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Biomedical subjects

K Hamaguchi

Publications and source records attributed to K Hamaguchi.

At least 163 records · Page 9Linked to original sources

Endoscopic clip-marking of lesions using the newly developed HX-3L clip.

Injection of India ink and clipping are relatively well-known methods for marking lesions of the gastrointestinal tract. The use of metal clips provides a radiologically recognizable mark, which is also palpable at surgery. In addition, clips can be extremely useful as landmarks in comparing endoscopic findings with the resected specimen. Previous reports of clip-marking have concentrated on the Olympus (Tokyo, Japan) HX-2L clip, but this clip has the disadvantages of having too wide a diameter to be used through most conventional endoscopes and also a relatively low clip-retention rate, as the depth of its bite is limited. Recently, Olympus has marketed a new clip (HX-3L) designed by the author for hemostasis in cases of gastrointestinal bleeding. This new clip is an improved version of the cassette-type J-clip that was previously reported by the author in this journal. The prime advantage of the HX-3L is that the endoscopist can use it via a panendoscope without any assistance. In addition, it has an excellent bite and a very high level of safety. In terms of function and application, it is completely different from the HX-2L. In addition, the tip (the portion that actually grasps tissue) of the HX-3L is longer and thinner than the HX-2L, thus permitting a firm grasp of the muscularis mucosae layer even when approaching from an upper oblique angle and this, in turn, improves the performance of the clip as a marker.(ABSTRACT TRUNCATED AT 250 WORDS)

Digestive System↗

Immunostimulation circumvents diabetes in NOD/Lt mice.

Diabetes susceptibility in non-obese diabetic (NOD) mice may entail faulty activation of immunoregulatory cells resulting from cytokine deficiencies. Depletion of T cells prevents disease onset in these mice. Since we had previously shown that IL-2 treatment in vivo restored the ability of NOD/Lt mice to produce self-restricted suppressor T cells (Ts) in a syngeneic mixed lymphocyte reaction (SMLR), we investigated the possibility that diabetes could be circumvented by treatment with immunostimulatory agents that increase cytokine production. By 20 weeks of age, 75% of vehicle-treated NOD/Lt female controls had become glycosuric, while glycosuria developed in only 17% of NOD/Lt females injected with human recombinant interleukin-2 (rIL-2, 250 U twice weekly) beginning at 6 weeks of age. Treatment of mice with Poly [I:C] alone [50 micrograms twice weekly, an inducer of Interferon (IFN) alpha/beta] or in conjunction with rIL-2 was even more effective, completely preventing glycosuria for 20 weeks. However, therapeutic effects required continuous administration of the immunostimulants since pancreatic insulin content declined and severity of insulitis increased following cessation of treatment. IL-2 treatment increased transcription of interleukin-1 (IL-1) mRNA in peritoneal macrophages and increased lipopolysaccharide (LPS)-stimulated IL-1 secretion in comparison to controls. In the presence of stimulators from IL-2-treated mice, T lymphocytes isolated from both controls and IL-2-treated NOD/Lt mice proliferated in a SMLR and acquired Ts function. Peritoneal macrophages from Poly [I:C]-treated mice exhibited increased IFN alpha gene transcription and LPS-stimulated IL-1 secretion. T cells isolated from Poly [I:C]-treated mice were capable of suppressing NOD-Lt T cell responses to alloantigens in a mixed lymphocyte culture without prior activation in a SMLR. Thus, Poly [I:C] treatment may recruit a different population of regulatory cells than those elicited by treatment with IL-2. However, the mechanisms by which autoreactive T-cell clones may be regulated by these two treatments in NOD/Lt mice may be synergistic. These results indicate that in addition to T-cell depletion protocols, diabetes in NOD mice can be prevented by treatment with immunostimulatory agents.

Animals↗

Isolation and fundamental properties of a phospholipase A2 inhibitor from the blood plasma of Trimeresurus flavoviridis.

Phospholipase A2 inhibitor was purified from the blood plasma of Habu, Trimeresurus flavoviridis, by Sephadex G-200 gel filtration, DEAE-cellulose chromatography, and Blue-Sepharose CL-6B column chromatography. The purified inhibitor was shown to be a glycoprotein with a molecular weight of about 100K. It was found to consist of four subunits whose molecular weights were around 20-24K. In order to examine the inhibition mechanism of the inhibitor, the interaction of the inhibitor with a phospholipase A2 from T. flavoviridis venom was examined by Sephadex G-100 gel filtration. One inhibitor molecule was found to bind directly to one phospholipase A2 molecule in both the presence and absence of Ca2+. The inhibitor inhibited the phospholipase A2 from T. flavoviridis venom with an apparent dissociation constant, Ki, of 1.7 X 10(-10) M, but not the porcine pancreas enzyme or the Agkistrodon halys blomhoffii enzyme belonging to the same family, Crotalidae, as T. flavoviridis, or the phospholipase C from Bacillus cereus.

Animals↗

Effects of combination treatment with FK506 and cyclosporine on survival time and vascular changes in renal-allograft-recipient dogs.

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

Animals↗

A study of drug efficacy in the treatment of ovarian cancer.

One hundred and nine cases of common epithelial ovarian cancer treated in our department during the past decade were entered into this study, which dealt with direct therapeutic effects and prognosis, comparing the groups administered cisplatin with those administered other anticancer drugs. 1) In 38 patients with measurable lesions, high response rates were achieved through the administration of anticancer drugs containing cisplatin in both the primary cancer and recurrent cancer groups. 2) Preventive chemotherapy was performed in patients in whom complete surgery was achieved at the initial operation. No significant difference in prognosis was observed through the administration of cisplatin and other anticancer drugs. 3) In patients in whom reduction surgery was carried out to the maximum possible degree at the initial operation, an improvement in prognosis was observed through the administration of cisplatin. These results imply that a cisplatin-based regimen should be aggressively used, except in cases that underwent complete debulking surgery.

Adenocarcinoma↗

[A case of meningoencephalitis caused by persistent Epstein-Barr (E-B) virus infection].

A 44-year-old man had several episodes of tingling sensation in his lower extremities, head and face over 1 year and presented mental disturbance 2 months prior to admission. He additionally suffered from dysuria and acute onset of gait disturbance 18 days before admission. Physical and neurological examination revealed marked splenomegaly, stupor, abnormal behavior, spastic tetraparesis and sphincter disturbances, and meningoencephalitis was suspected. There was lymphocytosis in peripheral blood, some of which showed atypical morphology. CSF examination revealed increased protein content and mononuclear pleocytosis. The titers of antibodies against E-B virus were elevated as follows; VCA IgM (X320), VCA IgG (X20,480), EA (X10,240) and EBNA (X10) in serum, and VCA IgM (X4), VCA IgG (X160), EA (X40) and EBNA (less than 1) in CSF. CT and MRI examination revealed ring enhanced lesion adjacent to left lateral ventricle with surrounding diffuse edema. Administration of intravenous glycerol and oral prednisolone induced substantial improvement in sensory, mental and sphincter disturbances and brain CT findings but not in splenomegaly and pyramidal tract signs. Antibody titer against VCA IgM also decreased. After withdrawal of prednisolone, CSF and CT findings worsened, and the antibody titer became elevated again, and CSF and CT findings improved by readministration of prednisolone. From the above signs and laboratory data, especially continuous elevation of antibody titer against E-B VCA IgM for as long as 1 year, this case was considered to be a meningoencephalitis caused by persistent E-B virus infection.

Adult↗

[A case of coronary artery fistula with angina pectoris].

A case of coronary artery fistula with myocardial ischemia is reported. A 57-year-old-man was admitted to our hospital complaining of anterior chest pain on exertion. Submaximal Treadmill exercise showed the depression of ST segment in leads II, III, aVF, V5 and V6. 75% stenosis of right coronary artery (segment 2) and congenital coronary artery fistula originating from both the right and left coronary arteries were demonstrated by the coronary arteriography. One abnormal artery was originated from proximal portion of the right coronary artery (segment 1) and entered the pulmonary artery trunk. Another one was originated from proximal portion of the left coronary artery and terminated in angiomatous plexus which then communicated with the pulmonary artery trunk. We speculate that myocardial ischemia resulted from decreased right coronary blood flow due to coronary steal and proximal organic stenosis of right coronary artery. Recently, the reviews of coronary artery fistula are increasing, but coronary artery fistula with myocardial ischemia is relatively rare. This case was followed with medical therapy, because antianginal agents were effective. Operative coronary ligation may be necessary, if he has angina or high output heart failure during follow-up.

Angina Pectoris↗

[Primary orthostatic hypotension syndromes without somatic neurologic signs--idiopathic orthostatic hypotension and primary sympathicotonic orthostatic hypotension].

Idiopathic orthostatic hypotension (IOH) and primary sympathicotonic orthostatic hypotension (PSOH) are conspicuous orthostatic hypotension syndromes without overt somatic neurologic signs. IOH, also referred as pure autonomic failure, is a syndrome of chronic pandysautonomia, and its clinical features include supine hypertension, anhidrosis, impotence, neurogenic urinary and bowel disturbances. PSOH is different from IOH in which it is not accompanied with autonomic features outside of cardiovascular symptoms, and has been most commonly described in German-Scandinavian literatures. The controversy in the nosology of IOH and PSOH has prevented the both concepts from world-wide acceptance, and little has been known about IOH in Japanese population. In the present study, statistical analyses were made to elicit the cases of orthostatic hypotension syndrome without somatic neurologic signs from the pooled results of hemodynamic autonomic functional tests in our laboratory. The subjects were 287 Japanese cases comprising 253 normotensive volunteers and 34 hypertensive patients. Apart from hypertension, none of the subjects exhibited abnormal findings on physical, neurological and routine laboratory examinations. The test of 70 degrees passive head-up tilt and other hemodynamic tests were performed upon the subjects, and the results were pooled by ages. By means of the method of maximum normed residual, statistically screened out were 7 cases with extremely great orthostatic fall in systolic blood pressure (OH-I). Another OH group (OH-II) consisted of 24 cases who showed orthostatic decrease in systolic blood pressure of 30 mmHg or more, but did no fall into the extreme observation. Assuming that the orthostatic regulation mechanism of blood pressure was well maintained in the remaining 256 cases, they were used as the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A case of right atrial myxoma with successful removal].

The incidence of primary cardiac tumors is very rare. However, the number of reported cases has recently increased due to the widespread use of echocardiography. This patient was a 67-year-old male whose main complaint was dizziness on standing. Right atrial myxoma was diagnosed by two-dimensional echocardiogram. Because of persistent right heart failure, open heart surgery was performed as a sub-emergency procedure. The myxoma was removed successfully and its weight was 93 g. The site of origin of the tumor was the lateral wall of the right atrium close to the entrance of the inferior vena cava.

Aged↗

[A case of psittacosis meningitis complicated with uveitis].

A 14-year-old boy was admitted to our hospital complaining of dull headache, high fever and decreased visual acuity of his left eye. Physical examination on admission revealed nuchal rigidity, positive Kernig's sign, slight hyperreflexia of deep tendon reflex, and decreased visual acuity of his left eye to 0.1. The chest was clear to percussion and auscultation, and no abnormal findings was observed on chest x-ray examination. On laboratory examination, leukocytosis (12,800/mm3) and increased erythrocyte sedimentation rate (83mm/hr) was observed. Cerebrospinal fluid (CSF) examination showed pleocytosis (308/3, mono 286, poly 22) and slight elevation of protein without decrease of glucose content (52mg/dl). On ophthalmologic examination, characteristic anterior and posterior uveitis was found in both eyes, more on the left. Antibody titer to psittaci was significantly elevated in both serum and CSF in his clinical course, therefore, this case was diagnosed as psittacosis meningitis complicated with uveitis. Minocycline (200mg/day) was administered from the 30th hospital day. The effect of this drug was dramatic, and fever and dull headache rapidly disappeared. In addition, fundus oculi examination on the 85th hospital day, revealed no abnormality in his eyes, and his visual acuity returned to normal level (1.0). This case was considered to be extremely rare case of psittacosis, because in addition to meningitis, the patient complicated with uveitis without any respiratory signs and symptoms.

Adolescent↗

Ultrastructural and functional studies of pancreatic B cells in Wistar rats treated with immunotherapeutic doses of cyclosporin.

Cyclosporin (CYA) was administered to Wistar rats at immunotherapeutic doses (20 mg/kg) and the functional and morphological effects on pancreatic B cells were observed. Serum CYA levels were kept in the range that is often encountered in clinical immunotherapy in humans. The treated rats had slightly elevated plasma glucose levels; on treatment days 6 and 13, their serum immunoreactive insulin and pancreatic insulin contents were low. Plasma immunoreactive glucagon levels were slightly elevated during treatment. Glucose tolerance was impaired on day 13. These functional abnormalities disappeared 2 weeks after drug withdrawal. B cells showed ultrastructural evidence of CYA toxicity, including cytoplasmic degranulation, nuclear inclusions, and cisternal dilatation of both the rough endoplasmic reticulum and the Golgi apparatus. These changes were observed on the third day of treatment and became more pronounced on the 6th and 13th days of treatment. By the second week after drug withdrawal, most of the B cells presented a normal ultrastructure. We confirmed that a dose of CYA similar to that used in clinical immunotherapy in humans produces ultrastructural disturbances in the pancreatic B cells of Wistar rats after relatively short-term administration.

Animals↗

Effects of ammonium sulfate on the unfolding and refolding of the variable and constant fragments of an immunoglobulin light chain.

The equilibria and kinetics of unfolding and refolding by guanidine hydrochloride of the VL and CL fragments of a type kappa immunoglobulin light chain were studied in the presence of ammonium sulfate using circular dichroism and tryptophyl fluorescence at pH 7.5 and 25 degrees C. The unfolding equilibria of the VL and CL fragments were described in terms of the two-state transition. The midpoints of unfolding in the absence of ammonium sulfate were at 0.9 and 1.2 M guanidine hydrochloride for the CL and VL fragments respectively. The transition curves were shifted to higher concentrations of guanidine hydrochloride by 1.4 and 1.6 M for the CL and VL fragments, respectively, per mole of ammonium sulfate. Unfolding reactions of the VL and CL fragments in 3 M guanidine hydrochloride followed first-order kinetics, and the rate constants for the two proteins were both greatly decreased by the presence of ammonium sulfate. The refolding reaction of the CL fragment in 0.3 M guanidine hydrochloride consisted of two phases, and the rate constants were increased a little by the presence of ammonium sulfate. The refolding reaction of the VL fragment in 0.3 M guanidine hydrochloride followed first-order kinetics, and the rate was not affected by the presence of ammonium sulfate. These results showed that ammonium sulfate stabilizes the CL and VL fragments mainly by decreasing the unfolding rate.

Ammonium Sulfate↗

Hydrogen-exchange kinetics of the indole NH proton of the buried tryptophan in the constant fragment of the immunoglobulin light chain.

The constant fragment of the immunoglobulin light chain (type lambda) has two tryptophyl residues at positions 150 and 187. Trp-150 is buried in the interior, and Trp-187 lies on the surface of the molecule. The hydrogen-deuterium exchange kinetics of the indole NH proton of Trp-150 were studied at various pH values at 25 degrees C by 1H nuclear magnetic resonance. Exchange rates were approximately first order in hydroxyl ion dependence above pH 8, were relatively independent of pH between pH 7 and 8, and decreased below pH 7. On the assumption that the exchange above pH 8 proceeds through local fluctuations of the protein molecule, the exchange rates between pH 7 and 8 through global unfolding were estimated. The exchange rate constant within this pH range at 25 degrees C thus estimated was consistent with that of the global unfolding of the constant fragment under the same conditions as those reported previously [Kikuchi, H., Goto, Y., & Hamaguchi, K. (1986) Biochemistry 25, 2009-2013]. The activation energy for the exchange process at pH 7.8 was the same as that for the unfolding process by 2 M guanidine hydrochloride. The exchange rates of backbone NH protons were almost the same as that of the indole NH proton of Trp-150 at pH 7.1. These observations also indicated that the exchange between pH 7 and 8 occurs through global unfolding of the protein molecule and is rate-limited by the unfolding.(ABSTRACT TRUNCATED AT 250 WORDS)

Bence Jones Protein↗

Immune responses in experimental allergic neuritis treated with corticosteroids.

The preventive and suppressive effects of methylprednisolone (MP) were investigated in 22 rabbits immunized with peripheral nerve myelin. Cellular reactivity to bovine P2 protein (P2) and anti-P2 antibody were also examined serially in these animals, using the lymphocyte proliferation test or enzyme-linked immunosorbent assay. Seven animals (preventive group), given 15 mg/day of MP subcutaneously from Days 0-28, showed a significant reduction in maximal severity and a delay in onset in comparison with 8 control animals. The remaining 7 animals (suppressive group), given the same dose of MP from Days 11-28, also showed significantly milder clinical signs than those observed in the controls. However, cellular hypersensitivity to P2 were manifested at Day 14 (just after clinical onset) in the controls, as well as in the preventive or suppressive groups. Furthermore, anti-P2 antibody was detected in each group after Day 14. These results suggested that the interference of inflammatory processes of immune-mediated disease might respond to the preventive and suppressive effects of MP.

Animals↗