DNA polymorphism of HLA class II genes in systemic lupus erythematosus

Abstract: We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA-DRB, -DQA, -DQB, -DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3- and DRw6-associated 7.00 kb DRB Taq I DNA fragment was found in SLE patients compared to normal controls (83.3% vs 35.5%; RR = 9.1, p < 10^-4). The frequencies of the DQA1*0501-associated 4.56 kb DQA Taq I fragment and the DRB3*01/03-associated 9.79 kb Taq I fragment were also found to be significantly increased in SLE patients (70.8% vs 29.7%; RR = 5.8, p < 10^-2 for the DQA fragment and 70.8% vs 36.1%; RR = 4.3, p < 0.05 for the DRB3 fragment). Less extensive and insignificant increases of the frequencies of the DR3-associated DQB and DPB fragments were observed. The frequencies of the DR2-associated DRB, DQA, and DQB fragments were comparable to those found in normal controls.     

Feline Coronavirus Serotypes 1 and 2: Seroprevalence and Association with Disease in Switzerland

To determine the prevalence of antibodies to feline coronavirus (FCoV) serotypes 1 and 2 in Switzerland and their association with different disease manifestations, a serological study based on immunofluorescence tests was conducted with Swiss field cats using transmissible gastroenteritis virus (TGEV), FCoV type 1 and FCoV type 2 as antigens. A total of 639 serum samples collected in the context of different studies from naturally infected cats were tested. The current study revealed that, with an apparent prevalence of 83%, FCoV serotype 1 is the most prevalent serotype in Switzerland. FCoV type 1 viruses induced higher antibody titers than FCoV type 2, and were more frequently associated with clinical signs and/or feline infectious peritonitis. The antibody development in seven cats experimentally infected with FCoV type 1 revealed that, with progressing duration of infection, antibodies to FCoV type 1 significantly increased over those to FCoV type 2. There was a significant relationship between antibody titers against TGEV, FCoV 1, and FCoV 2 and TGEV antigen detected the highest proportion of seropositive cats. We conclude that a vaccine against FCoV should be based on FCoV type 1-related antigens and that for serodiagnosis of FCoV infection TGEV should be used to attain the highest diagnostic efficiency. When serology is used in addition to clinical signs, hematology, and clinical chemistry results as an aid to diagnose clinical FIP, TGEV shows a diagnostic efficiency equal to that of a FCoV antigen.     

DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: Probably A different origin for infantile and adolescent germ cell tumours

The origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non-seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells. The presence of carcinoma in situ cells strongly suggested that the adolescent tumours arose from carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.     

Acute effects of light and darkness on sleep in the pigeon (Columba livia)

In addition to entraining circadian rhythms, light has acute effects on sleep and wakefulness in mammals. To determine whether light and darkness have similar effects in birds, the only non-mammalian group that displays sleep patterns comparable to mammals, we examined the effects of lighting changes on sleep and wakefulness in the pigeon. We quantified sleep behavior (i.e., bilateral or unilateral eye closure) in pigeons maintained under a 12:12 LD cycle, and immediately following a change from a 12:12 to a 3:3 LD cycle. During both LD cycles, sleep was most prevalent during dark periods. During the 3:3 LD cycle, darkness had the greatest sleep promoting effect during the hours corresponding to the subjective night of the preceding 12:12 LD cycle, whereas light suppressed sleep across circadian phases. As previously suggested, the light-induced decrease in sleep in the subjective night might be partly mediated by the suppression of melatonin by light. Although the sleep promoting effect of darkness was modulated by the circadian rhythm, sleep in darkness occurred during all circadian phases, suggesting that darkness per se may play a direct role in inducing sleep. In addition to the effects of lighting on behavioral state, we observed an overall bias toward more right eye closure under all lighting conditions, possibly reflecting a response to the novel testing environment.     

Novel KChIP2 isoforms increase functional diversity of transient outward potassium currents

Kv4.3 channels conduct transient outward K⁺ currents in the human heart and brain where they mediate the early phase of action potential repolarization. KChIP2 proteins are members of a new class of calcium sensors that modulate the surface expression and biophysical properties of Kv4 K⁺ channels. Here we describe three novel isoforms of KChIP2 with an alternatively spliced C-terminus (KChIP2e, KChIP2f) or N-terminus (KChIP2g). KChIP2e and KChIP2f are expressed in the human atrium, whereas KChIP2g is predominantly expressed in the brain. The KChIP2 isoforms were coexpressed with Kv4.3 channels in Xenopus oocytes and currents recorded with two-microelectrode voltage-clamp techniques. KChIP2e caused a reduction in current amplitude, an acceleration of inactivation and a slowing of the recovery from inactivation of Kv4.3 currents. KChIP2f increased the current amplitude and slowed the rate of inactivation, but did not alter the recovery from inactivation or the voltage of half-maximal inactivation of Kv4.3 channels. KChIP2g increased current amplitudes, slowed the rate of inactivation and shifted the voltage of half-maximal inactivation to more negative potentials. The biophysical changes induced by these alternatively spliced KChIP2 proteins differ markedly from previously described KChIP2 proteins and would be expected to increase the diversity of native transient outward K⁺ currents.     

Near‐infrared spectroscopy determined brain and muscle oxygenation during exercise with normal and resistive breathing

To elevate effects of carbon dioxide (CO₂) retention by way of an increased respiratory load during submaximal exercise (150 W), the concentration changes of oxy‐ (ΔHbO₂) and deoxy‐haemoglobin (ΔHb) of active muscles and the brain were determined by near‐infrared spectroscopy (NIRS) in eight healthy males. During exercise, pulmonary ventilation increased to 33 (28–40) L min^–1 (median with range) with no effect of a moderate breathing resistance (reduction of the pneumotach diameter from 30 to 14 and 10 mm). The end‐tidal CO₂ pressure (P_ETCO ₂) increased from 45 (42–48) to 48 (46–58) mmHg with a reduction of only 1% in the arterial haemoglobin O₂ saturation (S_aO ₂). During control exercise (normal breathing resistance), muscle and brain ΔHbO₂ were not different from the resting levels, and only the leg muscle ΔHb increased (4 (–2–10) μM , P < 0.05). Moderate resistive breathing increased ΔHbO₂ of the intercostal and vastus lateralis muscles to 6 ± (–5–14) and 1 (–7–9) μM (P < 0.05), respectively, while muscle ΔHb was not affected. Cerebral ΔHbO₂ and ΔHb became elevated to 6 (1–15) and 1 (–1–6) μM by resistive breathing (P < 0.05). Resistive breathing caused an increased concentration of oxygenated haemoglobin in active muscles and in the brain. The results indicate that CO₂ influences blood flow to active skeletal muscle although its effect appears to be smaller than for the brain.     

Amyloid deposits in aortic and mitral valves

Summary The material from 100 consecutive aortic and mitral valve operations has been studied histologically with particular reference to the presence of amyloid deposits. Sixty seven per cent were positive (aortic 88%, mitral 45%).The simultaneous occurrence of calcification of the valves and amyloid degeneration as well as of calcification and hyalinization was significant. Similarly there was significantly more amyloid in the older age groups, as well as a significant correlation between the degree of hyalinization of the valve and amyloid.]Thirty-two patients had previously suffered from rheumatic fever. The heart valves of these patients did not differ histologically from the others, whereas significantly more amyloid was observed in the stenotic mitral valves than in the mitral valves which were insufficient.     

ASO Visual Abstract: Prediction of Pathologic Complete Response in Breast Cancer Patients Comparing Magnetic Resonance Imaging with Ultrasound in the Neoadjuvant Setting

Annals of Surgical Oncology -     

Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis

Thirty-six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA-DPw1-w6 and the local specificity CDPHEI with bulk-expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA-DPw2 was 52.8% in PJCA patients and 16.7% in controls (relative risk, RR = 4.5; P less than 0.001). The antigens HLA-Dw5 and/or Dw8 were present in 50% of the patients and in 21.3% of the controls (RR = 4.2; p less than 10(-3)). DPw2 was not associated (in linkage disequilibrium) with Dw5/w8 in patients or in controls, and the DP and D associations with PJCA were independent of each other. However, the combined presence of DPw2 and Dw5 and/or Dw8 gave a significantly higher risk of PJCA than each antigen alone indicating interaction of DP and DR gene products. PJCA is the first disease definitely found to be associated with a DP antigen.