Molecular cloning of the human cDNA for a stimulatory GDP/GTP exchange protein for c-Ki-ras p21 and smg p21.

We have previously purified smg GDP dissociation stimulator (GDS) from bovine brain and isolated its cDNA from a bovine brain cDNA library. smg GDS stimulates the GDP/GTP exchange reaction of a group of small GTP-binding proteins (G proteins), including at least c-Ki-ras p21, smg p21A, smg p21B, rhoA p21 and rhoB p21, by stimulating the dissociation of GDP from and the subsequent binding of GTP to each small G protein. In this study, we have isolated and sequenced the cDNA of smg GDS from a human brain cDNA library using the cloned bovine smg GDS cDNA. The cDNA has an open reading frame encoding a protein of 558 amino acids with a calculated Mr value of 61,122. Human smg GDS shares 93% nucleotide and 96% amino acid sequence homologies with bovine smg GDS. The isolated cDNA is expressed in Escherichia coli, and the encoded protein shows the physical and functional properties similar to those of bovine smg GDS.     

Experience of cerebral angiography using gadolinium for renal insufficiency]

Angiography by means of iodinated contrast material, before endovascular or surgical treatment, may result in serious complications in patients with renal insufficiency or previous anaphylactoid reaction to iodine. Alternative techniques, such as magnetic resonance angiography or carbon dioxide angiography, have their own limitations. We report effectiveness and safety of cerebral angiography using gadolinium for a patient with right vertebral artery and basilar artery occlusion and renal insufficiency. A 66-year-old woman with diabetes under medical treatment suffered loss of consciousness and left hemiparesis following dehydration for 24 hours. She was transferred to our hospital. Emergent MRI suggested brain stem and cerebellar infarction due to vertebral artery occlusion with diffusion-perfusion mismatch. Because of renal insufficiency, the digital subtraction cerebral angiography using gadolinium was performed. Appropriate diagnosis was achieved by angiography using gadolinium of 0.4 mmol/kg. There was no any complication including deterioration of renal function. Gadolinium appears to be a safe and useful intraarterial contrast agent in patients with renal insufficiency.     

Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism

Background and aims: To compare the prognosis of chronic hemodialysis patients with or without parathyroidectomy. Methods: Among 158 chronic hemodialysis patients who underwent total parathyroidectomy between July 1998 and April 2009, 88 patients were matched with 88 controls for sex, age, underlying disease and prior dialysis history. Then a retrospective evaluation of their prognosis was performed over a median observation period of 4.41 years. Results: The overall survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control group. The cardiovascular death-free survival rate was 94.6% in the parathyroidectomy group and 76.3% in the control group. During observation, intact parathyroid hormone was measured every 6 months, and its average serum level was 37 ± 92 ng/L in the total parathyroidectomy group versus 274 ± 233 ng/L in the control group (p=0.0001). The total parathyroidectomy group had a significantly lower corrected calcium level and higher serum albumin level. Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and serum albumin were significant factors for both total and cardiovascular mortality. Conclusion: Total parathyroidectomy was associated with better survival, probably due to decreased cardiovascular mortality.     

A phase II study of oral S-1 with concurrent radiotherapy followed by chemotherapy with S-1 alone for locally advanced pancreatic cancer

Background/purpose

S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80?mg/m²/day given on days 1?C21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).

Methods

Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0?C1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4?weeks of chemoradiotherapy. S-1 was given orally at a dose of 80?mg/m²/day twice daily on days 1?C21. Radiotherapy was delivered in fractions of 1.25?Gy twice daily, 5?days per week for 4?weeks (total dose: 50?Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14?days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.

Results

Fifty patients were enrolled in this phase II study. Median follow-up was 14.6?months (range 5.4?C58.9?months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18?C45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7?months (95% CI, 4.7?C11.2?months) and 14.3?months (95% CI, 10.8?C20.8?months), respectively. Survival rates at 1 and 2?years were 62 and 27%, respectively.

Conclusions

Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.     

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m³ and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m³) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m³) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m³ thoron inhalation was lower than that after 500 Bq/m³ thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m³ and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m³ was more effective than that at 2000 Bq/m³, possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m³ and AA administration promoted an early recovery from alcohol-induced liver damage.     

Detection of New H5N1 High Pathogenicity Avian Influenza Viruses in Winter 2021–2022 in the Far East,Which Are Genetically Close to Those in Europe

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021–2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020–2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 10^4.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.     

67Ga citrate and99mTc(v)-DMSA scintigraphy in a case of maxillary sinus liposarcoma

Scintigraphic images with⁶⁷Ga citrate and^99mTc(v)-dimercaptosuccinic acid and MR image of a 16-year-old male with maxillary sinus liposarcoma (predominantly myxoid type) are reported. The MR image clearly indicated the exact location, size and anatomical relationship of the tumor. Scintigraphic evaluation was useful in suggesting the malignant nature of the tumor and showed no distant metastasis. Both examinations were effective in treating this case.     

Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma

BACKGROUND: Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. METHODS: The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90 years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I-IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. RESULTS: Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant (P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity (P = 0.0138). CONCLUSION: This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC.     

Analysis of muscle hardness in patients with masticatory myofascial pain.

PURPOSE: The aim of the present study was to access any changes in the muscle hardness of the masseter muscle between normal subjects and patients with myofascial pain during brief sustained isometric contractions at various bite force levels, and to compare muscle hardness, especially in terms of the recovery phase, after a clenching task. MATERIALS AND METHODS: Ten patients with masticatory myofascial pain and 10 age- and weight-matched normal healthy controls participated in this study. First, the hardness of the right masseter muscle was measured at the bite force of 0, 3, 6, and 9 kgf with a hand-held hardness meter. Then, the subjects were requested to exert a 9 kgf-clenching task for 30 seconds. The muscle hardness was again measured at 5, 30, and 120 seconds after the task, and the data obtained were compared with the muscle hardness before the clenching task. RESULTS: The results showed that there was no significant difference between the patients and the normal controls, while the muscle hardness increased with contraction in all subjects. The present findings also showed that the patients had a delayed return to baseline after the clenching task compared with the normal subjects, although an immediate increase after the clenching task was seen in all subjects. CONCLUSION: The results indicated that patients with masticatory myofascial pain have different muscle properties in the recovery phase after contraction, probably because of a slower intramuscular reperfusion.