Dose estimation by ESR on tooth enamel from two workers exposed to radiation due to the JCO accident

ESR dosimetry is useful to estimate the external dose for the general population as well as for occupational workers in a nuclear emergency. Three teeth were extracted from two exposed workers (A and B) related to the JCO criticality accident. Tooth enamel was carefully separated from other tooth parts and subjected to ESR dosimetry. Doses equivalent to the gamma-ray dose of 60Co were estimated as follows: for worker A, the buccal and lingual sides of the eighth tooth in the upper right side, 11.8 +/- 3.6 and 12.0 +/- 3.6 Gy, respectively; for worker B, the buccal and lingual sides of the fourth tooth in the upper right side and the fifth tooth in the upper left side, 11.3 +/- 3.4 and 10.8 +/- 3.3 Gy, 11.7 +/- 3.5 and 11.4 +/- 3.4 Gy, respectively. The estimated doses were found to be similar and not dependent on the tooth positions, whether the buccal or lingual sides in each tooth.     

The role of c-fos in cell death and regeneration of retinal ganglion cells

PURPOSE: To investigate the effect of c-fos on apoptotic cell death and regeneration of damaged retinal ganglion cells (RGCs) in tissue culture of retinal explants. METHODS: Retinas from transgenic mice carrying the exogenous c-fos gene under the control of the interferon (IFN)-alpha/beta inducible Mx-promoter (Mx-c-fos), c-fos-deficient mice, and littermate control mice were dissected and cultured in a three-dimensional collagen gel culture system, followed by an analysis of TdT-dUTP terminal nick-end labeling (TUNEL) staining and measurement of neurites that emerged from explants. RESULTS: Compared with littermate control mice, Mx-c-fos transgenic animals showed a higher ratio of TUNEL positivity in the RGC layer from early in the culture period that correlated with the small number of regenerating neurites. In contrast, the c-fos-null mutated mice showed a still-lower ratio of TUNEL-positive cells. Nevertheless, the number of regenerating neurites was significantly lower in the initial phase, although the drastic increase in density of neurite regeneration was observed in the late period of culture. CONCLUSIONS: These findings suggest that c-fos is involved in both apoptotic cell death and regeneration of damaged RGCs. Elucidation of the precise c-fos-mediated cascade involved in RGC apoptosis and regeneration is significant in realizing neuronal survival and regeneration.     

Clinical significance of multidrug resistance and P-glycoprotein expression in patients with gastric carcinoma

Twenty-four fresh tumors of gastric carcinoma were assessed by flow cytometric detection of P-glycoprotein (P-gp) using monoclonal antibody C219. Eight patients were P-gp positive. Differentiated gastric carcinomas contained significantly higher concentrations of P-gp positive. Incidence of P-gp positive was high in advanced stage. In 16 cases estimated chemosensitivity was test assessed by thymidine incorporation assay (TIA). Seven of nine multidrug-resistant cases according to TIA were P-gp positive and all of seven nonmultidrug resistant cases were P-gp negative. Expression of P-gp and multidrug resistance were closely correlated (P < 0.01). Also, in 89 patients with operable gastric carcinoma, the relation between in vitro chemosensitivity test (TIA) and their clinicopathologic features as well as their survival lengths were studied. Thirty-one of 89 specimens from gastric carcinoma patients were multidrug resistant according to TIA. Patients in the multidrug-resistant group had a significantly poorer cumulative survival rate than those who were not multidrug resistant (P < .05). The multivariate analysis showed that multidrug resistance is a useful indicator of prognosis (P < 0.1). We suggest that multidrug-resistant cases or P-gp-positive cases of gastric carcinoma are highly malignant, and these determinations are clinically useful. © 1995 Wiley-Liss, Inc.     

Dual pathway for angiotensin II formation in human internal mammary arteries

1. Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convert antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin II formation was due to another enzyme, identified as human heart chymase. In the human vasculature however, the predominance of either ACE or non-ACE conversion of angiotensin I remains unclear.
2. To study the effects of ACE- and chymase-inhibition on angiotensin II formation in human arteries, segments of internal mammary arteries were obtained from 37 patients who underwent coronary bypass surgery.
3. Organ bath experiments showed that 100 μM captopril inhibited slightly the response to angiotensin I (pD₂ from 7.09±0.11–6.79±0.10, P<0.001), while 100 μM captopril nearly abolished the response to [pro¹⁰] angiotensin I, a selective substrate for ACE, and the maximum contraction was reduced from 83±19%–23±17% of the control response (P=0.01). A significant decrease of the pD₂ of angiotensin I similar to captopril was observed in the presence of 50 μM chymostatin (pD₂ from 7.36±0.13–6.99±0.15, P<0.039), without influencing the maximum response. In the presence of both inhibitors, effects were much more pronounced than either inhibitor alone, and a 300 times higher dose was needed to yield a significant contraction response to angiotensin I.
4. These results indicate the presence of an ACE and a non-ACE angiontensin II forming pathway in human internal mammary arteries.

     

Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-Fu, and VP-16 for advanced esophageal cancer

Objectives

The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer.

Subjects and Methods

We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m² was administered on days 1 and 7. 5-FU at 500 mg/m² and VP-16 at 60 mg/m² were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation.

Results

Side-effects of severe anorexia (grade 3) and leukocytopenia (<1900/μl) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no a significant difference.

Conclusion

These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer.     

RETRACTED ARTICLE: Airway occlusion pressure is an indicator of respiratory depression with isoflurane

The purpose of this study was to elucidate the respiratory depressant effects of isoflurane (0%–1.0%) using airway occlusion pressure (P_0.1), a known index of the output of the respiratory centers, in ten anesthetized patients. P_0.1 was measured as the pressure change obtained after the first 0.1 sec of spontaneous inspiration against the occluded airway. A significant decrease in minute volume ( ) and a significant increase in Pa_{CO 2} were not observed during the periods of isoflurane 1.0% at the end-tidal concentration compared with those of control period (0% isoflurane) (P<0.05), whereas a significant decrease in P_0.1 was observed during the period of isoflurane 0.5%. Our results suggested that P_0.1 was a more sensitive indicator of respiratory depression than Pa_{CO 2} or , and the respiratory center was depressed with a considerably lower concentration (0.5%) of isoflurane.     

Analysis of the CMT1A-REP repeat: mapping crossover breakpoints in CMT1A and HNPP

The CMT1A-REP repeat sequence flanks a 1.5 megabase pair (Mb)segment of chromosome 17p11.2–12 which is duplicated inCharcot—Marie—Tooth neuropathy type 1A (CMT1A) anddeleted in hereditary neuropathy with liability to pressurepalsies (HNPP). The CMT1A-REP repeat is proposed to mediatemisalignment and unequal crossover resulting in reciprocal chromosomalrearrangements in CMT1A and HNPP. We have constructed a physicalmap of the proximal and distal CMT1A-REP repeats. Cloned fragmentsfrom CMT1A-REP repeat regions were used to determine the sizeof the repeats and to assess regions of homology. The crossoverbreakpoints were mapped in a series of 30 unrelated CMT1A patientsand 22 unrelated HNPP patients. The CMT1A-REP repeat spans approximately27 kilobase pairs and appears to be continuous. Locations ofrestriction enzyme sites are highly conserved for the proximaland distal CMT1A-REP repeats. All crossovers mapped within theCMT1A-REP repeat sequence and heterogeneity for breakpoint locationwas demonstrated. Seventy-seven percent (40 of 52) of CMT1Aand HNPP chromosomes contained breakpoints which mapped withina 7.9 kb interval, suggesting the presence of a possible ‘hotspot’for recombination in CMT1A-REP. DNA sequence analysis for 4kb of the interval containing the majority of crossovers revealedover 98% sequence identity between proximal and distal CMT1A-REPrepeat sequences. Probes useful for molecular-based diagnosisof CMT1A and HNPP are described.     

IL-17 and IL-17F modulate GM-CSF production by lung microvascular endothelial cells stimulated with IL-1beta and/or TNF-alpha

In this study, we investigated the roles of CD4 T cell cytokines IL-17 and IL-17F in GM-CSF production from lung microvascular endothelial cells (LMVECs). While a wide range of doses of IL-17 or IL-17F alone did not induce GM-CSF release from LMVECs, IL-17 had an enhancing effect on macrophage-derived IL-1beta- and TNF-alpha-induced GM-CSF mRNA expression and production, whereas IL-17F had an enhancing effect on IL-1beta-induced GM-CSF production, but a marked inhibitory effect on TNF-alpha-induced secretion. GM-CSF production was further enhanced with the combination of three cytokines IL-1beta, TNF-alpha and IL-17 or IL-17F. Additionally, when Th1 or Th2 cytokine was combined with IL-1beta or TNF-alpha, both Th1 and Th2 cytokines had a modest stimulatory effect on TNF-alpha-induced GM-CSF production, whereas IL-4 and IFN-gamma profoundly attenuated IL-1beta-induced secretion. Moreover, the regulation by IL-17 plus Th1 or Th2 cytokine of GM-CSF production from LMVECs treated with IL-1beta or TNF-alpha was dependent on the concentration of IL-17. Our findings indicate that IL-17 and IL-17F play a differential regulatory role in GM-CSF production by LMVECs stimulated with IL-1beta and/or TNF-alpha, which is sensitive to Th1 and Th2 cytokine modulation.     

METACHROMATIC LEUKODYSTROPHY. Report of Siblings with the Juvenile Type of Metachromatic Leukodystrophy

Two sisters with juvenile metachromatic leukodystrophy are described. The patients were 17 and 20 years old. The younger sister died and an autopsy was perfomed. The elder sister keeps alive. A sural nerve biopsy of both cases revealed an accumulation of metachromatic lipid granules in the Schwann cells and macrophages. The autopsy also disclosed these granules especially in the brain, gallbladder, kidney and pancreas. A lipid analysis of the cerebral white matter showed sulfatide accumulation that was 1.5 times that of controls. Histochemically, the accumulated lipid was different in the brain from that in other organs. An electron microscopic examination of the accumulated metachromatic lipid granules showed various structures such as concentric lamellar, tuffstone, herringbone and hexagonal honeycomb appearances, and some ultrastructural differences between the nervous system and other organs. ACTA PATHOL JPN 38: 1041∼1051, 1988.