Long-Term Survival in Patients with Small Cell Lung Cancer

Of the 66 patients with small cell lung cancer (SCLC) who weretreated by combination chemotherapy with or without radiationtherapy from July 1978 to December 1983 at the National CancerCenter Hospital, Tokyo, 12 (18%) sur vived over two years andnine (14%) have remained disease-free over three years. Thetwo-year survival rates were compared according to the patientcharacteristics of sex, performance status (PS), extent of disease,histologic subtype, regimen of the initial chemotherapy andresponse to treatment. Sex, extent of disease and response tothe initial chemotherapy were the most important prognosticfactors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patientswho were treated by surgical resection after chemotherapy, achievedcomplete response (CR) with chemotherapy with or without radiationtherapy. Eleven of the 12 two-year survivors achieved CR. Becauseof the small number of patients in our study, it will be necessaryto evaluate further the influence of prognostic factors in patientswith SCLC in future studies.     

Temporal and egional profiles of cytoskeletal protein accumulation in the rat brain following traumatic brain injury

Abstract To characterize the cytoskeletal aberration due to traumatic injury, temporal and regional profiles of changes in immunoreactivity of microtubule-associated protein 2 (MAP2), neurofilament heavy subunit protein (NFH) and heat shock protein 72 (HSP72) were investigated after different magnitudes of traumatic brain injury by fluid percussion. The experimental rat brain was perfusion-fixed at 1, 6 and 24 hours after traumatic brain injury. Conventional histological staining has demonstrated that the mildest traumatic brain injury (1.0 atm) induced no neuronal loss at the impact site and that neuron loss was apparent when traumatic brain injury was increased to 4.3 atm. The mildest traumatic brain injury, however, caused a significant increase in HSP72 immunoreactivity in the superficial cortical layers at the impact site as early as 1 hour after the injury. In the case of severe traumatic brain injury (4.3 atm), neuron loss was apparent in the area at the impact site, but the increase in HSP72 immunoreactivity was moderate, and it was observed only after 6 hours in the deep cortical layers under the necrotic area. The increased immunostaining of MAP2 was demonstrated in damaged axons and neuronal perikarya in the wider area surrounding the impact site at 6 and 24 hours after the injury. Six and 24 hours after the injury, perikaryal accumulation of neurofilament was observed, and the accumulated neurofilament was mostly phosphorylated. These results indicate that the severe traumatic brain injury of 4.3 atm triggers the abnormal accumulation of cytoskeletal proteins in neuronal perikarya, most probably due to an impairment of axonal transport. It is implied that the increased expression of HSP72 may be involved in the protective process of neurons after traumatic brain injury.     

Inhibition of platelet adhesion to collagen by monoclonal anti-CD36 antibodies

Monoclonal anti CD36 antibodies capable of inhibiting platelet adhesion to collagen have not previously been identified. We have now prepared two groups of monoclonal antibodies. One group was prepared using, as immunogen, highly purified (99+%) CD36 prepared by a denaturing procedure. These antibodies (Mo series) reacted strongly with CD36 on protein blots but did not immunoprecipitate native CD36 from platelet lysates nor inhibit platelet adhesion to collagen. The second group of monoclonal antibodies (131 series) was prepared using CD36 purified to >95% by a non-denaturing procedure. These antibodies reacted with control platelets, but not Nak^a-negative platelets which lack CD36, as measured by flow cytometry and by immunoprecipitation. Three monoclonal antibodies of this latter group (131.4, 131.5 and 131.7) inhibited platelet adhesion to collagen in static systems under Mg²⁺-independent conditions but had little effect in the presence of Mg²⁺. 131.4 and 131.7 also inhibited adhesion to collagen using citrated whole blood in a parallel plate flow chamber at physiological shear rates (800 s^?1), whereas 131.5 was without effect. These are the first anti-CD36 monoclonal antibodies shown to be capable of inhibiting platelet adhesion to collagen and provide further evidence that CD36 plays a role in platelet–collagen interaction.     

Evaluation of hepatic transport function by hepatobiliary scintigraphy

The transport kinetics of [99mTc]-pyridoxyl-5-methyltryptophan were studied by three-compartment model analysis for hepatobiliary scintigraphy in 45 patients with chronic viral liver diseases. Three-compartment model analysis was studied using the time-activity curves of the regions of the heart, liver, and biliary tract and intestine (excretory compartment). The k12 (hepatic uptake rate constant), k21 (hepatic efflux rate constant), and ke1 (hepatic excretion rate constant) were calculated by the nonlinear least-squares method. Among the three parameters obtained by model analysis, k12 values more prominently differed among diseases and correlated well with blood tests such as total bilirubin, total bile acids, or 15 min retention of ICG. In conclusion, three-compartment model analysis of the hepatic handling of [99mTc]-pyridoxyl-5-methyltryptophan is useful in evaluating hepatic transport function. k12 is the most sensitive parameter for this.     

Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.     

Basaloid-squamous cell carcinoma of the oral mucosa: Report of two cases and study of the proliferative activity

Two cases of basalold-squamous cell carcinoma (BSC) of the oral mucosa are described. The first case occurred at the floor of the mouth in a 58-year-old man, and the second case occurred at the mandibular gingiva in a 79-year-old woman. The laboratory data of the first case showed a positive response to hepatitis C virus antibody. in the first case, the tumor mass measured 4 times 4 cm in size, and was i-texl at the lingual side of the median mandible beside the sublingual gland. In the second case, the tumor mass measured 25 times 15 mm In size, and was located in the alveolar mucosa of the right mandible. Histologically, both tumors showed a neoplastic epithelium arranged in a solid pattern with evidence of peripheral palisading, central necrosis, and some squamous differentiation. The pro-ilferathfe activities of the BSC were compared with conventional squamous cell carcinomas (SCC) in the oral floor and gingiva, respectively, by employing a sensitive argy-rophillc nuclear organizer region (AgNOR) staining method. The number of AgNOR per nucleus of the BSC was higher than that of any other SCC cases. The results support the opinion that BSC of the oral mucosa has a worse prognosis than conventional SCC.     

Urinary pregnanetriol-3-glucuronide in children: Age-related change and application to the management of 21-hydroxylase deficiency

Urinary concentrations of pregnanetriol-3-glucuronide (PT-3-G) were determined in 485 normal Japanese subjects (277 males and 208 females), aged 5 days to 20 years, using an enzyme-linked immunosorbent assay (ELISA). The usefulness of urinary PT-3-G concentrations before giving the morning dose of medications in monitoring the adequacy of glucocorticoid treatment was assessed in eight patients with 21-hydroxylase deficiency (21-OHD). The ratio of PT-3-G to excreted creatinine (PT-3-G/Cre ratio) increased significantly during the first month and did not change from age 1 month to 1 year of life. The ratio decreased to a nadir at age 3 or 4 years followed by continuous, significant increase until late adolescence. In the subjects treated with corticosteroids for 21-OHD, PT-3-G/Cre ratios at the 50th percentile or below suggested a risk of excessive treatment, as judged by the patients' growth. Measurement of the PT-3-G/Cre ratio enabled recognition of corticosteroid overtreatment, which was not demonstrated by determining the serum concentrations of 17α-hydroxyprogesterone (17-OHP) On the other hand, ratios at the upper 95–99% tolerance limits seemed to be required for optimal control. The present study revealed the normal age-related changes in urinary excretion of PT-3-G and showed it to be a reliable marker for evaluating glucocorticoid treatment in young children with 21-OHD.