Nonenzymatic glycosylation of proteins and protease activities in granulation tissues in experimental diabetes

Serum proteins and hemoglobins show increased nonenzymatic glycosylation in diabetes mellitus. The measure of glycosylated proteins, particularly hemoglobin, is considered to be a preferred indicator in the control of diabetes. In a study of diabetes and inflammation, we assessed the extent of nonenzymatic glycosylation of proteins of granulation tissue from diabetic rats. Five, seven, and ten days after carrageenan injection, the granuloma proteins were extracted. Nonenzymatic glycosylation was measured in soluble and insoluble granuloma proteins by thiobarbituric acid assay. Protease activities and free amino groups were assayed in soluble extracts. Nonenzymatic glycosylation in soluble proteins of both groups reached a maximum on the seventh day. However, nonenzymatic glycosylation in soluble proteins of the diabetic granulomas was significantly greater than the controls on days five and seven. During the days after granuloma induction, nonenzymatic glycosylation in the insoluble granuloma tissue proteins gradually decreased without any significant differences between controls and diabetics. Significant decreases in the free amino groups in soluble proteins of the diabetic tissues were noted. Greater activities of cathepsins B and D were noted in diabetic tissues over controls. These observations suggest that, in addition to increased proteolysis, increased nonenzymatic glycosylation of tissue proteins could be associated with the impaired process of wound healing in diabetics.     

Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo.     

Is an aggressive surgical approach to the patient with gastric lymphoma warranted?

At the Mayo Clinic, from 1970 through 1979, 84 patients (52 males and 32 females) had abdominal exploration for primary gastric lymphoma. All patients were observed a minimum of 5 years or until death. The histologic findings for all 84 patients were reviewed. Forty-four patients had "curative resection," and 40 patients had either biopsy alone or a palliative procedure. The probability of surviving 5 years was 75% for patients after potentially curative resection and 32% for patients after biopsy and palliation (p less than 0.001). The operative mortality rate was 5% overall and 2% after potentially curative resection. Increased tumor size (p less than 0.02), increased tumor penetration (p less than 0.01), and lymph node involvement (p less than 0.02) decreased the probability of survival, whereas histologic classification did not affect survival. Radiation therapy after surgery did not significantly affect the survival rate for the entire group or the survival rate for patients who had potentially curative resection. Resectability was associated with increased patient survival--independent of other prognostic factors--when our experience was analyzed by the Cox proportional-hazards model (p less than 0.005). It was concluded that an aggressive surgical attitude in the treatment of primary gastric lymphoma is warranted. The role of radiotherapy remains in question.     

Konsekutive Serie von 100 Colonresektionen mit einer modifizierten fortlaufenden Nahttechnik

Zusammenfassung Es wird anhand einer konsekutiven Serie über eine modifizierte fortlaufende Nahttechnik am Colon berichtet, die gerade bei älteren Patienten eine sichere und rasche Methode der Anastomosierung darstellt. Die klinisch relevante Insuffizienzrate sowie auch die Letalitätsrate betrugen in dieser Serie je 2%, wobei die Ursachen für die Letalität aber keine Folge der Insuffizienz waren. Die Komplikationsrate betrug 11%, die urologischen Komplikationen mit 6% standen hierbei im Vordergrund.

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A consecutive series of 100 resections of the colon using a modified technique of continuous (running away) suture

Summary Based on a consecutive series it is reported about a modified type of continuous suture on the colon, used especially in elderly patients for being a secure and prompt method of anastomosing. The rate of insufficiency and mortality, as far as the clinical relevance is concerned, turns out to be 2% each and there was no relation between mortality and insufficient anastomosis. The complication rate was 11%, whereby the urological complications predominated with 6% of the total.

     

Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.     

The midsagittal area of the corpus callosum and total neocortical volume differ in three inbred strains of mice

Differences in the midsagittal area of the corpus callosum have been reported between human males and females, between handled and nonhandled rats, and both within and between various strains of mice. This measure has, in addition, been related to handedness in humans and "pawedness" in certain strains of mice. The present study investigated the between- and within-strain differences in three inbred strains of mice, two with autoimmune disorders and spontaneously occurring developmental neuropathology, in the midsagittal area of the corpus callosum, the total neocortical volume, and the asymmetry of the neocortex. These morphometric measures were obtained from coronally sectioned celloidin-embedded material from New Zealand Black (NZB/BINJ), BXSB/MpJ, and DBA/2J mouse strains. NZB mice had a total neocortical volume larger than that of either the BXSB or DBA strains, whereas the BSXB mice had a midsagittal area of the corpus callosum larger than that of either of the other two strains. In addition, there was a positive correlation between these two measures. There was no correlation between total neocortical asymmetry and midsagittal area of the corpus callosum in any of the three strains. Finally, there were no differences in any morphometric measure between animals with or without developmental neuropathology in any given strain.     

Occult breast carcinoma presenting with axillary lymph node metastases: a follow-up study of 48 patients

Breast carcinoma presenting with axillary metastases and no clinically apparent primary tumor in the breast is an uncommon form of stage II disease. Published studies have been characterized by small numbers and/or limited follow-up information. Although these patients are often looked on individually as having advanced disease, several published reports suggest that their prognosis is not exceptionally grave. The present study evaluated the largest series thus far described, consisting of 48 patients with a median follow-up of 5 years. Each presented with an axillary mass which proved to be metastatic adenocarcinoma, consistent with mammary origin when examined histologically. No patient had a palpable breast tumor. Mammography was negative in 28 patients (76%), and suspicious or positive in nine (24%). Nine (35%) of 26 metastases were positive for estrogen (ER) and progesterone (PR) receptors, 10 (38%) were negative for both receptors, and seven (27%) were ER positive/PR negative. Primary treatment was mastectomy and axillary dissection in 38 cases, 21 with adjuvant chemotherapy. A primary tumor was found pathologically in the breast in 36 cases (75%). Among 34 reviewed primary lesions, 27 (79%) were invasive and seven (21%) were histologically "noninvasive." Measured size was 0.1 to 6.5 cm (median, 1.5 cm). The number of involved lymph nodes was one to 65 with 20 cases having one to three positive and 20 having four or more positive. Follow-up ranged from 5 to 267 months (median, 60 months). Overall, 29 patients (60%) remained alive and disease free; two (4%) were disease free, but died of other causes; and the status of two (4%) was not known. Fifteen patients developed recurrent carcinoma, including 12 (25%) who died of disease. When compared with a matched series of stage II patients with equivalent extent of disease who presented with palpable breast tumors, patients with occult lesions had a more favorable prognosis overall, as well as when stratified by tumor size and nodal status, but the differences were not statistically significant. These results probably reflect the fact that the majority of stage II patients with clinically occult breast carcinoma usually have a grossly measurable invasive tumor detected pathologically. Consequently, the actual pathologic stage, which takes tumor size into consideration, determines prognosis rather than the apparent clinical stage described when the patient is first examined.