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Biomedical subjects

T Sakuma

Publications and source records attributed to T Sakuma.

At least 145 records · Page 8Linked to original sources

Levels of complement regulatory molecules in lung cancer: disappearance of the D17 epitope of CD55 in small-cell carcinoma.

The levels of complement-regulatory molecules (complement receptor type one [CR1], decay-accelerating factor [DAF], membrane cofactor protein [MCP], and an inhibitor of membrane attack complex [CD59]) in lung cancer cells were analyzed to investigate the relation between their expression and histological subtypes, and the possibility of homologous complement deposition on cancer cells. In 25 cell lines (10 adenocarcinoma, 3 large-cell carcinoma, 7 small-cell lung cancer [SCLC], and 5 squamous cell carcinoma), flow cytometric analysis revealed that MCP was expressed in all cell lines, whereas none of the cell lines was CR1-positive. CD59 was detected in all cells. The DAF epitope defined by IA10 was expressed in all cells except one large cell carcinoma cell line. However, another epitope for anti-DAF monoclonal antibody, D17, was not detected in 5 (71.4%) SCLC and in 4 (22.2%) non-small-cell lung cancer. This disparity was seen in most cell lines, irrespective of histological subtypes. The loss of D17 reactivity seemed to be pertinent to malignant phenotype, because most of the normal pulmonary cells possessed the D17 epitope. Furthermore, a cell line lacking DAF (IA10-/D17-) allowed alternative pathway-mediated homologous complement (C3) deposition after pretreatment with anti-MCP antibody. This raises a new possibility for immunotargeting of cancer. These cell lines should be useful in studying the biology of lung cancer.

Antigens, CD↗

Alveolar liquid and protein clearance in the absence of blood flow or ventilation in sheep.

The primary objective of these studies was to test the contribution of ventilation and blood flow to the removal of excess liquid from the air spaces and interstitium of the lung. First, after eliminating ventilation by clamping the left main bronchus in anesthetized sheep, alveolar and lung liquid clearance was not altered over 4 h compared with control sheep that were ventilated normally. Thus, removal of excess liquid across the alveolar epithelium was independent of the change in the transalveolar hydrostatic pressure gradient produced by ventilation. Second, to determine the effect of removing all blood flow to the lung, we developed a new in situ sheep lung model in which lung lymph flow was measured over 4 h with or without ventilation after the sheep had been exsanguinated. Alveolar liquid clearance, as measured by the percent increase in alveolar protein concentration over 4 h, was similar between sheep without blood flow (31 +/- 18%) compared with sheep with normal blood flow to the lungs (31 +/- 17%). Lung lymph flow contributed to only 10-15% of the clearance of the excess alveolar liquid that was transported to the interstitium, indicating that nonlymphatic pathways accounted for most of the excess lung liquid clearance in the absence of microvascular filtration. Third, because ouabain completely inhibited alveolar liquid clearance in this in situ sheep lung model, these data provide evidence that alveolar liquid clearance depends on an intact Na(+)-K(+)-ATPase-dependent pump mechanisms. Finally, this in situ model represents a unique experimental preparation that can be used to study the alveolar epithelial barrier without blood flow or ventilation for a short time (4 h) interval.

Anesthesia↗

Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits.

We developed an experimental model of acute Pseudomonas aeruginosa pneumonia in anesthetized ventilated rabbits to determine whether bacterial-induced injury to the alveolar epithelium would occur and the effect of the injury on the pleural space. Dose-response studies established that 10(9) colony-forming units of P. aeruginosa (wild-type strain, PAO-1) were required to injure the epithelial barrier and to cause pleural empyema with exudative pleural effusions that contained both the instilled alveolar protein tracer and P. aeruginosa. We explored the mechanisms of P. aeruginosa-induced lung and pleural injury by using three isogenic bacterial strains to compare several extracellular virulence products. PAO-S21, which carries an insertion mutation in a regulatory gene that prevents the production of exoenzyme S, resulted in no lung or pleural injury. PAO-R1, which carries a deletion in a regulatory gene that controls the production of elastase and alkaline protease, caused the same degree of lung and pleural injury as PAO-1 did. Instillation of PLC-SRN, which has both structural genes encoding phospholipase C activity deleted, resulted in a moderate reduction in alveolar epithelial injury. Although other products may be involved, exoenzyme S and phospholipase C are important in mediating injury to the alveolar epithelial barrier in acute P. aeruginosa pneumonia in rabbits.

Anesthesia↗

[A case of severe interstitial pneumonia probably due to Chlamydia pneumoniae].

A 64-year-old male was admitted to our hospital with dyspnea and high fever. The patient had a relative bradycardia and severe hypoxemia. Velcr rales were heard throughout the entire lung fields. Leucocytosis was absent. Chest X-ray showed bilateral diffuse reticular shadows. Corticosteroid pulse therapy and minocycline were introduced on the suspicion of either idiopathic interstitial pneumonia or Chlamydial pneumonia. Subsequently, his symptoms gradually improved. Although the patient had no history of exposure to birds, the titer of complement fixation test for Chlamydia was 1:32 during the acute illness. Microplate immunofluorescence antibody technique proved infection with Chlamydia pneumoniae. We consider this is a rare case of severe pneumonia caused by C. pneumoniae.

Antibodies, Bacterial↗

[Epidemiological study of snoring--a questionnaire survey in factory workers].

There has been no epidemiological study of snoring in Japan, and we therefore performed a questionnaire survey (in about 7,000 adult men working at a steel-making factory at the time of the yearly health examination, and investigated the relationship between the severity of snoring and 17 items including age, obesity, family history of snoring, daytime hypersomnolence, hypertension, smoking, alcohol intake and traffic accidents. We classified all the subjects into three groups, no snoring, mild snoring, and severe snoring group. We defined severe snorers as persons who snored loudly in both inspiratory and expiratory phases and those who snored loudly with apnea. We found that aging, obesity, smoking and alcohol intake are risk factors for snoring. Compared with non-snorers, severe snorers were found to have a high incidence of family history of snoring, daytime hypersomnolence, and history of treatment of hypertension. No relationship was found between the severity of snoring and the occurrence of automobile accidents. The proportion of severe snorers over 40 years old with obesity, daytime hypersomnolence and morning headache was 0.25%, representing the group that may have obstructive sleep apnea syndrome. The probable incidence of sleep apnea syndrome in men may be considerably lower in Japan compared with that in either U.S.A. or Europe.

Adolescent↗

[Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test.

Aged↗

Molecular cloning of monkey liver cytochrome P-450 cDNAs: similarity of the primary sequences to human cytochromes P-450.

Three cDNAs coding for monkey cytochrome P-450 (P450) 2C, 2E and 3A (MKmp13, MKj1 and MKnf2, respectively) were isolated from a lambda gt11 cDNA library of a liver from a 3-methylcholanthrene (3MC)-treated crab-eating monkey, using cDNA fragments for human P450 2C, 2E and 3A as respective probes. MKmp13 and MKnf2 were 1901 and 2032 bp long, containing entire coding regions for polypeptides of 490 and 503 residues, respectively. The deduced N-terminal amino acid sequences of MKmp13 and MKnf2 were identical with those of P450-MK1 and P450-MK2, which had been purified from liver microsomes of untreated and polychlorinated biphenyl (PCB)-treated crab-eating monkeys, respectively. MKj1 was 1508 bp long, encoding a polypeptide of 449 residues, which is presumed to lack N-terminal 45 residues as compared with the sequence for human P450 2E1. Northern blot analysis indicated that monkey P450 2C, 2E and 3A mRNAs were expressed constitutively in monkey livers. P450 2E and 3A mRNAs were induced by both 3MC and PCB, while P450 2C mRNA was induced only by PCB. The deduced amino acid sequences of four monkey cytochrome P-450 cDNAs, including P450 1A1 (MKah1) which we isolated previously, were more than 92% identical with those of corresponding human cytochrome P-450 cDNAs.

Amino Acid Sequence↗

Microscopic features of the regeneration of white pulp in autotransplanted spleens in rats.

The process of regeneration of white pulp in autotransplanted splenic tissue, implanted into a pocket made by the greater omentum in rats, was investigated histologically and immunohistochemically. Three days after transplantation, almost all implants were necrotic. At day 7, viable splenic tissue had gradually regenerated at the periphery of the implants. At day 10, lymphocytes accumulated around the arterioles. The accumulations resembled the periarteriolar lymphoid sheath of normal spleens in structure, but consisted mainly of B-lymphocytes, with a few scattered T-lymphocytes. However, by week 2, the localization peculiar to T- and B-lymphocytes became definite, and follicular dendritic cells were simultaneously observed in the lymph follicles. This regeneration of the white pulp in the autotransplanted spleens differed from the formation of the white pulp during ontogeny and during recovery after spleen irradiation.

Animals↗

Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP).

The mutations of codon 17, 23, 58, and 347 of rhodopsin gene were investigated in 24 unrelated Japanese families including 33 patients with autosomal dominant retinitis pigmentosa (ADRP). A patient with codon 17 mutation (Thr-17-Met, ACG-->ATG) and a family including 4 patients with codon 347 mutation (Pro-347-Leu, CCG-->CTG) were detected among them. Their clinical findings were extremely different between the two mutations. The former showed type 2 and the latter showed type 1 ADRP. No mutation of codon 23 and 58 was detected in any families so far analyzed in the present study. Clinical findings associated with the mutation in codon 17 and 347 of the rhodopsin gene show an existence of allelic heterogeneity.

Adolescent↗

Clearance of different-sized proteins from the alveolar space in humans and rabbits.

Investigation of the clearance of proteins from the air spaces is important for an understanding of the resolution of pulmonary edema and also because of current interest in delivery of therapeutic peptides via the distal air spaces. Few experimental studies have examined the size dependence for alveolar clearance of large macromolecules; there have been no human studies. In anesthetized rabbits, we measured clearance of cyanocobalamin and different-sized human proteins instilled into the air spaces. After 8 h, the amounts of instilled tracer recovered in the lungs were [57Co]cyanocobalamin, 19.4 +/- 3.0% (Stokes radius 0.65 nm); 125I-labeled insulin, 64.6 +/- 3.9% (1.2 nm); 131I-labeled albumin, 87.0 +/- 4.0% (3.5 nm); and 125I-labeled immunoglobulin G, 91.8 +/- 3.3% (5.5 nm) (P < 0.05). Sieving of different-sized proteins occurred across the alveolar epithelial barrier because tracer concentrations in air space lavage fluid after 8 h were decreased more for the smaller tracers than the larger ones. Size selectivity for alveolar protein clearance in humans with resolving alveolar edema was investigated by measuring the changes in albumin and total protein concentration. The fraction of total protein concentration made up of albumin was greater in the edema fluid than in the plasma initially. The albumin fraction decreased with time in 9 of 10 patients with resolving edema, from 0.62 +/- 0.2 to 0.58 +/- 0.10 (P < 0.05) after 10 +/- 5 h. Thus both rabbit studies and human studies provide evidence for size-dependent clearance of protein from the air spaces of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Migration of neutrophils from the lung into the pleural space after lung resection in humans and rabbits.

The origin of neutrophils that are found in pleural effusions after pulmonary resection is unknown. We measured neutrophil counts in pleural effusion sequentially for 48 h in patients who had undergone partial resection or pneumonectomy. Additionally, we measured neutrophil counts in the pleural effusions separately from the visceral pleura and parietal pleura in rabbits. In humans, we found that the maximum neutrophil counts in pleural effusion occurred more often in the patients who underwent partial resection (11.7 +/- 6.0 x 10(4) cells/microL) than in the patients who underwent pneumonectomy (3.7 +/- 1.2 x 10(4) cells/microL). There was no difference between neutrophil counts in blood of pneumonectomy group and that of the partial resection group. In rabbits, neutrophil counts were 1.5 times greater in the pleural effusion derived from the lung than in that derived from the parietal pleura. We conclude that movement of neutrophils occurs primarily from the lung into the pleural space after lung resection in humans and rabbits.

Animals↗

[A case of small epidermoid cyst in cauda equina with manifest regional hypesthesia].

This report concerns the 22-year-old female who has been suffering the paresthesia in the left buttock and thigh for three months. Neurological examination revealed nothing other than hypesthesia and hypalgesia which distributed in the third, fourth and fifth segments of left sacral region with the loss of anal reflex. Pain had not been noticed until when she came to our clinic. Myelography and MRI showed small irregular round mass occupying a third of the spinal canal behind the body of fourth lumbar spine. In the axial view of MRI, the mass was enhanced by the gadolinium (Gd) except for the small portion of its center. She underwent the surgical treatment which revealed the tumor entangling four nerves of cauda equina in its center as imaged in MRI. The tumor was epidermoid cyst which presumably caused the chemical meningitis and involved those nerves. That resulted in the sensory disturbance in the left sacral region, although the tumor was not large enough to compress the nerves.

Adult↗

[Surgery for the patients whose total pulmonary vascular resistance was over 700 dyne during unilateral pulmonary artery occlusion test].

To determine the indication for surgery from the point of pulmonary function, we have performed the unilateral pulmonary artery occlusion test in lung cancer patients. In these patients, we gave a surgery in 13 cases whose total pulmonary vascular resistance were over 700 dyne.sec.cm-5/M2 per body surface area. The pulmonary hemodynamics before and during pulmonary artery occlusion were 549 +/- 82 and 798 +/- 78 dyne.sec.cm-5/M2 in total vascular resistance, 18.7 +/- 3.8 and 27.2 +/- 4.3 cmHg in mean pulmonary arterial pressure and 2.69 +/- 0.36 and 2.73 +/- 4.3 L/min/M2 in cardiac index respectively. In 7 cases out of 13, we performed selective pulmonary artery occlusion test. In pulmonary function test, 10 cases had a chronic obstructive diseases, 2 cases had a disturbance of diffusion and one case has a contractive disease. We gave a lobectomy in 12 cases and completion pneumonectomy in one case. Two of lobectomy cases died in the early phase: 42 and 72 days after surgery due to pulmonary complications. One of these cases needed an additional completion pneumonectomy because of bronchial fistel. Surgical complications were seen in 12 cases. These 13 cases used to be recognized that they have no indication of surgery because of low pulmonary function, however it revealed that we can give a lobectomy through a high intensive care after surgery.

Adenocarcinoma↗

[Molecular biological study of the rhodopsin gene in Japanese patients with autosomal dominant retinitis pigmentosa].

The author analyzed codon 347 of the rhodopsin gene using PCR (polymerase chain reaction) amplification and restriction enzymes in 19 unrelated Japanese families including 28 patients with autosomal dominant retinitis pigmentosa (ADRP). An allele of codon 347 mutation was found in a family (father and daughter). Sequence analysis shows that the mutation is from CCG to CTG. This mutation appears to be the cause of one form of ADRP, since it was also found in Japanese cases of ADRP which have a different racial background from families reported by Dryja et al.

Codon↗

[Visual field change and risk factors for progression of visual field damage in low tension glaucoma].

The authors carried out a prospective study in an attempt to determine the possible effect of intraocular pressure (IOP) and some clinical factors on the clinical course of low tension glaucoma (LTG). During the study period all the patients were followed without any antiglaucoma medication. The enrollment criteria for the study were reproducible, mild to moderate field loss as defined as a mean defect (MD) of greater than 2 dB and less than 10 dB or corrected loss variance (CLV) of greater than 7 dB revealed by the Octopus 201, G1 program. Forty-two consecutive patients (56 eyes) who fulfilled this criteria were enrolled. Baseline and follow-up examinations included applanation tonometry, perimetry with G1 program, blood pressure and pulse rate. When the MD increased by 4 dB or more on two consecutive perimetry examinations, the field defect was judged as "progressed". During the follow-up period (6-51 months, 25.1 +/- 12.5 months), the field defect progressed in 14 eyes of 12 patients. The life-table analysis (Kaplan-Meier) revealed that the rate of nonprogression of visual field defects was 55.5% at 48 months. The rate of nonprogression was significantly lower in 16 eyes with a mean IOP equal to or higher than 15 mmHg as opposed to 40 eyes with that lower than 15 mmHg (34.3% and 67.2% respectively, p less than 0.05). The results seem to indicate that IOP is likely to be responsible for the aggravation of visual fields in LTG. Canonical discriminant analysis revealed that the discriminant function containing four variables gives the best separation between the "progressed" and "nonprogressed" group (discriminant efficacy: 83.9%).

Adult↗

[Radioaerosol inhalation and perfusion imaging studies in immediate postoperative phase after lobectomy].

In order to determine the changes in pulmonary ventilation-perfusion imaging after lobectomies, we examined 11 patients using radioaerosol inhalation and perfusion scintigraphies, before and after the operations. We employed 99mTc-labeled albumin aerosol generated by a jet nebulizer for the inhalation imaging, and 99mTc-labeled macroaggregated albumin for the perfusion imaging, respectively. Prior to the operations, there were no (major) defects of imagings on the lung fields. Immediately after the operations, however, we could not detect any abnormal findings on chest roentgenograms, we found detects of imagings on the lung fields in either inhalation or perfusion scintigraphy whose area were mismatching. It took more than 3 weeks for these defects of imagings to disappear. In conclusion, these findings suggest that postoperative hypoxemia might be occurred by these mismatchings.

Administration, Inhalation↗

Clinical features of Japanese family with autosomal dominant retinitis pigmentosa caused by point mutation in codon 347 of rhodopsin gene.

Four members in a Japanese family had autosomal dominant retinitis pigmentosa caused by a single point mutation in codon 347 of the rhodopsin gene. The youngest, an 11-year-old girl, had an abnormal electroretinographic response, although her fundus appeared normal. The other affected family members noticed night blindness in the second decade. Their fundi showed diffuse pigmentation with concentric visual field loss, and there was no recordable electroretinographic response. Cataract developed in the fourth decade in the older patients. Good visual acuity was retained however, even in the fifth decade, after cataract extraction. These clinical features were similar to those of American patients (European family origin) with the same mutation of the rhodopsin gene reported previously.

Adult↗