Structural features and anti-HIV-1 activity of novel polysaccharides from red algae Grateloupia longifolia and Grateloupia filicina.

Since sulphated polysaccharides have antiviral activity in vitro, we examined the structure and antiretroviral activity of native sulphated galactans extracted from the red algae, Grateloupia filicina (GFP) and Grateloupia longifolia (GLP). The sulphate contents of GFP and GLPE (the 1,4-alpha-d-glucan-glucanohydrolase digest of GLP) were 25.7 and 18.5%, respectively. The sulphate ester groups were located at carbon 2 for GFP and at carbon 2 and 6 for GLPE. Antiretroviral activity was investigated with a primary isolate (PI) of HIV-1 and human peripheral blood mononuclear cells (PBMCs) rather than T-cell line adapted (TCLA) HIV-1 and T-cell lines because it is more representative of the in vivo situation. Both compounds and their derivatives had potent anti-HIV-1 activity when added at the time of infection, and 2h post-infection (EC50s 0.010-0.003microM, EC(90s) 0.87-0.33microM) and low cytotoxicity. Their potential medical application as virucidal vaginal formulations is discussed.

Gender- and smoking-related bladder cancer risk.

BACKGROUND: There is growing evidence that, when smoking habits are comparable, women incur a higher risk of lung cancer than men. Because smokers are also at risk for bladder cancer, we investigated possible sex differences in the susceptibility to bladder cancer among smokers. METHODS: A population-based, case--control study was conducted in Los Angeles, CA, involving 1514 case patients with bladder cancer and 1514 individually matched population control subjects. Information on tobacco use was collected through in-person interviews. Peripheral blood was collected from study participants to measure 3- and 4-aminobiphenyl (ABP)-hemoglobin adducts, a marker of arylamine exposure. Data were analyzed to determine whether the risk of bladder cancer differs between male and female smokers and whether female smokers exhibit higher levels of ABP-hemoglobin adducts than male smokers with comparable smoking habits. All statistical tests were two-sided. RESULTS: Cigarette smokers had a statistically significant 2.5-fold higher risk (95% confidence interval = 2.1 to 3.0) of bladder cancer than never smokers. Use of filtered versus nonfiltered cigarettes, low-tar versus higher tar cigarettes, or the pattern of inhalation did not modify the risk. The risk of bladder cancer in women who smoked was statistically significantly higher than that in men who smoked comparable numbers of cigarettes (P =.016 for sex-lifetime smoking interaction). Consistent with the sex difference in smoking-related bladder cancer risk, the slopes of the linear regression lines of the 3- and 4-ABP--hemoglobin adducts by cigarettes per day were statistically significantly steeper in women than in men (P values for sex differences <.001 and.006, respectively). CONCLUSION: The risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes.

A psychosocial kinship model for family therapy.

Family therapy has traditionally centered on the nuclear family and thus has been typically oriented toward urban white middle-class families. A variety of modifications in therapeutic technique has evolved for work with the many modern families whose structure consists of a functional psychosocial family kinship. The authors have developed a formal theoretical framework and model for family therapy that encompasses the total psychosocial network, i.e., the extended kinships of the nuclear family and the functional kin such as friends, neighbors, and associates.

Sexual and seasonal differences in the vomeronasal epithelium of the red-backed salamander (Plethodon cinereus).

Sexually dimorphic behaviors often are associated with sexually dimorphic neural structures. Perinatal hormonal levels influence structural sexual dimorphism, and seasonal structural changes also can be the result of seasonal hormonal fluctuations. We compared the volume of vomeronasal organs of male and female red-backed salamanders (Plethodon cinereus) throughout the year. Odorants are delivered to vomeronasal receptors through nasolabial grooves when salamanders touch the bases of these grooves to objects (nose tapping). Males may locate and identify potential mates through nose tapping during the prolonged breeding season that lasts from October through May. We compared vomeronasal organ data through multiple regression by using total body size, sex, and season as variables that may influence vomeronasal organ volume. Gonads also were examined as an indicator of reproductive status. Total body size and sex significantly affect vomeronasal organ volume; as body size increases, so does vomeronasal organ volume, and males have significantly larger vomeronasal organs than females at all times of the year. During the summer, both males and females have larger vomeronasal organs than at any other time of the year. Summer also is a period of intense foraging and the initiation of a new cycle of gametogenesis. Previous studies of circulating hormone levels in amphibians have shown that the initial stages of gametogenesis correspond to a period of low estradiol and testosterone levels but high gonadotropin-releasing hormone levels. The functional significance of sexual and seasonal differences in the vomeronasal organs of P. cinereus may relate to the neurogenesis of specialized receptors for courtship and mating.

Propionibacterium acnes: pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulonephritis.

Propionibacterium acnes is a pleomorphic gram-positive anaerobic rod usually isolated as a contaminant from skin. We report three cases of P. acnes infection of central nervous system shunts for hydrocephalus. The organism was seen repeatedly on gram stain in a specimen of shunt fluid in all three cases; initially, it was regarded as a contaminant. In addition, two of the patients had precipitins to extracts of their organism. Serum from normal control subjects had no such precipitins. One of the patients had an immune-complex glomerulonephritis--an entity not previously associated with anaerobic organisms. All three patients recovered after removal of the shunt and treatment with antibiotics. P. acnes is a significant pathogen in patients with central nervous system shunts.

Inhibitory actions of opioid compounds on calcium fluxes and neurotransmitter release from mammalian cerebral cortical slices.

The effects of opioid agonists on veratrine-stimulated Ca2+ influx and amino acid neurotransmitter release in rat cerebrocortical brain slices were studied. Inhibitory effects were seen on both of these parameters with all of the opioid agonists used. None of the drugs used affected basal 45Ca2+ uptake, basal K+ content or basal amino acid release from the slices. At high concentrations (100 microM) fentanyl, tifluadom, U50,488H, butorphanol and bremazocine greatly inhibited the depolarization of the slices by veratrine as determined by the reduced release of K+. The opioid receptor subtypes at which the drugs were acting were characterized by the antagonistic effects of naloxone and WIN44441-3. The opioid-induced inhibition of stimulated Ca2+ uptake and amino acid release were not antagonized by WIN44441-2, the inactive enantiomer of WIN44441-3. It is concluded that opioid agonists acting through mu- and kappa-receptors and probably through delta- and sigma-receptors, have an inhibitory effect on Ca2+ uptake into cerebrocortical brain slices and the subsequent release of aspartate, glutamate and gamma-aminobutyric acid (GABA).

Morphine inhibition of calcium fluxes, neurotransmitter release and protein and lipid phosphorylation in brain slices and synaptosomes.

Morphine (1-100 microM) was found to inhibit several concomitant events in brain slices and synaptosomes which are augmented by depolarizing agents. Thus, 45Ca2+ uptake, amino acid neurotransmitter release, increases in 3',5' cyclic AMP levels and 32Pi incorporation to proteins and lipids induced by veratrine (25 microM) and by potassium (56 mM), were each inhibited in a dose related manner. These inhibitory actions of morphine were all prevented by naloxone (1 microM). Evidence is presented that morphine binding to a receptor on the synaptic membrane affects intracellular mechanisms involved in neurotransmitter release possibly via a second messenger system. An enhancing action of GTP on the inhibitory influences of morphine suggests that its actions are mediated at least in part, via a coupling of the receptor to adenyl cyclase in the outer membrane. This is supported by its inhibitory action on the capacity of depolarizing agents to increase cyclic AMP levels.

Self-mutilation of the eye.

While the act of self-enucleation is rare, other self-inflicted eye injuries may be more common. Six patients are reported who have documented histories of ocular self-mutilation. Several common factors are observed in these patients and in other cases reported in the literature: (1) the patient was judged to be psychotic; (2) the patient had a tyrannical conscience; (3) a source of guilt was present; (4) this guilt was displaced to the eye; and (5) an attempt at self-inflicted eye injury was followed by relief from anxiety when completed or by frustration when injury was prevented.

Surface-modified nanocrystalline ceramics for drug delivery applications.

Drug delivery systems comprised of various types of carriers have long been the object of pharmacological investigation. The search has been stimulated by the belief that carriers will lead to reduced drug toxicity, dosage requirements, enhanced cellular targeting and improved shelf-life. Among the carriers investigated are complex polymeric carbohydrates, synthetic proteins and liposomal structures. For the past four years, we have been experimenting with a radically new class of carriers comprised of surface-modified nanocrystalline ceramics. While the ceramics provide the structural stability of a largely immutable solid, the surface modification creates a glassy molecular stabilization film to which pharmacological agents may be bound non-covalently from an aqueous phase with minimal structural denaturation. As a consequence of maintained structural integrity and owing to concentration effects afforded by the surfaces of the nanocrystalline materials, drug activity following surface immobilization is preserved. We have used successfully surface-modified nanocrystalline ceramics to deliver viral antigens for the purpose of evoking an immune response, oxygenated haemoglobin for cell respiration and insulin for carbohydrate metabolism. The theoretical principles, technical details and experimental results are reviewed. Surface-modified nanocrystalline materials offer an exciting new approach to the well-recognized challenges of drug delivery.

Compartments and barriers in the sciatic nerve of the rabbit.

Near constant concentration of various radioactively labelled polar nonelectrolytes were maintained in the blood plasma of renal ligated rabbits. The uptake of [14C]urea, [51Cr]EDTA and [14C]inulin into sciatic nerve was interpreted in terms of a two-compartment model. There was a rapidly equilibrating space representing about 20% of the tissue weight which is almost certainly the interstitial fluid of the epineurium and outer layers of the perineurium. Urea penetrated the blood-nerve barrier at a similar rate to the entry of this compound into brain. Sucrose, chromium-EDTA and sulphate passed into the true interstitial fluid approaching a total volume of distribution of about 36% of the tissue weight at 6-8 h. Since movement of these 3 solutes is severely restricted by the blood-barrier, the blood-nerve barrier in the rabbit must contain channels of greater than 1 nm which are not present in the developed blood-brain barrier. Uptake of [3H]3-O-methylglucose into nerve was examined but the results did not give a conclusive answer to the question of whether there is specific transport of sugars at the blood-nerve barrier. The wet nerve contained (in mmole/kg) sodium 74.3; potassium 42.6 and chloride 48.8. Water was 64.6 ml/100 g. Intracellular electrolyte concentrations were estimated. Approximately 30% of the total sodium content cannot be accounted for as being free in the interstitial fluid at a Gibbs-Donnan distribution with plasma. Analysis of metabolically poisoned nerves which have equilibrated with salt solution in vitro suggests that negatively charged polyelectrolyte molecules retain about 14 mmole of sodium/kg wet normal nerve.

Inhibitory effects of noradrenaline and dopamine on calcium influx and neurotransmitter glutamate release in mammalian brain slices.

Noradrenaline and dopamine (0.1-100 microM) inhibited 45Ca2+ uptake and glutamate release induced by veratrine (25 microM) in cortical and striatal slices but were without effect when added alone. Each parameter was inhibited in a dose-dependent manner by noradrenaline in cortical slices (IC50 = 0.05 microM) and by dopamine in striatal slices (IC50 = 0.08 microM). Noradrenaline (0.01-100 microM) was without influence on veratrine-induced 45Ca2+ influx or glutamate release in the striatal preparation, and likewise dopamine was inactive in cortex slices. The use of adrenoceptor antagonists suggests that the action of noradrenaline is mediated by the alpha 2-receptor which is thought to be adenylate cyclase linked. Dopamine appeared to be acting through the D-2 receptor.

Continuous glutamate leakage from brain cells is balanced by compensatory high-affinity reuptake transport.

The glutamate (and aspartate) uptake blocker threo-3-hydroxyaspartate (20 microM) was added to superfusion fluids employed for in vivo microdialysis of corpus striatum, and to incubation medium for striatal slices (5 microM). In vivo it caused an increase in glutamate and aspartate concentrations in the superfusion fluid. In vitro it caused increases in the levels of glutamate, aspartate, GABA, taurine and glutamine in the incubation fluid. Tetrodotoxin (1 microM) did not influence the rises in glutamate or aspartate. It is concluded from these results that there is a continuous outward leakage of glutamate, and aspartate, from neural cells which is normally balanced by an inward flux due to reuptake processes. This leakage is distinct from synaptic release of these substances due to spike activity, since tetrodotoxin added to striatal slices did not diminish the action of threo-3-hydroxyaspartate. The significance of the findings for mechanisms leading to ischaemic or hypoxic brain damage, and basic mechanisms in epilepsy is discussed.

A very modest proposal for 1990s C/L psychiatry.

The prediction that consultation-liaison psychiatry would play an integral role in the management of all medical/surgical patients in large hospitals has not come to pass. The primary reason is that no adequate funding mechanism has ever been found to support such a large endeavor. The economic climate as we enter the 1990s makes such funding even less likely. The authors suggest that C/L psychiatry accept a lesser role, largely confined to teaching hospitals. That role, which has been successful at a large public teaching hospital for nearly 10 years, encompasses serving as a primary psychiatric teaching site for medical students, a primary teaching site for psychiatry residents and other postgraduate physicians rotating through psychiatry, a source of innovative dispositions for medically ill psychiatric patients, and a source of opportunity for interdisciplinary research.

The evaluation of interactions between anaesthetic agent vapours and carrier gases by laser refractometry.

A measurement system and technique have been developed for the evaluation of interactions between anaesthetic agent vapours and carrier gases. The refractivities of mixtures of anaesthetic agent and carrier gas have been compared to values derived from the addition of the absolute refractivities of the individual components. These results show that there is no significant interaction between the anaesthetic agent and the carrier gas at the +/- 0.06% level of uncertainty. Results for the anaesthetic agents isoflurane, sevoflurane, enflurane, halothane, chloroform and desflurane and the carrier gases nitrogen, oxygen and dry air will be presented.

Expression of cytochrome oxidase in hair cells of the teleost utricle.

Ultrastructural variation in some cytoplasmic organelles and synaptic structures is one characteristic distinguishing the types of hair cells in the teleost ear. In this study, we explored differences in mitochondria by analyzing mitochondrial reactivity for cytochrome oxidase (COX) in hair cells of the teleost utricle. The reactivity for COX within mitochondria in the subcuticular compartment directly beneath the cuticular plate differentiated among hair cells in utricles of three teleost species, Carassius auratus, Pantodon buchholzi, and Astronotus ocellatus. Mitochondria in the subcuticular region of hair cells in the striola reacted intensely. Within juxtastriola and extrastriolar hair cells near the striola, mitochondria reacted at a lowered intensity than in striolar hair cells. Subcuticular mitochondria of extrastriolar hair cells located distant from the striola reacted negligibly. The reactivity of mitochondria in other cytoplasmic compartments did not provide similar evidence for distinguishing among teleost hair cells. Mitochondria within intraepithelial branches of the eighth nerve terminals in the different utricular regions reacted to COX histochemistry commensurate with their respective presynaptic hair cells. Branches of sensory afferent neurons innervating striolar hair cells displayed a dense COX reaction. Sensory afferents innervating the extrastriolar hair cells did not display many mitochondria at synapses nor, when present, was the staining as dense. The presynaptic side of the hair cell-afferent nerve synapse usually, but not always, contained reactive mitochondria. The presynaptic side of the efferent nerve-hair cell synapse did not necessarily contain mitochondria. Mitochondria filling the cytoplasm in a type of juxtamacula cell revealed uniformly dense COX reactivity.

Serological reactions to Nocardia antigens.

Sera from 23 patients with nocardiosis were tested for the presence of precipitating antibodies against an extract of Nocardia asteroides. Sera from nine of 20 patients infected with Nocardia asteroides and one of three sera from patients with Nocardia brasiliensis produced one to three precipitin lines with the antigen. Sera from eight of 55 patients with tuberculosis and 11 of 13 patients with leprosy also contained Nocardia precipitins. None of 33 sera from patients with cryptococcosis, blastomycosis, actinomycosis, histoplasmosis, coccidioidomycosis, mucormycosis or candidiasis contained Norcardia antibodies. None of the sera from ten patients infected with Staphylococcus aureus, ten patients infected with Pseudomonas, or 16 sera from uninfected patients contained Nocardia precipitins.

A serologic response in human infection with Enterobacteriaceae.

Sera from patients infected with Escherichia coli, Proteus, Klebsiella, and Serratia were studied for precipitins to ultrasonic extracts of these organisms in gel-diffusion plates. Sera from 66 per cent of these patients contained precipitins when initially tested. Twenty-four per cent of sera tested in the first week after onset of infection contained precipitins, but this rose to 78 per cent by the third week. Cross-reactions of sera with Pseudomonas antigens were unusual, but were common with other enterobacterial antigen extracts. However, higher titers were usually present to homologous as compared to heterologus antigens. Sera from seven patients contained precipitins to a common enterobacterial antigen. Precipitins to E. coli, Proteus, Klebsiella, and Serratia were detected in only a small proportion of control sera.

Efficacy and safety of pentoxifylline in geriatric patients with intermittent claudication.

The effects of pentoxifylline on intermittent claudication were evaluated at a dose of 1200 mg/day in an open-label twelve-week study on geriatric patients with chronic occlusive arterial disease (COAD). Standardized treadmill testing and clinical signs and symptoms of COAD were followed up before and during drug administration. Twenty-four subjects with a mean age of 73.5 years, capable of walking between 20 and 200 meters on the treadmill, were entered into the trial; 22 participated for eight weeks and 19 completed the study in terms of treadmill walking distance measurements at 12 weeks. The mean walking distance for all patients was increased 111% over baseline at week 12. Thirteen subjects were considered drug responders (greater than or equal to 50% increase in treadmill walking distance) and 9 were considered nonresponders (less than 50% increase). Improvements in clinical signs and symptoms of COAD were noted. Decreases in elevated systemic systolic pressures (but not diastolic) were unexpectedly observed in many drug responders. Seven of 19 males reported sexual function improvements while receiving pentoxifylline. Fourteen (58%) of the 24 subjects reported mild side effects of dyspepsia, nausea, vomiting, dizziness, headache, or insomnia; no subjects were withdrawn from the study because of side effects. In summary, pentoxifylline improved function and symptoms in 13 of 22 geriatric patients with intermittent claudication; the drug was safe and well tolerated at the usual dosage in this geriatric patient population.

[HLA class I antigen expression correlates with histological cell type in uveal melanoma]. / HLA-I-Antigenexpression korreliert mit dem histologischen Zelltyp uvealer Melanome.

PURPOSE: The prognosis of uveal melanoma is correlated with its histologic cell type. The epithelioid cell type is associated with a higher metastatic rate than the spindle cell type. The Human Leucocyte Antigen Class I (HLA-I) expression of the melanoma also correlates with the prognosis. In this study, we analyzed HLA-I antigen expression of uveal melanomas to determine whether a relationship exist between antigenic expression and melanoma cell type. METHODS: Formalin-fixed, paraffin-embedded spindle cell type (n = 11) and epithelioid cell type (n = 11) uveal melanomas were immunostained with the HC10 antibody (1:80) for HLA-I antigen expression with appropriate positive and negative controls. Sections were assessed semiquantitatively according to the percentage of stained cells. RESULTS: Among the spindle cell type melanomas, 2 out of 11 (18%) stained with HC10 antibodies. The staining intensity was less than 25% of the cells in these two melanomas. Among the epithelioid cell type melanomas, 9 out of 11 (82%) stained with HC10. The staining intensity was more than 25% of the cells in 5 of these 9 melanomas. CONCLUSIONS: It is unknown why spindle and epithelioid cell type uveal melanomas have different prognoses. Human uveal melanoma cell lines with low HLA-I expression are susceptible to NK cell-mediated lysis in vitro and in murine studies. The prognostically more favorable spindle cell type melanoma expresses less HLA-I than the epithelioid cell type melanoma. These results stress the role of NK cells in the rejection of uveal melanoma.

A portable device for group modification of classroom attending behavior.

There is a need for a portable means of signalling appropriate classroom behavior that the teacher can carry with her as she moves about the room. An inexpensive wireless switch, adapted for classroom use, was used to turn on a clock when all children were attending to their work. When a movie was made contingent on accumulating a specific number of minutes on the clock, class-attending increased. Throughout these conditions, the records of class attending made by an independent observer with a stopwatch correlated highly with the remote controlled clock.