Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.     

Presence of ghost cells and the Wnt signaling pathway in odontomas

BACKGROUND: Although it has been reported that ghost cells are present in odontomas, the generation mechanism of these cells is unclear. To evaluate the presence of ghost cells and involvement of the Wnt signaling pathway, we examined the expression of hard keratins, beta-catenin and Lef-1 in odontomas. METHODS: Sixty-nine cases of odontoma were examined immunohistochemically with the use of antibodies against human hair proteins, beta-catenin and Lef-1. RESULTS: Expression of hard keratins was found only in the cytoplasm of ghost cells in 46 (66.7%) of the 69 odontomas. Compound odontomas (78.8%) showed a higher incidence of ghost cells than complex odontomas (29.4%). Histopathologically, ghost cells were found within odontogenic epithelium adjacent to immature enamel and in the centre of Liesegang-ring-like calcified materials. Expression of beta-catenin and Lef-1 was observed in the cytoplasm and nucleus of odontogenic epithelial cells adjacent to the ghost cells in immature odontomas. CONCLUSION: These findings suggest that odontoma is a hard keratin-expressing tumor-like lesion, and that the Wnt signaling pathway may be involved in the formation of ghost cells in odontomas.     

Pancreatic tumor antigen in transplantable adenocarcinomas induced by N-bis(2-hydroxypropyl)nitrosamine in hamsters

An attempt was made to detect a pancreatic tumor antigen (PTA) in transplantable pancreatic adenocarcinomas induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN) in hamsters. Antibody against antigenic protein was raised by immunizing rabbits with whole homogenate of the tumors transplanted into the back of hamsters. PTA was purified by affinity chromatography and shown to have the physicochemical properties of a glycoprotein with a molecular weight of 800,000, migrating in the beta regions upon agarose gel electrophoresis. Loss of immunological properties was observed after heating at 65 degrees C for 30 min. Enzyme immunoassay revealed that the levels of PTA in the serum and tissue showed a positive correlation with the induction of the presence of tumor, and size of the tumor. It is tentatively suggested that PTA values above 150 ng/ml serum are indicators of tumors, because in normal hamsters the PTA range is from 25 to 130 ng/ml serum. Immunohistochemically, PTA was demonstrated to be localized within the cytoplasm of epithelial tumor cells of well-differentiated tubular adenocarcinomas.     

Functional innervation patterns in the corpus spongiosum and glans in the dog

The neural control of smooth muscle cells in the corpus spongiosum, helicine artery and bulbus glandis of the dog was investigated in relation to the mechanism involved in erection, using isometric tension recording and micro-electrode methods. In the corpus spongiosum, field stimulation evoked twitch-like contractions followed by relaxations. These relaxations were enhanced and prolonged by neostigmine and partly suppressed by atropine. Guanethidine abolished the twitch-like contractions and increased muscle tone. The relaxations observed after pre-treatment with guanethidine were abolished by tetrodotoxin (TTX), thereby indicating that these muscles are innervated by adrenergic excitatory, cholinergic and non-adrenergic non-cholinergic inhibitory nerves. In the helicine artery and bulbus glandis, field stimulation evoked contractions and these contractions were abolished by guanethidine or TTX, indicating that these muscles are innervated by adrenergic excitatory nerve fibres. After pre-treatment with guanethidine and atropine, muscle relaxation appeared in response to field stimulation in the helicine artery but not in the bulbus glandis, indicating that the helicine artery in the corpus spongiosum is also innervated by non-adrenergic non-cholinergic inhibitory nerves in addition to the excitatory adrenergic nerves. In the smooth muscle cells of the corpus spongiosum, slow potential changes were correlated with spontaneous contractions and field stimulation evoked excitatory or inhibitory junction potentials. The neural mechanism involved in erection is discussed in relation to the topical difference in the autonomic innervation patterns in the corpus spongiosum, helicine artery and bulbus glandis.     

Epidemiological characteristics of acute pulmonary thromboembolism in Japan.

AIM: In Japan, acute pulmonary thromboembolism (APTE) is still rare, but the number of patients with APTE has been steadily increasing. It is important for early diagnosis and early management of APTE to recognize epidemiological characteristics of this condition. METHODS: We investigated the epidemiological characteristics of 252 patients with APTE who were admitted to our institutions between 1975 and 2001. APTE was more prevalent in women that in men. It was observed the most in the age group between 50s to 70s, especially in women. Many patients had prolonged immobilization, recent major operation, obesity, or cancer, as risk factors for venous thromboembolism. One hundred and thirty-eight patients developed APTE in hospital; 60 patients were in Department of Internal Medicine, 28 in General Surgery, 15 in Orthopedics, 15 in Obstetrics and Gynecology, and 20 in other services. RESULTS: Among 58 patients with malignancy, 43% had cancers in digestive organs, 21% in gynecological, and 17% in urological. Among 61 patients who were examined for the presence of thrombophilia, 13 patients had inherited thrombophilia (8 protein C deficiency, 4 protein S deficiency, and 1 antithrombin III deficiency) 11 had antiphospholipid antibodies which indicated thrombophilia. Five out of the above 61 patients (8%) had no obvious risk factors including thrombophilia. CONCLUSION: The findings in our patients were almost the same as those in Western patients, except for some points. These results might be useful to establish a preventive approach for APTE in Japan.     

Mapping of odor-related neuronal activity using a fluorescent derivative of glucose

Activity labeling was applied to the olfactory systems of the terrestrial slug Limax valentianus using 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescent derivative of glucose. 2-NBDG was incorporated into cultured Limax olfactory interneurons, and this was partially blocked by the presence of a high concentration of glucose in the medium, indicating that a part of the uptake of 2-NBDG is mediated by glucose transporters. Next, in order to map odor-related neuronal activity in the primary olfactory center, tentacular ganglion, we injected 2-NBDG into the body cavities of slugs and exposed them to odors or clean air (control). In the odor-stimulated animals, the cell mass region was strongly stained. The digit-like extensions and the neuropil region were also stained in some animals. The control animals showed no staining. The neurons in the cell mass are thought to be involved in generating oscillating activities in the tentacular ganglion, and their activation may imply modulation of oscillatory activity during odor processing. Our results show that 2-NBDG is useful for mapping neuronal activity in vivo.     

The effects of preoperative insertion of double-J catheter in transurethral lithotripsy (TUL)]

Transurethral lithotripsy (TUL) was performed in the cases in which the ureteral calculi were not destroyed by the extracorporeal shock-wave lithotriptor (Dornier HM-3, EDAP LT 01). Preoperative placement of double-J ureteral catheter (D-J catheter) caused ureteral dilation, allowing smooth insertion of the ureteroscope. We divided the 55 TUL cases into two groups, those with (27) or without (28) a D-J catheter placed preoperatively, and compared requirement of ureteral bougination, difficulty of ureteroscope insertion and duration of operation between the two groups. In all cases with a D-J catheter, ureteral bougination was not necessary, the insertion of ureteroscope was easier and the duration of operation was shorter than the cases without a D-J catheter. Bladder irritable symptoms were seen in some cases with a D-J catheter but did not require removal of the D-J catheter. On the follow-up term after TUL, there was no difference in the incidence of postoperative fever or postoperative ureteral stenosis, between the cases with and those without a D-J catheter.     

Tissue renin content in superficial, midcortical, and juxtamedullary afferent arterioles in rabbits]

Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity.