Stereochemistry in self-assembled encapsulation complexes: constellational isomerism

A previously uncharacterized form of stereochemistry, constellational isomerism, is described. The isomerism arises from different arrangements of small-molecule guests in the space of a self-assembled, cylindrical host. The cylindrical host detains three molecules each of CHCl(3), 1,2-dichloroethane, or isopropyl chloride. The exchange of guests in and out of the host is slow on the NMR time scale. The dimensions of the capsular host and the sizes of the guests hinder the mobility of molecules inside, and separate NMR signals are seen for guests at the ends of the capsule and those near its center. When two different guests are encapsulated, the spectra show up to four additional species: two sets of constellational isomers. In every pairwise combination of the three guests, all isomers could be identified. The equilibrium distributions of isomers depended on the concentrations of the guests in the bulk solution. The relative stability of the constellational isomers was a function of the polarity of the guest molecule and its ability to interact with the components of the capsule. The different arrangements represent information, and some possibilities for their use in data storage are proposed.     

Metastasis of rectal cancer to lymph nodes and tissues around the autonomic nerves spared for urinary and sexual function

PURPOSE: To clarify the indications for autonomic nerve-sparing operations for rectal cancer, the presence of lymph nodes and metastasis in the tissue around the autonomic nerve were examined in 28 rectal cancer patients. These were staged as pT2 in 8 patients, pT3 in 19 patients, and pT4 in 1 patient histopathologically. METHODS: The specimens of the autonomic nerve including the inferior mesenteric plexus, preaortic plexus, superior hypogastric plexus, hypogastric nerve, and pelvic plexus were removed with radical abdominopelvic lymphadenectomy after the autonomic nerve-sparing rectal cancer operation. RESULTS: In the tissue around the autonomic nerve, lymph nodes were 11.2±9.6 in number and 2.6±2.4 mm in size (mean ± standard deviation). The frequency of presence of lymph nodes was higher and the number of lymph nodes was larger in the inferior mesenteric plexus (70.4 percent; 3.6) and the preaortic plexus (66.7 percent; 2.1) than in the left and right pelvic plexuses (39.1 percent, 1; 36 percent, 1). Metastasis to the lymph nodes or lymphatic permeation in the tissue around the autonomic nerve were observed in four cases (14.3 percent) of lower rectal cancer, consisting of three with Stage III cancer (pT3, pN1-3, and M0) and one with Stage IV cancer (pT4, pN1, and pM1 (HEP)). CONCLUSION: Radical rectal excision that includes lymph nodes and adjacent tissue around the autonomic nerves may result in metastatic tumor removal that would otherwise be left in situ with nerve-sparing techniques for advanced rectal cancer in Stage III.     

A mutation in the extracellular cysteine-rich repeat region of the beta3 subunit activates integrins alphaIIbbeta3 and alphaVbeta3

Inside-out signaling regulates the ligand-binding function of integrins through changes in receptor affinity and/or avidity. For example, alphaIIbbeta3 is in a low-affinity/avidity state in resting platelets, and activation of the receptor by platelet agonists enables fibrinogen to bind. In addition, certain mutations and truncations of the integrin cytoplasmic tails are associated with a high-affinity/avidity receptor. To further evaluate the structural basis of integrin activation, stable Chinese hamster ovary (CHO) cell transfectants were screened for high-affinity/avidity variants of alphaIIbbeta3. One clone (AM-1) expressed constitutively active alphaIIbbeta3, as evidenced by (1) binding of soluble fibrinogen and PAC1, a ligand-mimetic antialphaIIbbeta3 antibody; and (2) fibrinogen-dependent cell aggregation. Sequence analysis and mutant expression in 293 cells proved that a single amino acid substitution in the cysteine-rich, extracellular portion of beta3(T562N) was responsible for receptor activation. In fact, T562N also activated alphaVbeta3, leading to spontaneous binding of soluble fibrinogen to 293 cells. In contrast, neither T562A nor T562Q activated alphaIIbbeta3, suggesting that acquisition of asparagine at residue 562 was the relevant variable. T562N also led to aberrant glycosylation of beta3, but this was not responsible for the receptor activation. The binding of soluble fibrinogen to alphaIIbbeta3(T562N) was not sufficient to trigger tyrosine phosphorylation of pp125(FAK), indicating that additional post-ligand binding events are required to activate this protein tyrosine kinase during integrin signaling. These studies have uncovered a novel gain-of-function mutation in a region of beta3 intermediate between the ligand-binding region and the cytoplasmic tail, and they suggest that this region is involved in integrin structural changes during inside-out signaling.     

Excessive zinc intake elevates systemic blood pressure levels in normotensive rats--potential role of superoxide-induced oxidative stress

OBJECTIVES: The present study was designed to examine whether or not excessive Zn intake affects systemic blood pressure (BP) levels in a normotensive state. METHODS: Systolic BP (SBP) and mean arterial pressure (MAP) before and after administration of the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) or the exogenous superoxide scavenger, tempol and the activity of the endogenous superoxide scavenger, Cu/Zn-superoxide dismutase (SOD) and levels of endothelial type (e)NOS mRNA and protein in the thoracic aorta were analyzed in male Sprague-Dawley rats fed a standard diet containing 0.005% Zn or a high Zn diet containing 0.5% Zn for 8 weeks. RESULTS: SBP and MAP levels observed at the end of dietary conditioning were significantly elevated in rats fed a high Zn diet relative to rats fed a standard diet. Administration of L-NAME caused an increase in MAP levels in rats fed a standard and a high Zn diet, demonstrating the involvement of the vasodilator, nitric oxide (NO) in the regulation of systemic BP in the two groups of rats. However, the expression of eNOS mRNA and protein in the thoracic aorta was not significantly different between rats fed a standard and a high Zn diet. On the other hand, administration of tempol led to a decrease in MAP levels in rats fed a standard and a high Zn diet, indicating the participation of the oxygen free radical, superoxide in the modification of systemic BP in the two groups of rats. As reported recently, the mechanism involved is due likely to a decrease in the action of the vasodilator, NO through the formation of peroxynitrite based on the non-enzymatic reaction of superoxide and NO. In addition, tempol treatment dramatically restored MAP levels in rats fed a high Zn diet to levels comparable with those observed in rats fed a standard diet, indicating that an elevation in systemic BP levels seen in rats fed a high Zn versus a standard diet is presumably brought by a reduction in the action of the vasodilator, NO resulting from an increase in the action of superoxide. The activity of Cu/Zn-SOD in the thoracic aorta was significantly reduced in rats fed a high Zn diet relative to rats fed a standard diet, appearing to at least in part, play a role in an increase in the action of superoxide in the vessel wall of rats fed a high Zn diet. CONCLUSIONS: Excessive Zn intake may be a factor to elevate systemic BP levels in a normotensive state presumably through the oxidative stress caused by superoxide.     

Range of Motion of the Temporomandibular Joint in Rheumatoid Arthritis: Relationship to the Severity of Disease

The purpose of this study was to determine the frequency and nature of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) patients with symptoms in this joint, and to investigate the relationship of symptoms to the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and Steinbrocker stage. Clinical examination of the range of motion of the TMJ was performed in 218 RA patients. In addition, correlations between the maximal mouth opening and the severity of RA were studied. Restriction in opening the mouth (defined as ≤ 30 mm movement in the central incisor region from the fully occluded to maximally open positions) was observed in 12.8% of the RA patients (28/218). The CRP, ESR and Steinbrocker stage were all correlated with maximal opening (p < 0.05). There was a positive correlation between the severity of RA and the range of motion of the jaw.     

The superior approach with the stomach roll-up technique improves intraoperative outcomes and facilitates learning laparoscopic distal pancreatectomy: a comparative study between the superior and inferior approach

Surgery Today - We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal...