Targeting of "T" lymphocytes against human hepatoma cells by a bispecific monoclonal antibody: role of different lymphocyte subsets.

In an attempt to construct bispecific monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4-8+ TCR alpha/beta+ and CD3+4-8-TCR gamma/delta+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3 + 4 + 8-TCR alpha/beta+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNF-alpha) by all the different subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.     

The indication of surgical treatment of cerebellar hemorrhage]

61 patients with cerebellar hemorrhage were studied. The age at onset ranged from 15 to 84 years with a mean of 57.4 years. 49 cases were treated conservatively and 12 surgically and the mortality rates of the two groups were 32.5% and 25% respectively. Based on this study, it is suggested that the clinical and CT indications of surgical treatment of hematoma are as follows; Severe disturbance of consciousness; Bilateral eyeball fixation; Volume of hematoma over 10 ml; Size of hematoma over 4 cm in diameter; Marked acute obstructive hydrocephalus; Compression of cisterna ambieus and quadrigeminus.     

Passive exercise system: effect on muscle activity, strength, and lean body mass.

There is little information concerning the effects of passive exercise training in healthy humans. This prompted an investigation to evaluate muscle activity and the associated changes in strength and lean body mass resulting from a passive exercise program. Twenty-eight healthy volunteers, aged 26 to 44 years, participated in this six-week study. Lean body mass changes were evaluated by tetrapolar bioelectric impedance measurements, strength changes by isokinetic strength evaluation, and muscle activity by surface EMG techniques. Reproducible muscle activity was recorded in all three muscles studied during two of three preselected exercises. This involuntary muscle activity was attributed to fusimotor and postural reflexes. No significant change (p greater than .05), however, occurred in muscle strength or lean body mass at the end of the six weeks. Lack of these physiologic changes in light of the documented muscle activity is attributed to insufficient training effect.     

Microwave technique in hepatic surgery: report of 70 cases]

70 hepatic resections were performed using 2450 MHz microwave scalpel. Primary diseased included hepatocellular carcinoma (46 cases), hemangioma (18), hepatobiliary tract stone (2), biliary cystadenoma (1), inflammatory pseudotumor of the live (1), metastatic liver cancer (2). Hemostasis was excellent despite liver cirrhosis in all cases. The average amount of blood loss and blood transfusion was 249 ml and 294 ml respectively. Blood transfusion was not necessary in 30 patients. All cases were free from postoperative bleeding from the liver stump and abdominal infection. No complications attributable to microwave coagulation were noted. We conclude that this new operative technique can be used safely and easily in the field of hepatic surgery.     

Fetal dexamethasone exposure affects basal ornithine decarboxylase activity in developing rat brain regions and alters acute responses to hypoxia and maternal separation

Although glucocorticoids are widely used to stimulate fetal/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions. Dexamethasone treatment produced an initial inhibition of basal ODC activity followed by postnatal elevations, a pattern known to be associated with delays in cell replication and differentiation. Dexamethasone also interfered with the ability of the 1-day-old neonate to turn off ODC acutely in response to a 2-h period of maternal separation; as this response conserves energy in the absence of the dam, the effect of dexamethasone is maladaptive. Additionally, dexamethasone sensitized the neonatal brain to hypoxia: the acute increase of ODC associated with a 2-h exposure to 7% O2 was exacerbated in 8-day-old rats exposed to dexamethasone prenatally. These results suggest that administration of dexamethasone, in doses that promote respiratory competence, delays cell development in the central nervous system and renders the brain more vulnerable to adverse neonatal conditions, such as maternal separation or hypoxia.     

Stable Transfection of Nonosteogenic Cell Lines with Tissue Nonspecific Alkaline Phosphatase Enhances Mineral Deposition Both in the Presence and Absence of β-Glycerophosphate: Possible Role for Alkaline Phosphatase in Pathological Mineralization

It is documented that alkaline phosphatase (AP) plays an important role in bone mineralization. Considering that TN-AP is expressed in periodontal ligament fibroblasts, renal epithelial cells, and vascular endothelial cells, and that TN-AP is both a calcium-/phosphate-binding protein and a phosphohydrolytic enzyme, we hypothesize that membrane-bound AP also plays an important role in the initiation of physiological and pathological mineralizations in tissues other than bone and cartilage. To test this hypothesis, nonosteoblast cell lines, including a fibroblast line, a renal epithelial line, and a capillary endothelial line, were stably transfected to express high levels of rat bone AP on their cell surfaces. These rat bone AP-expressing cells were then cultured on filter membranes in the presence or absence of β-glycerol phosphate. von Kossa staining for calcium phosphate and transmission electron microscopy with electron diffraction analysis for minerals were employed to investigate the effect of membrane AP on extracellular calcium phosphate mineralization. Our results indicated that AP expression on these nonosteoblast-like cell surfaces have induced extracellular hydroxyapatite (HAP) mineralization. Our findings support the concept that membrane-bound AP contributes to extracellular apatitic mineralization by mechanisms that do not necessarily involve its hydrolase activity. They also suggest that AP might be important for the initiation of pathological mineralization in nonosteogenic tissues. Received: 11 January 1996 / Accepted: 31 October 1996     

Soda pop vending machine injuries: an update.

Soda pop vending machine tipping continues to be a dangerous behavior that can result in lethal or crippling injuries. This study analyzes 64 cases of injuries secondary to crushing by a soda machine. All were male victims except one. The average age was 19.8 years with a range of 5-39 years. Thirteen victims sustained multiple trauma. Fifteen victims were killed. Increased public awareness coupled with support by the government and private industry has contributed to a sharp reduction in incidence of accidents and improved public safety.