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Biomedical subjects

R Kobayashi

Publications and source records attributed to R Kobayashi.

At least 235 records · Page 13Linked to original sources

A Saccharomyces cerevisiae Internet protein resource now available.

The QUEST Protein Database Center is now making available two Saccharomyces cerevisiae protein databases via the Internet. The yeast electrophoretic protein database (YEPD) is a database of approximately one hundred protein identifications on two-dimensional gels. The yeast protein database (YPD) is a database of gene names and properties of over 3500 yeast proteins of known sequence. These databases can be accessed via a World-Wide Web (WWW) server (URL http:@siva.cshl.org). YPD is available via public ftp (isis.cshl.org) as well, in a spreadsheet format, and in ASCII format. When accessed via WWW, both of these databases have hypertext links to other biological data, such as the SWISS-PROT protein sequence database and the Saccharomyces Genome Database (SacchDB), and to each other.

Computer Communication Networks↗

Intrathoracic transposition of the musculocutaneous flap in treating empyema.

Intrathoracic transposition of the musculocutaneous (MC) flaps of the latissimus dorsi and rectus abdominis was performed after open-drainage thoracotomy in 6 patients with empyema. The MC flaps were designed in such a way that the muscle-bearing skin paddle was extended well beyond the distal muscle borders. The MC flaps thus provided substantially larger pieces compared to muscle flaps. With the exception of one patient with persistent bronchopleural fistula whose empyema recurred due to the reopening of the fistula, the thoracic closure was successful in all patients. Postoperative magnetic resonance imaging revealed a well-preserved volume of subcutaneous tissue in the flaps, while the muscle portions of the flaps had atrophied. In conclusion, compared to muscle flaps, MC flaps have the advantages that (1) larger empyema cavities can be obliterated, and (2) the deformity of the thoracic wall can be minimized because of the small range of resected rib segments and well-preserved volume of subcutaneous tissue in the flap long after the transposition. The use of MC flaps is thus indicated for the empyema cavity remaining when a cavity is cleaned up of granulatous tissue with eradication of bronchopleural fistula.

Aged↗

Expanding intrathoracic hemorrhagic lesion penetrating the thoracic wall: a rare complication of chronic tuberculous pleurisy.

The patient was a 72-year-old woman with an expanding intrathoracic hemorrhagic lesion penetrated beyond the thoracic wall and was associated with chronic tuberculous pleurisy. Enhanced computed tomography revealed an extravasation of contrast medium into the lesion. The intrathoracic lesion and its penetrating lesion of the thoracic wall were resected. Microscopic examination revealed a hematoma with papillary structures lined with vascular endothelial cells, simulating organizing thrombus. An expanding intrathoracic hemorrhagic lesion is an extreme type of chronic tuberculous pleurisy, and can cause intrathoracic compression as the lesion increases in size.

Aged↗

The origin recognition complex in silencing, cell cycle progression, and DNA replication.

This report describes the isolation of ORC5, the gene encoding the fifth largest subunit of the origin recognition complex, and the properties of mutants with a defective allele of ORC5. The orc5-1 mutation caused temperature-sensitive growth and, at the restrictive temperature, caused cell cycle arrest. At the permissive temperature, the orc5-1 mutation caused an elevated plasmid loss rate that could be suppressed by additional tandem origins of DNA replication. The sequence of ORC5 revealed a potential ATP binding site, making Orc5p a candidate for a subunit that mediates the ATP-dependent binding of ORC to origins. Genetic interactions among orc2-1 and orc5-1 and other cell cycle genes provided further evidence for a role for the origin recognition complex (ORC) in DNA replication. The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes.

Amino Acid Sequence↗

Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats.

In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.

Animals↗

A DNA methylation site in the male-specific P450 (Cyp 2d-9) promoter and binding of the heteromeric transcription factor GABP.

The Cyp 2d-9 gene encodes the male-specific steroid 16 alpha-hydroxylase in mouse liver and shares a conserved regulatory element (-100TTCCGGGC-93) with another male-specific Slp promoter. As shown with the Slp promoter (N. Yokomori, R. Moore, and M. Negishi, Proc. Natl. Acad. Sci. USA 92:1302-1306, 1995), the male-preferential demethylation also occurs at CpG/-97 in the Cyp 2d-9 promoter. The transcription factor which specifically binds to the demethylated element has been purified. The peptide sequences reveal that the factor consists of GABP alpha and GABP beta 1 with Ets and Notch motifs, respectively. Both DNase I footprinting and gel shift assays indicate that the bacterially expressed glutathione S-transferase-GABP fusion proteins bind to the regulatory element only when CpG/-97 is demethylated. Moreover, Cyp 2d-9 promoter is trans-activated by coexpression of GABP proteins in HepG2 cells. Given the additional results that CpG/-50 of the female-specific steroid 15 alpha-hydroxylase (Cyp 2a-4) promoter is preferentially demethylated in the females, the sex-specific expressions of the P450 genes correlate very well with DNA demethylation. We also conclude that GABP is a methylation-sensitive transcription factor and is a potential transcription activator of the male-specific Cyp 2d-9 promoter.

Amino Acid Sequence↗

A nuclear factor (NF2d9) that binds to the male-specific P450 (Cyp 2d-9) gene in mouse liver.

Expression of the Cyp 2d-9 (steroid 16 alpha-hydroxylase) gene in mouse liver is male specific in such Mus musculus domesticus strains as FVB/N, whereas the corresponding P450 genes in the wild mouse species Mus spretus are not sex specific in their expression. These parental differences in the gene expressions were independently inherited in F1 offspring from crosses of FVB/N and M. spretus. A 5' flanking sequence (-110CTC CTCCCTATTCCGGGCC-92) was defined as a regulatory element (named SDI-A1) for the domestic Cyp 2d-9 promoter. The nucleotide which corresponds to T at position -99 within SDI-A1 was found to be substituted with C in the wild mouse P450 genes. The placing of C at position -99 abolished the transcriptional activity of SDI-A1 in HepG2 cells as well as the binding of SDI-A1 to a nuclear factor. This factor (designated NF2d9) was purified from mouse nuclear extracts, and its cDNA cloned. The purified NF2d9 bound to SDI-A1 but not to the mutated SDI-A1 with C at position -99. The deduced amino acid sequence revealed that NF2d9 is 72 and 94% identical to mouse CP2 and human LBP-1a, respectively. NF2d9 thus belongs to the CP2 family and is the mouse homolog of human LBP-1a, which modulates human immunodeficiency virus type 1 transcription. Anti-NF2d9, which was raised against the bacterially expressed protein, supershifted the SDI-A1 complex with the liver nuclear extract. Both the bacterially expressed and in vitro-translated NF2d9 inhibited SDI-A1 complex formation, although they did not bind to SDI-A1 directly. The results, therefore, indicate that the domestic Cyp 2d-9 gene can be regulated through a specific association of NF2d9 with SDI-A1.

Amino Acid Sequence↗

Characterization of the five replication factor C genes of Saccharomyces cerevisiae.

Replication factor C (RFC) is a five-subunit DNA polymerase accessory protein that functions as a structure-specific, DNA-dependent ATPase. The ATPase function of RFC is activated by proliferating cell nuclear antigen. RFC was originally purified from human cells on the basis of its requirement for simian virus 40 DNA replication in vitro. A functionally homologous protein complex from Saccharomyces cerevisiae, called ScRFC, has been identified. Here we report the cloning, by either peptide sequencing or by sequence similarity to the human cDNAs, of the S. cerevisiae genes RFC1, RFC2, RFC3, RFC4, and RFC5. The amino acid sequences are highly similar to the sequences of the homologous human RFC 140-, 37-, 36-, 40-, and 38-kDa subunits, respectively, and also show amino acid sequence similarity to functionally homologous proteins from Escherichia coli and the phage T4 replication apparatus. All five subunits show conserved regions characteristic of ATP/GTP-binding proteins and also have a significant degree of similarity among each other. We have identified eight segments of conserved amino acid sequences that define a family of related proteins. Despite their high degree of sequence similarity, all five RFC genes are essential for cell proliferation in S. cerevisiae. RFC1 is identical to CDC44, a gene identified as a cell division cycle gene encoding a protein involved in DNA metabolism. CDC44/RFC1 is known to interact genetically with the gene encoding proliferating cell nuclear antigen, confirming previous biochemical evidence of their functional interaction in DNA replication.

Amino Acid Sequence↗

Protein 1 (Clara cell protein) serum levels in healthy subjects and patients with bacterial pneumonia.

Serum levels of protein 1 (P1), a Clara cell secretory protein, were studied in 942 healthy subjects in relation to sex, age, and smoking habits and in 117 patients with bacterial pneumonia in relation to prognosis. P1 values in bacterial pneumonia patients at disease onset were compared with those in 234 healthy control subjects matched by sex and age. P1 values in healthy males were highest in those 30 to 39 yr of age and highest in healthy females > or = 70 yr of age but lowest in those 30 to 49 yr of age. P1 values in healthy males were significantly higher than those in females in the 30- to 39-yr age group (p < 0.05). Male smokers showed higher P1 values than nonsmokers, but without a significant difference. P1 values in patients with pneumonia were significantly lower than in control subjects (p < 0.0001). P1 values were significantly lower in patients treated with a respirator than in in patients treated without a respirator (p < 0.05). In 59 patients, whose P1 values could be followed up until the outcome of pneumonia, all 37 recovered patients showed significantly increased P1 values after recovery (p < 0.001), and all 22 who died of their illness showed significantly decreased P1 values just before death (p < 0.01). We thus conclude that P1 serum levels were significantly affected by sex and by the degree of seriousness in bacterial pneumonia.

Adolescent↗

Protein 1 (Clara cell protein) serum levels in lung cancer patients receiving chemotherapy.

As many antineoplastic drugs can cause injury to alveolar pneumocytes, Clara cells (nonciliated, nonmucous epithelial cells of the bronchioles) may also be damaged by such drugs. Protein 1 (P1) is an alpha-microprotein secreted by Clara cells. The effect of antineoplastic drugs on Clara cells is examined by the measurement of serum levels of P1 in patients with lung cancer receiving chemotherapy. Serum levels of P1 were studied in 36 patients with lung cancer, before chemotherapy and 5-7, 10-12 and 14-18 days after chemotherapy. One hundred and eight healthy subjects, matched by sex and age, acted as controls. There was no significant difference in P1 serum levels between patients with lung cancer and healthy controls. P1 serum levels decreased significantly 5-7 and 10-12 days after chemotherapy, recovering thereafter. We conclude that P1 serum levels do not differ between lung cancer patients and healthy controls, and that antineoplastic drugs inhibit the synthesis or secretion of P1 by Clara cells in the early period after the administration of medication.

Aged↗

Columbin isolated from calumbae radix affects the sleeping time of anesthetized mice.

In a screening series of bioactive components in edible and medicinal plants, we found that Calumbae Radix (Colombo root, 1% powdered feed, for 5 d) and its component, columbin (20-40 mg/kg/d, for 5 d, orally), shortened the sleeping time induced by a urethane and alpha-chloralose mixture and prolonged the sleeping time induced by hexobarbital in mice.

Anesthesia↗

[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium].

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.

Animals↗

Solitary, thin-walled cavitary lung metastasis of osteogenic sarcoma.

Three years after removal of a femoral osteosarcoma, a solitary, thin-walled cavitary lesion (diameter 1 cm) appeared in the lung of a young man. When the lesion enlarged, it was resected. Histology showed sarcoma metastasis with central necrosis and involving a peripheral bronchus. Cavitary metastasis can occasionally result from drainage of necrotizing tumor cells via a peripheral bronchus.

Adult↗

[Epidural injection for postoperative pain relief after thoracoscopic surgery].

For the pain relief after thoracoscopic surgery, the epidural injection of buprenorphine was performed in 46 cases. In 28 cases, intermittent injection was performed before awaking from anesthesia. The effect was excellent in 6 cases, who were free from pain without any more injection after returning to the ward, and good in 27 cases, who sometimes felt dull pain and had another analgetics (intermittent epidural injection in 16 cases, intermittent epidural injection and another medication in 5 cases). In 18 cases, continuous injection was performed. The effect was excellent in 9 cases and good in 9 cases. It was concluded that the epidural injection had effective analgesic effect after thoracoscopic surgery, both in intermittent injection group and continuous injection group. For limited medication, the intermittent epidural injection was considered the first choice after thoracoscopic surgery.

Analgesia, Epidural↗

[A case of Von Recklinghausen's disease associated with a hemothorax due to a rapidly growing malignant schwannoma].

A 17-year-old man with Von Recklinghausen's disease was admitted to our hospital because of progressive dyspnea on exertion. A chest X-ray film showed a massive left pleural effusion. Thoracentesis revealed dark blood. Hemothorax was diagnosed, and digital subtraction angiography (DSA) was done. DSA revealed a large mass that was supplied with blood via the inferior phrenic artery, but revealed no active bleeding. An intercostal tube was inserted and 1700 ml of dark blood was drained. A chest X-ray film taken after drainage revealed a giant mass showing an extra-pleural sign in the left lung field. A thoracotomy was done to determine the source of bleeding. A giant tumor with hypervascular tissue was seen, and was diagnosed as a malignant schwannoma. No spontaneous hemorrhage from the artery was seen. The source of the hemothorax was believed to be hemorrhage from the tumor vessels. The tumor was treated conservatively, but it continued to grow rapidly and the patient died of respiratory failure. Five other patients have been reported to have hemothorax associated with Von Recklinghausen's disease. The sources of the hemothorax were reported to be hemorrhage from tumor vessels, or spontaneous rupture of the subclavian artery, an intercostal artery, or an intercostal vein.

Adolescent↗

[The effects of the treatment with oxitropium bromide after one month or more in patients with pulmonary emphysema--evaluation of pulmonary function tests, exercise tests, and a questionnaire].

Chronic effects of oxitropium bromide were studied in patients with pulmonary emphysema. Pulmonary function tests, an exercise test, and a questionnaire were used. Seven subjects underwent two successive studies, including a questionnaire on QOL, pulmonary function tests, and an exercise test before and after one month or more of regular inhalation of ocitropium bromide (600 micrograms/day). The complaint of breathlessness was significantly reduced and the ability to perform activities of daily living had improved slightly after the treatment. There were no significant differences in the values of arterial oxygen pressure at rest. The VC, RV/TLC, and peak expiratory flow rate improved. A significant decrease in oxygen uptake at rest, a slight decrease in minute ventilation at rest, and a significant prolongation of exercise time were observed after the treatment. No other changes were noted. We conclude that oxitropium bromide may improve lung mechanics and reduce the work of respiratory muscles.

Administration, Inhalation↗

[Obstructive sleep apnea syndrome associated with superior vena cava syndrome].

A 43-year-old man was admitted suffering from dyspnea on exertion and edema of the neck and face. Chest X-ray film and CT scan revealed a mediastinal tumor and a right pleural effusion. A biopsy of the tumor revealed poorly differentiated carcinoma. Severe snoring at night and excessive daytime sleepiness were noticed after admission. Nocturnal oxygen desaturation was documented with a pulse oximeter, and obstructive sleep apnea syndrome was diagnosed on the basis of results of respiratory inductive plethysmography. The severity of snoring and oxygen desaturation during sleep correlated well with the progression of facial swelling. Combination chemotherapy (carboplatin 300 mg/m2 day 1, vindesine sulfate 3 mg/m2 day 1 and 8) was started but no improvement was seen. An expandable metallic stent was inserted into the stenotic vena cava, and the facial swelling, snoring, and oxygen desaturation during sleep were promptly relieved. In this case, obstructive sleep apnea was caused by edema and vascular congestion in the upper airway, and by the decrease in pharyngeal inspiratory muscle function caused by superior vena cava syndrome.

Adult↗