Structural determinants of calcium signaling by RGD peptides in rat osteoclasts: integrin-dependent and -independent actions

Extensive characterization of the vitronectin receptor (VNR), a member of the integrin group of cell adhesion molecules, which is abundantly expressed in osteoclasts, has revealed a role for this receptor in osteoclast adhesion as well as bone resorption. Earlier evidence from our laboratory suggests that VNR is also capable of transducing intracellular signals following receptor ligand interaction, although this function is poorly understood. Thus, addition of peptides containing the minimal tripeptide Arg-Gly-Asp (RGD) integrin recognition sequence elicits transient increases in intracellular free calcium ions, with maximal responses seen with a bone sialoprotein peptide, BSP-IIA. In the present study we have attempted to determine some of the structural requirements for calcium signaling in osteoclasts using derivatives of the peptide PRGDN/T sequence found in bone sialoprotein. While some peptides, such as the parent sequence PRGDN, can induce both signaling and retractile events, it was found that minor structural modifications yielded peptides such as PRADN which elicited a transient increase in intracellular free calcium ions without promoting a reduction in osteoclast spread area (retraction). Conversely, certain other modifications resulted in peptides, such as PrGDN and benzoyl-RGDN, which effect osteoclast retraction, while having minimal Ca2+ signaling capabilities. Osteoclast adhesion, and hence retraction, are known to be RGD-dependent and integrin-dependent events. However, intracellular Ca2+ signaling is RGD-independent and, based on lack of inhibition by an anti-beta 3 integrin antibody F11 and echistatin, very likely integrin-independent. These data suggest that signaling is not always via VNR and as yet unknown receptors on the osteoclast membrane play a role in osteoclast signaling and hence function.     

Colour Doppler flow in normal axillary lymph nodes

81 women with carcinoma of the breast who underwent axillary nodal dissection were studied pre-operatively with colour Doppler ultrasound. The presence of colour Doppler flow was demonstrated in 83.6% of normal lymph nodes compared with 87.5% of metastatic lymph nodes. Using the presence of colour Doppler signal as the sole diagnostic criterion for the diagnosis of metastasis gave a sensitivity of 92.5%, specificity of 9.52%, accuracy of 50%, positive predictive value of 49.3% and negative predictive value of 57.1%. Using grey scale sonographic criteria, where a metastatic node was defined as a node with loss of central fatty hilum and/or eccentric cortical hypertrophy, a sensitivity of 79.5%, specificity of 94.0%, accuracy of 87.6%, positive predictive value of 91.2% and negative predictive value of 85.5% were obtained. Colour Doppler studies of the axillary nodes in a second group of 106 women who attended for breast cancer screening and had no significant breast or axillary pathology also showed colour Doppler signal in 86.7% of nodes. It is concluded that colour Doppler flow signals can be demonstrated in both normal and metastatic axillary lymph nodes, and is highly non-specific when used as the sole diagnostic criterion in the diagnosis of malignancy.     

Effectiveness of a worksite smoking cessation program in the military. Program evaluation

1. A program evaluation was conducted to evaluate the effectiveness of the smoking cessation program. Substantiating data enhances the value of health promotion programs as key components of the health care delivery system. 2. Persons enrolled in the 8 week smoking cessation program and members of a comparison group were administered an evaluation tool prior to participating in the program, with a second evaluation tool upon completion of the program. Afterward, the smoking status of the members of both groups was evaluated at 3 month intervals for a period of 1 year. 3. Of the participants, 26.7% were not smoking 12 months after the program, compared to 6.9% of the comparison group. Of those participants who resumed smoking, 64% smoked less than half the amount they smoked before taking the class.     

The airway resistance-lung volume plot as a measurement of the closing volume

Following abdominal surgery, insulin and glucose concentrations in the portal vein, and a peripheral vein are compared in patients during control periods and after oral administration of glucose. During the control period, the glucose concentrations are identical in both veins. After glucose loads with the prompt increase of portal glucose concentration the portal-peripheral difference also increases (p less than 0.01). During the control period the insulin concentration in the portal vein is double as compared to peripheral blood (p less than 0.005). After glucose load the increasing portal insulin as well as the peripheral and portal glucose correlate with the portal-peripheral insulin difference (p less than 0.001). Furthermore, there is a significant positive correlation between the peripheral glucose area as a parameter of glucose tolerance and the portal insulin area as a semiquantitative parameter of insulin secretory capacity (p less than 0.001). It can be concluded that in the early postoperative period in patients with a diminished oral glucose tolerance (large glucose areas) there is an even greater insulin response in comparison to patients with normal oral glucose tolerance. On the other hand, however, in those patients with diminished glucose tolerance, the insulin response is essentially delayed.     

Development of neurosurgery in southern California and the Los Angeles county/University of Southern California Medical Center

We reported a case of successful treatment of bilateral pulmonary metastasis from rectal cancer with high-dose 5'-DFUR plus MMC combination chemotherapy. A woman born in 1948 showed a recurrence in the bilateral lung about 29 months after low anterior resection. High-dose 5'-DFUR plus MMC combination chemotherapy was started in March, 1991. The chest X-ray examination 8 weeks after beginning this therapy showed a remarkable decrease in the size of the pulmonary metastatic foci and CEA decreased in the same way. The dose of 5'-DFUR was reduced after 5 courses, and then CEA increased. No remarkable side effect was encountered and the patient could be safely treated at an outpatient clinic. During this therapy no recurrence has been detected, and we performed a resection of the bilateral pulmonary metastasis by median sternotomy in October, 1991. The above findings suggested that this was an effective and safe therapy for pulmonary metastasis from colon cancers and could be a neo-adjuvant chemotherapy for surgical resection of pulmonary metastasis.     

Superinfection exclusion by bacteriophage T7

Only two of the early genes of bacteriophage T7 were found to play a significant role in exclusion of superinfecting bacteriophage T3 particles; genes 0.3 and 1. Protein synthesis by the preinfecting phage particle was not required for efficient exclusion. These findings are discussed with regard to the known functions of these genes during T7 development.