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Biomedical subjects

R Saito

Publications and source records attributed to R Saito.

At least 91 records · Page 5Linked to original sources

[Pulmonary hypertrophic osteoarthropathy associated with primary lung cancer].

The patient was a 61-year-old man admitted with the complaints of cough, arthralgia, and swelling of the legs. A chest roentgenogram and chest computed tomographic scan revealed a giant mass in the right upper lobe. Transperitoneal lung biopsy was performed, and a diagnosis of poorly differentiated adenocarcinoma was made. Physical examination confirmed swelling of the legs and clubbing of fingers on both hands. Bone scintigrams showed marked accumulation of 99 m-Tc-MDP in the long bones, bones of the hands, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer. Although a high serum level of growth hormone was also detected, immunohistochemical analysis did not find growth hormone in the tumor itself. Chemotherapy and radiotherapy were performed but did not stop progression of the disease. The patient subsequently experienced worsening arthralgia and swelling of the legs. Steroid therapy rapidly alleviated the arthralgia and swelling, but not the clubbing of the fingers. Thereafter, the patient's serum CRP and ICTP dropped to normal levels, and the abnormal findings of bone scintigrams subsequently disappeared. The pulmonary hypertrophic osteoarthropathy was not clearly attributable to growth hormone. Steroid therapy was effective in this case. Bone scintigrams and serum CRP and ICTP may be useful indicators in the therapeutic follow-up and monitoring of patients with pulmonary hypertrophic osteoarthropathy.

Adenocarcinoma↗

[A phase II study of irinotecan combined with cisplatin in non-small cell lung cancer. CPT-11 Lung Cancer Study Group].

Based upon the results of phase I study of irinotecan (CPT-11) combined with cisplatin (CDDP) on non-small cell lung cancer (NSCLC), a combination phase II study on NSCLC was carried out from Feb., 1992 to Sep., 1992. CPT-11 (60 mg/m2) and CDDP (80 mg/m2) were administered by i.v. drip infusion, with administration schedules of Days 1, 8, 15 and only Day 1, respectively. This therapy course was repeated every 4 weeks. Subjects were NSCLC patients of stage III B or IV disease. Those without prior chemotherapy (Group A) and those with prior therapy (Group B) were enrolled separately. Seventy patients were entered into Group A and 32 patients into Group B. One of the patients of Group A was ineligible. The characteristics of the eligible cases of Group A were: male/female, 51/18; median age, 61 years old; PS 0/1/2, 18/39/12; stage IIIB/IV, 26/43; and adeno/squamous/large, 51/15/3. Those of group B were: male/female, 20/12; median age, 62 years old; PS 0/1/2, 5/18/9; stage I/IIIB/IV, 1/7/24, adeno/squamous/large/ad-sq, 28/2/1/1. Thirty-three patients (47.8%) responded in Group A and B patients (25.0%) responded in Group B. Major adverse reactions (grade 3 or higher) of Group A/Group B were neutropenia (80.3%/73.3%), anemia (35.3%/34.4%), diarrhea (18.8%/28.1%) and nausea/vomiting (34.8%/34.4%). Median survival times for Group A and Group B were 308 and 295 days, respectively. CPT-11 in combination with CDDP is effective against NSCLC, suggesting that further studies are needed to determine the usefulness of this therapy.

Adult↗

Computer analyses of complete genomes suggest that some archaebacteria employ both eukaryotic and eubacterial mechanisms in translation initiation.

The translation initiation mechanism of archaebacteria is still not clearly understood. Our previous work showed that ATG triplets before start codons have been strongly depleted in eukaryotic genomes, presumably because ribosome of eukaryotes scans mRNA from the 5' to 3' direction to find proper start codons. Extra ATG triplets before start codons would confuse the process and thus they have been negatively selected in eukaryotic genomes. In eubacterial genomes, on the other hand, ribosome binds to the Shine-Dalgarno (SD) sequence at once without mRNA scanning, and the characteristic patterns of ATG triplet depletion were not observed (Saito, R., Tomita, M., 1999. On negative selection against ATG triplets near start codons in eukaryotic and procaryotic genomes. J. Mol. Evol. 48, 213-217). The ATG triplet analysis on archaebacterial genomes revealed that Methanococcus jannaschii and Pyrococcus horikoshii show patterns similar to eukaryotes, implying that these species employ scanning of mRNA from the 5' to 3' direction in the process of translation initiation. On the other hand, our earlier study found that these archaea have SD-like sequences, which are complementary to the 3' end sequence of 16S rRNA, as in eubacterial translation initiation (Osada, Y., Saito, R., Tomita, M. Analysis of base-pairing potentials between 16S rRNA and 5' UTR for translation initiation in various procaryotes. Bioinformatics, in press). These two results combined lead us to conclude that these archaea probably use a hybrid mechanism; their ribosome scans mRNAs from the 5' to 3' direction and then 16S rRNA binds to the SD-like sequence of the 5' UTR.

5' Untranslated Regions↗

Roles of nitric oxide in the spinal cord in cardiovascular regulation in rats.

The roles of nitric oxide (NO) in the spinal cord in regulation of blood pressure were examined in anesthetized rats. Intrathecal (i.t.) injection of an inhibitor of NO synthase (NOS), N(omega)-nitro-L-arginine methylester (L-NAME), caused marked dose-dependent increase in the blood pressure. The pressor response to L-NAME was attenuated by pretreatment with L-arginine (10 micromol, i.t.). Pretreatment with the ganglionic blocker pentolinium (10 mg/kg, i.v.) and alpha1- and beta-adrenoceptor antagonists significantly inhibited the pressor response induced by L-NAME. The pressor responses to L-NAME was blocked by pretreatment with the selective N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5) (50 nmol, i.t.), but not by pretreatment with a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In addition, the pressor response to L-NAME was reduced by spinal cord transection. These results suggest that L-NAME causes activation of the sympathetic nervous system by reduction of NO in the spinal cord, and that this reduction of NO by L-NAME may activate glutamatergic neurons in the medulla oblongata.

Animals↗

Sequence patterns observed in 5' flanking regions of primate Alu elements.

Retrotransposons have generally been known to integrate randomly into host genomes. Jurka, however, showed some consensus sequence patterns at insertion sites of some mammalian retrotransposons and proposed enzymatic involvement that mediates integration. Jurka used about 400 complete human Alu and rodent ID sequences which retain full length with identical flanking sequences at both ends. In our study, more than 25,000 Alu sequences longer than 250 bp were used for comprehensive analysis to identify any consensus sequence(s) preceding the 5' end of Alu elements. "Entropy" at each nucleotide position within 500 bases of the 5' Alu end was computed. Significant drop of entropy was observed between position -20 and -10 of the 5' end of Alu, suggesting the existence of certain consensus sequence(s) in the region. Frequencies of all possible triplets (total of 64) were measured in the same region. Observation that frequencies of triplets "aaa," "taa," and "tta" in the 5' flanking sequences were high is consistent with Jurka. However, frequencies of triplets "att" and "aca" were also significantly high, which are not the primary candidates for nick site in Jurka.

Alu Elements↗

Correlation between the status of the p53 gene and survival in patients with stage I non-small cell lung carcinoma.

The association of p53 abnormalities with the prognosis of patients with non-small cell lung carcinoma (NSCLC) has been extensively investigated to date, however, this association is still controversial. Therefore, we investigated the prognostic significance of p53 mutations through exons 2 to 11 and p53 protein expression in 103 cases of stage I NSCLC. p53 mutations were detected in 49 of 103 (48%) tumors. Two separate mutations were detected in four tumors giving a total of 53 unique mutations in 49 tumors. Ten (19%) of mutations occurred outside exons 5-8. Positive immunohistochemical staining of p53 protein was detected in 41 of 103 (40%) tumors. The concordance rate between mutations and protein overexpression was only 69%. p53 mutations, but not expression, were significantly associated with a shortened survival of patients (P<0.001). Furthermore, we investigated the correlation between the types of p53 mutations and prognosis. p53 missense mutations rather than null mutations were associated with poor prognosis (P < 0.001 in missense mutations and P=0.243 in null mutations). These results indicated that p53 mutations, in particular missense mutations, rather than p53 expression could be a useful molecular marker for the prognosis of patients with surgically resected stage I NSCLC.

Alleles↗

Esophageal cancer associated with right aortic arch: report of two cases.

We report herein two cases of thoracic esophageal cancer with a right aortic arch. Both cases were elderly males who complained of dysphagia. Computed tomography and aortography revealed a right aortic arch with a mirror-image branching and a diverticulum of the right descending aorta in both cases. They underwent an esophagectomy and a mediastinal lymph node dissection in a left thoracotomy, and we also added a median sternotomy in the second case for a lymph node dissection in the right mediastinum. The ductus arteriosus was divided in the first case, but he died of a rupture of the aortic diverticulum 13 months later. In conclusion, for a successful esophagectomy and mediastinal lymph node dissection, a median sternotomy should be added to the left thoracotomy, while careful attention should also be paid to the aortic diverticulum and the ductus arteriosus.

Aged↗

Postoperative lung volume calculated by chest computed tomography in patients with esophageal cancer.

It has been reported that, due to the severe surgical stress of thoracotomy, respiratory function after esophagectomy under thoracotomy worsened as late as a month after surgery. To investigate the mechanism of the reduction of the respiratory function, we utilized chest CT to analyze separately the changes in the lung volume of the thoracotomized side and the other side. Here, we reported the results of our comparative study of lung volume and respiratory function, which was performed by spirogram before esophagectomy and 6 months afterwards. We selected twenty-three patients who had undergone esophagectomy under right thoracotomy. Fourteen of the selectees received standard thoracotomy, while the other nine had the anterior serratus muscle and the latissimus dorsi muscle preserved. Total lung volume was found to have decreased from a preoperative value of 4077 +/- 674 ml (mean +/- SD) to a postoperative value of 3964 +/- 774 ml, and right-lung volume significantly decreased from 2229 +/- 397 to 2023 +/- 397 ml, while left-lung volume tended to increase. While right-lung volume in standard thoracotomy displayed a significant decrease from 2264 +/- 334 to 1949 +/- 424 ml, that in muscle-preserving thoracotomy showed almost no change. Spirogram revealed that vital capacity had decreased from 3574 +/- 601 to 2666 +/- 576 ml, and forced expiratory volume in the first second showed a significant decrease from 2680 +/- 500 to 2249 +/- 485 ml. Comparing the decreasing rate, the correlation coefficients between right-lung volume and %VC was 0.58. These results suggested that a change of lung volume in the thoracotomized side could play a role in the post-operative decrease of vital capacity and that muscle-preserving thoracotomy might induce less surgical stress than standard thoracotomy.

Adult↗

On negative selection against ATG triplets near start codons in eukaryotic and prokaryotic genomes.

The frequencies of ATG triplets in the genomes of various species were systematically analyzed, and the frequency of ATG triplets was significantly low around start codons in both prokaryotic and eukaryotic genomes. In eukaryotes, however, the frequency decrease before the start codon is much more evident than that after the start codon. In prokaryotes, on the other hand, the ATG frequency pattern around the start codon is less evident, and-more importantly-symmetric. We also computed average distances between a start codon and its nearest upstream-located ATG triplet and found a general tendency for the average distances to be longer in higher organisms.

Animals↗

The cyclin-dependent kinase inhibitor p27 as a prognostic factor in advanced non-small cell lung cancer: its immunohistochemical evaluation using biopsy specimens.

The expression of p27, which is known as a cyclin-dependent kinase inhibitor, on surgically resected specimens has considerable value for the prognosis of non-small cell lung cancer (NSCLC) patients. We immunohistochemically investigated the expression of the p27 protein in the biopsy specimens taken from 69 advanced NSCLC patients and assessed its clinical value. There was no significant correlation between p27 positivity and clinical parameters, including sex, age, histological type, clinical stage, smoking index and performance status. Furthermore, p27 positivity was not associated with response to chemotherapy. However, the Kaplan-Meier curve demonstrated that low p27 expression was significantly related to poor prognosis (P = 0.0019, by the log-rank test). Using multivariate analysis, p27, age and serum total protein level were found to be the independent prognostic parameters. The p27 positivity in the biopsy specimens of advanced NSCLC appears to be a useful prognostic marker.

Aged↗

The relationship between facial annular erythema and anti-SS-A/Ro antibodies in three East Asian women.

A distinct annular erythema developed on the cheeks of three East Asian women who had anti-SS-A/Ro (SSA) antibodies. The erythema was characterized by a wide, elevated border and central pallor. Histologically, there was a coat-sleeve-like infiltration of lymphocytes around the blood vessels, appendages, and secretory gland cells in the dermis. Immunohistological analysis clarified that the majority of infiltrating lymphocytes were CD4-positive T cells. Abnormal expression of HLA-DR antigens in the perivascular, appendage, and secretory gland cells in the dermis was also observed. The differential diagnosis of the three patients lay between Sjögren syndrome (SjS), Sjögren/systemic lupus erythematosus overlap syndrome and an asymptomatic clinical state. These results are consistent with recent findings of major histocompatibility complex class II expression on target organs in various autoimmune diseases. Based on these findings, erythema appears to represent a broad cutaneous manifestation of these diseases. Furthermore, the presence of SSA antibodies, aberrant HLA-DR expression, and sun exposure may be responsible for the development of erythema.

Adult↗

Acquired reactive perforating collagenosis associated with diabetes mellitus: eight cases that meet Faver's criteria.

Reactive perforating collagenosis (RPC) is characterized by umbilicated papules with a central adherent keratotic plug. Histologically, this condition shows transepidermal elimination of altered dermal collagen bundles into a cup-shaped epidermal depression. The present paper describes eight patients with associated diabetes mellitus who meet the diagnostic criteria for the acquired form of RPC (ARPC). Although half of these patients underwent dialysis, the lesions did not tend to develop after dialysis. Pruritus and the Koebner phenomenon were common, and histologically a microvasculopathy was noted in the dermis of all patients. We speculate that this disease is triggered by a cutaneous response to superficial trauma. Furthermore, this response acts synergistically with vasculopathy in the dermis, primarily in the case of diabetes mellitus. A secondary sign of ARPC may be degenerated collagen fibres as a result of transepidermal elimination.

Adult↗

Chronic radiodermatitis following repeated percutaneous transluminal coronary angioplasty.

We review three patients who developed chronic radiodermatitis subsequent to undergoing multiple percutaneous transluminal coronary angioplasties (PTCAs). All patients had had chronic ischaemic heart disease (IHD) and had undergone lengthy PTCA on several occasions. The skin eruption was characterized by an atrophic rectangular plaque on the left upper back, presenting as mottled hyper- and hypopigmentation with reticulate telangiectasia. Histologically, the eruption demonstrated epidermal atrophy, hyalinized and irregularly stained collagen, and telangiectasia of superficial vessels in the dermis. Although the risk of radiation injury in most patients undergoing cardiac catheterization is low, this danger should not be ignored. In particular, patients with long-standing IHD and numerous repeated catheterizations to only one or two occluded coronary arteries should be considered at high risk.

Angioplasty, Balloon, Coronary↗

Overexpression of p2lWaf1/Cip1 immunohistochemical staining in Bowen's disease, but not in disseminated superficial porokeratosis.

Disseminated superficial porokeratosis (DSP) consists of multiple small lesions of porokeratosis. Although the pathogenesis of DSP remains unclear, localized cloning of abnormal epidermis has been hypothesized. Malignant cutaneous neoplasms, especially Bowen's disease, have been frequently reported in DSP. Immunopositive p53 has been demonstrated in a variety of human malignant tumours, and its role in oncogenesis and tumour progression is thought to be important. p21Waf1/Cip1 is thought to mediate the signal of p53 induced by DNA damaging agents to arrest the cell cycle. To clarify the role of p53 and p21Waf1/Cip1 in Bowen's disease and DSP, we analysed 12 cases of Bowen's disease and eight cases of DSP by immunohistochemistry. In five of the 12 Bowen's disease patients and two of the eight DSP patients, positive p53 staining was detected. In contrast, whereas p21Waf1/Cip1 overexpression was detected in all Bowen's disease patients, it was not seen in DSP. The present data suggest that p53 immunostaining provides relevant information concerning the pathogenesis of Bowen's disease and DSP. Furthermore, high p21Waf1/Cip1 expression appears to be a useful indicator of tumour activity in Bowen's disease.

Aged↗

De-epithelialised anterior (anterolateral and anteromedial) thigh flaps for dead space filling and contour correction in head and neck reconstruction.

Anterior (anterolateral and anteromedial) thigh flaps based on the descending branch of the lateral circumflex femoral vessels provide a long vascular pedicle and a large flap without sacrificing main vessels and muscles. Twenty-eight de-epithelialized anterior thigh flaps were transferred for reconstruction of head and neck defects following tumour ablation. Two flaps were lost in patients that had previously undergone high-dose radiotherapy following free tissue transfer. Vascularised fibula, vascularised iliac bone and other tissues were combined with anterior thigh flaps in 13 cases utilising the distal end or derivative branches of the vascular pedicle. Salivary fistula was seen in only one case, although there were many minor and major complications. In five cases, double skin flaps were harvested from the ipsilateral thigh. One of these flaps was used for coverage of intraoral defects, while the other was placed in the submandibular area to fill dead space. Compared with other methods, this multi-flap method is considered to be most suitable for dead space filling and contour correction.

Adult↗

Serum pro-gastrin-releasing peptide is a useful marker for treatment monitoring and survival in small-cell lung cancer.

We investigated the usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for diagnosis, treatment monitoring and the prediction of relapse and prognosis in patients with small-cell lung cancer (SCLC). Serum samples were obtained from 127 patients with primary lung cancer (48 patients with small-cell carcinoma, 31 with adenocarcinoma, 36 with squamous cell carcinoma and 11 with large-cell carcinoma). The cutoff levels of serum Pro-GRP and neuron-specific enolase (NSE) were set at 46 pg/ml and 10 ng/ml, respectively. The specificity of Pro-GRP was significantly higher than that of NSE (Pro-GRP: 93.7%, NSE: 65.8%, p < 0.01). According to the histological type of lung cancer, the positive rates of Pro-GRP were 75% (36/48) in the small-cell carcinomas, 9.7% (3/31) in the adenocarcinomas, 5.6% (2/36) in the squamous cell carcinomas and 0% (0/10) in the large cell carcinomas. The median levels of Pro-GRP in limited disease (LD) and extensive disease (ED) patients were 199 and 295.5 pg/ml, whereas those of NSE were 14.8 and 29.3 ng/ml, respectively. The positive rates of Pro-GRP in LD and ED patients were 80.0% (16/20) and 71.4% (20/28), whereas those of NSE were 70.0% (14/20) and 89.3% (25/28), respectively. The positive rate of NSE tended to elevate with the progression of disease, whereas that of Pro-GRP was already high at an early stage. Among the 29 patients with SCLC who could be followed, the serum Pro-GRP levels of 18 responders were significantly decreased after treatment (p < 0.01), whereas those of the 11 nonresponders were not significantly different between before and after treatment (p = 0.72). In the 9 patients with SCLC who relapsed, the serum Pro-GRP levels were again elevated at the time of relapse. Seventeen patients whose ratio of the Pro-GRP level after treatment to the level before treatment was below 50% (taking the levels before treatment as 100%) survived significantly longer than did the patients whose ratio was over 50% (p < 0.01). The results of the present study suggest that serum Pro-GRP has high specificity and could be a useful marker of SCLC for treatment monitoring and prognosis.

Aged↗

Incomplete Sjögren-Larsson syndrome in two Japanese siblings.

Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder characterized by ichthyosis, spastic diplegia and mental retardation. Biochemical studies have pinpointed the pathogenesis resulting in the deficiency of the fatty aldehyde dehydrogenase (FALDH) component of the fatty alcohol NAD+ oxidoreductase complex. Histochemical analysis revealed a reduction in alcohol dehydrogenase (AD) activity in the skin. SLS patients have been categorized biochemically into two groups: complete and incomplete reduction according to the degree of FALDH deficiency. Our patients demonstrated incomplete clinical features, including a 1/3 reduction in FALDH activity, and decreased AD activity in the ichthyotic lesion. The phenotypical differences between our cases and classic SLS are probably due to the partial FALDH deficiency.

Aldehyde Oxidoreductases↗