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Biomedical subjects

Y Suga

Publications and source records attributed to Y Suga.

At least 73 records · Page 4Linked to original sources

Premature termination codons on both alleles of the type VII collagen gene (COL7A1) in three brothers with recessive dystrophic epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. In the most severe, dystrophic (scarring) forms of EB, blisters form below the cutaneous basement membrane at the level of the anchoring fibrils, which are composed of type VII collagen. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the type VII collagen locus (COL7A1) have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. We have recently cloned the entire cDNA and the gene for human COL7A1. In this study, we describe distinct mutations in both COL7A1 alleles in three brothers with severe, mutilating recessive dystrophic EB (the Hallopeau-Siemens type, HS-RDEB). The patients are compound heterozygotes for two different mutations, both of which result in a premature termination codon in COL7A1, and the parents were shown to be clinically heterozygous carries of the respective mutations. Premature termination codons in both alleles of COL7A1 appear to be the underlying cause of severe, recessive dystrophic EB in this family.

Adolescent↗

N-alkylated 1,4-dihydropyridines: new agents to overcome multidrug resistance.

New N-alkylated 1,4-dihydropyridine derivatives were synthesized and their ability to overcome multidrug resistance was examined in vincristine-resistant P388 cells (P388/VCR cells). Compounds that possessed an arylalkyl substituent on the dihydropyridine ring nitrogen were more potent than verapamil in potentiating the cytotoxicity of vincristine against P388/VCR cells. However, neither drug effectively enhanced the antitumor activity of vincristine in tumor-bearing mice. Introduction of basic nitrogen-containing substituents on the side chain of 1,4-dihydropyridines gave improved activity in vitro and in vivo. The piperazine derivative 12c and 12o were more than 10 times as potent as verapamil in vitro. Four compounds selected for in vivo testing showed superior antitumor activity in P388/VCR-bearing mice in combination with vincristine. The structure-activity relationships of the compounds are discussed.

Alkylation↗

[Clinical evaluation of the small solitary pulmonary nodule].

The diagnostic process for small solitary pulmonary nodules was retrospectively analyzed. Three hundred and forty-three patients, each with a solitary pulmonary lesion of less than 3 cm on chest radiography, were evaluated. The patients were seen at our hospital between September 1986 and December 1993. They consisted of 138 with malignant diseases (114 with lung cancer and 24 with metastatic tumors), and 205 with benign diseases. There were 146 patients (71%) with benign lesions of less than 2 cm. The diagnosis in 118 patients (86%) with malignant disease was made by lung biopsy. Of these 118 patients, 19 underwent biopsy of the lung through a thoracoscope or open lung biopsy via a thoracotomy. Benign diseases were diagnosed in 167 patients (81%) by various laboratory tests and imaging techniques, including chest radiography. Thinsection CT was done in 132 patients. In 72 of these 132 patients (16 with lung cancer, 23 with metastatic tumors, and 33 with benign tumors), a judgement regarding whether the lesion was malignant or not could not be made. Therefore, open lung biopsy was done in 5 patients. Twenty-four patients were only observed, 43 underwent biopsy, and 35 underwent surgery. A decision tree needs to be established to select therapeutic options for management of patients whose diagnoses remain indeterminate even after thin-section CT. Formulation of a decision tree based not only on clinical findings but also on the results of diagnostic imaging is necessary to improve clinical decision making regarding small solitary pulmonary nodules.

Aged↗

Quantification of infarct size by thallium-201 single-photon emission computed tomography using the unfolded map method. Comparison with QRS score and angiographic infarct size at 4 weeks after infarction.

A new technique of data processing, the unfolded map method, was used with thallium-201 single-photon emission computed tomography to quantify infarct size in 35 patients with single-vessel disease at 4 weeks after their first myocardial infarction (24 anterior and 11 inferior infarcts), and the results were compared with those obtained by electrocardiography and contrast left ventriculography. The myocardial borders and the infarcted region were defined using the threshold technique and a cutoff value of 55%. Count profile data for each short-axis slice were unfolded zonally into single planes with the same ratio, and their areas were calculated from the slice thickness and radius. Thus, the size of the unfolded map represented the actual left ventricular myocardial area Infarct size was quantitated from the ratio of pixels in the infarcted region to those in the whole map, and the ratio itself was used as the percent infarct size. Although a defect 1 cm in diameter (0.8 cm2) could not be detected in a phantom study, defects > or = 2 cm in diameter (> or = 3.1 cm2) could be measured satisfactorily. The infarct size and percent infarct size determined by the unfolded map method correlated well with the QRS score (r = 0.841 and r = 0.838), the percentage of abnormally contracting segments on left ventriculography (r = 0.835 and r = 0.877), and the ejection fraction (r = -0.835 and r = 0.856). These data indicate that the unfolded map method provides adequate quantification of infarct size, even in the chronic phase, without complicated data processing.

Adult↗

An attempt to treat intractable skin ulcers with autologous dermal graft.

Five patients with a total of seven chronic intractable skin ulcers and impaired peripheral blood circulation were treated with autologous dermal grafts which did not contain any epidermal component. These ulcers were refractory to conventional therapy. Results from the dermal grafting were variable, with four of the ulcers (in two patients) healing 1-8 months after 1-5 graftings. These findings suggest the possibility that dermal grafting may be a simple yet effective treatment for deep, super-infected skin ulcers in which tendons and bones have become exposed. Dermal grafting may also provide an additional method by which to treat chronic skin ulcers which do not respond to conventional surgical therapy and where amputation of affected extremities is being considered.

Adult↗

Stoichiometry of the reaction catalyzed by skin sulfhydryl oxidase.

The stoichiometry of the reaction catalyzed by skin sulfhydryl oxidase was investigated. Dithiothreitol (DTT) was used as the substrate for skin sulfhydryl oxidase. The consumption of DTT, consumption of oxygen, and production of hydrogen peroxide were measured during the enzyme reaction. The molar ratio of DTT:O2:H2O2 in the enzyme reaction was 1:1.02:0.89. Correspondingly, the stoichiometry of the enzyme reaction was calculated to be [formula: see text]

Animals↗

[Sarcoidosis of the skin].

Sarcoidosis is characterized by formation of epithelioid-cell tubercules, without caseation, of the affected organ systems. The mediastinum, peripheral lymph nodes and eyes, in addition to the skin, are most frequently affected. Between 10% and 30% of patients with systemic sarcoidosis in Japan have skin lesions. Skin sarcoidosis is morphologically classified into three basic groups, erythema nodosum, scar sarcoidosis and skin sarcoid. Skin sarcoid is characterized by specific cutaneous lesions of sarcoidosis, and may take nodular, plaque, angiolupoid, subcutaneous and some other forms. Clinical manifestations of the cutaneous lesions are usually asymptomatic and polymorphous. Skin biopsy is, however, often highly useful for confirming a diagnosis of sarcoidosis.

Humans↗

[The estimation of effective renal plasma flow (ERPF) based on two compartment analysis using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3)].

The effective renal plasma flow (ERPF) of patients with renal-urinary disorders were estimated employing 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and a newly-developed clearance method which needs no blood sampling and is based on two-compartment fitting of the cardiac time-activity curves. In comparison with 123I-ortho-iodohippurate (123I-OIH) (n = 9), the disappearance rate constants and ERPF values estimated by the clearance method and the ERPF values by Schlegel's method showed a good correlation between the two agents (r = 0.88, r = 0.83 and r = 0.85, respectively). The ERPF values evaluated using 99mTc-MAG3 and the clearance method correlated well with those by Schlegel's method (n = 11, r = 0.95). These results suggest that 99mTc-MAG3 shows pharmacokinetics which are similar to those of 123I-OIH and that it might be a useful diagnostic tool for estimating the ERPF in patients with renal disorders.

Adult↗

Successful management of Hailey-Hailey disease with potent topical steroid ointment.

In order to know the real effect of steroid for Hailey-Hailey disease, seven patients were treated with strong steroid ointments in conjunction with antibiotics and/or antimycotic ointments. All patients were infected by various kind of bacteria and fungus. All patients showed remission within 2-16 weeks. Four patients maintained remission from 1.5 to over 4 years when ointments were continuously applied. No serious side-effects except skin atrophy and contact dermatitis were observed. These findings suggest that strong steroid ointment was really effective for this disease when secondary infection was prevented by the application of antibiotics and/or antimycotics, and that this disease is controllable with strong steroid ointments.

Administration, Topical↗

Skin proteasomes (high-molecular-weight protease): purification, enzymologic properties, gross structure, and tissue distribution.

Proteasomes (high-molecular-weight protease) were purified from rat skin, and their enzymologic properties, gross structure, and tissue distribution were investigated. Skin proteasomes were purified by successive (NH4)2SO4 fractionation and by phenyl Sepharose CL-4B and HPLC gel filtration chromatography. The molecular weights of the proteasomes were estimated from gel filtration to be 750 kD. On sodium dodecylsulfate-polyacrylamide gel electrophoresis, the purified enzymes dissociated into several bands, the majority falling into the range of 36-20 kD. Two-dimensional electrophoretic analysis demonstrated approximately 10-15 separate protein spots with pl values varying between 3 and 10. As analyzed by electron microscopy, the gross structure of the enzymes showed an almost symmetrical ring-shaped particle with a small hole in the center. Succinyl-leucyl-leucyl-valyl-tyrosine-4-methylcoumaryl-7-amide, a fluorogenic substrate for serine proteinases, demonstrated the highest activity in terms of substrate specificity. Sodium dodecylsulfate, Ca++, and some free fatty acids activated enzyme activity. Activity was inhibited by diisopropylfluorophosphate, leupeptin, N-ethylmaleimide, iodoacetamide, and chymostatin. These results show that both serine and cysteine residues are related to the enzyme activity of proteasomes. Total and specific enzyme activities in the epidermis were, respectively, 10 and 20 times higher than in the dermis. Immunohistochemical studies utilizing the avidin-biotin complex method with monoclonal antibody revealed that the enzyme is distributed throughout the epidermis. These findings indicate the epidermal localization of proteasomes.

Animals↗

[Usefulness of blood disappearance corrected hepatic uptake ratio (LHL/HH) as a hepatic functional index using 99mTc-galactosyl serum albumin].

The authors introduced blood disappearance corrected hepatic uptake ratio (LHL/HH) as an index of hepatic function using 185 MBq/3 mg of 99mTc-galactosyl serum albumin (GSA). Three ratio parameters, the hepatic uptake ratio (LHL15), blood disappearance ratio (HH15), and LHL15 divided by HH15 (LHL/HH) were evaluated with percent injected dose of 99mTc-GSA in blood at 15 min after injection (%ID15) and hepatic functional severity graded by Child-Turcotte criteria score. Seventy eight patients with chronic liver disease were studied. There was a poor linear correlation between the LHL15 and %ID15, because the LHL15 formed a plateau phase in the lower-value range for %ID15. In contrast, LHL/HH showed an excellent linear correlation with %ID15 in its whole range. In the comparison with the clinical functional severity, LHL/HH gave a more highly significant difference (p < 0.001) than LHL15 (p = 0.005) between the normal and mild dysfunction groups and gave a significant difference (p = 0.032) between the mild and moderate groups, in which HH15 showed no meaningful difference (p = 0.07). This index is obtained with no difficult procedures and can be regarded as a unified parameter for hepatic uptake and blood disappearance. It is hoped that LHL/HH will prove useful in the diagnosis of hepatic functional severity using 99mTc-GSA.

Adult↗

[A case of squamous cell carcinoma of the trachea in a female cigarette smoker].

A rare case of squamous cell carcinoma of the trachea in a female cigarette smoker is reported. The patient was a 72-year-old female with smoking index of 440 who developed wheezing and dyspnea on December 18, 1991. She was diagnosed as having bronchial asthma and hospitalized, but the symptoms were not improved. Bronchofiberscopic examination was performed and revealed a tracheal tumor on April 24, 1992. She was then referred to this cancer center. CT scan of the neck on admission showed a solid tumor which was 19 x 18 mm in diameter and protruded from the membranous portion and the right side of the tracheal wall into the lumen. Bronchofiberscopic findings revealed a soft polypoid tumor with a whitish coat on the surface and a tendency to bleed, at the second tracheal ring from the vocal cord. Histological findings of the biopsied specimen were compatible with poorly differentiated squamous cell carcinoma. A segmental resection of the trachea with end-to-end anastomosis was performed on May 6th, 1992. Postoperative radiation therapy (50.4 Gy) was added because of the residual microscopic cancer in the distal membranous portion of the tracheal wall. Female cases of squamous cell carcinoma of the trachea have been rarely reported in Japan. The relationship between squamous cell carcinoma of the trachea and smoking is considered.

Aged↗

[The right chest electrocardiogram in normal subjects].

Right chest electrocardiograms (ECGs) of 75 healthy subjects (19 men and 56 women; age 18 to 25 years) were recorded in order to study characteristic features of right precordial ST-T and QRS waves. The diagnostic criteria for right ventricular infarction (RVI) by ECG were also tested in healthy subjects to reascertain their value for diagnosing RVI. 1) The QRS configuration in right chest leads was usually the rS pattern in normal subjects (95% of V3R and 80% of V4R). 2) The Q wave was found in 5% of V4R, 20% of V5R and 51% of V6R. 3) ST elevation of 0.05-0.1 mV at 40 ms and 80 ms after the end of QRS deflection was found in 16 and 28% of V3R, 3 and 4% of V4R, respectively. 4) The T waves were usually negative in all right chest leads (79-88%). 5) The Q waves in V5R and V6R and ST elevation in V3R were relatively frequent findings in normal subjects. Therefore, the presence of a Q wave or ST elevation in these leads are not necessarily specific indicators of RVI by ECG. Furthermore, our data revealed that ST elevation with a Q wave in right chest leads was not present in any of the healthy subjects. This finding may be a more specific indicator for the diagnosis of RVI by ECG.

Adolescent↗

A study of pharyngeal symptoms caused by bronchofiberscopy.

We investigated the occurrence of pharyngeal symptoms in 100 patients who had undergone bronchofiberscopies by conducting a post-examination survey of the patients. Eighty-four patients complained of having a problem. Seventy-five patients, including 26 with dysphagia, complained of pharyngeal symptoms. The proportion with pharyngeal symptoms whose symptoms appeared on the day of examination was a high 89.4%. In 70.6% of cases, the duration of symptoms was less than four days. The pharyngeal symptoms were particularly common among patients who had undergone a bronchofiberscopy on a previous occasion or whose examination lasted for 15 min or more. A greater dysphagia incidence was noted among patients who had required an endotracheal tube (P = 0.03) and among those whose examination had lasted for 15 min or more (P = 0.01). Based on the results, we are now studying methods of alleviating pharyngeal symptoms, including dysphagia.

Adult↗

[A case of pulmonary metastasis from carcinosarcoma of uterus with subcutaneous implantation of tumor cells along the needle tract after percutaneous needle biopsy of lung].

A 68-year-old female who had undergone total hysterectomy for carcinosarcoma five months previously was noted to have a solitary nodular shadow in the right lung on chest X-ray. Percutaneous needle biopsy of the lung was performed via the right anterior chest wall, and the histologic findings showed metastasis from carcinosarcoma of uterus. Two months after needle biopsy, a chest wall mass appeared of the site of puncture of the lung needle biopsy. The mass was resected to relieve the chest wall pain and the specimen showed carcinosarcoma of uterus histologically. We consider that tumor cells were implanted to the chest wall along the needle tract after percutaneous needle biopsy of the lung. The postoperative chest computed tomogram showed the route of tumor implantation from the metastasis of right lung into the right chest wall. Dissemination and chest wall implantation of malignant cells after percutaneous lung needle biopsy have been rarely reported. However there are no reports of tumor implantation of sarcoma. The possibility of implantation of tumor cells along the needle tract after percutaneous lung needle biopsy should be carefully considered in cases of carcinosarcoma.

Aged↗

[Phase I clinical study on 99mTc-GSA, a new agent for functional imaging of the liver].

Technetium-99m-DTPA-galactosyl human serum albumin (99mTc-GSA) is a new radiopharmaceutical which binds to the asialoglycoprotein receptors located specifically on the hepatocytes. Phase I study of 99mTc-GSA was performed on seven normal volunteers, who were intravenously injected with 185 MBq (5 mCi) and 1-10 mg of 99mTc-GSA. None of adverse reactions, abnormal findings of laboratory test and anti-99mTc-GSA antibody production was recognized. The livers were clearly visualized in all subjects. In the pharmacokinetic analyses on five subjects, 99mTc-GSA was rapidly taken up by the livers immediately after the injection and was slowly excreted through the biliary tracts and the urinary tracts. Dose-dependency which is a specific feature for the receptor-mediated agents was observed; the blood clearances of 99mTc-GSA were prolonged in proportion to the injected ligand doses. These results suggest that 99mTc-GSA may be a potential agent for evaluating hepatic functions based on the hepatic receptor quantities.

Adult↗