Fine mapping of human HOX gene clusters

The chromosome localization of human HOX gene clusters has been reinvestigated by fluorescence in situ hybridization (FISH). Three loci were precisely localized in 7p15.3 (HOXA@), 17q21.3 (HOXB@) and 12q13.3 (HOXC@). The localization of HOXD@ was confirmed to 2q31.     

The gene product of human cytomegalovirus open reading frame UL56 binds the pac motif and has specific nuclease activity

Using the cis-acting human cytomegalovirus (HCMV) packaging elements (pac 1 and pac 2) as DNA probes, specific DNA-protein complexes were detected by electrophoretic mobility shift assay (EMSA) in both HCMV-infected cell nuclear extracts and recombinant baculovirus-infected cell extracts containing the HCMV p130 (pUL56) protein. DNA-binding proteins, which were common in uninfected and infected cell extracts, were also detected. Mutational analysis showed that only the AT-rich core sequences in these cis-acting motifs, 5'-TAAAAA-3' (pac 1) and 5'-TTTTAT-3' (pac 2), were required for specific DNA-protein complex formation. The specificity of the DNA-protein complexes was confirmed by EMSA competition. Furthermore, a specific endonuclease activity was found to be associated with lysates of baculovirus-infected cells expressing recombinant p130 (rp130). This nuclease activity was time dependent, related to the amount of rp130 in the assay, and ATP independent. Nuclease activity remained associated with rp130 after partial purification by sucrose gradient centrifugation, suggesting that this activity is a property of HCMV p130. We propose a possible involvement of p130 in HCMV DNA packaging.     

The correlation between skin electrical conductance and the score of qi vacuity

In traditional Chinese medicine, the syndrome of qi vacuity means that the patient's body has a low level of energy to react to stress. Recently, we used a score, the QV score, by scaling the severity of symptoms and signs of qi vacuity in patients with tiredness. The aim of this study was to investigate the relationship between QV score and skin electrical conductance in patients with tiredness. One hundred and forty-three healthy controls and 103 patients with tiredness were involved. Each subject received a weak electrical stimulation with constant voltage (1.75 volt), and conductance was measured between two different limbs. The mean value of skin conductance among four limbs was calculated and expressed by a special unit, namely Chin. The correlation between the skin conductance and QV score was analyzed by a linear regression analysis. The results showed that skin electrical conductance of healthy controls was negatively correlated with age (r-coefficient = -0.51, P = 0.000). The skin conductance of patients with tiredness was significantly lower than that of healthy controls with matching age (P = 0.000 by Student's t-test). Moreover, there was a positive correlation between the decrease of skin conductance and the QV score in patients with tiredness (r-coefficient = +0.68, P = 0.000). These results suggest that a decrease in skin electrical conductance may be closely related to the severity of qi vacuity. The skin conductance test is a simple, reliable, and quantitative method for detection of syndrome of qi vacuity.     

Anticentromere antibodies in rheumatologic practice are not consistently associated with scleroderma

Anticentromere antibodies identified by indirect immunofluorescence are a valuable aid to the diagnosis and prognosis of patients with systemic sclerosis since they are associated in 50% to 80% of cases with limited cutaneous systemic sclerosis, a pattern usually associated with a good prognosis. We studied clinical presentations in rheumatology patients with anticentromere antibodies by indirect immunofluoresence and by ELISA and/or Western blot, but without scleroderma or Raynaud's phenomenon. Eight of 34 (23.5%) rheumatology clinic patients with centromere antibodies met these criteria, seven women and one man, with a median symptom duration of six years (range 1-20 years). Four had Sj?gren's syndrome, one had isolated xerostomia, one systemic lupus erythematosus, one seronegative symmetric polyarthritis and one primary biliary cirrhosis with arthralgia. The mean anticentromere antibody titer in these eight patients was similar to that in the patients who had at least Raynaud's phenomenon. Given the low incidence of scleroderma, these data illustrate the poor predictive value of anticentromere antibodies for the diagnosis of scleroderma in rheumatology clinic patients.     

Role of glutamate receptor subtypes in the differential release of somatostatin, neuropeptide Y, and substance P in primary serum-free cultures of striatal neurons

The objective of this study was to determine if hyperthyroidism affects the responses of Müller's muscle to alpha-1 adrenoceptor agonists and consequently, if these responses might explain thyroid eyelid retraction. Sprague-Dawley adult rats (n = 37) were divided into control and treated groups and given either placebo or intraperitoneal triiodothyronine (250 micrograms/kg/d) for 1, 2, or 3 weeks. A suture was passed through their upper eyelid and connected to a force transducer that measured Müller's muscle contractions. Responses to phenylephrine (0.015-0.61 mmol) were compared with respect to peak amplitude and 50% duration of action. Mean maximum force values [+/-1 standard error of the mean (SEM)] in response to phenylephrine were 1.254 +/- 0.071 gr for controls and 0.963 +/- 0.062 gr for thyroid-treated subjects (p = 0.005). Mean 50% duration of response values (+/-1 SEM) were 9.143 +/- 1.108 min for controls and 5.763 +/- 0.973 min for thyroid-treated subjects (p = 0.014). Hyperthyroid rats had a significantly lower Müller's muscle response amplitude than control rats; however, duration of response was not significantly different between the groups. We believe that hyperthyroidism caused intrinsic changes in Müller's muscle that resulted in eyelid retraction. Based on hypotheses discussed in this article, we expect that further studies will localize these changes to the thyroid hormone receptor on Müller's muscle or calcium-triggered intracellular second messengers. Clinical significance would then be the ability to treat hyperthyroid eyelid retraction with drugs. This study provides the first evidence of functional impairment of Müller's muscle due to hyperthyroidism in an animal model.     

Characterization of four toxins from Buthus martensi scorpion venom, which act on apamin-sensitive Ca2+-activated K+ channels

What are the relative roles of imitation, improvisation and invention in the development of large song repertoires in species of the songbird family Mimidae? This question was addressed in a laboratory study of the vocal development of young grey catbirds, Dumetella carolinensiscollected from western Massachusetts. Two groups heard a repeated 10-s, tape-tutored segment of catbird song, two other groups heard a repeated 16-min segment and a fifth group heard no tape-tutored songs. One male selected for study from each group developed a large repertoire of seemingly normal songs, and wild males responded strongly to songs of the male that had heard no tape-tutored song. Relying little on precise imitation and largely on improvising or inventing, each male developed a highly unique repertoire. A geographical survey of catbird song revealed little to no evidence of song sharing or microgeographical variation, which is consistent with the idea that imitation plays a relatively minor role in song development. Perhaps simultaneous selection for large repertoires and reduced geographical variation has led to such an emphasis on song individuality and non-imitative developmental processes.     

Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes

In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20-year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and who had been followed up for at least 1 year following that biopsy (total follow-up with advanced disease 2,010 patient years) were identified (243 female, 30 male). Patients who developed HCC were identified and their confounding risk factors were excluded. Mayo risk scores were calculated for each clinic attendance and expected survival for each time point was compared with subsequent actual survival. Sixteen cases of HCC were seen in the patients with stage III or IV disease on last biopsy, providing an overall incidence of 5.9% in this group. Fourteen of these patients had died of HCC related causes, and 2 patients were alive at the census point. The incidence of HCC was significantly higher in males with stage III/IV disease than in females (20% vs. 4.1%, P < .005). Nine of one hundred and eight (8.3%) total female deaths in this group was attributable to HCC compared with 5 of 11 (45.5%, P < .05) male deaths. HCC was not seen in any of the 394 patients with stage I and II PBC followed-up over the same time period. Throughout the disease course of all PBC patients with HCC, the Mayo prognostic model over-predicted survival. Whereas it is a relatively rare complication of cirrhotic PBC in women, HCC is a relatively common cause of death in male PBC patients with cirrhosis. HCC typically develops several years after the onset of cirrhosis, and is poorly predicted by prognostic models. In view of these findings, consideration should be given to careful screening for HCC in male PBC patients with cirrhosis. The risk of HCC development may be an additional reason to consider earlier transplantation in these patients.