The needs of persons with lupus and health care providers: a qualitative study aimed toward the development of the Lupus Interactive Navigator™.

OBJECTIVE: Systemic lupus erythematosus is an inflammatory autoimmune disease associated with high morbidity and unacceptable mortality. A major challenge for persons with lupus is coping with their illness and complex care. Our objective was to identify the informational and resource needs of persons with lupus, rheumatologists, and allied health professionals treating lupus. Our findings will be applied toward the development of an innovative web-based technology, the Lupus Interactive Navigator (LIN™), to facilitate and support engagement and self-management for persons with lupus. METHODS: Eight focus groups were conducted: four groups of persons with lupus (n=29), three groups of rheumatologists (n=20), and one group of allied health professionals (n=8). The groups were held in British Columbia, Ontario, and Quebec. All sessions were audio-recorded and transcribed verbatim. Qualitative analysis was performed using grounded theory. The transcripts were reviewed independently and coded by the moderator and co-moderator using 1) qualitative data analysis software developed by Provalis Research, Montreal, Canada, and 2) manual coding. RESULTS: Four main themes emerged: 1) specific information and resource needs; 2) barriers to engagement in health care; 3) facilitators of engagement in health care; and 4) tools identified as helpful for the self-management of lupus. CONCLUSION: These findings will help guide the scope of LIN™ with relevant information topics and specific tools that will be most helpful to the diverse needs of persons with lupus and their health care providers.

High-level semi-synthetic production of the potent antimalarial artemisinin.

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Robotic training and kinematic analysis of arm and hand after incomplete spinal cord injury: a case study.

Regaining upper extremity function is the primary concern of persons with tetraplegia caused by spinal cord injury (SCI). Robotic rehabilitation has been inadequately tested and underutilized in rehabilitation of the upper extremity in the SCI population. Given the acceptance of robotic training in stroke rehabilitation and SCI gait training, coupled with recent evidence that the spinal cord, like the brain, demonstrates plasticity that can be catalyzed by repetitive movement training such as that available with robotic devices, it is probable that robotic upper-extremity training of persons with SCI could be clinically beneficial. The primary goal of this pilot study was to test the feasibility of using a novel robotic device for the upper extremity (RiceWrist) and to evaluate robotic rehabilitation using the RiceWrist in a tetraplegic person with incomplete SCI. A 24-year-old male with incomplete SCI participated in 10 sessions of robot-assisted therapy involving intensive upper limb training. The subject successfully completed all training sessions and showed improvements in movement smoothness, as well as in the hand function. Results from this study provide valuable information for further developments of robotic devices for upper limb rehabilitation in persons with SCI.

Comparative study of torsional and bending properties for six models of nickel-titanium root canal instruments with different cross-sections.

This study investigated the influence of cross-section profile on the mechanical behaviors of six commercial nickel-titanium (NiTi) root canal instruments using the finite element method. The nonlinear mechanical characteristics of the NiTi alloy were taken into account. The six root canal instruments studied were ProTaper, Hero642, Mtwo, ProFile, Quantec, and NiTiflex. Mathematical models for these instruments were constructed and their performances were analyzed under equal torque conditions. The ProTaper and Hero642 models achieved the lowest stress levels that made them the most torque-resistant while the NiTiflex model was the poorest. The maximum stress value and the stress distribution in a model were found strongly influenced by the cross-section profile. Factors affecting the stress distribution include the cross-sectional inertia, depth of the flute, area of the inner core, radial land, and peripheral surface ground. As the area of the inner core of the cross-section increased, the model was more torque-resistant.

Brachial plexus catheter reservoir for the treatment of upper-extremity cancer pain: technical case report.

OBJECTIVE AND IMPORTANCE: Infiltration of the brachial plexus with anesthetics can provide relief of upper-extremity pain from invasive cancer. Because the analgesia is short-lived, however, repeated invasive treatments are necessary. We describe the implantation of a catheter reservoir system, in which anesthetic injections through a subcutaneous port resulted in anesthetic infiltration of the brachial plexus. CLINICAL PRESENTATION: A 47-year-old Hispanic man with squamous cell carcinoma of the larynx had undergone surgical resection, radiation treatment, and chemotherapy. Two years later, he had locally recurrent disease involving the brachial plexus, neck, and chest wall. The patient's pain was minimally responsive to narcotics, which also caused severe nausea and anorexia. TECHNIQUE: The brachial plexus was localized percutaneously with a needle electrode stimulator. Contrast injection under fluoroscopy confirmed entry into the plexus sheath. With use of the Seldinger technique, two Silastic catheters were placed within the brachial plexus and attached with a "Y" connector to a reservoir. The patient experienced complete relief of upper-extremity pain after a test injection with xylocaine. Thereafter, serial injections of bupivacaine with triamcinolone at 1-week intervals provided complete pain relief. After the treatments were initiated, the patient reported improved sleep and an improvement in his quality of life. CONCLUSION: A catheter reservoir system for brachial plexus analgesia can provide safe and effective analgesia for upper-extremity pain. This technique negates the need for repeated invasive procedures and avoids the complications of neurolysis.

Brain metastasis from prostate carcinoma: antemortem recognition and outcome after treatment.

BACKGROUND: In patients with prostate carcinoma, brain metastasis has most commonly been reported in autopsy series. Symptomatic brain metastasis from prostate carcinoma has occasionally been detected. METHODS: The authors retrospectively studied a series of 38 patients with antemortem intracerebral metastasis found on review of 7994 patients treated over an 18-year period at the University of Texas M. D. Anderson Cancer Center. RESULTS: The mean time from diagnosis of prostate carcinoma to discovery of brain metastasis was 28 months, with a mean survival of 9.2 months after the discovery of the brain metastasis. The brain metastasis was treated only with whole brain irradiation in 29 patients, with craniotomy and irradiation in 8 patients, and with surgery alone in 1 patient. Small cell carcinomas and primary transitional cell carcinomas of the prostate were much more likely to produce brain metastasis than were adenocarcinomas. Also noted among the overall prostate carcinoma cohort was a second group of 16 patients with prostate carcinoma and brain metastasis that had developed from a second primary tumor, which in all was either lung carcinoma or melanoma. CONCLUSIONS: The occurrence of brain metastasis in prostate carcinoma patients is rare, usually signifies a late stage of the disease, and may in some patients be produced by a tandem extraprostatic tumor.

Craniospinal dissemination of central neurocytoma. Report of two cases.

Central neurocytoma was first described in the literature in 1982 and has been noted to be a benign neuronal tumor usually located in the ventricular system. Of the more than 100 reported cases, only seven recurrences have been reported, all of which have been local. The authors report two cases of recurrent central neurocytoma that disseminated through the ventricular system with seeding to the spine, as evidenced by magnetic resonance images and positive cerebrospinal fluid cytology. The histological appearance of these two tumors was typical for the lesion and lacked evidence of malignant change. Central neurocytoma may not be as benign as previously thought, and the recognition of this more malignant behavior has implications for patient follow up and therapy.

Expression of glutamate uptake transporters after dibutyryl cyclic AMP differentiation and traumatic injury in cultured astrocytes.

Our findings indicate that differentiation of primary astrocytes by dibutyryl cyclic adenosine monophosphate (dBcAMP) and scratch injury together resulted in increased glutamate transporter gene expression. Confluent primary cultures were prepared from cerebral cortex of normal new born rat pups. The primary cultures were then divided into four groups each: control and scratch-injured, and dBcAMP-treated control and scratch-injured cultures. Total RNA was extracted at 0, 1, 2, 4, and 7 days after injury. Expression of the electrogenic glutamate transporters, GLAST, GLT-1, and EAAC-1, was quantitated by the reverse transcriptase-polymerase chain reaction method (RT-PCR) and slot blot hybridization followed by densitometric scanning. Triplicate cultures were analyzed for each time-point. Our studies indicate that all these astrocyte cultures expressed the two glial transporters, GLAST and GLT-1, while none of the cultures expressed the neuronal transporter, EAAC-1. The expression of the two transporters in the dBcAMP-treated primary cultures were markedly increased from the non-treated cultures. The dBcAMP-treated cultures had 2- to 4-times increase in levels of GLAST and GLT-1-mRNA expression both before and after scratch injury, as compared to untreated non-injured and injured primary cultures. All of the cultures expressed GLAST in greater proportion than GLT-1.

Enhancement of GABAA receptor-mediated conductances induced by nerve injury in a subclass of sensory neurons.

1. The effects of axotomy on the electrophysiologic properties of adult rat dorsal root ganglion (DRG) neurons were studied to understand the changes in excitability induced by traumatic nerve injury. Nerve injury was induced in vivo by sciatic nerve ligation with distal nerve transection. Two to four weeks after nerve ligation, a time when a neuroma forms, lumbar (L4 and L5) DRG neurons were removed and placed in short-term tissue culture. Whole cell patch-clamp recordings were made 5-24 h after plating. 2. DRG neurons were grouped into large (43-65 microns)-, medium (34-42 microns)-, and small (20-32 microns)- sized classes. Large neurons had short duration action potentials with approximately 60% having inflections on the falling phase of their action potentials. In contrast, action potentials of medium and small neurons were longer in duration and approximately 68% had inflections. 3. Pressure microejection of gamma-aminobutyric acid (GABA, 100 microM) or muscimol (100 microM) onto voltage-clamped DRG neurons elicited a rapidly desensitizing inward current that was blocked by 200 microM bicuculline. To measure the peak conductance induced by GABA or muscimol, neurons were voltage-clamped at a holding potential of -60 mV, and pulses to -80 mV and -100 mV were applied at a rate of 2.5 or 5 Hz during drug application. Slope conductances were calculated from plots of whole cell current measured at each of these potentials. 4. GABA-induced currents and conductances of control DRG neurons increased progressively with cell diameter. The mean GABA conductance was 36 +/- 10 nS (mean +/- SE) in small neurons, 124 +/- 21 nS in medium neurons, and 527 +/- 65 nS in large neurons. 5. After axotomy, medium neurons had significantly larger GABA-induced conductances compared with medium control neurons (390 +/- 50 vs. 124 +/- 21; P < 0.001). The increase in GABA conductance of medium neurons was associated with a decrease in duration of action potentials. In contrast, small neurons had no change in GABA conductance or action potential duration after ligation. The GABA conductance of large control neurons was highly variable, and ligation resulted in an increase that was significant only for neurons > 50 microns. The mean action potential duration in large neurons was not significantly changed, but neurons with inflections on the falling phase of the action potential were less common after ligation. There was no difference in resting potential or input resistance between control and ligated groups, except that the resting potential was less negative in small cells after axotomy.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of a promoter region supporting transcription of a novel human beta-galactoside alpha-2,6-sialyltransferase transcript in HepG2 cells.

In humans, two transcripts encoding beta-galactoside alpha-2,6-sialytransferase (EC 2.4.99.1.) have previously been described. One of the transcripts is widely expressed, whereas the other is restricted to mature B-cells. In this study we demonstrate the existence of a third transcript in the hepatoma cell-line HepG2. The expression of this transcript is controlled by a promoter region which efficiently supports transcription in HepG2 cells, and which harbours putative binding sites for liver-enriched and acute phase inducible transcription factors.

Cell-specific expression of human beta-galactoside alpha 2,6-sialyltransferase transcripts differing in the 5' untranslated region.

In humans, two cDNAs have been isolated encoding beta-galactoside alpha 2,6-sialyltransferase, differing only in part of the 5' untranslated region. Primer extension data show that the two cDNAs are near full-length clones. RNase protection analysis of different cell types showed that the transcript corresponding to the alpha 2,6-sialyltransferase cDNA isolated from a B-cell library resided only in mature B cells. In contrast, the transcript corresponding to the alpha 2,6-sialyltransferase cDNA isolated from a placenta library was found in all cells tested. Our results also indicate the existence of a third alpha 2,6-sialyltransferase transcript in the hepatoma cell line HepG2. Mature B cells were found to express high amounts of alpha 2,6-sialyltransferase mRNA, compared to other cell types tested, as shown by Northern blot analysis. Moreover there was an increased expression of beta-galactoside alpha 2,6-sialyltransferase mRNA in activated B cells compared to resting B cells. In vitro transcription and translation of the cDNAs resulted in a protein of 45 kDa, but the transcripts were translated with different efficiency, suggesting a role for the 5' untranslated region in regulation of translation. We have also made an alpha 2,6-sialyltransferase construct lacking the specific 5' regions of the two cDNAs. A transcript generated from this construct was translated more efficiently in vitro than the two alpha 2,6-sialyltransferase cDNAs.

Three types of sodium channels in adult rat dorsal root ganglion neurons.

Several types of Na+ currents have previously been demonstrated in dorsal root ganglion (DRG) neurons isolated from neonatal rats, but their expression in adult neurons has not been studied. Na+ current properties in adult dorsal root ganglion (DRG) neurons of defined size class were investigated in isolated neurons maintained in primary culture using a combination of microelectrode current clamp, patch voltage clamp and immunocytochemical techniques. Intracellular current clamp recordings identified differing relative contributions of TTX-sensitive and -resistant inward currents to action potential waveforms in DRG neuronal populations of defined size. Patch voltage clamp recordings identified three distinct kinetic types of Na+ current differentially distributed among these size classes of DRG neurons. 'Small' DRG neurons co-express two types of Na+ current: (i) a rapidly-inactivating, TTX-sensitive 'fast' current and (ii) a slowly-activating and -inactivating, TTX-resistant 'slow' current. The TTX-sensitive Na+ current in these cells was almost completely inactivated at typical resting potentials. 'Large' cells expressed a single TTX-sensitive Na+ current identified as 'intermediate' by its inactivation rate constants. 'Medium'-sized neurons either co-expressed 'fast' and 'slow' current or expressed only 'intermediate' current. Na+ channel expression in these size classes was also measured by immunocytochemical techniques. An antibody against brain-type Na+ channels (Ab7493)10 labeled small and large neurons with similar intensity. These results demonstrate that three types of Na+ currents can be detected which correlate with electrogenic properties of physiologically and anatomically distinct populations of adult rat DRG neurons.

Intranuclear Ca2+ transients during neurite regeneration of an adult mammalian neuron.

Depolarization-induced increases in cytoplasmic and intranuclear Ca2+ were visualized in adult mammalian dorsal root ganglion (DRG) neurons during different stages of neurite extension by using confocal laser scanning microscopy and the long-wavelength Ca2+ indicator dye fluo 3-AM (acetoxymethyl ester of fluo 3). In neurons beginning to extend neurites, depolarization led to pronounced increases in nuclear and nucleolar Ca2+ levels severalfold greater than corresponding increases in the cytoplasm. The nucleolar Ca2+ signal often exceeded that of the nucleus, indicating regional heterogeneity of the nucleus. The subcellular calcium transients were dependent on extracellular Ca2+ and the level of depolarization, indicating the importance of transmembrane Ca2+ fluxes in triggering the nuclear events. After neurite extension, the nuclear Ca2+ signals were attenuated and never exceeded cytoplasmic levels. These results indicate that activity-dependent modulation of intranuclear Ca2+ levels is greater in DRG neurons during early neurite extension. Given the importance of Ca2+ in gene expression, the results may be relevant to Ca(2+)-dependent nuclear events responsible for axonal regeneration.

Current-clamp analysis of a time-dependent rectification in rat optic nerve.

1. Rat optic nerves were studied using intra-axonal and whole-nerve recording techniques in a sucrose-gap chamber. Constant-current pulses were applied across the outer compartments of the chamber to achieve a current clamp. 2. The nerves displayed a prominent time-dependent conductance increase elicited by a hyperpolarizing constant-current pulse, as evidenced by a relaxation or 'sag' in membrane potential towards resting potential. The inward current began at about 80 ms and reached a steady level over the next 100-200 ms. Its magnitude progressively increased with increasing levels of hyperpolarization. 3. The inward current elicited by hyperpolarization was reduced, but not abolished, when Na+ was reduced from the normal bath concentration of 151 mM to 0 mM. In Na(+)-free solutions the bath K+ concentration, [K+]o, was varied between 0 and 5 mM; the inward current was greatest when [K+]o was 5 mM and was abolished when [K+]o was zero. 4. The inward current was not abolished by tetrodotoxin (TTX), tetraethylammonium (TEA) or 4-aminopyridine (4-AP) suggesting that conventional voltage-dependent sodium and potassium channels do not underlie the time-dependent conductance increase. Low concentrations of Cs+ completely blocked the inward current, and Ba2+ induced a partial block. External application of divalent cations (Cd2+ and Mg2+) did not block the inward current. These properties are similar to the inwardly rectifying conductance observed in a central nervous system neurone. 5. Stimulus-response curves obtained during the hyperpolarization pulse, before and during the conductance increase, indicate that excitability is increased during the conductance increase. This along with the intra-axonal recordings demonstrates that the origin of the increased conductance is axonal and not glial. 6. It is concluded that central nervous system myelinated fibres in rat optic nerve display a prominent time-dependent conductance increase in response to hyperpolarization that depends on both Na+ and K+ and is blocked by Cs+. This conductance is similar to an inward rectifier described for a variety of neurone types. The increased axonal excitability observed during the conductance increase suggests that its functional role may be to maintain or stabilize axonal excitability during periods of intense action potential activity.

Development of 4-AP and TEA sensitivities in mammalian myelinated nerve fibers.

1. The sensitivities of mammalian myelinated axons to potassium channel blockers was studied over the course of development using in vitro sucrose gap and intra-axonal recording techniques. 2. Application of 4-aminopyridine (4-AP; 1.0 mM) to young nerves led to a delay in return to base line of the sciatic nerve compound action potential and to a postspike positivity (indicative of hyperpolarization) lasting for tens of milliseconds. These effects were very much attenuated during the course of maturation. 3. Tetraethylammonium chloride (TEA; 10 mM) application alone had little effect on the waveform of the compound action potential at any age. However, the 4-AP-induced postspike positivity was blocked by TEA, Ba/+, and Cs+. This block was observed in Ca2+-free electrolyte solutions containing EGTA (1.0 mM). 4. Immature sciatic nerves (approximately 3 wk postnatal) were incubated in a potassium-free electrolyte solution containing 120 mM CsCl for up to 1 h in an attempt to replace internal potassium with cesium. When the nerves were tested in the sucrose gap chamber using solutions containing 3.0 mM CsCl substituted for KCl, the compound action potential was broadened and a prolonged depolarization appeared, but there was no postspike positivity; the CsCl effect was similar to the combined effects of 4-AP and TEA. 5. Intra-axonal recordings were obtained to study the effects of 4-AP and TEA on individual axons. In the presence of 4-AP a single stimulus led to a burst of action potentials followed by a pronounced afterhyperpolarization (AHP) in sensory fibers. The AHP was blocked by TEA. In motor fibers 4-AP application resulted in action potential broadening with no AHP. 6. Repetitive stimulation (200-500 Hz; 100 ms) was followed by a pronounced AHP in both sensory and motor fibers at all ages studied. This activity-elicited AHP was sensitive to TEA at all ages. 7. The results indicate that 4-AP and TEA sensitivity change over the course of development in rat sciatic nerve. The effects of 4-AP are much more pronounced in immature nerves than in mature nerves, suggesting that 4-AP-sensitive channels become masked as they are covered by myelin during maturation. However, the TEA-sensitive channels, demonstrable after repetitive firing, remain accessible to TEA after myelination. These channels therefore may have a nodal representation.

Tumor response to interferon inducer and radiation effect of serum interferon levels.

The effect of interferon inducing complex of polyriboinosinic, polyribocytidylic acid with poly-L-lysine and carboxymethylcellulose - Poly (ICLC) - on the response of Lewis lung carcinoma in C57B1 mice to radiation treatments was studied. Improved tumor response was obtained in mice receiving 1.5 mg/m2 or higher of Poly (ICLC). Such doses have induced more than 1000 mu/ml of serum interferon. The same doses of Poly (ICLC) potentiated the epilation effect of radiation. The injection of 0.15 mg/m2 of Poly (ICLC) led to protection of the tumor and the stimulation of it's growth. It also did not potentiate the epilation effect. In this study, one weekly administration of Poly (ICLC) was as effective as three times per week treatment. The cellular mechanism of the increased radiosensitivity caused by Poly (ICLC) was reflected in the reduction of the width of the shoulder on the cell survival curve, which was dependent on the dose of the drug. In cell cultures, doses of 100 micrograms/ml synchronized the cell division, thus contributing to the increase in radiosensitivity.

A simple quantitative analysis system for coronary cineangiograms using a personal computer.

We have developed a simple quantitative analysis system for coronary cineangiograms using a personal computer and a standard projector-video camera system. The selected frame of cinefilm was projected onto the target area of a CCD video camera. To decrease spatial fluctuations due to quantum noise, the digital data were smoothed spatially by applying a moving averaged filter and a median filter. Following the smoothing process, the digital data with gray level were transformed to binary data by quantifying the threshold property of their gray level. To minimize the geometric influence, mainly pincushion effect, a cinefilm of a 1 cm grid was placed against the input screen of the image intensifier to correct the distortion by using 3rd degree polynomials. The accuracy of the contour detection procedure was validated on the basis of phantom models filled with a contrast medium. Despite the potential influence of many radiographic variables on computerized diameter measurements, the overall accuracy was found to be 0.26-0.33 mm over a wide range of clinically relevant artery diameters and radiographic conditions. Using this system we demonstrated one method of examining the effects of acetylcholine and nitroglycerin on coronary artery diameter in adult humans.

Activity-dependent changes in extracellular potassium and excitability in turtle olfactory nerve.

The excitability properties of turtle olfactory nerve (o.n.) were studied in vitro using potassium-sensitive microelectrodes (KSM), a modified sucrose gap chamber, and a standard nerve chamber to measure conduction velocity. A pronounced supernormal period (SNP), as indicated by increased conduction velocity of the o.n. fiber volley, lasting up to several seconds, was observed following a single stimulus. The compound action potential recorded in the sucrose gap chamber showed a prolonged depolarization with a similar time course to the SNP. When stimulation intensity was submaximal the response amplitude, and the extracellular potassium concentration [K+]o, continuously increased during repetitive stimulation. In contrast, when supramaximal stimuli were applied, the amplitude of the o.n. fiber volley was reduced during a high-frequency stimulus train for all responses after the initial one even though latency was maximally reduced, i.e., during supernormal conduction. Superfusion with various levels of K+ elicited changes in the excitability of the o.n. fibers. Small increases in [K+]o above the resting concentration of 2.6 mM led to an increase in resting excitability, whereas larger increases resulted in decreased excitability and conduction block. The SNP was eliminated when extracellular potassium was elevated between 3 and 4 mM above resting levels. Microstimulation of a small bundle of o.n. fibers led to an increase in [K+]o along the bundle but also around adjacent nonactivated fibers. The excitability of these neighboring nonactivated fibers was increased, further indicating the importance of activity-dependent changes in [K+]o in modulating axonal excitability. These results demonstrate the importance of activity-dependent increases in extracellular potassium in modulating nonmyelinated o.n. fiber excitability. They also indicate that increases in [K+]o and an associated membrane depolarization contribute to the increased excitability observed during fiber recruitment and the supernormal period.

Functional differences between 4-aminopyridine and tetraethylammonium-sensitive potassium channels in myelinated axons.

Intracellular recordings from rat sciatic nerve fibers showed that the potassium channel blocking agents 4-aminopyridine (4-AP) and tetraethylammonium (TEA) had different effects on action potential waveform. When applied alone, TEA did not appreciably alter the waveform of an individual action potential, whereas 4-AP application resulted in action potential broadening and, in some axons, repetitive firing. A prolonged afterhyperpolarization which was blocked by TEA occurred subsequent to repetitive firing. These results indicate the presence of at least two pharmacologically defined potassium channels in mammalian peripheral nerve fibers. The 4-AP-sensitive potassium channels are important for rapid action potential repolarization and the TEA-sensitive potassium channels may serve to modulate axonal excitability during repetitive firing.

Studies on human low serum IgD phenotype and Gm markers.

The human "low serum IgD phenotype" was studied by simultaneous Gm typing and IgD immunoassay of several populations. An association between Gm (f+b+) haplotype and low human IgD was confirmed and extended to the "low serum IgD phenotype"--as defined from population distribution and genetic studies by Dunnette et al. 1978. Further, it was shown that Black American sera determined by Gm haplotype, had a similar percentage of "low serum IgD phenotype" samples (16%) although they lacked the "associated" Gm(f+b+) haplotype of White American samples. Sardinian sera showed a low incidence of the "low serum IgD phenotype" which was not correlated with Gm haplotype distribution. Familial aggregation of the "low serum IgD phenotype" was observed. No association was found between "low serum IgD phenotype" and serum IgE values. Age related abiotrophy of IgD could not be attributed to selective survival of "low serum IgD phenotype" persons.