The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium.

The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity is modulated by voltage, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.

Cytokeratin intermediate filament pattern in uterine cervical biopsies.

Twenty-seven uterine cervical biopsies with histological diagnoses ranging from normal through dysplasia to invasive carcinoma were analysed for cytokeratin pattern in two-dimensional gel electrophoresis. No direct correlation between histological diagnosis and cytokeratin pattern was observed.

[Histopathological studies of the acute and chronic toxic effects of 2 N-nitroso compounds on the blue mussel (Mytilus edulis)]. / Histopatologiske studier af akut og kronisk toksisk effekt af to N-nitrosoforbindelser hos blåmuslingen (Mytilus edulis).

The acute and chronic effects of two N-Nitroso compounds (N-Nitrosodimethylamine) (DMN) and N-Methyl-N-Nitro-N-Nitrosoguanidine (MNNG) were studied by light microscopy after injection of the chemicals into the foot of the mussel, Mytilus edulis. Acute toxic effects: DMN produced dose-dependent (0.1 to 0.8 mg DMN/mussel) tissue alterations characterized by extensive inflammatory reactions in the Leydig cell tissue of the digestive gland, and necrosis in the germinal epithelium lining the genital ducts. MNNG produced dose-dependent (0.063 to 0.5 mg MNNG/mussel) tissue alterations characterized by extensive necrosis in the epithelial lining of the tubules of the digestive gland. Chronic toxic effects: 0.2 mg DMN/mussel given once a week for 8 weeks, and examined over a period of 30 weeks, revealed tissue alterations characterized by extensive collagenous scar tissue formation in between the tubules of the digestive gland, presence of numerous granulocytomas, and necrosis of the germinal epithelium of the genital ducts. 0.125 mg MNNG/mussel given once a week for 4 weeks, and examined over a period of 7 months, produced tissue alterations mainly characterized by encapsulation or replacement of damaged digestive tubules by collagenous scar tissue.

Hypereosinophilia in a patient with acute lymphoblastic leukemia.

A case of a coincident acute lymphoblastic leukemia and marked eosinophilia is presented. The clinical and pathological features of this case are discussed with special emphasis on the hypereosinophilic syndrome versus secondary hypereosinophilia that can be found to accompany ALL. Special immunological studies may be helpful in the diagnostic procedures.

Cytokeratin intermediate filament pattern and human papillomavirus type in uterine cervical biopsies with different histological diagnosis.

The cytokeratin pattern and the presence of human papillomavirus (HPV) were analyzed in 53 uterine cervical biopsies. The biopsies were histologically characterized and the diagnosis ranged from normal through dysplasia to carcinoma. The cytokeratins were identified by their immunological reactivity with the monoclonal antibodies AE1 and AE3. The tissue was typed for the presence of HPV types 11, 16 and 18. We have previously shown that there was no correlation between the expression of cytokeratins No. 14, 15, 16 and 19 (K14, K15, K16 and K19) and the histological diagnosis of cervical biopsies. The present study shows that the cytokeratin pattern cannot be correlated to HPV infection of the cervical tissue either.

Oral acyclovir suppressive therapy in severe recurrent genital herpes. A double-blind, placebo-controlled cross-over study.

A randomised, double-blind, placebo-controlled cross-over study was conducted in 24 patients, nine females and 15 males, with a history of more than eight recurrences of genital herpes in the past year. The patients received a first treatment course with 400 mg acyclovir or matching placebo by mouth, twice daily, for 12 weeks. After cross-over patients received alternative medication for another 12 weeks. The patients were followed without treatment for a further three-month period. During acyclovir therapy, recurrences were completely prevented in 17 patients (71%) and the remaining seven patients had nine recurrences as compared to 18 recurrences while receiving placebo. The placebo treatment did not reduce the recurrence rate. No adverse effects were attributable to the acyclovir treatment period. All virus isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe. A continuous suppressive therapy with acyclovir offers a basis for a normal sexual life to those patients severely incapacitated by their disease, but once medication is stopped, patients shed virus as before suppression.

Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study.

BACKGROUND: Previous studies have shown an increased risk of inflammatory bowel disease (IBD) among relatives of patients with Crohn disease and ulcerative colitis. In the present study the probandwise concordance rates for ulcerative colitis and Crohn disease among mono- and dizygotic twins were estimated. Further we aimed to evaluate whether smoking habits might influence the concordance, and to look for clinical characteristics of concordant versus discordant twin pairs. METHODS: Among the 38,507 identified twins born in Denmark from 1953 to 1982, a questionnaire was sent to the 34,076 who previously had accepted to participate in studies. For twins reporting IBD, the diagnosis was verified by applying standard criteria to records requested from hospitals or practitioners. RESULTS: Among the 29,421 (86.3%) twins answering the questionnaire, 103 pairs had at least one twin who suffered from IBD. In the Crohn disease group five of 10 monozygotic pairs, but none of 27 dizygotic pairs were concordant. In the ulcerative colitis group three of 21 monozygotic, and two of 44 dizygotic pairs were concordant. The probandwise concordance rate among monozygotic pairs was 58.3% for Crohn disease and 18.2% for ulcerative colitis; among the dizygotic pairs the rates were 0 and 4.5%, respectively. The frequency of smokers was higher among twins with Crohn disease and lower among twins with ulcerative colitis compared to the frequency in the twin register. Furthermore, smoking habits were found to be of significance for discordance for disease. Regarding the clinical characteristics no homogenous pattern was observed within the concordant pairs and the differences between concordant and discordant pairs were not significant. CONCLUSION: The observation of a significantly higher concordance rate among monozygotic than among dizygotic twin pairs strongly points to a genetic influence on occurrence of IBD, which seems to be more pronounced with regard to Crohn disease than to ulcerative colitis. Differences in smoking habits among the members of the discordant twin pairs may influence the discordance.

Topical tromantadine in the treatment of genital herpes. A double-blind placebo controlled study.

A randomised double-blind placebo controlled trial was performed to assess the efficacy and safety of tromantadine ointment 1% in male patients with genital herpes. 45 patients with penile genital herpes of less than three days duration were randomised to local treatment with tromantadine ointment 1% or placebo (ointment base alone) five times daily up to 12 days. No difference in time of healing could be detected between the two groups (p = 1.0). Both the objective signs (vesicles, pustules, ulceration, and glandular swelling) and the subjective symptoms (itching, burning, pain and dysuria) all diminished simultaneously in the two groups.

Intellectual and social function of patients surviving cardiac arrest outside the hospital.

Thirteen survivors of cardiac arrest outside the hospital were examined by clinical and psychological tests 1-3 years after the incidence, and compared to a matched control group of 13 patients with acute myocardial infarction without cardiac arrest. Psychological tests revealed that 7 patients with previous cardiac arrest and 4 control patients had mild-moderate to moderate-severe dementia. The demential symptoms were not detectable by a clinical interview. Four patients in each group exhibited pronounced anxiety symptoms. There were no clear differences between the two groups in respect of changes in cardiac function and social status after the incidence.