First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Different HLA-D associations in adult and juvenile rheumatoid arthritis.

HLA-D typing was performed in 126 patients with juvenile rheumatoid arthritis. HLA-DW4, the antigen found in previous studies to characterize adult rheumatoid arthritis, had a significantly lower frequency in children with arthritis than in normal controls (P less than 0.04). By contrast, in children the antigens HLA-DW7 (P less than 0.03) and HLA-DW8 (P less than 0.01) were increased compared to controls. The antigen TMo, detected with homozygous typing cells from a child with juvenile rheumatoid arthritis, was found to be related to the cross-reactive specificities HLA-DW7 and DW11. 46% of the patients with persistent pauciarticular arthritis of childhood typed for the antigen TMo, compared to only 1% of normal controls. Thus the relative risk for persistent pauciarticular arthritis in relation to the presence of TMo was 67.7 (P less than 0.0001). These results provide evidence of fundamental differences between adult rheumatoid arthritis and arthritis of childhood. The latter group appears to include a population distinguishable clinically and characterized in these studies by the HLA-D determinant TMo.

Lymphotoxin formation by lymphocytes and muscle in polymyositis.

Muscle pieces from 11 patients with dermatomyositis or polymyositis were incubated with autologous peripheral blood lymphocytes and the supernates examined for the production of lymphotoxin, a mediator of delayed hypersensitivity, using human fetal muscle monolayers as the target cell. In the case of all 10 active patients, production of lymphotoxin was demonstrated. This mediator was also demonstrated when muscle alone was incubated from two patients with extensive cellular infiltration. Lymphotoxic activity was not found in supernates obtained by incubation of muscle from nine control subjects with their autologous peripheral blood lymphocytes. Addition of methyl prednisolone to active cultures inhibited the action of lymphotoxin on the muscle monolayers. Lymphotoxin was not demonstrated when breast tumor tissue from a patient with dermatomyositis was incubated with autologous lymphocytes. The lymphotoxic agent in the active supernates had similar chromatographic properties to those of a sample of purified lymphotoxin. These findings suggest that muscle injury in polymyositis is a result of a cellular immune response to an antigen present in involved muscle tissue.

Juvenile arthritis, HLA-A2 and binding of DEK oncogene-peptides.

Previous studies have shown that susceptibility to Pauciarticular Juvenile Arthritis is associated with HLA-A*0201. Recently, autoantibodies against the protein of the DEK oncogene have been found in sera of patients with this disease. If T cells are involved in the pathogenesis of joint lesions, it is possible that they target autoantigens presented by HLA-A*0201. Therefore, we investigated whether DEK-derived peptides can bind efficiently to HLA-A*0201. Nonameric peptides selected considering anchor positions 2 and 9, and preferred amino acids at other positions, were incubated either with the human TAP-deficient cell line 174CEM.T2 (T2) or with the homozygous B cell line JESTHOM (A*0201, B*2705, Cw1), previously depleted of endogenous peptides. Binding was measured as the increase of detection of fully assembled, HLA-A*0201 molecules by flow cytometry with the anti-HLA-A2 monoclonal antibody (mAb) BB7.2. Three out of ten selected DEK-derived peptides showed binding to HLA-A*0201, which was peptide concentration-dependent (1 microM to 100 microM). DEK155-163 (AMLKSICEV), which also has two preferred amino acid residues at positions 6 and 8, yielded the highest binding. DEK163-171 (VLDLERSGV) and DEK72-80 (SLQREPFTI), which also has one preferred amino acid residue at position 8, also were able to bind to HLA-A*0201. Furthermore, peptide-induced, fully assembled, HLA-A*0201 molecules were immunoprecipitated with the BB7.2 mAb from metabolically-labeled T2 cells incubated with DEK72-80, DEK155-163, and DEK163-171. A faint band was observed in the immunoprecipitates of cells incubated with DEK65-73 (it carries a preferred amino acid residue at position 6), suggesting that this peptide interacts weakly with HLA-A*0201. These results indicate that several nonameric peptides derived from the DEK protein can bind to HLA-A 0201 and suggest that the complexes formed may be able to stimulate CD8+ T cells in patients with Pauciarticular Juvenile Arthritis.

Prognosis of children with poststreptococcal reactive arthritis.

Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia. We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients. During the initial episode all had arthritis or arthralgia and a documented streptococcal infection. None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months). One patient developed classic ARF with valvulitis 18 months after the initial episode. Two children had later episodes of arthritis and two had at least one additional episode of arthralgia. Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered.

Overview of corticosteroid therapy in the different rheumatic diseases of childhood.

As an introduction to the workshop on corticosteroid use in childhood rheumatic disease, the types of preparations and the methods of administration are discussed. The specifics of steroid use in juvenile arthritis, dermatomyositis and systemic lupus erythematosus are given, with illustrative cases described. The use of steroids in other connective tissue diseases of childhood are briefly described.

HLA associations in juvenile arthritis.

This review of the current status of HLA associations in juvenile arthritis begins with a discussion of the terms used to identify these patients and an approach for their clinical classification. The authors suggest that seven different types should be identified on the basis of clinical features and associated immunogenetic factors and that each of them should be recognized and called by a separate name. Different combinations of patients have been included in the studies performed in different cities and this fact may explain some of the observed differences in HLA associations in various reports. Results from an on-going study in Dallas are compared with published reports from Prague, Cincinnati, and Houston. HLA alleles associated with susceptibility in pauciarticular patients include certain DR and DQ alleles, one DP allele (DPB1*0201) and one HLA class I allele (HLA-A*0201). Susceptibility for polyarticular onset disease was found by the authors to be uniquely associated with DPB1*0301. Important interactions were observed between alleles at the different loci, with markedly increased odds ratios when combinations of susceptibility alleles were analyzed. The possibility that interaction between class I and class II susceptibility factors might be due to the effect of an allele at one of the TAP loci was examined by probing for polymorphic variants of the TAP1 and TAP2 genes. In addition, class I alleles associated with resistance for the development of juvenile arthritis were discussed. The main allele associated with rheumatoid arthritis (DRB1*0401) appears to be protective for the development of several forms of arthritis prevalent in children.

Actinomycotic splenic abscesses presenting with arthritis.

An 18-month-old Caucasian female began with a high fever. She developed swelling in one finger and one toe. Abdominal ultrasound revealed multiple abscesses in her spleen. Multiple blood culture and splenic abscess aspirations grew no pathogens. She had transient response to multiple antibiotics and splenic abscess drainage, but fever returned along with subcutaneous nodules. Culture of splenic tissue from her second splenic drainage eventually grew one organism identified as Actinomyces naeslundii. Therapy with high dose penicillin followed by amoxicillin p.o. and total splenectomy led to complete recovery.

Lymphocyte subpopulations in Kawasaki disease.

The relative percentages of subpopulations of peripheral T lymphocytes in children with Kawasaki Disease (KD) was investigated using matched antibodies directed against the T3, T4 and T8 antigens. The percentage of B cells was determined with antibodies against human surface immunoglobulins. Subjects were six children with acute KD who were compared to normal, age matched controls. The percentage of peripheral lymphocytes positive for OKT3 was 61% for KD children and 64% for controls; for OKT4 they were 41% and 44% respectively and for OKT8 both were 19%. The B cell percentages were 13% in KD and 11% in controls. Thus no abnormalities in the distribution of lymphocyte subtypes in children with KD was found. Previous studies of immune function in KD are reviewed.

Childhood polymyositis/dermatomyositis.

Children with PM/DM differ in many respects from adults with PM/DM. The most characteristic and distinctive feature is the presence of a widespread vasculopathy. Although the pathogenesis is unknown, roles for both humoral and cell-mediated immunity have been proposed. Most intriguing is the evidence for a viral agent that is capable of precipitating an ongoing, immunologically mediated reaction damaging muscles and endothelial cells. Much remains to be discovered, however, regarding the pathogenesis of this disease.

Vasculitis.

Inflammatory changes in blood vessels are a prominent feature of several diseases, which can be categorized by the size of the vessels, the nature of the inflammatory exudate, and the specific organs involved. The clinical and laboratory findings are variable and frequently nonspecific. Therapy ranges from essentially just observation to high-dose steroids combined with immunosuppressive agents, but treatment must be individualized. Early and correct diagnosis is thus important, but because there is considerable overlap between diseases, especially in the leukocytoclastic vasculitis group, one should never delay initiation of therapy while one is trying to finalize the diagnosis, particularly when the patient may be deteriorating rapidly.

Clinical and genetic evidence that juvenile arthritis is not a single disease.

Ample evidence shows that what was formerly called "juvenile rheumatoid arthritis" is not a single disease. At least six separate diseases were included as subgroups or subtypes of juvenile rheumatoid arthritis in other classifications. The clinical and laboratory features that differentiate these diseases are discussed. Genetic differences, primarily within the HLA system but also for T-cell receptor genes are described and correlated with the new clinical classification of arthritis.

Persistent hypertransaminasemia as the presenting finding of childhood muscle disease.

Four children with isolated, persistent elevations of serum transaminases were investigated for hepatic disease and followed for 4 to 24 months before serum creatine kinase determinations were obtained and found to be markedly elevated. Evidence of muscle disease was obtained by close questioning, retrospectively, and mild abnormalities were found on physical examination. Review of laboratory tests in our center for 6 months revealed 30 additional cases of anicteric hypertransaminasemia (20% of those with elevated enzymes), only two of which were unexplained by the admitting diagnosis. Serum transaminase values are elevated in a variety of diseases of different organ systems. Creatine kinase determinations may provide the clue to the diagnosis of occult muscle disease in some children with unexplained anicteric hypertransaminasemia.

Back pain as the presenting symptom in juvenile dermato/polymyositis.

Juvenile dermato/polymyositis is an inflammatory myopathy that usually presents with symmetrical hip and shoulder girdle muscle weakness, with or without a skin rash. In our series of 78 patients with dermato/polymyositis, we found eight children whose initial complaint was back pain, a rare symptom at the onset of other pediatric rheumatic diseases. This unusual presentation significantly delayed the correct diagnosis in most of our cases.

The clinical features, course, prognosis and treatment of juvenile arthritis.

The author's classification of juvenile arthritis (JA) differs from most by utilizing both the type of onset and the disease course separated into individual subgroups. The clinical aspects of each are described in detail, along with the special tests and studies to be done to differentiate them. Particular attention is given to the differences between the four subgroups of the pauciarticular onset group. There are different genetic factors for each subgroup and new data on HLA typing utilizing DNA techniques may be helpful in the prognosis of the disease course. The therapy of JA begins with non-steroidal anti-inflammatory drugs, continues with second-line drugs such as gold and penicillamine, and finally leads to the use of immunosuppressive agents. The range of doses, the maximal dose, and the frequency of administration is given for each medication. The long-term prognosis is generally good, with a low death rate, primarily seen in the systemic onset patients. The causes of death vary around the world. Prognosis for continued joint activity and joint function is determined significantly by the type of onset and is worse in the rheumatoid factor positive polyarticular onset group.

The role of the streptococcus in poststreptococcal reactive arthritis and childhood polyarteritis nodosa.

Poststreptococcal reactive arthritis is most likely a form of acute rheumatic fever. However, it frequently differs by early development of arthritis after pharyngitis, more prolonged arthritis or arthralgia and a less dramatic response to aspirin. The use of prophylactic penicillin is discussed and advocated. Childhood polyarteritis may be divided into a cutaneous form and a more generalized form that usually involves the kidney but frequently also the gastrointestinal tract, heart, or nervous system. Nine children with polyarteritis nodosa are described and their disease related to a prior streptococcal infection.