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Biomedical subjects

T Nose

Publications and source records attributed to T Nose.

At least 19 recordsLinked to original sources

Endothelin-1 concentration increases in the cerebrospinal fluid in cerebral vasospasm caused by subarachnoid hemorrhage.

BACKGROUND: Endothelin-1 (ET-1) was originally identified as a potent vasoconstrictor peptide. Numerous reports have suggested its roles in various disorders. Although there is a great deal of evidence establishing the relationship between ET-1 and cerebral vasospasm in animals, this relationship still remains to be clarified in humans. METHODS: The concentration of ET-1 in cerebrospinal fluid (CSF) was measured by radioimmunoassay in 23 subarachnoid hemorrhage patients. CSF samples were collected every 10 days after surgery from the cisternal drainage tube. RESULTS: Initial concentrations of ET-1 in the CSF collected the first day after operation were all increased compared with the control CSF. In seven of the eight vasospasm patients, the concentrations of ET-1 had increased before the observation of vasospasm and then decreased before the disappearance of the vasospasm. In 13 out of the 15 patients without vasospasm, the concentrations of ET-1 in CSF decreased with time. CONCLUSION: We confirmed that the concentration of ET-1 in CSF increased before the onset of cerebral vasospasm caused by subarachnoid hemorrhage. The ET-1 concentration in the CSF could be a useful marker to detect cerebral vasospasm after subarachnoid hemorrhage.

Adult

[Usefulness of Doppler echocardiography in patients with ischemic cerebrovascular disease].

We carried out transthoracic Doppler echocardiography on 213 patients with ischemic cerebrovascular disease to examine cardiac functions. The prevalence of valvular regurgitation, left ventricular diastolic function (E/A ratio), and ejection fraction (EF) of each patient were studied by transthoracic Doppler echocardiography. In patients with embolic strokes, the prevalence of valvular regurgitation of the left ventricular system such as mitral regurgitation was significantly higher than that of normal controls. In contrast, there was no significant difference in the prevalence of valvular regurgitation in the right ventricular system. Although there was no significant difference in the ejection fraction between groups, the E/A ratio in patients with ischemic cerebrovascular disease showed a significantly lower value than that in normal controls. Patients with ischemic cerebrovascular disease showed a tendency to have an atherosclerotic change in the systemic arteries including cerebral and coronary arteries, reflecting an aggravation of cardiac wall compliance and diastolic dysfunction resulting in lowering of the E/A ratio. Thus, transthoracic Doppler echocardiography was useful to evaluate cardiac diastolic dysfunction and valvular regurgitation in patients with ischemic cerebrovascular disease.

Acute Disease

[Clinical usefulness of diffusion-weighted magnetic resonance imaging in patients with ischemic cerebrovascular disease].

Diffusion-weighted magnetic resonance imaging was performed to determine the detectability of ischemic changes in patients with ischemic cerebrovascular disease. We retrospectively reviewed 103 patients with symptoms suggestive of ischemic cerebrovascular disease. All patients underwent computed tomography, routine magnetic resonance imaging, and diffusion-weighted imaging. Of 103 patients, 18 were imaged within 3 hours after onset, 57 were imaged between 3 and 24 hours, and 29 were imaged between 24 and 144 hours. Eighty-eight patients were diagnosed as ischemic cerebrovascular disease. Magnetic resonance imaging was performed at a 1.0 Tesla clinical machine using single-shot spin-echo/echo-planar imaging sequence. In each case, three sets of DWI with motion-probing gradient pulses in the x, y, and z directions were taken. The detectability of ischemic changes of each imaging modality was compared. DWI detected ischemic changes in 83 of 88 cases with clinical diagnoses of cerebral ischemia(sensitivity; 94.3%). In contrast, DWI showed negative findings in 15 of the 15 patients with diagnoses other than cerebral ischemia(selectivity; 100.0%). DWI detected ischemic changes in 16 out of 18 patients(88.6%) within 3 hours after the onset. In contrast, T 2-weighted image did not detect any ischemic changes in the same period. These results suggest that DWI is considered to be highly useful for the early diagnosis of cerebral ischemia.

Adolescent

A new boronated porphyrin (STA-BX909) for neutron capture therapy: an in vitro survival assay and in vivo tissue uptake study.

A new boronated porphyrin compound (STA-BX909) was developed as a possible agent for boron neutron capture therapy. The boron concentration was measured by an in vivo rat experimental brain tumor model and an in vitro cell culture study. This agent was compared to sodium borocaptate (BSH) which has been used in clinical trials of boron neutron capture therapy. In the 9L rat brain tumor model, STA-BX909 achieved a higher boron tumor/blood ratio 24 h after injection in comparison to BSH. A boron concentration study in cultured glioma cell lines (U-251, U-87, 9L) demonstrated an increased boron concentration as a function of exposure time to STA-BX909, while the boron concentration remained stable with increasing exposure time to BSH. Use of a colony forming assay with thermal neutron irradiation revealed more cytotoxicity with STA-BX909 than BSH when the same concentration of 10B was administered. We concluded that STA-BX909 may be an effective drug for use in boron neutron capture therapy and that it merits further investigation.

Animals

A novel molecular design of thrombin receptor antagonist.

In a computer modeling of transmembrane domains of human thrombin receptor, Lys-158 was found near the ligand binding site. To capture this basic residue, analogs of peptide ligand containing a series of acidic amino acids were synthesized and assayed for human platelet aggregation, and Ser-(p-F)Phe-Aad(= alphaaminoadipic acid)-Leu-Arg-Asn-Pro-NH2 was found to be a potent antagonist.

Antithrombins

Design of serine protease inhibitors with conformation restricted by amino acid side-chain-side-chain CH/pie interaction.

A novel type of conformationally restricted peptides with the structure of H-D-Xaa-Phe-NH-CH2-C6H5 has been developed as inhibitors of serine proteinase chymotrypsin. The D-Xaa-alkyl and Phe-phenyl groups resulted in a formation of the hydrophobic core due to the side-chain-side-chain CH/pie interaction. Their spatial proximity was evidenced by 400 MHz 1H-nmr measurements, observing large upfield shifts of proton signals of D-Xaa-alkyl and nuclear Over-hauser effect (NOE) enhancements between the D-Xaa-alkyl and Phe-phenyl groups. This conformational restriction brought by CH/pie interaction produced an inhibitory structure, in which the C-terminal amide-benzyl group fits the chymotrypsin S1 site and the hydrophobic core binds to the S2 site. The inhibitory conformation was demonstrated crystallographically for the complex between the dipeptide H-D-Leu-Phe-NH-CH2-C6H4(p-F) and gamma-chymotrypsin. Detailed structure-activity studies have substantiated the structure of dipeptides in the active center of the enzyme.

Binding Sites

Intracranial hemorrhage in an infant owing to vitamin K deficiency despite prophylaxis.

A 3-month-old male infant with intracranial hemorrhage attributable to a vitamin K deficiency is reported. Vitamin K2 was administered orally at birth and then at 5 days and I month of age. Oral antibiotics were also given 2 days before the onset of bleeding. Although the incidence of intracranial hemorrhage resulting from vitamin K deficiency has decreased since the introduction of vitamin K2 prophylaxis, spontaneous intracranial hemorrhages are still being reported in infants. We suggest that vitamin K prophylaxis is needed especially for breast-fed infants and for those undergoing antibiotic therapy.

Cerebral Hemorrhage

Expression of P27kip1 and Ki-67 in pituitary adenomas: an investigation of marker of adenoma invasiveness.

Mirroring the ambiguities noted with other endocrine tumours, histology is a poor predictor of the invasiveness of pituitary adenomas. Accordingly, the proteins p27Kip1 (p27) and Ki-67, which respectively block cell-cycle progression and reflect proliferative activity of cells, were studied immunohistochemically in 123 specimens of pituitary adenomas including 57 clinically verified invasive cases. Only Ki-67 had a significant association with invasiveness; only p27 differed significantly between functioning and nonfunctioning adenomas, with a higher frequency of cell labelling in the former. No relationship between Ki-67 and p27 was obtained. Ki-67 detected by MIB-1 is thus an important marker related to the invasive potential of adenomas, and thereby may be helpful in planning postoperative management of patients with pituitary adenomas.

Adolescent

Dumbbell-shaped trigeminal neurinoma in a child.

We experienced a case of solitary trigeminal neurinoma in a 10-year-old boy without stigmata of neurofibromatosis. This boy presented with progressive cerebellar ataxia, right abducens palsy and right hemiparesis. Magnetic resonance images (MRI) demonstrated a tumour extending into both the middle and posterior fossas forming a dumbbell-shaped mass lesion with a size of 35 x 30 x 45 mm. The tumour was successfully removed free of complications by a two-stage operation composed of right subtemporal and suboccipital retromastoid approaches. It is extremely rare for a solitary neurinoma to occur at this site in a child without neurofibromatosis. Surgical approaches in this type of tumour are discussed with a review of the literature.

Child

Chronic progressive hematomyelia: case reports and review of the literature.

BACKGROUND: Hematomyelia usually has an acute onset and rapid progression, which results in a poor prognosis. However, there have been a few cases in which the clinical symptoms have progressed chronically, with a good prognosis. These two different clinical courses should be analyzed separately. The differential diagnosis of spinal tumor and other chronic progressive diseases due to the similarity of the clinical courses is also important. CASE DESCRIPTION: Two cases of hematomyelia with slowly progressive symptoms are reported. Unlike the acute onset and rapid progression or recurrent episodic deterioration usually seen in hematomyelia, the symptoms of chronic hematomyelia progressed over months and resulted in a better clinical prognosis than the acute course. The cases of "chronic progressive hematomyelia" from the literature are briefly summarized. CONCLUSIONS: Chronic progressive hematomyelia should be considered as a different clinical entity from the acute version because of its slowly progressive clinical course and good outcome. Magnetic resonance imaging is the procedure of choice to exclude spinal tumors or other slowly progressive intraspinal diseases.

Chronic Disease

Embolization of a ruptured aneurysm of the distal anterior inferior cerebellar artery: case report and review of the literature.

BACKGROUND: Aneurysms of the distal anterior inferior cerebellar artery (AICA) are rare and almost all of them have been treated surgically, by wrapping or trapping, in the previous literature. Most cases of aneurysms associated with the auditory artery resulted in a hearing disturbance from the surgical procedure, although aneurysms far from the auditory artery had no deficit from trapping. METHODS: An 81-year-old woman presented with a ruptured aneurysm of the distal AICA. We planned a delayed treatment with intravascular embolization because of her advanced age and poor clinical status. Embolization of the distal anterior inferior cerebellar artery using detachable coils remote from the auditory artery was successful. RESULTS: Magnetic resonance imaging after embolization demonstrated no remaining lesion. The patient has been through rehabilitation and has gradually improved. CONCLUSION: Intravascular treatment of distal AICA aneurysms remote from the auditory artery may be safer and simpler than surgical treatment.

Aged

Changing incidence of hip, distal radius, and proximal humerus fractures in Tottori Prefecture, Japan.

A survey of all fractures in patients > or =35 years of age for hip, distal radius, and proximal humerus was performed in Tottori Prefecture, Japan. Hip fracture survey was done for the years 1986-1988, and also 1992-1994. A distal radius and proximal humerus fracture survey was done for the years 1986-1988, 1992, and 1995. The age- and gender-specific incidence rates of these three types of fracture among Japanese were substantially lower than those of whites living in North America or northern Europe. The age-adjusted incidence rates of hip fracture (per 100,000 person-years) were 40.7 and 114.1 in 1986 and 57.1 and 145.2 in 1994 for men and women, respectively, showing a significant increase with time for women. Upon examination of individual fracture types, there was no significant increase in cervical fractures, whereas a significant increase was observed in trochanteric fractures for women. The age-adjusted incidence rates of distal radius fractures for women were 164.9 in 1986 and 211.4 in 1995, showing a significant increase with time; however, no increase was observed among men. Incidence of proximal humerus fractures was 10.3 and 42.0 in 1986 and 17.1 and 47.9 in 1995 for men and women, respectively, and these increases were significant for both genders.

Adult

Copper/zinc superoxide dismutase, nuclear DNA content, and progression in human gliomas.

To our knowledge, there have been no previous reports regarding the immunohistochemistry and image cytometry to demonstrate elevated Copper/zinc superoxide dismutase (Cu/Zn SOD) expression and numbers of the clonal cells in human gliomas. In 30 well-studied patients with gliomas, immunoreactivity for Cu/Zn SOD and cytometric evidence of DNA ploidy in the G2M cell cycle phase were evaluated from routinely prepared tissue blocks. Cu/Zn SOD positive tumor cells were shown in 8 of 13 glioblastomas (mean quantitative immunoreactivity SOD score; 1), 3 of 8 anaplastic gliomas (score; 0.6), and none of 9 low-grade gliomas. The differences in SOD score was not significant. In hypertetraploid glioblastomas, time to progression was shorter than for hypertetraploid of anaplastic gliomas, while SOD scores were not significantly different. The same relationship held for tetraploid specimens. Considering variables in combination, hypertetraploid gliomas with high SOD immunoreactivity showed a significantly short time to progression (p < 0.05) (1-5 months after radiotherapy and chemotherapy) compared with hypertetraploid, low-SOD immunoreactivity gliomas or tetraploid, low-SOD immunoreactivity gliomas. The tumor cells with high SOD activity also tended to be resistant for radiotherapy and anticancer drugs. Those results were suggested that the high grade glioma with a single clone and low SOD activity were effective for radiotherapy associated with oxidative stress, and that the high grade gliomas with more than two clones and high SOD activity were very less effective for same therapy. Cu/Zn SOD activity and the degree of the clonality in human gliomas should be very important factors influencing a choice of oxidative cytotoxic treatment.

Adult

Design and synthesis of para-fluorophenylalanine amide derivatives as thrombin receptor antagonists.

An antagonist specific for the thrombin receptor is expected to be a remedy for thrombosis. Structure-activity studies of thrombin receptor-tethered ligand SFLLRNP have revealed the importance of the Phe-2-phenyl group in receptor recognition and the replacement of the Phe-2 by para-fluorophenylalanine [(p-F)Phe] was found to enhance its activity [Nose, T. et al. (1993) Biochem. Biophys. Res. Commun. 193, 694-699]. In order to obtain a small sized antagonist, a series of (p-F)Phe derivatives was designed and synthesized novel structural elements essential for receptor interactions being introduced at both the N and C-termini. beta-Mercaptopropionyl (betaMp) or its derivative activated by S-3-nitro-2-pyridinesulphenyl (Npys) was introduced at the N-terminus, and phenylmethyl amines were coupled to the C-terminus. All compounds were inactive when assayed for human platelet aggregation, indicating that they are not agonists. beta-Mercaptopropionyl derivatives were also inactive as antagonists. However, Npys-containing analogs were found to inhibit the agonist activity of SFLLRNP. In particular, SNpys-betaMp-(p-F)Phe-NH-R [R = -CH(C6H5)2 and -CH2-CH-(C6H5)2] potently suppressed platelet aggregation. The results suggested that (p-F)Phe can be used as a structural core to construct an effective antagonist conformation.

Amides

Exploration of universal cysteines in the binding sites of three opioid receptor subtypes by disulfide-bonding affinity labeling with chemically activated thiol-containing dynorphin A analogs.

A ligand containing an SNpys group, i.e. 3-nitro-2-pyridinesulfenyl linked to a mercapto (or thiol) group, can bind covalently to a free mercapto group to form a disulfide bond via the thiol-disulfide exchange reaction. This SNpys chemistry has been successfully applied to the discriminative affinity labeling of mu and delta opioid receptors with SNpys-containing enkephalins [Yasunaga, T. et al. (1996) J. Biochem. 120, 459-465]. In order to explore the mercapto groups conserved at or near the ligand binding sites of three opioid receptor subtypes, we synthesized two Cys(Npys)-containing analogs of dynorphin A, namely, [D-Ala2, Cys(Npys)8]dynorphin A-(1-9) amide (1) and [D-Ala2, Cys(Npys)12]dynorphin A-(1-13) amide (2). When rat (mu and delta) or guinea pig (kappa) brain membranes were incubated with these Cys(Npys)-containing dynorphin A analogs and then assayed for inhibition of the binding of DAGO (mu), deltorphin II (delta), and U-69593 (kappa), the number of receptors decreased sharply, depending upon the concentrations of these Cys(Npys)-containing dynorphin A analogs. It was found that dynorphin A analogs 1 and 2 effectively label mu receptors (EC50 = 27-33 nM), but also label delta receptors fairly well (160-180 nM). However, for kappa receptors they showed drastically different potencies as to affinity labeling; i.e., EC50 = 210 nM for analog 1, but 10,000 nM for analog 2. Analog 2 labeled kappa receptors about 50 times more weakly than analog 1. These results suggested that dynorphin A analog 1 labels the Cys residues conserved in mu, delta, and kappa receptors, whereas analog 2 only labels the Cys residues conserved in mu and delta receptors.

Affinity Labels