Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Spleen cells, peripheral lymphocytes, and soleus muscles were removed from male Sprague-Dawley rats that had been run on a treadmill (24 m/min) for either 20, 40, or 60 min or to exhaustion (86 +/- 41 min) and were labeled in vitro with [35S]methionine at 37 degrees C. Similar tissues from nonrunning control rats were labeled in vitro at either 37 or 43 degrees C (heat shock). Fluorographic analyses of one- and two-dimensional polyacrylamide gel electrophoretic separations of the proteins from cells and tissues of exercised rats demonstrate the new or enhanced synthesis of proteins of approximately 65, 72, 90, and 100 kDa. Although synthesis of these proteins is low or not detectable in tissues from control rats labeled at 37 degrees C, they are prominent products of similar tissues labeled under heat-shock conditions (43 degrees C) and, in fact, correspond in Mr and pI with the so-called heat-shock proteins. These results suggest that exercise is a sufficient stimulus to induce or enhance the synthesis of heat shock and/or stress proteins in mammalian cells and tissues.

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The fine structure and the distribution of an esterase have been studied in the cuticle of Galleria larvae, Tenebrio larvae and pupae, and in the wax-secreting cuticle of the honey bee, and compared with those in the cuticle of the caterpillar of Calpodes. In Galleria and Tenebrio the pore canals are spaces passing through the lamellate endocuticle from the epithelium to the epicuticle. They contain a filament from the cells which may be concerned in their formation. The shape of the pore canal is probably determined by the orientation of the fibres making up the lamellae in the endocuticle and is not a regular helix. The pore canals also contain numerous filaments of another sort which pass on through the epicuticle and are believed to be the origin of the surface wax. They are particularly abundant in the pore canals of the honey bee wax-secreting cuticle and extend into the cell in long pockets surrounded by an envelope of the plasma membrane. The esterase is probably concerned with the final stage of wax synthesis, for its distribution is similar to that of the lipid filaments.

In the larva of the butterfly Calpodes ethlius, the fat body begins to store protein in the form of granules at about 30 to 35 hours before pupation, at a time when the endocuticle is being resorbed. At least two sorts of granule can be distinguished. The first granules to arise are those within vesicles of the Golgi complex. These may increase in size by incorporating material from microvesicles at their surface and by coalescence with one another. Later, at about 10 hours before pupation, another sort of granule arises by the isolation of regions of the endoplasmic reticulum (ER) within paired membranes derived from Golgi vesicles. Several of these ER isolation bodies coalesce, with fusion of their outer isolating membranes. The ribosomes and membranes may then disappear and the granules become indistinguishable from the protein granules formed from Golgi vesicles, or the ribosomes may remain and be embedded in dense crystalline protein, forming a storage body for both protein and RNA. Mitochondria are isolated within paired membranes in the same way as regions of the ER. The isolated mitochondria also coalesce in a similar manner. When the inner membranes are lost, the structure of a group of isolation bodies is indistinguishable from that of a cytolysome. Isolation within paired membranes, as described here, may be of general importance in segregating regions of massive lysis or massive sequestration.

Techniques for staining (silver, osmium, metal sulfides, ink) and microphotography (epi-illumination) of polished bone surfaces have been developed to visualize the three-dimensional structure of the shafts of mammalian long bones. Bone is a two-compartment system with capillaries and some kinds of connective tissue in one compartment separated from fibers of bone collagen, often forming lamellae, in the other. Laminar bone consists of stacks of lamellae separated by vascular spaces containing capillary network sheets. It is deposited at the periosteal and endosteal surfaces. Osteonic bone, well described in the literature, consists of cylinders of lamellae with central vascular spaces. The primary structure of the shafts of mammalian long bones is laminar and laminae often remain as the main component. Secondary osteons are a replacement within laminae. As laminar bones mature, some of the irregular longitudinal capillary spaces in the network sheets enlarge and become less crooked to form secondary osteons. Parts of the random networks become ordered longitudinal ones, resulting in collapse of those network spaces not converted to osteons. The residual capillaries become bloodless, making the surviving network spaces difficult to resolve. This may account for them being overlooked in descriptions of bone structure. For example, laminar bone occurs with osteonic bone in the human femur, although it is rarely figured. Nearly mature bones switch the kind of primary bone deposited at the peripheral (periosteal) surface from laminar to primary osteonic.

Heat-shock protein 72 (HSP72), the inducible isoform of the HSP70 family, is constitutively expressed in rat hindlimb muscles in proportion to the content of type I muscle fibers. To determine whether this relationship was maintained after fiber transformation, male Sprague-Dawley rats were treated with 3,5,3'-triiodo-DL-thyronine (T3) for 40 days or underwent surgical removal of the left gastrocnemius muscle, after which the left plantaris muscle was allowed to hypertrophy for 30 days. Hypertrophied plantaris muscles exhibited an increased number of type I fibers, type I myosin heavy-chain (MHC) protein, and HSP72 content compared with contralateral muscles. Soleus muscles from rats administered T3 exhibited an increased number of type II fibers, citrate synthase activity, and decreased HSP72 content compared with soleus muscles from controls. These results indicate that the relationship between HSP72 content and type I muscle fiber-MHC composition is maintained when muscles undergo fiber transformation and substantiate that HSP72 content in rat skeletal muscle is not directly linked to a muscle's oxidative capacity.