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G L Ong

Publications and source records attributed to G L Ong.

16 recordsLinked to original sources
PubMed1992

Analysis of high complement levels in Mus hortulanus and BUB mice.

BUB/BnJ mice were previously identified as having exceptionally potent complement activity, relative to common mouse strains, in the lysis of antibody-coated human tumor cells. We describe herein our investigation into the molecular and genetic basis for this difference between mouse strains, and also our results with wild mice and mouse strains recently derived from the wild, to determine whether low complement levels are characteristic of wild mice. BUB complement was compared with complement from BALB/c and C57BL/6 mice. BUB mice had higher levels of most individual classical pathway components, except for C1, than the other two strains, but the difference was generally only 2-3-fold, so insufficient to fully explain the difference observed with tumor target cells. CH50 titers on antibody-coated sheep erythrocytes also demonstrated only a 2-4-fold difference. However, CH50 titers on antibody-coated human erythrocyte target cells demonstrated a difference similar in magnitude to that seen with human tumor targets. These results suggest that the difference between mouse strains depends partly on the use of human, rather than sheep, target cells. In an assay for alternative complement pathway activity using neuraminidase-treated human erythrocytes as targets, complements of BALB/c and BUB mice were similar in activity, suggesting that the difference between mouse strains is manifested in the early steps of complement activation. Analysis of F1 and backcross mice suggested that the difference in complement level between BUB and BALB/c or C57BL/6 mice is controlled by semi-dominant genes, and cannot be attributed to a single gene. Wild mice and mice recently derived from the wild generally had low complement levels, similar to most laboratory mice. However, three strains of aboriginal mice, including Mus hortulanus (spicilegus) and Mus spretus, had complement levels higher than that of BUB mice, and as high as sera from the rabbit or rat, which are the most potent known complement sources for the lysis of human tumor cells. In comparison with BUB mouse sera, M. hortulanus sera had at least four-fold higher levels of C3, C6, C8 and C9, and some or all of these differences may explain its higher total complement activity. In the lysis of antibody-coated human erythrocytes, M. hortulanus serum was more potent than any other complement source tested, including sera of the guinea pig, rat, rabbit or human. These strains may be useful in investigating the role of complement in various pathological processes, and in investigating the genetic regulation of the complement system.

Animals↗
PubMed1992

The fate of antibodies bound to the surface of tumor cells in vitro.

The fate of monoclonal antibodies binding to the surface of human tumor cells in vitro was investigated. Seven antibodies, labeled with 125I, were tested on four cell lines, which included a melanoma and carcinomas of the ovary, kidney, and lung. The antibodies were selected only by the criterion that they not be rapidly internalized via coated pits, so that they would be representative of most antibodies reacting with cell surface antigens. After allowing binding during a 2-h incubation, unbound antibody was removed, and the release of intact or degraded antibody in the supernatant was monitored. The data demonstrate that most bound antibody was gradually degraded and released from the cell over a 2-3-day period, probably via internalization, while only a small fraction, less than 20% for most antibodies, appeared to dissociate intact. One exceptional antibody, MW207, dissociated largely intact. The release of intact antibody was virtually complete within 4 h, and radioactivity released after this time was predominantly in degraded form. These results demonstrate that antibody binding to the surface of viable cells must in general be considered irreversible, and hence the concept of affinity is not applicable. Since an Fab fragment of one of the antibodies dissociated rapidly, such irreversible binding appears to require bivalent attachment. Another conclusion of this study is that most antibodies binding to the cell surface are gradually internalized, which we suggest is due to the normal turnover of cell surface constituents via non-clathrin-dependent endocytosis. Several experimental approaches indicated that a large fraction of antibody retained by the cells, for at least 2 days after binding, was present at the cell surface.

Ammonium Chloride↗
PubMed1992

Achalasia complicated by oesophageal squamous cell carcinoma: a prospective study in 195 patients.

To determine the incidence of oesophageal carcinoma in patients with achalasia and to establish the efficacy of endoscopic surveillance, 195 consecutive patients with achalasia (90 men and 105 women, mean age 52 years), who were treated by pneumatic dilatation in our institution between 1973 and 1988 were prospectively studied. None of the patients had undergone cardiomyotomy. Follow up totalled 874 person years after pneumatic dilatation. In this period three patients developed an oesophageal squamous cell carcinoma. The mean age at diagnosis of the oesophageal carcinoma was 68 years (37, 77, and 89 years). The mean period between the onset of dysphagia and the diagnosis of the tumour was 17 years (19, 28, and 5 years); the mean interval between the diagnosis of achalasia and carcinoma was 5.7 years (5, 8, and 4 years). The incidence of oesophageal squamous cell carcinoma in this series (3.4/1000 patients per year) is significantly higher than the statistically expected incidence (0.104/1000 patients per year) using age and sex specific incidence data from the population of the Netherlands (Poisson statistics: p less than 0.001). The risk of developing oesophageal squamous cell carcinoma in patients with achalasia is therefore increased 33 fold. Periodic endoscopy showed the potential for detecting early stage oesophageal carcinoma in two cases but a larger study with a longer follow up is required to determine the efficacy of endoscopic screening in improving the prognosis for patients with achalasia who develop oesophageal squamous cell carcinoma.

Adult↗
PubMed1991

Galactose-conjugated antibodies in cancer therapy: properties and principles of action.

Galactose conjugation of antibodies causes them to be recognized by the hepatic asialoglycoprotein receptor and therefore cleared very rapidly from the blood. In these investigations, some effector functions of galactose-conjugated antibodies were assayed, and several applications to experimental tumors in vivo were demonstrated. Galactose conjugation did not interfere with two antibody functions in addition to antigen binding, namely complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity. This conjugation procedure was originally developed for its potential use in localized immunotherapy, such as i.p. Injection of galactose-antibody conjugates i.p. demonstrated, more conclusively than other methods that have been used, that the presence of ascites causes prolonged retention of antibody in the peritoneal cavity and that this effect is correlated with the volume of ascites present. In mice bearing i.p. tumor xenografts, i.p. injection of galactose-antibody conjugates resulted in high tumor/nontumor ratios at 28 h after antibody injection, with values of 40:1, 43:1, 77:1, and 11:1 for the blood, kidney, lung, and spleen, respectively, although the ratio was only 4:1 for the liver. Control experiments demonstrated that i.p. injection of unconjugated antibody or a galactose-conjugated nonreactive antibody produced much lower tumor/nontumor ratios. In investigations of possible systemic application of galactose-antibody conjugates, we found that injection of large amounts of an inhibitor that binds competitively to the hepatic receptor, asialo-bovine submaxillary mucin, can block clearance of galactose-conjugated antibodies for 2-3 days. In this way, high blood levels of antibody can be maintained for 2-3 days, thus allowing penetration and binding to solid tumors, followed by very rapid blood clearance. With this approach, using a human carcinoma growing s.c. in nude mice, high tumor/nontumor ratios were obtained 4 days after injection, with mean values of 43:1, 18:1, 17:1, and 15:1 for the blood, kidney, lung, and spleen, respectively, although the ratio for the liver was only 1.7:1. The blood level at this time was 0.04 +/- 0.02% (SD) of the injected dose/g, while the tumor level was 1.69 +/- 1.29% of the injected dose/g. In conclusion, galactose-conjugated antibodies appear to have diverse applications in regional or systemic immunotherapy.

Animals↗
PubMed1990

Changes in oxytocin and vasopressin content in posterior pituitary and hypothalamus following pantethine treatment.

Pantethine, a cysteamine precursor, depletes somatostatin in the cerebral cortex and hypothalamus and prolactin in the anterior pituitary and hypothalamus. This study investigated the effect of pantethine on oxytocin and arginine vasopressin content in the posterior pituitary and hypothalamus. Male Long-Evans rats were injected intraperitoneally with escalating doses of pantethine (i.e., 146.7 mg, 293.4 mg and 586.6 mg/100 gm body weight). Hormone content was determined by radioimmunoassay. Three hours after pantethine treatment, the oxytocin content in the posterior pituitary and the hypothalamus was markedly reduced with all doses of the drug. Vasopressin content in the posterior pituitary and hypothalamus was decreased but to a lesser extent than oxytocin and only with the highest dose of pantethine. Pantethine may act to reduce oxytocin and vasopressin content through intracellular conversion to cysteamine. The exact mechanism of action of pantethine on oxytocin and vasopressin remains to be elucidated.

Analysis of Variance↗
PubMed1990

Hypervolaemic haemodilution in an anaemic Jehovah's Witness.

We report the effects of acute hypervolaemic haemodilution, induced before operation, on haemodynamics and systemic oxygenation. Major surgery in an anaemic Jehovah's Witness patient was facilitated with this technique. Some hours after operation, a perioperative decrease in haemoglobin concentration of less than 5% was observed, in spite of a blood loss of nearly 50% of the calculated blood volume.

Adult↗
PubMed1989

Mouse strains with typical mammalian levels of complement activity.

Common laboratory mouse strains have very low complement levels relative to humans, rats, guinea pigs, rabbits and other mammals, which limits the value of the mouse as an experimental model. We therefore tested serum complement levels of 43 mouse strains and 11 rat strains, for the purpose of selecting a convenient laboratory animal having high complement levels. Total complement activity was determined with both erythrocytes and human tumor cells as targets. Eight mouse strains were identified that have complement levels comparable to those of other mammals. These mouse sera lyse tumor cell targets as well as sera from humans, rats or guinea pigs, although they are somewhat less active than rabbit sera. They are relatively inefficient in lysing erythrocyte targets, yet are as active as rabbit serum in this assay. Target cell lysis was demonstrated to be via the classical pathway of complement activation. Of the eight 'high complement' mouse strains, four were recently derived from wild mice, and one, SF/CamEi, was derived from wild mice in 1951. The three other strains, BUB/BnJ, DA/HuSn and RIIIS/J, were developed more than 40 years ago, but apparently were not tested previously for complement activity. Using the BUB mouse as a representative of the 'high complement' mice, we assayed levels of the nine complement components, in an attempt to identify the cause of high complement activity. No difference in levels of C1, C2, C4, C8 or C9 was detected between BUB and BDF1 mice. C2 activity was very low in both strains. C3, C5, C6 and C7 activities were higher in BUB mice than in BDF1 mice, indicating that variation in these complement components is responsible for the difference in total complement activity. The genes determining the 'high complement' phenotype appeared to be semi-dominant in F1 hybrids. The 'high-complement' mouse strains, and recombinant strains derived from them, will be useful in a wide range of biomedical research.

Animals↗
PubMed1989

Penetration and binding of antibodies in experimental human solid tumors grown in mice.

Monoclonal antibody localization to human carcinoma xenografts in nude mice was investigated by injecting biotinylated antibody. The antibody used in most experiments, MA103, reacts with a widely distributed human antigen present at a high density on the cell surface and has a relatively high effective affinity, 5.8 x 10(9) M-1. Various doses of antibody were injected, and tumors were collected at various times after injection. Frozen sections were stained by the immunoperoxidase method to detect bound antibody, and adjacent sections were stained with the same antibody in vitro to demonstrate total antigen distribution. In complementary experiments, unconjugated MA103 was injected in high doses to determine whether subsequent in vitro staining of frozen sections by biotinylated MA103 would be inhibited. The results demonstrate that: (a) approximately 0.5 mg antibody was sufficient to saturate antigenic sites on viable tumors cells; (b) saturation was achieved on viable tumor cells throughout the tumor 3 days after injection; (c) in necrotic areas, some antigen was accessible to antibody in vivo, but a considerable fraction of the antigen was inaccessible; (d) at 1 day after injection, stained cells were confined to areas near the blood vessels in the stroma; (e) for i.p. tumors, there was no difference between i.p. and i.v. injection of antibody and no indication of solid tumor penetration directly from the peritoneal cavity; and (f) nonspecific localization of a nonreactive biotinylated monoclonal antibody was weakly detectable and when present was seen as diffuse staining in the connective tissue only. A more limited range of experiments was performed with a second biotinylated antibody, MH99, which reacts with an epithelial cell surface antigen also recognized by many other antibodies, including 17-1A, AUA1, and KS1/4. Results were generally similar, except that a higher dose, 1.5 mg, was required to obtain homogeneous dark staining of tumor cells, and there appeared to be a considerable amount of antigen in viable areas of the tumor that was not accessible in vivo, possibly because it was intracellular. This approach appears to demonstrate tumor localization of antibody more impressively than other methods that have been used. This is partly because of the excellent resolution attained, since the reactive antibody produces a sharp membrane-staining pattern that is totally absent using a nonreactive control antibody. In addition, use of a target antigen that is predominantly on the cell surface, as opposed to cytoplasmic or secreted, is probably important. These data will be of value in attempting to use antibodies for immunotherapy.

Animals↗
PubMed1988

Immobilization stress affects oxytocin and vasopressin levels in hypothalamic and extrahypothalamic sites.

Oxytocin (OT) and vasopressin (VP) have been localized in various sites within the central nervous system outside the classic hypothalamo-neurohypophyseal axis. This study investigated the effect of immobilization stress on the levels of OT and VP in the hypothalamus, pons-medulla, and the cervical, thoracic, and lumbosacral segments of the spinal cord. Male Long Evans rats were immobilized for 1 min and sacrificed by guillotine. The tissues were dissected out and homogenized in 0.1 N HCl. The hormone content was determined by radioimmunoassay (RIA) in Sep-pak extracted samples. The data show a decrease in OT content of 33.6% (P less than 0.02) and 42.4% (P less than 0.01) in the hypothalamus and pons-medulla, respectively. In the spinal cord, however, OT levels were increased by 39.1% (not significant), 51.1% (P less than 0.05), and 87.6% (P less than 0.001) in the cervical, thoracic, and lumbosacral segments respectively. The VP content of the hypothalamus and pons-medulla did not change. However, in the spinal cord, the VP content was also increased by 101.4% (P less than 0.01) and by 143.7% (P less than 0.01) in the cervical and lumbosacral segments. The levels of VP in the thoracic segment did not change. The data demonstrate that stress can alter hypothalamic and extra-hypothalamic levels of OT as well as spinal cord levels of VP. The exact physiological effects of these changes, particularly within the spinal cord, remain to be elucidated.

Animals↗
PubMed1988

Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours.

UNLABELLED: Two patients with metastatic endocrine pancreatic tumours initially responded well to therapy with the long-acting somatostatin analogue SMS 201-995. In the first patient with an insulinoma both the number of hypoglycemic attacks and the increased insulin levels decreased initially, but returned to pretreatment intensity and concentrations within 9 days after the start of therapy with 200-300 micrograms SMS 201-995 daily. After a short interruption, no effect was observed of re-institution of therapy at a dose of 400 micrograms SMS 201-995 daily. In the other patient with a metastatic vipoma both diarrhea, hypokalemia and plasma VIP levels reacted initially well to SMS 201-995 treatment with 300 micrograms per day, but resistance to therapy developed after 2 weeks. An increase in the dose of the analogue to maximally 600 micrograms/day was followed by a transient improvement, but finally both the volume of diarrhea and the levels of vasoactive intestinal polypeptide were higher than those before the start of therapy. CONCLUSIONS: Development of resistance to SMS 201-995 both with regard to the clinical effect and to the inhibitory effect on tumour hormone secretion can be expected in some patients with metastatic endocrine pancreatic tumours. On the basis of our clinical observations down-regulation of somatostatin receptors is suggested to be one of the mechanisms of this development.

Adenoma, Islet Cell↗
PubMed1987

Correlations of serum potassium fluctuations with body temperature after major surgery.

We have observed an association between hypothermia and hypokalemia in a number of postoperative patients. In order to analyze the incidence and consequences of this correlation, 108 patients undergoing major operations were prospectively studied. Rectal temperature, serum and urinary potassium, arterial blood gases, blood glucose, and routine monitoring were analyzed. Hypothermia occurred in 35 (32%) patients, of whom 20 (57%) suffered from hypokalemia. Hypothermia was accompanied by an undercompensated metabolic acidosis in 15 (75%) and hyperglycemia in 18 (89%), while nine (45%) patients had cardiac dysrhythmias. Urinary potassium excretion was lower in hypothermic patients and therefore cannot explain the finding of hypokalemia. Administration of NaHCO3, insulin, digitalis, and calcium in patients suffering from hypothermia must be done with caution because hypokalemia may coexist with low body temperature and predispose the patients to lethal dysrhythmias.

Acidosis↗
PubMed1987

Cyclic variations in spinal cord levels of oxytocin and vasopressin during the stages of the rat estrous cycle.

Oxytocin (OT) and vasopressin (VP) have been localized to numerous central nervous system locations outside the classic hypothalamo-neurohypophyseal tract including all levels of the spinal cord. To date, the physiological function of these peptides within the spinal cord is unknown. The purpose of this study was to determine if the variations exhibited by pituitary OT and VP during the stages of the estrous cycle in the rat were also present in the spinal cord. The stage of the estrous cycle was determined by vaginal smears in female Long Evans rats. Following decapitation, the cervical, thoracic, and lumbosacral segments of the spinal cord were isolated and homogenized, and the hormones were extracted from the tissue with the Sep-pak method. OT and VP content were determined by RIA. A cyclic variation in spinal cord OT and VP was present, with maximal levels occurring in diestrus, a time in the estrous cycle when LH and estradiol levels are lowest. Our results suggest that spinal cord OT and VP may be regulated by ovarian hormones. These data represent the first documented changes in spinal cord levels of OT and VP under physiological conditions.

Animals↗
PubMed1987

Causes of failure in operations for hyperparathyroidism.

After a mean follow-up period of 6.1 years, a series of 862 patients who had undergone surgery for suspected hyperparathyroidism were evaluated to determine the reasons treatment failed. Incorrect diagnosis was found to be the cause of failure in 27 cases (3%). In 89 patients who required reoperation to achieve euparathyroidism, the three major reasons for failure were inexperience with the surgical procedure (n = 37), abnormal localization (n = 36), and multiglandular disease (n = 39). In patients with monoglandular involvement, the disease never recurred. However, of the 41 patients with more than one enlarged parathyroid gland, 20 had persistent disease and 21 others had recurrent disease with a normocalcemic interval of 1.2 to 17 years. In general, recurrent hyperparathyroidism occurs more frequently than is usually realized and thus patients with multiglandular involvement require very long follow-up periods. Persistent monoglandular disease is largely avoidable.

Clinical Competence↗