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Biomedical subjects

H Ogata

Publications and source records attributed to H Ogata.

At least 19 recordsLinked to original sources

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND: The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS: TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS: Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS: OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.

Aged

Separation of hematopoietic stem cells into two populations and their characterization.

Two populations of hematopoietic stem cells (HSC) in mouse bone marrow (BM) are defined on the basis of the presence or absence of interleukin-3 (IL-3) receptor-associated antigen (IL-3RAA). HSC were purified by depletion of mature lymphoid-lineage cells followed by collection of the low-density fraction and sorting of wheat germ agglutinin-binding (WGA+) cells using a fluorescein-activated cell sorter. WGA+ cells were further separated into two populations (IL-3RAA+/WGA+ and IL-3RAA-/WGA+) by a monoclonal antibody (MoAb) against IL-3RAA. IL-3RAA+/WGA+ cells formed CFU-S on day 8; this population consisted mainly of cells in the cycling phase. IL-3RAA-/WGA+ cells form CFU-S on day 12; this population consisted mainly of dormant cells (cells in the G0 phase). When two populations obtained from C3H/HeN mice were injected into lethally irradiated (C57BL/6 x C3H/HeN)F1 mice, donor-derived cells in the peripheral blood (PB) appeared significantly earlier in mice injected with IL-3RAA+/WGA+ cells than in those injected with IL-3RAA-/WGA+ cells, whereas the reconstruction efficiency of IL-3RAA-/WGA+ cells had overtaken that of IL-3RAA+/WGA+ cells 6 weeks after injection. Long-term observation showed no significant difference between these two populations, however. The radioprotective ability (RPA) (30-day survival) of these two populations was therefore compared. The RPA of IL-3RAA-/WGA+ cells was significantly higher than that of IL-3RAA+/WGA+ cells. These findings therefore suggest that the former population is more primitive.

Animals

[The effect of the thyrotropin releasing hormone (TRH) on the motor speech disorder in spinocerebellar degeneration].

A prospective study regarding the effect of TRH on the motor speech disorder of three patients with spinocerebellar degeneration (SCD), the first with hereditary cortical cerebellar atrophy, the second and third with sporadic olivo-ponto-cerebellar atrophy, was performed. The effect was analyzed by using speech evaluation, such as the auditory impression, the questionnaire of the consciousness for verbal communication, the phonetic evaluation and the acoustic analysis. The results of the analysis and the mechanism of the improvement of the motor speech disorder are discussed. Only the first patient showed a remarkable improvement subjectively. In addition, the improvement of phonation and articulation was demonstrated quantitatively in the evaluation of the first patient. On the other hand, by phonation analysis using VISI-PITCH, it was seen that there were a decrease in the perturbation of the voice pitch and an increase in voice range in all three patients. Therefore, it was concluded that the improvement of phonation plays a major role in the improvement of the motor speech disorder. Such improvement of the phonation seems to have resulted from the improvement of coordination, mainly due to the normalization of the muscle tone of the larynx by TRH administration. Although a remarkable beneficial effect of TRH may be obtained in exceptional patients of SCD, the mechanism of such an effect of TRH should be more extensively studied using the quantitative clinical evaluation of phonation and articulation.

Articulation Disorders

Glycolipid of human pancreatic cancer; the appearance of neolacto-series (type 2 chain) glycolipid and the presence of incompatible blood group antigen in tumor tissues.

Glycolipid isolated from normal and cancerous human pancreatic tissues were characterized chemically and immunologically. The major neutral glycolipids in both normal and cancerous tissues were composed of globo-series glycolipids and lacto-series glycolipids. The mole percentage of fucolipids in the total neutral glycolipids of normal tissues was 20-40%, and in general the fucolipids corresponded to blood group glycolipids related to the patient's blood group, however, in cancerous tissues the amount of these fucolipids was decreased. Immunostaining revealed that normal tissues contained only lacto-series (type 1 chain) glycolipids. In contrast, cancerous tissues contained the neolacto-series (type 2 chain) glycolipids as well as the lacto-series glycolipids. Incompatible blood group antigens, A active glycolipids in a blood type O patient and B active glycolipids in a blood type A patient, were also detectable in the neutral glycolipid fractions of the pancreatic cancer tissues.

Adenocarcinoma

An exploration of the binding site of aldolase using alkyl glycolamido phosphoric esters and alkyl monoglycolate phosphoric esters.

Alkyl glycolamido phosphoric esters (P-O-CH2-CO-NH-(CH2)n-CH3) and alkyl monoglycolate phosphoric esters (P-O-CH2-CO-O-(CH2)n-CH3), which are analogs of the aldolase substrate fructose-1-phosphate, were synthesized and use for probing the active site of rabbit muscle aldolase. The inhibition constants (Ki) were affected by the length of the alkyl groups of these compounds and a maximum value of Ki was observed between the number of methylene groups 2 and 4, depending on the type of compound. In the previous investigation, N-(omega-hydroxyalkyl)-glycolamido bisphosphoric esters (P-O-CH2-CO-NH-(CH2)n-O-P) and alkanediol monoglyclolate bisphosphoric esters (P-O-CH2-CO-O-(CH2)n-O-P) have a minimum Ki value between the number of methylene groups 1 and 4. The difference spectra of aldolase caused by binding of alkyl glycoamido phosphoric esters or alkyl monophosphates resembled that of their analogous bisphosphoric esters, but the intensity of absorbance was smaller than that of the bisphosphoric ester analogs. These results suggest that rabbit muscle aldolase has two binding sites for the phosphate groups on the entrance end of the active site cavity, the singly wound beta-barrel of the parallel alpha/beta class structure. The distance between the phosphate binding site Lys-107 in the beta-sheet structure (c) and Arg-148 in the beta-sheet structure (d) may possibly be expanded or contracted by the forms of the bending structure of the biphosphate compounds. Also, the change of distance between the beta-sheet structure (c) and (d) containing Trp-147, may have an effect on the environment of the tryptophan and cause a change of the absorbance of aldolase especially at 295-299 nm. On the other hand, the synthetic monophosphate compounds bind at only one of the two phosphate binding sites and have very little effect on the absorbance of Trp-147, in a similar manner as orthophosphate. The alkyl groups of monophosphate may be repelled by the ionic amino acid side chains, Asp-33, Lys-146, Glu-187 and/or Lys-229 in the middle of the active site cavity. However, the end of the long alkyl group of some monophosphates may possibly contact the hydrophobic bottom of the active site cavity without effect on the environment of Trp-147.

Binding Sites

Detection of chronic hepatitis C virus infection by four diagnostic systems: first-generation and second-generation enzyme-linked immunosorbent assay, second-generation recombinant immunoblot assay and nested polymerase chain reaction analysis.

Serum samples from 100 patients with non-A, non-B hepatitis-related chronic liver disease and 100 patients with hepatitis B-related chronic liver disease were tested by first-generation and second-generation enzyme-linked immunosorbent assays, a second-generation recombinant immunoblot assay and the nested polymerase chain reaction. In non-A, non-B hepatitis-related chronic liver disease, second-generation enzyme-linked immunosorbent assay (anti-c22 and/or c200) and second-generation recombinant immunoblot assay showed 98% positivity, whereas first-generation enzyme-linked immunosorbent assay (anti-c100-3) showed 89% positivity. The two second-generation recombinant immunoblot assay-negative samples were positive by nested polymerase chain reaction, but one second-generation recombinant immunoblot assay-positive sample was polymerase chain reaction negative. However, when this second-generation recombinant immunoblot assay-positive sample was tested by polymerase chain reaction using another set of primers, it was polymerase chain reaction positive. Therefore, 100% of the non-A, non-B hepatitis-related chronic liver disease serum samples were hepatitis C virus RNA positive by polymerase chain reaction. Nine hepatitis B-related chronic liver disease samples were first-generation enzyme-linked immunosorbent assay positive. Of the eight second-generation enzyme-linked immunosorbent assay-positive hepatitis B-related chronic liver disease samples, six were first-generation enzyme-linked immunosorbent assay positive and five were second-generation recombinant immunoblot assay positive and polymerase chain reaction positive. One indeterminate second-generation recombinant immunoblot assay sample was polymerase chain reaction negative. Therefore, second-generation recombinant immunoblot assay appears to be as useful as polymerase chain reaction for detecting a chronic hepatitis C virus infection, although some discrepancies were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Gastric emptying of tablets and granules in humans, dogs, pigs, and stomach-emptying-controlled rabbits.

Rates of gastric emptying of nondigestible tablets and granules in humans were compared with those in three animal models: dogs, minipigs, and stomach-emptying-controlled rabbits. The rates of gastric emptying of both dosage forms in dogs tended to be faster than or similar to those in humans, whereas the rates in pigs were slower. In stomach-emptying-controlled rabbits, no tablets were emptied from the stomach because of their large size. The rate of gastric emptying of granules in rabbits was slow and variable. Food delayed gastric emptying in dogs, especially for tablets. In rabbits, the rate of gastric emptying of granules was faster when the granules were given before feeding, in comparison with that after feeding or under fasting conditions. We concluded that the dog is a better animal model for bioavailability studies under fasting conditions than the pig and the rabbit.

Adult

Production of a negative regulator of IL-3 by bone marrow cells in response to the supernatant of IL-3-producing STIL-3 leukemia cells.

When spleen cells of mice grafted with STIL-3 C5 cells, a leukemic T-cell line producing IL-3, are cultured in vitro, a high IL-3 activity is detectable in the culture supernatant. However, when bone marrow cells of the same grafted mice are cultured under similar conditions, hardly any IL-3 activity is detectable. To elucidate the mechanism of this difference, we examined whether the bone marrow cells either suppress IL-3 production by STIL-3 C5 cells or produce an IL-3 inhibitor. When STIL-3 C5 cells were cultured in the presence of normal bone marrow cells, the culture supernatant showed a significantly reduced IL-3 activity as assessed by growth stimulatory effects on IL-3-dependent DA-1 cells and mast cells. The conditioned medium (CM) did not inhibit the growth of IL-3-independent cell lines. Heat treatment of the CM resulted in a recovery of the IL-3 activity, indicating that the effect was mediated by a heat-labile inhibitor rather than by suppression of IL-3 production. CM of bone marrow cells alone did not inhibit the IL-3 activity. The inhibitor was produced by a stem cell-enriched fraction of the bone marrow, and not by fractions of T cells, granulocytes, or adherent cells including macrophages. Stimulation of the stem cell-enriched fraction of bone marrow with STIL-3 C5-CM also induced the production of the IL-3 inhibitor, which was recovered in a MW 50-100 kD fraction after ultrafiltration. These results suggest a possible presence of a feedback mechanism against the IL-3 effect on hemopoietic stem cells and progenitors in the bone marrow.

Animals

Electrophysiological study of four patients with Fisher syndrome: a mechanism of areflexia.

Electrophysiological studies were performed on four patients with the Fisher syndrome (two 4-year-old boys, a 5-year-old boy and a 9-year-old girl). Motor nerve conduction velocity (MNCV), nerve action potential, F wave, H reflex and T reflex were measured at the stage when areflexia was present but ataxia and ophthalmoplegia had recovered. MNCV and SNCV by compound mixed nerve potential were normal in all our patients. The amplitude of the muscle responses (M-responses) and compound mixed nerve action potentials were also within normal limits. The latencies of the F waves and F wave conduction velocities were normal. However, H-reflexes and T-reflexes were absent in all four cases. Our results suggested that areflexia in the Fisher syndrome is attributed to the desynchronization of the impulses or the partial conduction block of GIa fibers.

Ataxia

A case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia in childhood.

We report here a case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia. The patient was a 13-year-old girl with struma and hyperthyroidism which began at age 12. Two weeks following the initiation of treatment against hyperthyroidism she developed left blepharoptosis, diplopia, and dysphagia, which responded promptly to edrophonium administration. An increase of the anti-acetylcholine receptor antibody was found in the serum. A chest CT showed a large soft tissue mass in front of the ascending aorta, which was proven histopathologically as thymic hyperplasia. The patient underwent an extensive thymectomy and was placed on combination therapy with an anti-thyroid drug, glucocorticosteroid, and an anti-cholinesterase drug. Her symptoms and signs have been well controlled by this treatment. Coexistence of myasthenia gravis, hyperthyroidism, and thymic hyperplasia in childhood have never been documented in literature.

Adolescent

Hydrocephalus due to acute aqueductal stenosis following mumps infection: report of a case and review of the literature.

An acquired form of hydrocephalus due to aqueductal stenosis developing as a sequela of mumps virus infection of the central nervous system is presented. Percutaneous third ventriculostomy and interventriculostomy (aqueduct cannulation) were performed using a flexible fiberoptic ventriculoscope. The aqueduct was blocked with amorphous material but was cleared with the scope. This is the first case of a fulminant phase of mumps ventriculitis leading to aqueductal stenosis, which has been treated using a ventriculoscope for the first time.

Acute Disease

[Analysis of urinary tract infections in hospitalized elderly patients, with particular reference to the use of diapers].

We investigated the clinical and laboratory data of 215 hospitalized patients (mean age were 76.9 +/- 12.1) to analyze both the characteristics of senile UTI and the influence of the way of urination. UTI was present in 121 of 1897 patients (6.4%), 95 of whom (78.5%) were female. Comparison of the parameters between non-infected and infected patients were as follows: body temperature was 36.57 +/- 0.64 degrees C vs. 37.49 +/- 0.77 degree C; WBC, 5410 +/- 2040/microliters vs. 7260 +/- 3230/microliters; CRP, 1.2 +/- 2.4 mg/dl vs. 3.5 +/- 3.4 mg/dl; mean class of urinary RBC, 0-1/hpf vs. 3-5/hpf; and mean class of urinary WBC, 5-10/hpf vs. 30-50/hpf. All parameters were significantly elevated (p < 0.001) in the patients with UTI. The rate of detection of causative bacteria was 88.7%; with 14.8% Escherichia coli, 12.8% Providencia species, 9.6% Enterococci, and 8.7% Pseudomonas aeruginosa. Patients with UTI were divided into three groups according to their method of urination: normal urination, use of diapers and catheterization. Body temperature (> or = 37.5 degrees C) was 2.8%, 10.1% and 34.9%; WBC (> or = 9.000), 2.7%, 6.1%, and 14.3%; CRP, 16.9%, 36.1% and 51.1%; urine RBC (> or = 6-10/hpf), 8.4%, 7.1% and 36.1%; urine WBC (> or = 15-30/hpf), 20.4%, 44.4% and 76.9%, respectively. There was a significant difference (p < 0.05-0.001) between all parameters except for urine RBC between the normal-urination patients and diaper using patients. This investigation suggested that the use of diapers was a risk factor for UTI in elderly patients.

Adult

Histochemical and immunological analyses of differentiating skeletal muscle fibers of the postnatal rat.

Fiber type differentiation as revealed by myosin ATPase activities and the immunological analysis of myosin light chains (MLC) by the Western blotting method were done on the postnatal rat soleus and extensor digitorum longus (EDL) muscles. In the soleus, type 1 (slow-twitch) muscle fibers gradually increase in percentage after postnatal day 10, and, in the EDL, the differentiation of type 2A and 2B (fast-twitch) muscle fibers is also pronounced between postnatal days 10 and 15. The present immunological analysis of MLC indicates that the antigenicity of Lc1S becomes more intense with a rapid decrease in antigenicity of Lc2F from postnatal day 7 in the soleus, while the antigenicity of Lc1F becomes noticeable during the same period in the EDL. These results suggest that the differentiation of slow-twitch fibers is mainly due to that of Lc1S in the soleus and the differentiation of fast-twitch fibers is mainly due to that of Lc1F in the EDL.

Age Factors

Gastric emptying rate of drug preparations. III. Effects of size of enteric micro-capsules with mean diameters ranging from 0.1 to 1.1 mm in man.

The gastric emptying rates of three enteric micro-capsule preparations with mean diameters of 1.1 mm and less (1.1, 0.5 and 0.1 mm) were compared. The gastric emptying rate was evaluated by determining the pharmacokinetic parameters of pyridoxic acid, including Vmax (peak excretion rate) and Tmax (time to reach peak excretion rate) after oral administration of micro-capsules containing pyridoxal phosphate as a marker drug to five healthy subjects. When given under fasting conditions, the gastric emptying rates of these preparations, according to Tmax, differed significantly; the preparations with smaller particle sizes were emptied from the stomach at a faster rate than those with larger particle sizes. However, under non-fasting conditions the gastric emptying rates were virtually the same, regardless of particle size, and all the preparations were emptied from the stomach at a much slower rate than when administered under fasting conditions.

Adult

Late results after repair of complete atrioventricular canal.

Twenty-five patients with complete atrioventricular canal including 10 Down's syndrome patients repaired since 1972 were analyzed with respect to their physical activities, hemodynamics, ECG, reoperation and late mortality. Follow-up period ranged from 1 to 17 years with an average of 7.0 years. There was 1 late death. Actuarial survival rate was 0.86 +/- 0.13 (mean +/- S.D.) at 12 years. Fourteen patients (70%) of 20 evaluated were in New York Heart Association functional class I, and 4 (20%) were in class II and 2 (10%) in class III. In 23 patients without pulmonary stenosis, preoperative values of peak pulmonary to systemic pressure ratio (Pp/Ps) and pulmonary to systemic arterial resistance ratio (Rp/Rs) were 0.64 +/- 0.28 and 0.36 +/- 0.31, respectively. Postoperative Pp/Ps and Rp/Rs significantly decreased to 0.37 +/- 0.14 and to 0.20 +/- 0.14, respectively. In Down patients, postoperative Pp/Ps, Rp/Rs and pulmonary arterial resistance were significantly greater than in non-Down patients (0.50 +/- 0.07 vs. 0.25 +/- 0.05, 0.30 +/- 0.13 vs. 0.10 +/- 0.03 and 4.4 +/- 1.8 vs. 1.8 +/- 0.6 units.m2, respectively). Complete heart block developed in 1 patient postoperatively. Sick sinus syndrome was observed in 3 patients, transient Mobitz II A-V block in 2, ventricular premature contractions of Lown's Grade II in 1 and atrial fibrillation in 1. Five patients demonstrated severe mitral regurgitation equal to or more than Grade III and 2 of them underwent mitral valve regurgitation equal to or more than Grade III and 2 of them underwent mitral valve replacement 6 months and 12 years after the initial operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The mechanism of action of serum immunosuppressive factor in Crohn's disease: it blocks the growth of mitogen-stimulated lymphocytes in early G1 phase through an inhibition of transferrin receptor expression.

The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.

Cell Cycle

[Clinical aspects of acid-base disorders].

Acid-base disorders are frequently recognized in a wide variety of clinical settings such as severe systemic hospitalized patients. The principal object is to assessment of acid-base equilibrium and to obtain an appropriate guide to therapy. The approach is centered to a systemic analysis of blood gas evaluation. To establish this complex matter is followed. Is an acid-base disorder present? Is the disorder a simple or a mixed abnormality? What is the primary cause? These evaluations should be obtained by accurate history taking, physical examination, and routine laboratory tests. In addition, the supporting analysises such as anion gap (AG) calculation, urine AG assessment, urine chloride concentration and so on are also useful for correct diagnosis. In view of the complexty and difficult expression of acid-base disorders, it is desirable that clinicians must have full knowledges of systemic approach to the blood gas analysis and its evaluation.

Acid-Base Imbalance