Chromium51 Uptake as A Function of Platelet Age

This investigation was supported by the U. S. Atomic Energy Commission Contract AT (30–1) 3590. It is known that chromate uptake by platelets is mediated by a bimodal transport mechanism with a diffusional and a saturable transport component. These models of uptake were studied in rat platelet cohorts of different age, obtained during the recovery phase of thrombocytopenia induced by specific hetero-antibody. At low concentrations of chromate in the medium the saturable transport mechanism prevailed and was found to be markedly dependent on platelet age. Platelets one day or less in age accumulated more than twice the amount of randomly-aged platelets. At high concentrations of chromate at which diffusional transport predominates, no difference in total chromate accumulation was noted in these two platelet populations. The inhomogeneous distribution of ⁵¹Cr in a platelet population may have important bearing on the interpretation of platelet survival curves since by the generally employed labelling method, chromate concentrations are utilized well within the range in which saturable transport prevails and younger platelets are more heavily labelled than older ones.     

Behavioural studies in rats treated with monosodium l-glutamate during the early stages of life

Behavioural observations were made on rats given repeated high, subneurotoxic doses of monosodium l-glutamate (MSG), or large amounts of MSG in the diet, during the early stages of life. Multiple injections of 4 g/kg MSG to neonates caused low grip strength, hypoactivity, changes of spontaneous motor activity pattern in a day, deficit of learning ability and tail mutilation. The same treatment at the infant stage resulted in only slight behavioural abnormalities at a later stage of life, or yielded nothing at all. Administration of subneurotoxic doses either by s.c. injection or forced intubation, or at high levels in a diet provided ad libitum, were without behavioural effect. Adverse behavioural effects were not induced when the brains were free from histological evidence of damage.     

A Recent Trend of Drug Dependence in Kurume District (Southem Japan)

With the intention of grasping the trend of drug dependence in recent years, a comparative study was made of the relative prevalence of three different types of drug dependence, i.e., the sociopathic, neurotic and iatrogenic types, in each of the three postwar decades among patients seen at the neuropsychiatric clinic of Kurume University. As a result it was found that the recent trend of drug dependence has the following features: (1) multiplicity of drugs involved, (2) a continuing high incidence of the iatrogenic types, (3) resurgence of the sociopathic type, making the recent pattern of drug dependence similar to that prevailing in postwar years, and (4) prevalence of dependence or abuse among the younger generation. Consideration was also given to the sociopathologic significance of these recent features of drug dependence.     

On the methods calculating mean survival time in 51Cr-platelet survival study

The International Committee for Standardization in Hematology recommended three methods for calculating objectively the mean platelet survival time, ie, weighted mean of linear estimate and logarithmic estimate, truncated exponential model, and gamma model. For determining which method is better, data of the survival study were fitted to each of three methods, as well as the Paulus polynomial and exponential polynomial models, and the mean survival time and the mean square error were compared. Mean survival obtained by each method was always longest in healthy controls and shortest in ITP. In 3rd degree of polynomial estimate and 2nd and 3rd degrees of logarithmic estimate, several cases showed practically outlying mean survival time of more than 12 days. In healthy controls, highest mean square error was observed in 1st degree logarithmic estimate, and in cases with short mean survival time the highest one was obtained in 1st degree polynomial estimate. Mean square error in ITP pre- and postsplenectomy and in aplastic anemia was smallest in the gamma model. Among nine methods recommended by the International Committee for Standardization in Hematology and by Dr. Paulus, the gamma model so far provides the best method for calculating the mean survival time of ⁵¹Cr-platelets.     

Difficult placement of Univent tube blocker due to aberrant right subclavian artery aneurysm

There have been few reports on aneurysms of the anomalous branch of the aortic arch. We present a rare case in which correct placement of the movable blocker of a Univent tube was difficult due to an aberrant right subclavian artery aneurysm. A 72-year-old man with a history of hypertension had manifested coughing and wheezing for four months prior to admission to our hospital. A chest computed tomogram revealed that his aortic arch had four branches and that the right subclavian artery did not originate from the first branch, but was the fourth branch. The angiogram disclosed that an aneurysm had developed in the anomalous artery close to the aorta, and behind the other three branches, trachea, and esophagus. The aneurysm not only had pushed the trachea out of place but was also pressing against it. After anesthetic induction, his trachea was intubated using an endotracheal tube with a movable blocker, the Univent tube, for single-lung ventilation. The blocker could not be advanced into the left main bronchus due to the tracheal deviation caused by the aneurysm. Several methods of blocker placement, including those recommended in the manual attached to the product, were attempted without success. Finally, the trachea was intubated again using a Univent tube with the blocker tip bent manually, which permitted entrance of the blocker into the bronchus. Blocker placement should be modified to suit patients with a problem in the trachea or bronchi.     

Effects of KRN2391 on ionic currents in rabbit femoral arterial myocytes

The effects of KRN2391, an ATP-sensitive K+ channel opener (KCO) which also acts as a nitrate, on ionic membrane currents in rabbit femoral arterial myocytes were examined. Under whole-cell clamp conditions where cells were superfused with physiological salts solution containing 5.9 mM K+, KRN2391 elicited an outward current at a holding potential of -30 mV. KRN2391-induced current had a reversal potential of -78 mV and was abolished by glibenclamide (glib). KRN2391 was approximately 25 times more potent than nicorandil to activate an ATP-sensitive K+ current (I:(KATP)). On the other hand, 10 microM KRN2391 did not affect either voltage-dependent Ca(2+) or delayed rectifier K+ channel currents. In the inside-out patch configuration, KRN2391 activated 47 pS K+ channels in the presence of nucleotide diphosphates (NDPs) under the symmetrical 140 mM K+ conditions. Glib and intracellular ATP reversibly inhibited the activity of the 47 pS K+ channels. The 47 pS K+ channels activated by KRN2391 are similar in their conductance and other properties to NDP-sensitive K+ channels (K(NDP) channels) described in other smooth muscles and the cloned channels. KRN2391 is a potent activator of the 47 pS K+ channels and the activation can contribute to the KRN2391-induced vasodilation in arterial muscles.     

Aichi Cancer Center 10-year experience with conservative breast treatment of early breast cancer: retrospective analysis regarding failure patterns and factors influencing local control

Purpose: We analyzed the clinical results of conservative breast therapy in our institute to determine the risk factors influencing local and distant disease recurrence.

Methods and Materials: From 1989 to 1997, 301 breasts of 295 women with early breast cancer were treated with conservative surgery and adjuvant radiotherapy. There were 212 incidences of Stage I breast cancer, and 89 of Stage II. Patients were routinely treated with local resection, axillar dissection, and 46–50 Gy irradiation given in 23–25 fractions. Some also received a radiation boost to the tumor bed.

Results: The 5-/8-year overall survival, disease-free survival, and local control rates were 93.2/91.5%, 86.0/80.6%, and 95.1/92.5%, respectively. Using both univariate and multivariate analyses, tumor volume, estrogen receptor status, and age < 40 years were significant prognostic factors for disease-free survival. Both age < 40 years and surgical method had a strong effect on local control by uni- and multivariate analysis. Surgical margin status was a significant prognostic factor for local control at the univariate level (p < 0.0001), though it had only borderline significance at the multivariate level (p = 0.08). No patient experienced severe morbidity due to radiotherapy.

Conclusion: The results obtained are comparable to previously reported data. Although the follow-up period was too short to draw definite conclusions about long-term outcomes, the outcome from conservative breast treatment was acceptable.     

Therapeutic results of alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: its usefulness and controversial points

BACKGROUND: The present study was conducted to evaluate the therapeutic results of alternating chemoradiotherapy for locally advanced nasopharyngeal cancer (NPC). METHODS: The subjects consisted of six patients with stage III nasopharyngeal cancer and 26 patients with stage IV nasopharyngeal cancer. Using 6 MV photons, radiotherapy was performed at an exposure of 1.8-2.0 Gy five times per week. That is, a total absorbed dose of 36-40 Gy was irradiated between the base of the skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 26-30 Gy was additionally given thereafter. One course of chemotherapy consisted of the administration of 5-fluorouracil (5-FU) at a dose of 700 mg/m2/24 h for 5 days (days 1-5) and cisplatin (CDDP) at a dose of 50 mg/m2/24 h for 2 days (days 6-7) and a total of 2-3 courses of chemotherapy were performed. During the alternating chemoradiotherapy, chemotherapy was performed initially and 3-5 days after completing the chemotherapy, radiotherapy was performed for 3-4 weeks. Thereafter, chemotherapy and radiotherapy were performed alternately. RESULTS: The scheduled courses of alternating chemoradiotherapy were completed in 30 (94%) of 32 patients. Although one patient developed shock induced by metal allergy to CDDP, no severe adverse effects were noted in any other patients. In these 32 patients, the overall 5-year survival rate was 75% (95% confidence interval: 60-90%) and the progression-free survival rate was 63% (95% CI: 46-89%). CONCLUSIONS: This method of alternating chemoradiotherapy yielded higher or at least similar survival rates and lower toxicities than concurrent chemoradiotherapy and is worth trying in a multi-institutional study.     

Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes

Growth hormone (GH) is well known to induce in vivo insulin resistance. However, the molecular mechanism of GH-induced cellular insulin resistance is largely unknown. In this study, we demonstrated that chronic GH treatment of differentiated 3T3-L1 adipocytes reduces insulin-stimulated 2-deoxyglucose (DOG) uptake and activation of Akt (also known as protein kinase B), both of which are downstream effects of phosphatidylinositol (PI) 3-kinase, despite enhanced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, association of IRS-1 with the p85 subunit of PI 3-kinase, and IRS-1-associated PI 3-kinase activity. In contrast, chronic GH treatment did not affect 2-DOG uptake and Akt activation induced by overexpression of a membrane-targeted form of the p110 subunit of PI 3-kinase (p110(CAAX)) or Akt activation stimulated by platelet-derived growth factor. Fractionation studies indicated that chronic GH treatment reduces insulin-stimulated translocation of Akt from the cytosol to the plasma membrane. Interestingly, chronic GH treatment increased insulin-stimulated association of IRS-1 with p85 and IRS-1-associated PI 3-kinase activity preferentially in the cytosol. These results indicate that cellular insulin resistance induced by chronic GH treatment in 3T3-L1 adipocytes is caused by uncoupling between activation of PI 3-kinase and its downstream signals, which is specific to the insulin-stimulated PI 3-kinase pathway. This effect of GH might result from the altered subcellular distribution of IRS-1-associated PI 3-kinase.     

Streptococcal preparation OK-432 promotes the capacity of dendritic cells (DCs) to prime carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocyte responses induced with genetically modified DCs that express CEA

Cancer immunotherapy using dendritic cells (DCs) adenovirally transduced with the whole tumor-associated antigen (TAA) gene is an effective approach. Streptococcal preparation OK-432 is useful for stimulating DCs in terms of maturation. In this study, we established carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes (CTLs) using in vitro stimulation with adenovirally modified human DCs that express CEA. We investigated whether OK-432 stimulation could be more effective in inducing CEA-specific CTLs compared with other typical stimuli. DCs adenovirally transduced with the CEA gene were cultured under various conditions with tumor necrosis factor (TNF)-alpha, lipopolysaccharide (LPS), or OK-432. A cytotoxicity assay using peripheral blood mononuclear cell (PBMC)-derived CTLs was performed in a 4 h-51Cr release assay. OK-432 stimulated immature DCs to acquire a mature phenotype and to produce significant amounts of T-helper 1 cytokines. In all groups (immature DCs, TNF-alpha/DCs, LPS/DCs, OK-432/DCs), CEA-specific CTLs were generated. OK-432-stimulated DCs (HLA-A24) induced the most potent cytotoxic activity against CEA-expressing targets (A24) but not against controls. OK-432/DCs were able to induce markedly potent CTLs specific to target cells pulsed with CEA652 peptide (HLA-A24-restricted peptide), although others failed to induce potent CTLs. In conclusion, the CTL induction protocol using adenovirally modified DCs that express CEA after maturation with OK-432 showed a potent antitumor activity against CEA-expressing target cells, and is therefore promising for clinical applications as a cancer vaccine therapy.