Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3

Genetic linkage studies have indicated that chromosome 14q24.3harbours a major locus for early-onset (onset age <65 years)Alzheimer's disease (AD3). Positional cloning efforts have identifieda novel gene S182 or presenilin 1 as the AD3 gene. We have mappedS182 in the AD3 candidate region between D14S277 and D14S284defined by genetic linkage studies in the two chromosome 14linked, early-onset AD families AD/A and AD/B. We have shownthat S182 is expressed in lymphoblasts and have determined thecomplete cDNA in both brain and lymphoblasts by RT-PCR sequencing.S182 is alternatively spliced in both brain and lymphoblastswithin a putative phosphorylation site located 5' in the codingregion. We identified two novel mutations, Ile143Thr and Gly384Alalocated in, respectively, the second transmembrane domain andin the sixth hydrophilic loop of the putative transmembranestructure of S182. As families AD/A and AD/B have a very similarAD phenotype our observation of two mutations in functionallydifferent domains suggest that onset age and severity of ADmay not be very helpful predictors of the location of putativeS182 mutations.     

Evaluation of the in vitro Cytotoxicity of some Sesquiterpene Lactones on a Human Lung Carcinoma Cell Line Using the Fast Green Dye Exclusion Assay.

Amongst the properties associated with the sesquiterpene lactones, their cytotoxicity is probably the most valuable. In this IN VITRO study cytotoxicity of some sesquiterpene lactones from EUPATORIUM CANNABINUM L. and related compounds have been tested on a human small cell lung carcinoma cell line, using the Fast Green dye exclusion assay (FGA). From the results certain conclusions could be drawn about structure activity relationship. Eupatoriopicrin, eupatoriopicrin acetonide, "substance 1" and hiyodorilactone E showed highest cytotoxicity (ID50 1-2 microg/ml) following 1 h incubation. Moieties of the sesquiterpene lactones (alpha-methylene gamma-butyrolactone, eupatolide, angelic and tiglic acid) and related compounds (alantolactone and isoalantolactone) were less or not active at these concentrations. From the results of the experiments it can be concluded that the entire molecule (germacranolide ester) is necessary for optimal cytotoxicity IN VITRO and that cytotoxicity increases with decreasing hydrophilicity.     

Anastomotic insufficiency in small bowel surgery —incidence and treatment

Summary In the period 1977–1981 234 small bowel anastomoses were constructed in 143 patients. Eight anastomoses showed leakage (3.4%) and from nine anastomoses a fistula developed (3.8%): a total rate of disturbed healing of small bowel anastomoses (7.3%). In the presence of intra-abdominal infection this rate was 14.8%, in the absence of infection 0.8%. The results of treatment with oversewing and with resection and immediate anastomosis were disappointing. Better results were obtained by dismantling of the anastomosis, establishment of a split-enterostomy and reestablishment of continuity in a second stage. Mortality was 3/17 (18%). The literature is reviewed.

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Insuffizienz von Dünndarmanastomosen — Ineidenz und Therapie

Zusammenfassung In dem Zeitraum 1977–1981 wurden bei 143 Patienten 234 Dünndarmanastomosen angelegt. Acht Anastomosen zeigten eine Nahtleckage (3,4%), bei neun entwickelte sich eine Fistel (3,8%): die Gesamthäufigkeit von Wundheilungsstörungen bei Dünndarmanastomosen war 7,3%. Bei gleichzeitigem Vorliegen intraabdominaler Infektionen betrug die Häufigkeit 14,8%, ohne diese 0,8%. Die Resultate einer Therapie durch Übernähung oder Resektion mit sofort anschließender Reanastomosierung waren enttäuschend. Befriedigendere Ergebnisse wurden durch Aufheben der Anastomosen, Anlage einer split enterostomy unter Wiederherstellung der Kontinuität in einer zweiten Sitzung erzielt. Die Mortalität betrug 3/17 (18%). Ein Literaturüberblick wird gegeben.

     

Autistic Traits,Empathizing–Systemizing,and Gender Diversity

Archives of Sexual Behavior - Previous research indicates a link between autism and transgender and gender-diverse identities, though the association is not yet fully understood. The current study...     

The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast

Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.     

Modelling and monitoring organochlorine and heavy metal accumulation in soils,earthworms, and shrews in Rhine-delta floodplains

In the Rhine-delta, accumulation of microcontaminants in floodplain foodwebs has received little attention in comparison with aquatic communities. To investigate organochlorine and metal concentrations in a terrestrial foodchain, samples of soil, earthworms (Lumbricus rubellus), and shrew (Crocidura russula, Sorex araneus) livers and kidneys were taken from two moderately to heavily polluted floodplains.Chlorobiphenyl residues in earthworm fat were 0.10 to 3.5 times the concentrations in soil organic matter, whereas ratios for other organochlorines varied between 0.87 and 8.8. These ratios are one order of magnitude lower than expected from laboratory experiments with earthworms, and laboratory and field studies on aquatic invertebrates. Bioconcentration ratios for heavy metals are in accordance with literature values for other locations, confirming the high potential for cadmium accumulation in Lumbricidae.Concentrations of organochlorines in shrew liver lipids were 1.0 to 13 times the residues in earthworm fat. These values are higher than lipid-corrected biomagnification ratios for laboratory rodents, but equal to those measured for benthivorous birds in the Rhine-delta. On a dry weight basis, kidney-earthworm ratios for cadmium were about one order of magnitude lower than previously reported values for insectivores.Soil concentrations of many compounds in both floodplains did not meet Dutch quality standards. Yet, hexachlorobenzene, chlorobiphenyl 153 (PCB153), -hexachlorocyclohexane, DDT, and dieldrin residues in earthworms and shrews did not exceed diet levels expected to be safe for endothermic species. An exception was noted for cadmium in worms and shrew kidneys.Heavy metal pollution in soil was close to levels that are critical to earthworms in laboratory studies. Cadmium concentrations in shrew kidneys were below levels suggested to be safe for Sorex araneus, but above those that were critical to the rat.     

Familial congenital bilateral agenesis of the acromion: a radiologically illustrated case report

Summary Familial congenital bilateral acromion absence was found in four members of one family. Only one of them presented with gradually increasing pain in his left shoulder, resembling a shoulder impingement syndrome. The other members did not have any symptoms. This is the first report of familial occurrence of this extremely rare congenital anomaly.

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Agénésie familiale bilatérale de l'acromion : une observation illustrée radiologiquement

Résumé L'absence congénitale bilatérale de l'acromion a été observée chez quatre membres d'une même famille. L'un d'eux seulement présentait des douleurs de l'épaule gauche progressivement croissantes ressemblant à un syndrome de blocage de l'épaule. Les autres membres n'avaient aucun symptôme. Il s'agit de la première observation familiale de cette anomalie congénitale extrêmement rare.

     

Rebound thymic hyperplasia after chemotherapy in a patient treated for pulmonary metastases

A 38-year-old patient presented with an anterior mediastinal mass after chemotherapeutic and surgical treatment for lung metastases from a malignant histiocytoma. Because of the risk for tumour recurrence the thymic mass was resected. Thymic hyperplasia was found on pathological examination. In this case thymic hyperplasia is a rebound phenomenon aflcer chemotherapy. It appears to atrophy during the administration of chemotherapy and regrow afterwards. Surgical resection provides the definitive diagnosis and treatment.     

Rapid emergence of resistant coagulase-negative staphylococci on the skin after antibiotic prophylaxis

One approach for prosthetic vascular surgery is to continue antimicrobial prophylaxis while intravascular lines and catheters are in place. However this may give rise to antimicrobial resistance in the colonizing bacterial flora. We studied 37 patients undergoing vascular surgery, who received either co-amoxyclav for three days (group 1), ofloxacin plus metronidazole for three days (group 2) or for one day (group 3), respectively. Seventeen hospitalized patients not undergoing surgery or receiving antibiotics were studied as controls. In groups I and II there was a significant decline in susceptibility to cloxacillin (12.8% respectively 23.6%) and ofloxacin (0.5% and 85% respectively) in skin staphylococci. The results from group 3 were intermediate. Molecular typing showed that the patient's susceptible community-derived strains were replaced by genetically unrelated resistant strains, probably hospital derived. Long-term prophylaxis should be avoided as colonization occurs with resistant strains.