Metabolic expression of intrinsic developmental programs for dentine and enamel biomineralization in serumless,chemically-defined,organotypic culture

Summary Biomineralization was investigated using embryonic mouse mandibular first molars (M₁) cultured in the presence or absence of fetal calf serum. Metabolic features including cell division and Ca²⁺ and phosphate incorporation into dentine and enamel extracellular matrices were analyzed. The relative timing and magnitude of DNA synthesis for serumless cultures was comparable toin vivo controls. Isotopic calcium and phosphate incorporation into the mineral phase of dentine and enamel matrices, in the absence of serum, fluctuated during development. Molar tooth morphogenesis, cytodifferentiation, and extracellular matrix formation approximated late crown-stage development in serumless cultures. Von Kossa histochemical staining indicated calcium phosphate salt formation in serumless cultures. Analysis of anhydrous fixation-prepared enamel and dentine representing serumless cultured explants indicated that crystal size and orientation were comparable toin vivo enamel and dentine. In contrast, serum-supplemented cultures showed atypical crystal size and orientation. Calcium/phosphorous (Ca/P) ratio values for serumless cultures after 21 days showed Ca/P enamel values of 2.03 (SD±0.04, p<0.025) and dentine values of 1.89 (SD±0.01, p<0.025). Electron diffraction patterns of enamel and dentine formed in serumless cultures were principally those of highly-ordered crystalline hydroxyapatite. Our results suggest that tissue-specific dentine and enamel biomineralization is regulated by endogenous factors intrinsic to the developmental program of embryonic tooth organs during serumless culture.     

A case of Nasu-Hakola's disease with T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen]

A 30-year-old female received a head injury at the age of 22 years. Subsequently neurological and psychiatric symptoms, such as personality change, urinary incontinence, dementia and gait disturbance developed. On admission, her cognitive function was severely impaired. Brain CT disclosed cerebral atrophy, dilatation of the lateral ventricle and calcification of the basal ganglia. Pathologically membranous structures were recognized in bone marrow. On the basis of these clinical findings, a diagnosis of Nasu-Hakola's disease was made. In this case, a T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen was characteristic. This finding may be related to intracranial calcification.     

Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder.

BACKGROUND: Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD. METHODS: The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34). RESULTS: Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects. CONCLUSIONS: The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.     

Assessment of on-pump beating coronary artery bypass surgery performed after introduction of off-pump approach.

OBJECTIVE: To clarify the position of on-pump beating coronary artery bypass (CAB) and to define preoperative indicators of intentional conversion to the procedure in the era of advancement of off-pump CAB (OPCAB), we assessed on-pump beating CAB performed after the introduction of OPCAB. SUBJECTS AND METHODS: We assessed 130 patients who underwent single CAB [117 (90%) with OPCAB and 13 (10%) with on-pump beating CAB] between August 1999 (when OPCAB was selected as the first-line surgical procedure) and December 2004. RESULTS: No significant differences were seen between the groups in the number of coronary lesions or the prevalence of left main trunk (LMT) lesion. Reduced left cardiac function, cardiac dilatation, and mitral regurgitation (MR) were more remarkable in the on-pump beating CAB group. Preoperative ischemic condition was generally unstable in the both groups. A conversion to on-pump beating CAB occurred at anastomosis for the left anterior descending (LAD) branch in 61% and for the left circumflex (LCX) branch in 15%. LAD patients had more severe left cardiac dysfunction and cardiac dilatation than LCX patients. CONCLUSION: To perform safe and reliable CAB surgery, cardiovascular surgeons should define preoperative indicators of difficult OPCAB and convert OPCAB to on-pump beating CAB intentionally without hesitation when unstable hemodynamics is detected.     

Cystic thyroid masses: ultrasonographic and pathologic correlation

Forty-nine patients with 63 cystic thyroid masses who had undergone preoperative sonography were retrospectively reviewed. 52 lesions (83%) were benign and others (17%) were malignant. Among various sonographic findings of cystic thyroid masses, oval cystic lesions with polyp or dome like solid component projecting into the lumen were all diagnosed adenomatous goiter. Irregular cystic structures with more than 2 cm finger like pedunculated mass extended into and/or out of the lumen were all diagnosed papillary carcinoma. Small oval cysts (less than or equal to 1 cm) with strong echo were all diagnosed colloid goiter. The other sonographic type of cystic thyroid masses had somewhat malignancy (12-30%), not having characteristics which differentiate benign from malignant lesions. Pathologic findings of malignant lesions showed that cancer cells existed rather in pericystic portion than in cyst wall except for finger like solid component projecting into the lumen which was papillary carcinoma itself. Ultrasonically guided needle biopsy should be performed to get samples of above portions.     

Inhibition of erythrocyte 5-aminolaevulinate hydrolase activity by tin and its prevention by selenite.

Mice were injected with either SnCl2 (intraperitoneal) or Na2SeO3 (subcutaneous) alone or together at doses of 50 mumol/kg body weight. After 20 hours blood was collected and the concentrations of tin (Sn) and Selenium (Se) and the activity of 5-aminolaevulinate hydrolyase (ALA dehydratase, EC 4.2.1.24) in blood were determined. The concentrations of Sn in whole blood were 4.9 (SD 1.5) nmol/ml (n = 4) and ALA dehydratase activity was 10% of the control in Sn treated animals. Concentrations of Sn were 2.6 (SD 0.6) nmol/ml and ALA dehydratase activity was 92% of that in control animals when Sn and Se were simultaneously injected. The supernatant from lysed erythrocytes from Sn treated mice were applied to a Sephacryl S-300 column. The predominant peak containing Sn was eluted at the position of haemoglobin; a second peak was eluted at the position of ALA dehydratase. When the supernatant of lysed erythrocytes from mice injected with Sn and Se was chromatographed, a negligible amount of Sn was detected in the ALA dehydratase fraction. It thus appears that Sn binds to ALA dehydratase molecules and inhibits enzyme activity, and that simultaneous injection of Se prevents Sn binding to ALA dehydratase, thereby preventing the inhibition of ALA dehydratase activity by Sn.     

Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)--effect on pain threshold and inhibition by naloxone

It has been claimed that the mechanism of acupuncture analgesia can be explained in part by endogenous opioids. If so, it might be possible to enhance the analgesic effect of acupuncture by the administration of endorphins. If D-phenylalanine (DPA), an inhibitor of the endorphin degrading enzyme, is administered, the analgesic effect of acupuncture should be prolonged due to the increased level of endorphins. From the changes of the pain threshold (PT), we investigated whether or not the pre-administration of DPA can enhance the analgesic effect of acupuncture in humans. In addition, we examined the inhibitory effect of naloxone. 1) In all five subjects whose PT was raised after acupuncture anesthesia (respondents), the rise in PT was significantly prolonged by DPA. 2) Out of 10 subjects whose PT remained almost unchanged after acupuncture anesthesia (non-respondents), the PT was increased by DPA in 5 cases. 3) The rise in PT was most prominent when DPA was administered 30 minutes before the start of acupuncture anesthesia. 4) In all 4 respondents in whom the rise in PT persisted after DPA and acupuncture anesthesia, their raised PT dropped after the intravenous injection of naloxone (10 mg). 5) These findings show that DPA enhances the analgesic effect of acupuncture by the "endorphin mechanism."     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.