Time-Reversal Measurement of the p-Wave Cross Sections of the

The cross sections of the ^{7}Be(n,α)^{4}He reaction for p-wave neutrons were experimentally determined at E_{c.m.}=0.20-0.81 MeV slightly above the big bang nucleosynthesis (BBN) energy window for the first time on the basis of the detailed balance principle by measuring the time-reverse reaction. The obtained cross sections are much larger than the cross sections for s-wave neutrons inferred from the recent measurement at the n_TOF facility in CERN, but significantly smaller than the theoretical estimation widely used in the BBN calculations. The present results suggest the ^{7}Be(n,α)^{4}He reaction rate is not large enough to solve the cosmological lithium problem, and this conclusion agrees with the recent result from the direct measurement of the s-wave cross sections using a low-energy neutron beam and the evaluated nuclear data library ENDF/B-VII.1.

Candidate Resonant Tetraneutron State Populated by the

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene.

OBJECTIVE: Severe congenital neutropenia (SCN), also known as Kostmann syndrome (SCN3, OMIM 610738), includes a variety of haematological disorders caused by different genetic abnormalities. Mutations in ELA2 are most often the cause in autosomal dominant or sporadic forms. Recently, mutations in HAX1 have been identified as the cause of some autosomal recessive forms of SCN, including those present in the original pedigree first reported by Kostmann. We sought to determine the relationship between HAX1 gene mutations and the clinical characteristics of Japanese cases of SCN. METHODS: The genes implicated in SCN (ELA2, HAX1, Gfi-1, WAS, and P14) were analysed in 18 Japanese patients with SCN. The clinical features of these patients were obtained from medical records. Immunoblotting of HAX1 was performed on cell extracts from peripheral blood leucocytes from patients and/or their parents. RESULTS: We found five patients with HAX1 deficiency and 11 patients with mutations in the ELA2 gene. In HAX1 deficiency, a homozygous single base pair substitution (256C>T), which causes the nonsense change R86X, was identified in three affected individuals. Two sibling patients showed a compound heterozygous mutation consisting of a single base pair substitution (256C>T) and a 59 bp deletion at nucleotides 376-434. There was no detectable phenotype in any heterozygous carrier. All patients with HAX1 deficiency had experienced developmental delay. Three patients carrying R86X also suffered from epileptic seizures. In contrast, no SCN patient with heterozygous mutations in the ELA2 gene suffered from any neurodevelopmental abnormality. CONCLUSIONS: These findings suggest that the R86X mutation in the HAX1 gene is an abnormality in Japanese SCN patients with HAX1 deficiency and may lead to neurodevelopmental abnormalities and severe myelopoietic defects.

Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency.

HAX1 deficiency has recently been identified as a cause of severe congenital neutropenia (SCN), but little is known about the phenotype. We described an SCN patient with a homozygous 256C-to-T transition causing an R86X mutation in the HAX1 gene. Notably, the patient has been complicated by epilepsy and severe delay of motor, cognitive, and intellectual development; each developmental quotient was 21-26 at 7 years old. Growth failure and dental development delay were also noted. Neurodevelopmental delay in this patient expands the clinical phenotype of HAX1 deficiency and suggests an important role of HAX1 on neural development as well as myelopoiesis.

Enhancement of antitumor effects of 1-hexylcarbamoyl-5-fluorouracil combined with hyperthermia on Ehrlich ascites tumor in vivo and Nakahara-Fukuoka sarcoma cell in vitro.

1-Hexylcarbamoyl-5-fluorouracil (HCFU) was found to be hydrolyzed to 5-fluorouracil (5-FU) depending on temperature. In this study, the antitumor effects of HCFU with hyperthermia were studied on Ehrlich ascites in tumor-bearing CD-1 mice and Nakahara-Fukuoka sarcoma cells. Concurrently, the change of 5-FU concentration in the Ehrlich tumor was also observed. In vivo, Ehrlich cells were transplanted in the foot pads of mice. HCFU (80 mg/kg) and 5-FU (40 mg/kg) (same molarity) were administered orally on the 3rd, 6th, and 9th days after transplantation and simultaneously hyperthermia (43.5 degrees C, 45 min) was induced. The antitumor effect was evaluated by the tumor volume. On the 9th day after transplantation, HCFU (150 mg/kg) and 5-FU (75 mg/kg) were administered with or without hyperthermia (43.5 degrees C, 45 min) and the tumor tissues were taken for 5-FU concentration analysis. In addition, Nakahara-Fukuoka sarcoma cells were incubated (42 degrees C various times) with our without HCFU and 5-FU (both 1 x 10(-4) M) in vitro. The cytotoxicity was evaluated by colony forming assay. The most effective condition was found to be the combination of HCFU with hyperthermia in vitro and in vivo. The highest 5-FU concentration was observed by the treatment of HCFU combined with hyperthermia in vivo. Hence, HCFU could be clinically useful in thermochemotherapy.

Atypical alkaline phosphatase isozymes in serum and urine of patients with renal failure.

BACKGROUND: Alkaline phosphatases (ALPs) originating from different organs are frequently detected in the serum and urine of patients with renal failure. METHODS: We investigated the characteristics of ALPs in the serum and urine of 108 patients with chronic renal failure (CRF) and of 106 healthy control subjects. RESULTS: In polyacrylamide gel electrophoresis, three atypical ALP bands in serum of patients were designated as atypical-s1, -s2 and -s3, respectively. In contrast, five atypical bands (u1, u2, u3, u4 and u5) were detected in the urine of patients. The atypical ALPs were electrophoretically isolated and assayed to determine their biochemical properties, i.e., neuraminidase sensitivity, heat stability, reactivity to anti-intestinal or anti-tissue nonspecific ALP antibodies, molecular sizes and sugar chain heterogeneities. From these results, we found that atypical-s1 and -s2 were the intestinal-type ALP, while s3 was the tissue-unspecific type ALP. Atypical-u1, -u2 and -u3 were high-molecular type ALPs, which we suggested as the ones that originated from the intestine. Atypical-u4, a tissue-unspecific type ALP, was detected with considerable frequency in the urine of patients. In patients with CRF, the appearance of these atypical ALPs was accompanied by a deterioration of the creatinine clearance. CONCLUSIONS: The appearance of atypical ALPs in the serum and urine of patients with CRF may be a useful marker for renal disease.

Serum lipid metabolism abnormalities and change in lipoprotein contents in patients with advanced-stage renal disease.

BACKGROUND: Arteriosclerosis is the major cause of death in patients with chronic renal failure. There is much interest in the lipid metabolism of patients treated with hemodialysis. METHODS: We analyzed low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in chronic renal failure (CRF) patients according to patients on hemodialysis (HD), patients with diabetic nephropathy before initiation of dialysis (DN), and patients with chronic glomerulonephritis in the conservative stage (CGN); and compared the lipid metabolic abnormalities in patients on hemodialysis and those not yet on hemodialysis. We also analyzed the qualitative abnormalities of LDL and HDL and their relationship with the pathological stages. RESULTS: Electrophoretic patterns identified small LDL particles and small HDL particles in the three groups, and the degree of denaturation was more enhanced in CRF patients in the conservative stage than in HD patients. For LDL susceptibility to oxidation LDL (oxLDL) by addition of Cu(2+), the lag time was approximately 57 min in healthy controls and CGN patients, but was prolonged to approximately 75 min in HD and DN patients. For HDL susceptibility to oxidation HDL (oxHDL), HD, DN and CGN patients showed lag times shorter than those found in healthy control subjects. These results showed that LDL and HDL in the serum of CRF patients were in a state of enhanced susceptibility to oxidative modification. In Western blot analysis using anti-human-denatured LDL and anti-human-oxidized HDL monoclonal antibodies, bands of low molecular oxLDL at 150-197 kDa were detected in all CRF patients, with marked tailing in CGN patients. Similarly, bands of small oxHDL particles at 110 and 120 kDa were found in HD, DN and CGN patients. CONCLUSIONS: Oxidative modification of both LDL and HDL occurs in patients with advanced CRF resulting in small lipoproteins. Increased production of oxLDL and oxHDL is the main cause of lipid metabolic abnormality in CRF patients.

Effects of thermochemotherapy [1-hexylcarbamoyl-5-fluorouracil (HCFU) combined with hyperthermia]: a basic study on the most effective timing and sequence in vivo.

1-Hexylcarbamoyl-5-fluorouracil (HCFU) is known to be hydrolyzed to 5-fluorouracil (5-FU) by heating. We have previously reported the enhancement of the antitumor effects of HCFU when combined with hyperthermia (1). This study aimed at determining the most effective timing schedule for HCFU combined with hyperthermia for clinical application. On the third, 6th, 9th, 12th and 15th day after transplantation, HCFU (80 mg/kg) was administered and hyperthermia induced. The antitumor effect was evaluated by the measurement of tumor volume. 5-FU concentration in the tumor tissue was analyzed on the 12th day after transplantation after administering 150 mg/kg HCFU, with or without hyperthermia (43.5 degrees C, 45 min). 5-FU concentration in serum and other tissues (kidney, liver and submandibular gland) were also analyzed. The concentration was measured by a high performance liquid chromatograph (HPLC) following Mori et al 's method (2). An enhanced antitumor effect and a significant increase in 5-FU concentration in tumor tissue were observed in post-heated groups of mice as compared with pre-heated groups and groups given HCFU alone. The results showed that HCFU given 1 to 2 hours prior to hyperthermia was the most effective treatment.

Antitumor effect of carboplatin combined with hyperthermia on Ehrlich-ascites tumor in vivo.

We examined the optimal timing for the enhancement of antitumor effects of CDDP analogues, cis- diammine-1,1- cyclobutane dicarboxylate platinum (II); CBDCA combined with hyperthermia against the CD-1 mice bearing Ehrlich ascites tumor (EAT) cells in vivo. The prolonged tumor doubling time was observed when two modalities were combined. The longest tumor doubling time was obtained by simultaneous administration of CBDCA combined with hyperthermia. The findings indicated that the most effective condition was the simultaneous combination of CBDCA with hyperthermia. An increase in intratumoral platinum concentration was observed by the treatment of CBDCA simultaneous combined with hyperthermia.

Enhancement of antitumor effects of new analogue of platinum, cis-diammine (glycolato) platinum (254-S) combined with hyperthermia in vivo.

Cis-diammine (glycolato) platinum (254-S) is a second generation platinum complex with reduced nephrotoxicity. In this study the antitumor effect of 254-S combined with hyperthermia in vivo in mice was studied. On the 6th day after inoculation of the Ehrlich ascites tumour cells, 254-S (15mg/kg) was administered intraperitoneally (i.p.) and hyperthermia was induced by using a circulating water bath at 42.5 degrees C for 45 min. The antitumour effect was evaluated by relative tumour volume. Furthermore, platinum concentration in tumour tissue was determined by using atomic absorption spectrophotometry. The most effective condition was found to be the combination of 254-S with hyperthermia. A significantly higher concentration of platinum in the tumour tissue was observed when treatment with 254-S was combined with hyperthermia, than with treatment using 254-S alone. Our study suggested that the accumulation of 254-S in the tumour tissue, and its retention at a high concentration within the tumour tissue long term was one of the reasons for the enhancement of antitumour effect of 254-S treatment when combined with hyperthermia.

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Radiotherapy for squamous cell carcinoma of the nasal cavity.

The management of squamous cell carcinoma of the nasal cavity, a relatively rare tumor, is described, with results of long-term follow-up. We treated five such patients by means of radiotherapy combined with surgery in all but one case. Three patients received a dose of 40 Gy preoperatively, one received 60 Gy of radical radiotherapy, and one received 38 Gy of postoperative radiotherapy. During the follow-up period, one patient developed a local recurrence and two patients developed distant metastases. Nasal cavity tumors in our patients were diagnosed early, and local control using a combination of radiotherapy and surgery was relatively effective. Distant metastases occurred in two of five patients during the follow-up period, suggesting that the possibility of distant metastases during follow-up was considered.

Pharmacokinetics and radiosensitizing effect of PR-350.

PURPOSE: The in vivo pharmacokinetics and sensitizing effects of PR-350, a newly developed, highly water-soluble radiosensitizer were examined. MATERIALS AND METHODS: C3H/HeJ mice bearing SCC-VII tumor cells were used in the experiments. Results were compared with those of PR-28 and SR-2508. RESULTS: The intratumoral concentration of PR-350 reached the maximum value of 77.7 mg/kg 20 min after intravenous injection. The concentration in the brain was below the detection limit. The enhancement ratios of PR-350 calculated using the growth delay method were 0.9 for PR-350 at 50 mg/kg and 1.4 for PR-350 at 100 mg/kg, compared with 1.4 for SR-2508 at 100 mg/kg and 1.0 for PR-28 at 100 mg/kg. CONCLUSION: PR-350 and SR-2508 revealed similar sensitizing effects. The side effects of PR-350 are expected to be equal to or less than those of SR-2508. PR-350 seems to be a promising radiosensitizer.

Intraluminal irradiation for T2M0 esophageal cancer: effect of patient selection on prognosis.

The contribution of intraluminal irradiation to the prognosis of T2M0 esophageal cancer was examined with reference to patient selection. To determine the effect of patient selection, we used esophagrams to assess the potential difficulty of inserting a tube for intraluminal irradiation in 39 patients who were treated with external irradiation prior to 1982. Twenty-two patients were assessed as likely to have been able to undergo intraluminal irradiation (group 1) while 17 were assessed as unlikely to have been able to undergo the procedure (group 2). Of 36 patients treated after 1983, 19 patients were treated with a combination of intraluminal irradiation and external beam therapy (group 3) and 17 by external irradiation alone (group 4). The median survival times of groups 1, 2, 3, and 4 were 10.8, 6.4, 12.0, and 8.5 months, respectively. The prognosis of patients treated with combination therapy (group 3) was superior to that of those treated before 1982 (groups 1 + 2). However, there was no improvement in the prognosis of T2M0 esophageal cancer treated by radiotherapy after the introduction of intraluminal irradiation, and the difference between the survival curves of patients treated by combination therapy (group 3) and with a wide esophageal lumen (group 1) was not significant. Our study thus showed that the selection of patients according to the insertability of the intraluminal therapy tube affected the prognosis.

[Inter-examiner reliability of nerve conduction measurements].

A total of 122 patients were performed motor and sensory nerve conduction studies of the upper limb by two examiners (1. doctor, 2. medical technician) to know the inter-examiner reliability of nerve conduction measurements. Subjects contained normal individuals and various types of neuropathy patients. Motor nerve conduction studies were carried out in the median nerve, and antidromic sensory nerve conduction studies were performed in the median and ulnar nerves. F-wave latency of the median nerve and sensory conduction velocity between finger and wrist of the median and ulnar nerves presented the equal mean value between two examiners. A relatively good correlation between two examiners was pointed out in the distal motor latency and F-wave latency. Inappropriate measurements were caused by the differences in the site of placement of stimulating or recording electrodes and effects of submaximum stimuli or stimulus spread to other nerves. In sensory nerve conduction studies, especially in the ulnar nerve, careful attention should be paid to avoid the influence of motor artifact in giving supramaximum stimuli. Amplitude measurements showed larger inter-examiner difference than latency or velocity measurements. We reported the present condition of measurement reliability. We should do our best to minimize the error.

[Expression of CD44 variant 6 and its metastatic potential in squamous cell carcinoma of the oral cavity].

Using antihuman CD44 variant 6 monoclonal antibody (2F10), immunohistochemical screenings were performed for 38 oral squamous cell carcinoma cases and 10 oral mucosa in healthy cases as normal counterpart. Normal epithelium in the oral surface was stained intensely by the antibody. The reactivity was particularly strong in the spinous layers of stratified squamous epithelium. Cells in the basal layers exhibited moderate staining. In contrast, expression of CD44v6 tended to be downregulated in 38 oral squamous cell carcinoma materials. Interestingly, more faint or no staining by the anti-CD44v6 monoclonal antibody was found in the primary squamous cell carcinomas involving regional lymphnode metastasis. Downregulation of CD44v6 isoform was suggested to occur during regional lymphnode metastasis on oral squamous, cell carcinomas.

[Hemodynamic change in the liver following hepatic resection in the dog. A comparative study by the 198Au colloid method, KICG and the H2 clearance method].

On the basis of our hypothesis that blood flow in the residual hepatic parenchyma is a determinant factor of posthepatectomy liver function, measurements were made of blood flow in the residual liver after 40% hepatic resection in dog. Adult mongrel dogs were divided into two groups, i.e., normal control and 40% hepatectomy, and evaluated for hepatic hemodynamics by 198Au colloid method, KICG and H2 clearance method. Blood biochemistry and, histology of the liver were also examined. The results are as follows: In the control group, hepatic blood flow by 198Au colloid method, KICG and H2 clearance method was found to correlate significantly with each other. In the 40% hepatectomy group, the hepatic blood flow index by both 198Au colloid method and KICG decreased in proportion to the amount of resected hepatic tissue initially and then increased as the liver regenerated. H2 clearance method showed that hepatic blood flow per unit weight of tissue decreased in the face of reduced hepatic volume in early stage of posthepatectomy period and returned to the preoperative level as the liver regenerated.