The ultrastructure of multilamellar bodies and surfactant in the human lung

Summary Normal tissues from human lungs were dehydrated through Epon 812 resin to retain many of the lipids and carbohydrates in thin section. The three-dimensional structure of the multilamellar body was determined. The paired layer of phospholipid heads (PH) is 36Å thick; the layer of fatty-acid tails (FA) is 31Å, the same as reported previously for non-human primates and rodents. The human multilamellar body is apparently unique: the lamellae of the major focus divide into two or three lamellae; the matrix material of the core is without vesicular bodies and a projection core is present. When compared with those of the rat, human tissues contain a greater number of lamellar foci and fewer lamellae per focus. The presence of a peripheral layer of lamellae, an ever-present external limiting membrane, and the fusion of multilamellar bodies are also characteristic. Tubular myelin surfactant has the same appearance as in other mammals.Multilamellar bodies were observed in direct communication with Golgi vesicles. Their origin from multivesicular bodies and their maturation through secretion and exocytosis were demonstrated.Untransformed multilamellar bodies in the alveolar space demonstrated three periodicities (P): (1) compact regular lamellae, PH = 36Å, FA = 31Å, P = 66Å; (2) compact broad lamellae, PH = 72Å, FA = 22Å, P = 94Å; (3) loose lamellae, PH = 36Å, FA = 36Å, FA = 31Å with a variable interlamellar space.Appreciation is expressed to Nuket Olson and Phil Offenhauser for their technical assistance. Supported by a grant from the American Lung Association     

The taxonomic affinities of the genus Ripogonum

The genus Ripogonum J. R. et G. Forst. is usually included in either the Smilacaceae or Liliaceae, but it has been accorded family rank. A numerical taxonomic study of the phenetic relationships of Ripogonum and all genera of the Smilacaceae, Dio-Scoreaceae, Petermanniaceae, Philesiaceae and Luzuriagaceae has been undertaken in terms of 56 characters. The results support the view that Ripogonum is only distantly related to either Smilacaceae or Dioscoreaceae and instead has affinities with Luzuriagaceae. None-the-less Ripogonum merits family status and so Ripogona-ceae are formally validated.     

Prostaglandin E2 attenuates preoptic expression of GABAA receptors via EP3 receptors

Prostaglandin E(2) (PGE(2)) has been shown to produce fever by acting on EP3 receptors within the preoptic area of the brain. However, there is little information about the molecular events downstream of EP3 activation in preoptic neurons. As a first step toward this issue, we examined PGE(2)-induced gene expression changes at single-cell resolution in preoptic neurons expressing EP3. Brain sections of the preoptic area from PGE(2)- or saline-injected rats were stained with an anti-EP3 antibody, and the cell bodies of EP3-positive neurons were dissected and subjected to RNA amplification procedures. Microarray analysis of the amplified products demonstrated the possibility that gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunits is decreased upon PGE(2) injection. Indeed, we found that most EP3-positive neurons in the mouse preoptic area are positive for the alpha2 or gamma2 GABA(A) receptor subunit. Moreover, PGE(2) decreased the preoptic gene expression of these GABA(A) subunits via an EP3-dependent and pertussis toxin-sensitive pathway. PGE(2) also attenuated the preoptic protein expression of the alpha2 subunit in wild-type but not in EP3-deficient mice. These results indicate that PGE(2)-EP3 signaling elicits G(i/o) activation in preoptic thermocenter neurons, and we propose the possibility that a rapid decrease in preoptic GABA(A) expression may be involved in PGE(2)-induced fever.     

In vivo contact kinematics and contact forces of the knee after total knee arthroplasty during dynamic weight-bearing activities

Analysis of polyethylene component wear and implant loosening in total knee arthroplasty (TKA) requires precise knowledge of in vivo articular motion and loading conditions. This study presents a simultaneous in vivo measurement of tibiofemoral articular contact forces and contact kinematics in three TKA patients. These measurements were accomplished via a dual fluoroscopic imaging system and instrumented tibial implants, during dynamic single leg lunge and chair rising-sitting. The measured forces and contact locations were also used to determine mediolateral distribution of axial contact forces. Contact kinematics data showed a medial pivot during flexion of the knee, for all patients in the study. Average axial forces were higher for lunge compared to chair rising-sitting (224% vs. 187% body weight). In this study, we measured peak anteroposterior and mediolateral forces averaging 13.3% BW during lunge and 18.5% BW during chair rising-sitting. Mediolateral distributions of axial contact force were both patient and activity specific. All patients showed equitable medial-lateral loading during lunge but greater loads at the lateral compartment during chair rising-sitting. The results of this study may enable more accurate reproduction of in vivo loads and articular motion patterns in wear simulators and finite element models. This in turn may help advance our understanding of factors limiting longevity of TKA implants, such as aseptic loosening and polyethylene component wear, and enable improved TKA designs.     

Functional interactions between Sae2 and the Mre11 complex

The Mre11 complex functions in double-strand break (DSB) repair, meiotic recombination, and DNA damage checkpoint pathways. Sae2 deficiency has opposing effects on the Mre11 complex. On one hand, it appears to impair Mre11 nuclease function in DNA repair and meiotic DSB processing, and on the other, Sae2 deficiency activates Mre11-complex-dependent DNA-damage-signaling via the Tel1-Mre11 complex (TM) pathway. We demonstrate that SAE2 overexpression blocks the TM pathway, suggesting that Sae2 antagonizes Mre11-complex checkpoint functions. To understand how Sae2 regulates the Mre11 complex, we screened for sae2 alleles that behaved as the null with respect to Mre11-complex checkpoint functions, but left nuclease function intact. Phenotypic characterization of these sae2 alleles suggests that Sae2 functions as a multimer and influences the substrate specificity of the Mre11 nuclease. We show that Sae2 oligomerizes independently of DNA damage and that oligomerization is required for its regulatory influence on the Mre11 nuclease and checkpoint functions.