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Biomedical subjects

K Hamada

Publications and source records attributed to K Hamada.

At least 397 records · Page 22Linked to original sources

Density and localization of alpha 1-adrenoceptors in hypertrophied prostate.

Alpha-adrenoceptors have been considered to play an important role in the regulation of the voiding force. In order to determine the density and localization of the alpha-adrenoceptors in the prostate, binding assays for alpha-adrenoceptors were performed with [3H]prazosin and [3H] yohimbine in membrane preparations from enucleated hyperplastic prostate tissues. Furthermore, autoradiographic analysis of alpha-adrenoceptors in the sliced tissue specimens from benign prostatic hypertrophy was performed. Specific binding of both ligands were saturable and of high affinity in membrane preparations, and Scatchard analyses indicated Bmax = 104 fmole/mg. protein, Kd = 0.488 nM for [3H]prazosin, and Bmax = 41 fmole/mg, protein, Kd = 1.83 nM for [3H] yohimbine. Bmax and Kd for [3H]prazosin were greater in the adenoma than in the submucosal tissue of the prostatic urethra. No relationship was noted between the size of enucleated prostate and the density of alpha-adrenoceptors. Image analysis of autoradiograms using [3H]prazosin showed specific binding sites could not be clearly demonstrated, but only [125I]HEAT slightly exposed specific binding sites in the prostate.

Aged↗

[A clinical study on five cases of respiratory infections caused by Neisseria meningitidis].

Five cases of the respiratory infections, in which Neisseria meningitidis was isolated upon the examination of the transtracheal aspiration (TTA), were reported. Patients studied were four males at the ages of 18, 56, 66 and 78 years, and a 18-year old female. Five cases were bronchopneumonia (two cases), acute bronchitis (two cases) and diffuse panbronchiolitis (DPB) (one case). Underlying diseases were as follows: lung cancer or acute myocardial infarction in cases of bronchopneumonia, and interstitial pneumonia or pulmonary tuberculosis in cases of acute bronchitis. There was a case in which only N. meningitidis was cultured from specimens obtained by TTA, although another different organism, in addition to N. meningitidis, was recovered from the patient of other cases. Other organisms found together with N. miningitidis were H. influenzae (2 cases), S. dysgalactiae (1 case) and M. tuberculosis (1 case). Predisposing factors were common cold in the female patient and bronchoscopic examination in the cases of lung cancer and of interstitial pneumonia. Two of the five cases occurred consecutively in the same room and so they were considered as nosocomial infections. With these findings, it can be posturated that N. meningitidis might be one of the etiological agents of the respiratory infections.

Acute Disease↗

Regulation of the mouse alpha A-crystallin gene: isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes.

We have shown by site-directed mutagenesis that the sequence between positions -69 and -40 of the mouse alpha A-crystallin gene is crucial for tissue-specific gene expression in a transfected mouse lens epithelial cell line transformed with the early region of simian virus 40. Gel retardation experiments with synthetic oligodeoxynucleotides revealed a mouse lens nuclear protein which bound specifically to the palindromic sequence 5'-GGGAAATCCC-3' at positions -66 to -57 in the alpha A-crystallin promoter. By screening a bacteriophage lambda gt11 expression library of the transformed lens cells, we isolated a 2.5-kilobase-pair cDNA encoding a fusion protein which bound to this sequence and to the regulatory element of the major histocompatibility complex (MHC) class I gene. This cDNA hybridized to a 10-kilobase-pair polyadenylated RNA present in many different tissues, including lens. It encoded a protein, tentatively called alpha A-CRYBP1, containing at least two zinc fingers. alpha A-CRYBP1 is either homologous or very similar to the human nuclear proteins MBP-1 (Baldwin et al., Mol. Cell. Biol. 10:1406-1414, 1990), PRDII-BFI (Fan and Maniatis, Genes Dev. 4:29-42, 1990), and HIV-EP1 (Maekawa et al., J. Biol. Chem. 264:14591-14593, 1989), which bind to regulatory elements of the MHC class I, beta interferon, and human immunodeficiency virus genes, respectively. Our results suggest that the lens-specific alpha A-crystallin, MHC class I, beta interferon and other genes have a similar cis-acting DNA regulatory motif that shares alpha A-CRYBPI, MBP-1, PRDII-BF1, HIV-EP1, or other closely related proteins as trans-acting factors.

Amino Acid Sequence↗

[Pharmacological studies of celiprolol: I. Beta-blocking effect, intrinsic sympathomimetic activity, vasodilating and hypotensive effects].

The beta-blocking effect, intrinsic sympathomimetic activity (ISA), and vasodilating and hypotensive effects of celiprolol were tested. 1. Celiprolol competitively antagonized the isoproterenol-induced positive chronotropic and inotropic effects in guinea pig right atrial and papillary muscles and isoproterenol-induced guinea pig tracheal relaxation with pA2 values of 8.03, 7.98 and 6.43, respectively. 2. In dogs, isoproterenol-induced increases in cardiac contractility and heart rate were markedly inhibited by celiprolol (83.1 and 84.8%, respectively), while isoproterenol-induced hypotension was suppressed only by 16.8%. 3. Celiprolol increased the beating rate of the right atrium and relaxed the trachea isolated from normal and reserpinized guinea pigs. Celiprolol also potentiated the contractility of the left atrium isolated from reserpinized animals. These effects of celiprolol were antagonized by propranolol. 4. Celiprolol concentration-dependently relaxed rat femoral arteries contracted by methoxamine. The concentration-relaxation curve was shifted to the right by pretreatment with propranolol. 5. Orally administered celiprolol produced long lasting hypotension in conscious SHR without any heart rate change. 6. These results indicate that celiprolol is a highly cardioselective beta-blocker with a significant ISA, which contributes to its vasodilatory and hypotensive effects.

Adrenergic beta-Antagonists↗

[Analysis of scintigrams using fuzzy theory].

Textural features for phantom images were extracted. Texture parameters which represent RI distribution--skew, energy, entropy and angular second moment were used. But, it was difficult to analyse the images using discriminant analysis for textural features, because textural features had statistical noise. Therefore fuzzy reasoning was adapted to analyse the images. Textural features for six kinds of images were showed using membership function. The possibility to the image was evaluated using the value of membership function on each images. Fuzzy reasoning could be done easily using max-min composition formula. The reasoning was found more suitable to analyse the images than discriminant analysis and will be considered useful for analysis of clinical scintigrams.

Algorithms↗

Axoplasmic electrolyte contents measured by X-ray microanalysis in experimental uremic neuropathy.

We investigated the mechanism of uremic neuropathy using experimental acute and chronic renal failure models in rats. After induction of renal failure, the motor nerve conduction velocity, axoplasmic electrolyte content, and cross-sectional area of myelinated fibers in the sciatic nerve were determined. The axoplasmic Na, K, Cl, and Ca contents were measured by electron probe X-ray microanalysis employing with sections from freshly freeze-dried sciatic nerves. The results obtained for both the acute and chronic renal failure models were similar. The sciatic motor nerve conduction velocity was significantly decreased in both cases as compared to that in the controls. The sciatic nerve axoplasmic Na content was significantly lower than that of the controls in both acute and chronic renal failure, and a significant reduction in the cross-sectional area of the myelinated fibers was observed in both renal failure models. These results suggest that impairment of the axonal membrane Na permeability and shrinkage of the myelinated fibers may play an important role in the decrease of motor nerve conduction velocity in uremic neuropathy.

Acute Kidney Injury↗

[An autopsy case of amyotrophic lateral sclerosis associated with cervical syringomyelia].

An autopsied case of amyotrophic lateral sclerosis complicated by cervical syringomyelia was reported. The case was a 59-year-old man, who first noticed weakness of both lower extremities at 54-year-old. The weakness spread to both upper extremities within 2 years. Cervical myelography revealed multi-level cervical spondylosis and anterior fusion of C5-C7 was done. But the weakness and atrophy of proximal muscle, diminished deep tendon reflex on upper extremities, hyperreflexia and pathological reflexes on both legs, tongue fasciculation and respiratory muscle weakness developed successively, and the patient died of respiratory distress at 59-year-old. Autopsy revealed multiple independent four syrinxes located at the level between C2-C7. One of these syrinxes had ependymal cell lining and thought to be idiopathic syringomyelia. The other three syrinxes were considered to be the cavitation in association with cervical spondylotic myelopathy. Degeneration and decreasing of spinal anterior horn cells, atrophy of medullary pyramis and Bunina bodies were observed as features of typical amyotrophic lateral sclerosis. Cervical spondylosis as causative lesion of multiple syrinxes was discussed, and relationship between ALS and the syrinxes was not indicated clearly.

Amyotrophic Lateral Sclerosis↗

[Antitumor activity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea, LY 186641 against various human cancers using subrenal capsule assay].

An analog of diarylsulfonylurea, LY 186641 has a broad spectrum activity against murine solid tumors including Colon 26 and LX-1. Preclinical evaluation of the anticancer activity of LY 186641 using the subrenal capsule assay was performed in fresh human tumor samples derived from 87 patients with various cancers and 70 (80%) samples were evaluable. The overall chemosensitivity rate of LY 186641 was 37% and the average tumor growth inhibition rates (TGIRs) of malignant lymphoma, esophageal cancer and colorectal cancer were 51 +/- 19%, 51 +/- 20% and 48 +/- 12%, respectively. The antitumor effect obtained by LY 186641 was comparable to that of the standard anticancer drugs including adriamycin, 5-fluorouracil and cisplatin evaluated in this assay simultaneously. Based upon these results, LY 186641 is considered to have antitumor activity against some human cancers.

Antineoplastic Agents↗

Pathology and pathogenesis of bursal-side rotator cuff tears viewed from en bloc histologic sections.

Histologic sections from 12 en bloc surgical specimens were studied in order to clarify the pathogenesis of bursal-side rotator cuff tears (BSRCTs). The specimens consisted of the bony insertion, the partially torn area, and the musculotendinous junction of the supraspinatus tendon. There were eight men and four women, with an average age of 48.7 years. Trauma was noted in three instances. All patients exhibited clinical evidence of subacromial impingement, which was confirmed at surgery. Histologic sections were stained with azan or hematoxylin and eosin. All the tears developed from within 1 cm of the insertion. The depth of the tears varied from a superficial flap to a nearly full-thickness tear. Microscopically, the sections demonstrated several abnormalities in addition to degeneration. At the site of insertion and in the distal stump, local disruptions of the normal four layers of enthesis and areas of hypervascularity were observed in all sections. The proximal stumps were rounded, retracted, and avascular, with abundant chondrocytes. No active repair was noted in the proximal stumps. The pathogenesis of BSRCTs appears to be related to: (1) a combination of aging and precarious vascularity of the tendon, (2) repetitive movements of the arm at above-horizontal levels, (3) injury, and (4) especially subacromial-tendon impingement.

Acromion↗

Roentgenographic findings in massive rotator cuff tears. A long-term observation.

It is difficult to determine the size and localization of rotator cuff tears preoperatively. But with the special arthrographic technique, a diagnosis with about 80% accuracy was possible in 65 surgically confirmed rotator cuff tears. With this technique, 22 massive cuff tears were found in conservatively treated patients. In these patients, the plain roentgenograms obtained at the initial examination were also analyzed. The roentgenographic findings included narrowing of the acromiohumeral interval and degenerative changes of the humeral head, the tuberosities, the acromion, the acromioclavicular joint, and the glenohumeral joint. Based on these data, five roentgenographic grades of massive cuff tears were identified. Of seven patients with massive tears, which had been treated conservatively and followed for more than eight years, the roentgenographic grades advanced in five. One shoulder progressed to cuff-tear arthropathy. Based on these observations, it is proposed that the following pathogenetic mechanisms are responsible for the progressive roentgenographic changes: (1) arm elevation in activities of daily living, (2) rupture of the long head of biceps tendon, (3) the abnormal fulcrum of the humeral head against the acromion and the coracoacromial ligament, and (4) the weakness of external rotation. A massive cuff tear will progress to cuff-tear arthropathy, with each step of progression accompanied by characteristic roentgenographic changes.

Acromion↗

Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.

Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor-binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE.

Animals↗

Distinct localization of prostaglandin D2, E2 and F2 alpha binding sites in monkey brain.

Autoradiographic localization of binding sites for [3H]prostaglandin D2, E2 and F2 alpha in the monkey brain was investigated by using in vitro labeling and an image processing system. Specific binding sites were distinctly localized in various nuclei in the hypothalamus, thalamus, and limbic system and their localization well correlated to the known functions of PGs in the brain by pharmacological and neurophysiological experiments. Furthermore, no direct relation was observed between the localization of PG binding sites and that of muscarinic cholinergic, alpha 1-adrenergic, and mu-opioid receptors in the preoptic area and hypothalamus.

Animals↗

H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, but not to other MHC cis-acting sequences or to mutant region II sequences, similar to the naturally occurring region II factor in mouse cells. The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors. Although sequence similarity in other regions was minimal, H-2RIIBP has apparent modular domains characteristic of the nuclear hormone receptors. Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene. The ERE is composed of a palindrome, and half of this palindrome resembles the region II binding site of the MHC CRE. These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences. Sequences homologous to the H-2RIIBP gene are widely conserved in the animal kingdom. H-2RIIBP mRNA is expressed in many mouse tissues, in agreement with the distribution of the natural region II factor.

Amino Acid Sequence↗

Location on the chromosome of the lac gene in a lactose-fermenting Salmonella litchfield strain.

We present conclusive evidence for the chromosomal location of the lac gene in a lactose-fermenting Salmonella litchfield strain (AO Lac+). Two Hfr strains constructed from AO Lac+ had abilities to transfer the lac gene to S. typhimurium LT2 at relatively high frequencies. Detailed characterization of the transconjugants suggested that the lac in AO Lac+ was located on the host chromosome between galE (18 min) and trpB (34 min). Transduction experiments using P22 phage showed that the lac was cotransduced with gal, but not with trpB. These results clearly indicate that the lac gene is located at a position near 18 min of the linkage map of Salmonella.

Chromosome Mapping↗

[The effect of erythromycin treatment on natural killer (NK) cell activity in patients with chronic lower respiratory tract infections].

We measured NK activity before and after administration of erythromycin in 7 cases of chronic respiratory infection, and investigated the relationship between NK activity and improvement of the clinical syndrome. 1) We saw a significant rise in NK activity after treatment of erythromycin. Values before and after ranged from 40.0 +/- 21/2% to 62.0 +/- 32.7%. 2) There was no correlation between treatment period of erythromycin and the rate of rise in NK activity in the various cases such as rapidly rising cases or slowly rising cases, etc. 3) We saw a rise in NK activity before improvement of the clinical syndrome. Therefore it is suggested that treatment of erythromycin affects a rise in NK activity.

Adult↗

A small nuclear RNA, U5, can transform cells in vitro.

Low-molecular-weight RNA exhibiting transforming potential was identified in chemically induced lymphoma cells by the transformation of mink lung cells after transfection. The RNA was sequenced by the direct chemical method and was shown to be a small nuclear RNA, U5. The transforming potential of the RNA was further studied in quantitative transformation assays using 3Y1, a rat fibroblastic cell line. Transformed foci appeared with a latency of 3 to 4 weeks after transfection. U5-transformed 3Y1 cells frequently carried an amplified c-myc oncogene. In addition, U5 induced chromosome aberrations in transfected cells, indicating that the RNA acts as a clastogen. Transforming and clastogenic potentials were specifically inactivated when U5 was incubated with RNase H in the presence of a complementary oligonucleotide. We discuss a possible mechanism of U5-induced cell transformation.

Animals↗

[Changes in plasma estradiol, progesterone and LH level in the menstrual cycle of the adult female Japanese monkey during the mating season].

Adult 15 female Japanese monkeys showing regular menstrual cycles were subjected to the daily blood sampling for the measurement of estradiol (E2), progesterone (P) and biological LH in the mating season. Monkeys were maintained under controlled conditions in a standardized environment. Of the 35 cycles observed, 18 (51.4%) were estimated as anovulatory cycles and 17 (48.6%) were ovulatory cycles. The anovulatory cycles were classified into three types according to the peak level of E2 (Type I: E2 less than 50 pg/ml 3 cycles, Type II: E2 less than 170 pg/ml 7 cycles, Type III: E2 greater than 170 pg/ml 8 cycles). The ovulatory cycles were classified into two Types according to the peak level of P (Type IV: P less than 5.0 ng/ml 5 cycles, Tyep V: P greater than 5.0 ng/ml 12 cycles). The menstrual cycle was 27.5 +/- 7.8 days. The differences between mid cycle LH surge and P level in Type IV and in Type V were statistically significant. It was revealed that female Japanese monkeys kept under controlled condition in the mating season showed high incidence of various types of anovulatory cycles and that the ovulatory cycles with low P elevation in the mid luteal phase showed low LH and P secretions on the mid cycle date.

Animals↗