant tests using an adaptation of the mouse ring-test. In rats, CP 55,940 substituted for delta 9-THC at both 30 and 90 min postinjection at a dose of 0.1 mg/kg that had minimal effects on rates of responding. Doses of delta 9-THC (greater than 3.0 mg/kg) and CP 55,940 (greater than 0.1 mg/kg) that reduced response rates by greater than 50% also produced substantial increases in catalepsy. CP 55,940 and delta 9-THC had a similar time course for discriminative stimulus effects, but CP 55,940 was about 30 times more potent. In monkeys, the training dose of delta 9-THC ranged from 0.04 to 0.16 mg/kg i.m., adjusted individually to minimize response-rate disruption. After training, monkeys were tested with various doses of delta 9-THC and CP 55,940 at 30 min postinjection.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression cloning of a cDNA encoding the murine interleukin 4 receptor based on ligand binding.

Interleukin 4 (IL-4) is a potent mediator of growth and differentiation for various lymphoid and myeloid cells. To isolate a cDNA encoding the murine IL-4 receptor, we have developed an expression cloning method that uses biotinylated ligand as a probe and that may be generally applicable to cloning of receptor genes. COS-7 cells transiently transfected with the cloned full-length cDNA bind murine IL-4 specifically with a Kd = 165 pM. Crosslinking of 125I-labeled IL-4 to COS-7 cells transfected with the cDNA reveals binding to proteins of 120-140 kDa. IL-4-responsive cells also express IL-4-binding proteins of 120-140 kDa but show additional bands at 60-70 kDa; the relationship of the smaller proteins to the larger ones is unclear. The nucleotide sequence indicates that the full-length cDNA encodes 810 amino acids including the signal sequence. While no consensus sequence for protein kinases is present in the cytoplasmic domain, a sequence comparison with the erythropoietin receptor, the IL-6 receptor, and the beta chain of the IL-2 receptor reveals a significant homology in the extracellular domain, indicating that the IL-4 receptor is a member of a cytokine receptor family.