Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts

To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, which contacted principal cell dendrites; deep pyramids, which could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with nontufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary. In addition to synaptic connectivity (by AMPA/kainate, NMDA, and GABA(A) receptors), we also included electrical coupling between dendrites of interneurons, nRT cells, and TCR cells, and--in various combinations--electrical coupling between the proximal axons of certain cortical principal neurons. Our network model replicates several observed population phenomena, including 1) persistent gamma oscillations; 2) thalamocortical sleep spindles; 3) series of synchronized population bursts, resembling electrographic seizures; 4) isolated double population bursts with superimposed very fast oscillations (>100 Hz, "VFO"); 5) spike-wave, polyspike-wave, and fast runs (about 10 Hz). We show that epileptiform bursts, including double and multiple bursts, containing VFO occur in rat auditory cortex in vitro, in the presence of kainate, when both GABA(A) and GABA(B) receptors are blocked. Electrical coupling between axons appears necessary (as reported previously) for persistent gamma and additionally plays a role in the detailed shaping of epileptogenic events. The degree of recurrent synaptic excitation between spiny stellate cells, and their tendency to fire throughout multiple bursts, also appears critical in shaping epileptogenic events.     

A method for modulation transfer function determination from edge profiles with correction for finite-element differentiation

In this paper we describe a technique for determining the modulation transfer function (MTF) of an imaging system from an experimentally obtained edge profile. The technique includes an exact correction for the frequency passband of the finite-element differentiation required to obtain the line spread function from the edge spread function. This correction has been ignored by investigators in the past and is required whenever finite-element differentiation is used rather than analytic differentiation of a model fitted to the edge response data. The magnitude of the MTF correction is approximately 11% at f = fc/2 and approximately 57% at f = fc, where fc = fs/2 is the maximum frequency reproducible without aliasing with a sampling rate of fs. The correction is performed in the spatial frequency domain by multiplying the uncorrected MTF by 1/sinc (pi f/2fc). A computer simulation is presented to demonstrate the effect and the correction procedure. An experimental MTF of an x-ray image intensifier system obtained using this technique is found to be consistent with an MTF obtained using a bar pattern test phantom.     

Naturally occurring double-stranded RNA and immune responses. III. Immunogenicity and antigenicity in animals.

Naturally occurring, double-stranded RNA (ds-RNA)) was immunogenic when injected into mice, rats, guinea-pigs, rabbits, dogs and baboons. The response to native material administered intravenously (i.v.) was strongest in rabbits and mice, and weakest in baboons. Mice, guinea-pigs and baboons injected with ds-RNA complexed with methylated BSA emulsified in Freund's complete adjuvant all gave high antibody responses. When ds-RNA was given in aerosol form to mice and guinea-pigs the response was weaker than that following i.v. injection, and baboons did not respond to antigen given as an aerosol. In most species the immune response obtained was predominantly IgM in nature, and there was no evidence for cell-mediated immunity in any species. The only evidence of an adverse reaction associated with repeated administration of ds-RNA was a systemic anaphylactic-type response in a small group of mice given ds-RNA repeatedly in aerosol form and challenged with ds-RNA i.v.     

RecurrentStreptococcus pneumoniae endocarditis

A case of recurrent endocarditis due toStreptococcus pneumoniae, a rare cause of endocarditis, is reported. The first episode of infection resulted in valvular damage, necessitating replacement of the aortic and mitral valves, and the second episode was treated successfully with antibiotics alone. Recurrence occurred even though the organism was fully susceptible to the antibiotics used and the patient showed no evidence of immune deficiency.     

Requirement for matching T cell and B cell subsets in secondary anti-hapten antibody responses.

The in vitro secondary anti-hapten response to trinitrophenylated keyhole limpet hemocyanin (TNP-KLH) has been investigated using B and T cells from the same or a pool of identically primed syngeneic individuals. The optimum antibody response obtained from B cells of any given animal was seen when the same individual's T cells were used as a helper cell source. This individual preference was lost if secondary challenge in culture was made with TNP on a heterologous carrier, with the helper cells obtained from suitably primed individuals or a pool thereof. These data are interpreted in terms of a network theory for the regulation of immune responses under physiological conditions.     

The development of a computer controlled system to simulate in rats, the rapid, frequent changes in oxygen experienced by preterm infants developing retinopathy of prematurity

Preterm infants that develop severe ROP have significantly more fluctuations in their transcutaneous oxygen compared to mild or no ROP, despite the fact that all these infants are kept within clinically 'safe' limits. Current animal models do not accurately reflect this oxygen environment. Our aim was to custom build equipment capable of reproducing the transcutaneous oxygen (TcPO2) levels recorded by infant cotside monitoring equipment in a rat model and assess the equipment's precision. Using previously published data for the rat that translates TcPO2 into the equivalent inspired FiO2, a profile was derived from a datalog of TcPO2 values recorded every minute for 14 days in an infant that had developed severe ROP. This profile was controlled in the animal chamber by software algorithms which calculated the amount and type of gas to be injected to move oxygen to each new set-point. CO2 regulation within the chamber was also possible. Absolute differences between the datalog set-points (n = 17,465) and the oxygen sensor were median 0.3% oxygen, IQR 0.2-0.7% oxygen, with 95% of the differences < +/- 2% oxygen. The equipment is capable of reproducing the oxygen environment experienced by a preterm ventilated infant, giving a satisfactory level of precision.     

Screening for cervical cancer in HIV-infected women receiving care in the United States

OBJECTIVE: We examined the sociodemographic, clinical and provider factors associated with screening for cervical cancer among HIV-infected women. METHODS: We studied a national sample representing 43,490 women receiving treatment of HIV infection who completed first follow-up surveys of the HIV Cost and Service Utilization Study (HCSUS). All women were asked, "In the past 12 months, have you had a Pap test?" Women reporting an abnormal Pap test result were asked whether they had been told antibiotics could cure abnormal cells, and whether they were scheduled for another Pap test or for a colposcopy within 3 months. RESULTS: Of the population represented, 81% had had a Pap test in the past 12 months. Women who reported having a gynecologist and primary care physician at the same clinical site were almost twice as likely (odds ratio, 1.9; 95% confidence interval, 1.3-3.0) as other women to report Pap testing. Among women who reported abnormal Pap test results and were not told antibiotics could cure abnormal cells, 95% were scheduled for a repeat Pap test or colposcopy, but 15% of the women had not received their repeat Pap test or colposcopy. CONCLUSION: Although Pap test rates and appropriate referral for abnormal findings were high among HIV-tested women, many women with initially abnormal Pap test results did not actually receive follow-up Pap testing or colposcopy. Providing gynecologic care at the same site as primary HIV care would likely improve delivery of needed gynecologic care for women.     

Ontogeny of the antibody-forming cell line in mice. III. The generation of mature anti-sheep red blood cell-specific B cells is antigen-dependent.

A role for antigen in the generation of fully mature splenic type B cells has been shown. In adoptive transfer experiments, cells from bone marrow or fetal liver required a longer period to give an anti-sheep red blood cell plaque-forming cell (PFC) response than those from spleen. This delay was not overcome by allowing the cells a 7-day sojourn in the irradiated host before antigen challenge. A two-stage protocol was designed in which the in vivo generation of fully mature cells could be measured by their ability to give PFC in lipopolysaccharide-stimulated cultures in vitro. These experiments showed that a critical factor which influences the final differentiation of bone marrow or fetal liver cells into mature, splenic type B cells is exposure to antigen.     

Rapidly progressive osteoarthrosis of ochronotic origin. A pathologic study

A case of hip osteoarthrosis associated with ochronosis in a 65-year-old woman is reported. Characteristic features of both conditions were observed macroscopically and on light and electron microscopic examination. In the cartilage the pigment deposits were located on and between thick collagen fibrils. In the synovial membrane there were embedded packets of cartilage shards of which the collagen fibrils and pigment were phagocytosed, as well as calcified bone debris whose disaggregation might have explained the presence of some apatite deposits free of any underlying collagen structure. As also previously observed, the present case of ochronotic hip osteoarthrosis is remarkable for the minor osteophyte formation and for the inclusion of pigmented cartilage shards in the osteomedullar remodeled territory. It also demonstrates a collapse of the femoral head cortex presumably related to the rapid clinical and radiologic evolution. By the well-known origin of its chondropathy and by the pigment labeling of the cartilage, ochronotic arthropathy provides an almost experimental model for analyzing a broader problem, i.e., that of the various components of an osteoarthrotic remodeling.