Biomedical subjects

T Kuwata

Publications and source records attributed to T Kuwata.

At least 73 records · Page 4Linked to original sources

PubMed1998

Oral tolerance is not influenced by oral application of oil-emulsified proteins.

A 2-week program of feeding protein antigens as an oil-in-water emulsion to naive mice elicited a significant serum IgG antibody response, whereas their aqueous preparations did not at all. The unresponsive immune state that had been developed after feeding aqueous antigen was not disturbed by subsequent oral challenge with the same antigen in the presence of oil. These results suggest that the principle of oral tolerance is a feasible strategy for prophylaxis of hypersensitization to protein antigens, where protein tolerogens, in this case, are to be given without any additives at their first introduction.

Administration, Oral↗

PubMed1998

Effects of orally ingested Bifidobacterium longum on the mucosal IgA response of mice to dietary antigens.

To study the effects of lactic acid bacteria on the mucosal defence against dietary protein antigens, we compared the mucosal IgA responses to beta-lactoglobulin (beta-LG) of two groups of mice fed a whey protein diet with and without a culture condensate of Bifidobacterium longum. Both total IgA and anti-beta-LG IgA levels in tissue extracts of the small intestinal wall were significantly higher in mice fed the B. longum diet for 2 weeks than in control ones. Peyer's patch (PP) cells from B. longum-fed mice had a much larger increase in in vitro IgA production than ones from control mice. Furthermore, the in vitro IgA response to beta-LG was detected only when PP cells from B. longum-fed mice were assayed. These results suggest that orally ingested lactic acid bacteria may protect a host from invasion of the intestinal mucosa by dietary antigens that have escaped enzymatic digestion in the intestine.

Animal Feed↗

PubMed1998

Rapid and progressive CD4+ decline in a monkey infected with an SIV+HIV-1 chimeric virus.

We previously constructed a simian immunodeficiency virus+human immunodeficiency virus type 1 (HIV-1) chimeric virus, NM-3rN to generate a pathogenic HIV-1 in macaque monkeys. During the in vivo passage of this virus in several monkeys, a viral strain, R43-56 was obtained which acquired a better replication ability in vivo. MM121, one of the three monkeys inoculated with the R43-56, showed weight loss, diarrhea and a rapid and continuous decrease in CD4+ lymphocytes at the moribund stage. An autopsy revealed generalized lymphadenopathy, dehydration, and ileocecal intussusception. In situ hybridization showed that the virus infection was in systemic lymphoid organs. We are presently monitoring the survivors to obtain candidates for a more virulent virus. R43-56 may be a better challenge virus and useful tool for human acquired immunodeficiency syndrome research.

Acquired Immunodeficiency Syndrome↗

PubMed1998

[A case of agraphia due to cerebral infarction in the left parietal lobe].

A case of agraphia due to cerebral infarction in the left parietal lobe was reported. A 63-year-old right-handed man was admitted to our hospital with writing disturbance. His spontaneous speech was fluent, and object naming, word fluency, repetition, verbal comprehension, and reading were fully preserved. However, his writing was slow and required effort. He showed hesitation in spontaneous writing and dictation. His power to copy was better than his power to write spontaneously or to take dictation, but he had some difficulty in copying letters and complex figures. The patient showed abnormal sequences of strokes and completed his strokes by piecing out of several fragments. CT scan and MRI showed a cerebral infarction in the left parietal lobe which included the superior parietal lobule. The amytal (Wada) test, which was performed via the left internal carotid artery, revealed that the left hemisphere was dominant for language. The characteristics of his agraphia much more closely resembled "apractic agraphia", as reported by Alexander et al (1992), than spatial agraphia or pure agraphia. Agraphia in this patient might result partially from the loss or unavailability of the memory of motor patterns necessary for writing letters.

Agraphia↗

PubMed1998

[When do strokes occur?--analysis of diurnal variation and activity during the onset].

The diurnal variation and activity during the onset of stroke were examined in more than 700 consecutive patients. 304 cases with hypertensive intracerebral hemorrhage (HIH), 214 cases with subarachnoid hemorrhage (SAH) and 201 cases with obstructive cerebrovascular disease (OCVD) were investigated about the time of onset. Concerning the activity during the onset, 296 cases with HIH, 215 cases with SAH and 198 cases with OCVD were examined. HIH occurred frequently between 1500-1800 hours, 0600-0900 hours and 1800-2100 hours. SAH occurred frequently between 0900-1200 hours, 1500-1800 hours and 1800-2100 hours. Both HIH and SAH were least likely to occur between 0000-0300 hours. OCVD exhibited a small peak incidence between 0900-1200 hours, but there were no differences between the groups for the other time periods. Both HIH and SAH were likely to occur frequently in the lavatory, while bathing and during meals. HIH also occurred frequently during physical work, while SAH occurred as frequently during mental work or housework as during hard physical labor. OCVD commonly occurred during sleep or relaxation. The relationship between diurnal variation in stroke and the circadian variation of blood pressure is discussed. The incidence of all three types of strokes during work was higher in the non-aged group (patients under 66 years) than in the aged group (patients over 66 years). HIH and SAH occurred associated with alcohol consumption more frequently in the non-aged group than in the aged group. It is likely that the difference of the time and of the activity during the onset between aged group and non-aged group reflects the difference of life-style between aged and non-aged people.

Activities of Daily Living↗

PubMed1998

[A clinical study of substance dependence patients combined with other psychiatric disorders].

The present study was conducted for clarifying the comorbidity of substance dependence and other psychiatric disorders in outpatients of four psychiatric hospitals in May, 1995. The results were as follows; 7.4% (N = 234) of the total 3155 psychiatric outpatients were diagnosed as substance dependence. Among those substance dependence patients, alcohol dependence accounted for 82.5% and the percentage of the other substance dependence were very small, i.e., methamphetamine dependence 6.4%, solvent dependence 1.7%, multiple substance dependence 9.4%, respectively. The percentage of comorbidity of substance dependence and psychiatric disorders was 23.9% (N = 56) of 234 substance dependence patients. The percentage of co-morbid alcohol dependence patients with affective disorder in all affective disorder patients was 5.0%; the percentage of comorbidity of alcohol dependence in neurotic patients 4.1%; the percentage of alcohol dependence comorbidity in schizophrenic patients 0.7%. In many cases, onsets of substance dependence and psychiatric disorders were within 2 years, which suggests the common backgrounds for substance dependence and psychiatric disorders, such as disruption of family and occupational life, stress and individual vulnerability, and substance use for self-medication. The study indicates that the percentages of diagnosed comorbidity of substance dependence and psychiatric disorders are generally smaller in Japan than in the U.S., which may be based on the differences of diagnostic standards between the two countries. Further studies are needed on the comorbidity of substance dependence and psychiatric disorders in other general hospital and psychiatric clinic patients.

Adult↗

PubMed1997

Comparison of in vitro and in vivo infectivity of different clade B HIV-1 envelope chimeric simian/human immunodeficiency viruses in Macaca mulatta.

The use of HIV-1 env/SIVmac chimeric viruses expressing divergent HIV-1 envelopes of clinical isolates, facilitates homologous and heterologous evaluation of various recombinant HIV-1 envelope vaccine candidates in lower primates. In this study we compare the in vitro and in vivo infectivity, via intravenous (IV) and intravaginal (IVAG) routes of infection, of stocks of chimeric viruses expressing env from four different clade B HIV-1 isolates. The TCID50/ml was 7.1 x 10(4), 1.0 x 10(4), 6.3 x 10(4), and 1.2 x 10(3) for SHIVsf13, SHIVHan2, SHIVNM-3rn, and SHIVW6.1D, respectively, with a MID50/ml upon IV inoculation of 3.2 x 10(3), 3.2 x 10(4), 3.2 x 10(4), and 3.2 x 10(3), respectively. The same SHIVsf13 stock was infectious after IVAG administration, requiring a 300-fold higher virus dose. Plasma antigenemia and cell-associated viremia were generally highest at weeks 2 or 4 after infection and decreased to subdetectable levels after 8-12 weeks. All infected animals tested developed anti-HIV-1 gp120 antibodies. Inoculated virus dose showed no (linear) quantitative correlation with cellular virus load, duration of viremia, plasma antigenemia, and anti-gp120 antibody titers. No significant changes in peripheral blood CD4 cell levels were observed and none of the animals has shown evidence of disease progression to date (i.e., 13 months postinfection). Four in vivo passages of cell-associated SHIVW6.1D did not result in increased virulence. Vaccine development studies in macaques monkeys have become feasible with the use of various clade B HIV-1 env SHIV chimeras.

Animals↗

PubMed1997

Regulation of thymocyte lineage commitment by the level of classical protein kinase C activity.

Thymocyte-positive selection involves signaling through TCR and accessory molecules, and the signaling intensity appears to be critical for this event. The specific inhibitor of classical Ca2+-dependent protein kinase C (cPKC), Gö 6976, inhibited positive selection in fetal thymus organ culture, indicating that cPKC activation is essential for positive selection. The major protein kinase C isoforms in CD4+ CD8+ thymocytes are cPKC-alpha, cPKC-beta, and the novel Ca2+-independent protein kinase C, nPKC-epsilon. To analyze the effect of cPKC activation level on positive selection, we used thymocytes from TCR transgenic mice with nonselecting and RAG-2 -/- backgrounds as they were developmentally arrested at the CD4+ CD8+ stage without positive selection signals. These thymocytes survived and acquired CD4/CD8 lineage commitment in suspension culture upon transient stimulation with limited concentrations of the selective activator of cPKC-alpha and -beta, thymeleatoxin, and the calcium ionophore, ionomycin. However, neither 12-deoxyphorbol 13-phenylacetate 20-acetate, which selectively activates cPKC-beta, nor ingenol 3,20-dibenzoate, which selectively activates nPKC-epsilon, exerted such an effect. The thymeleatoxin/ionomycin concentrations corresponded to those that inhibit glucocorticoid-induced apoptosis in thymocytes and were lower than those that induce proliferation of mature T cells. The CD4 lineage commitment required a higher level of cPKC activity than the CD8 lineage commitment. CD8alpha or CD4 mRNA expression was down-regulated. Functional helper and killer T cells were induced from the CD4 and CD8 lineage-committed cells, respectively, by additional stimulation. These results suggest that thymocyte lineage commitment in positive selection is regulated by the level of cPKC-alpha activity or by the levels of cPKC-alpha and -beta activities.

Animals↗

PubMed1997

Calcium-to-creatinine ratio in spot urine samples in early pregnancy and its relation to the development of preeclampsia.

We investigated the relation between an alteration in calcium (Ca) excretion in early pregnancy and the risk of preeclampsia in 1,147 pregnant women. We measured Ca and creatinine (Cr) concentrations in spot urine samples obtained at 12 weeks or less of gestation. Seventy-one (6.2%) had hypertension alone, nine (0.8%) developed superimposed preeclampsia, 39 (3.4%) developed proteinuria alone, and 13 (1.1%) developed preeclampsia; 1,015 women did not develop hypertension or proteinuria. The Ca/Cr ratio was significantly reduced in the 39 women who eventually developed proteinuria (0.116 +/- .103) and 13 who developed preeclampsia (0.121 +/- .063) compared with 1,015 women who had neither hypertension nor proteinuria (0.158 +/- .239). The relative risk of development of preeclampsia, proteinuria, or superimposed preeclampsia was 1.98 (95% confidence interval, 1.22 to 3.22) for women with a Ca/Cr ratio less than the 30th percentile (0.082) compared with women with a Ca/Cr ratio greater than the 30th percentile. These results suggest that preeclampsia may be related, in part, to a relative Ca intake deficiency. Determination of the Ca/Cr ratio in spot urine samples in the first trimester is of only limited clinical value for identifying women with an increased risk of preeclampsia.

Biomarkers↗

PubMed1997

Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes.

To clarify whether regulatory cytokines inhibit hematopoiesis in patients with myelodysplastic syndromes (MDS), malignancies characterized by the formation of cytopenias despite the presence of cellular bone marrow, expression of TNF-alpha and IFN-gamma by bone marrow cells was investigated using specific reverse transcriptase-polymerase chain reaction assays. An enhanced expression of the mRNA for TNF-alpha was observed in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML (0/2) or control cases (0/8). The expression of IFN-gamma was also enhanced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and control cases (0/6) showed very low levels of IFN-gamma mRNA expression. Immunohistochemical examination confirmed the scattered presence of TNF-alpha or IFN-gamma producing cells in the bone marrow of MDS patients. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MDS might be caused by enhanced production of inhibitory regulatory cytokines especially TNF-alpha and occasionally IFN-gamma by bone marrow macrophages.

Adult↗

PubMed1997

Simplified preparation of a refined milk formula comparable to rat's milk: influence of the formula on development of the gut and brain in artificially reared rat pups.

BACKGROUND: Milk formulas for artificially reared (AR) rat pups are mostly based on complex cow's milk products, prepared by laborious and time-consuming processes. The aim of this study was to develop a simplified procedure for preparing a refined formula and to examine its influences on gut and brain development. METHODS: The formula comprised a combination of purified cow's casein and whey proteins, five kinds of edible oil, minerals, and vitamins. Detailed analyses showed that the composition of macro- and micro-nutrients, osmolarity, and pH of the new formula closely resembled those of rat's milk. Rat pups, each with an intragastric cannula implanted at age 5 days, were artificially reared for the following 10-15 days. RESULTS: The body weight gain of AR pups matched that of mother-reared (MR) pups. Histoplanimetrical analyses showed that the small intestine in AR pups was more developed in relation to area of a transverse section, number and length of villi, and thickness of tunica muscularis than that of MR pups. Fat components in the formula influenced the fatty acid composition and the cholesterol-to-phospholipid ratio in the small intestinal microvillus membrane (MVM) of AR pups, but not the MVM fluidity. Brain weight was not significantly different between the two groups at age 15-20 days. CONCLUSION: This formula is useful for artificial rearing of rats and for identifying dietary components contributing to metabolic adaptation during the suckling period.

Animals↗

PubMed1997

Protection of monkeys vaccinated with vpr- and/or nef-defective simian immunodeficiency virus strain mac/human immunodeficiency virus type 1 chimeric viruses: a potential candidate live-attenuated human AIDS vaccine.

Two simian immunodeficiency virus strain mac (SIVmac)/human immunodeficiency virus type 1(HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env derived from HIV-1 and defective vpr (plus defective nef for NM-3), were inoculated into seven macaques. These macaques were transiently or persistently infected and most of them produced long-lasting neutralizing antibodies and Env-specific killer T cells to HIV-1 with no AIDS-like symptoms. When they were challenged with another SHIV with intact vpr and nef (designated NM-3rN), all were protected as judged by virus recovery, DNA detection by PCR and antibody responses. Anti-HIV-1 Env-specific killer T cells were considered to have played a major role in this protection, but a non-specific defence mechanism as well as specific immunity also appeared to be involved. Thus, these two non-pathogenic SHIVs induced long-lasting protective immunities in macaques, suggesting the possibility of gene-defective SHIVs as attenuated live vaccines for human use.

AIDS Vaccines↗

PubMed1997

Infection of an HIV-1/SIVmac chimeric virus having HIV-1 env to macaque monkeys via the vaginal cavity.

We previously reported that an HIV-1/SIVmac chimeric virus (designated as NM-3rN) having HIV-1 env efficiently infected macaque monkeys by intravenous inoculation. In this study, this chimeric virus was atraumatically inoculated into the vaginal cavity of two rhesus and one cynomolgus monkeys. Although antibody response and detection of proviral genome by PCR were observed in both rhesus monkeys, virus recovery was only once from PBMC in one of them. In the cynomolgus monkey, no virus was recovered and proviral DNA detection was rare. Thus, vaginal inoculation with NM-3rN resulted in poor systemic infection, implying the presence of selective pressure while passing through mucosal membranes.

Animals↗

PubMed1997

The rapid spread of recombinants during a natural in vitro infection with two human immunodeficiency virus type 1 strains.

We quantified a population of recombinants in a natural in vitro infection, using wild-type viruses without any pressure. It was found that recombinants emerged early after infection and constituted more than 20% of the whole proviral population 15 days after infection. Furthermore, recombinants were isolated as infectious viruses by simple limiting dilution. These results imply that, in addition to the high mutation rate of human immunodeficiency virus type 1 (HIV-1), recombination among HIV-1 strains plays a significant part in the development of the high diversity of HIV-1.

Base Sequence↗

PubMed1997

Elevation of the serum uric acid level preceding the clinical manifestation of preeclampsia in twin pregnancies.

To assess changes in the serum uric acid level in the third trimester of twin pregnancies, a total of 152 consecutive women with twin pregnancies were examined. Serum uric acid levels were analyzed in the women at varying gestational weeks in the presence or absence of preeclampsia. A receiver operating characteristic curve was used to determine the optimal cutoff value of serum uric acid between 30 and 31 weeks of gestation predicting subsequent development of preeclampsia. Forty-four women (29%) developed preeclampsia (preeclampsia group) at 33.2 +/- 1.9 weeks (mean +/- SD) and gave birth at 35.4 +/- 1.5 weeks of gestation. The remaining 108 women (71%) gave birth at 35.6 +/- 1.7 weeks of gestation (control group without preeclampsia). Serum uric acid levels rose gradually with advancing gestation in both groups. In the preeclampsia group, they were already increased at 30-31 weeks of gestation and corresponded to those seen in the control group at 37 weeks. The cutoff value at 30-31 weeks was 5.5 mg/dl, with a sensitivity of 73% and a specificity of 74%. These results suggest that an elevation in serum urate preceded the onset of preeclampsia. Determination of the serum level of uric acid between 30 and 31 weeks of gestation was useful for detecting a higher risk of late-onset preeclampsia in twin pregnancies.

Cohort Studies↗

PubMed1997

[Syringomyelia appearing in a short term after brain abscess].

We describe a rare case of syringomyelia that developed within only 4 months after the cure of the focal cerebritis and abscess. An 18-year-old man who had suffered from meningitis and brain abscess 1.5 years before, presented with pain and sensory disturbance in his left shoulder. Magnetic resonance image (MRI) showed a syrinx formation extending from the upper cervical to the lower thoracic cord. Investigation by MRI during the course of the brain abscess had the appearance of posterior cerebellar arachnoid cyst 3 months after the onset of brain abscess and syrinx developed within 9 months. After posterior fossa decompression and reopening of the Magendie's foramen, his symptom and MRI abnormality improved after one month. In contrast to reported cases of syringomyelia following cerebritis, syrinx formation in our case appeared in relatively a short time. We speculated that basal arachnoiditis and the formation of posterior cerebellar arachnoid cyst caused syrinx formation in a short term after cerebritis.

Adolescent↗

PubMed1997

[A case of cerebral aneurysm using a goose neck snare to stabilize the guiding catheter during embolization].

Severe arteriosclerotic changes often prevent navigating a guiding catheter into an appropriate position during aneurysm embolization. A basilar superior cerebellar artery aneurysm was found in a patient who had had subarachnoid hemorrhage 6 months previously. We selected embolization for this aneurysm using Guglielmi detachable coils (GDC) because of its highly located position from the dorsum sellae. We could not introduce a guiding catheter into the distal portion of the vertebral artery because of severe arteriosclerotic changes and it easily prolapsed into the aorta when a microcatheter was navigated through the guiding catheter positioned in the proximal vertebral artery. We were able to successfully perform embolization of the aneurysm by fixing a guiding catheter at the origin of the left vertebral artery with a goose neck snare wire introduced from the left brachial artery. The authors emphasize that a snare wire is useful not only for retrieval of foreign bodies but also for fixing a guiding catheter during aneurysm embolization, especially in which prolapse of the guiding catheter may cause a serious complication.

Catheterization↗

PubMed1996

Mutational analysis of two zinc finger motifs in HIV type 1 nucleocapsid proteins: effects on proteolytic processing of Gag precursors and particle formation.

To clarify the physiological function of two zinc finger motifs in the nucleocapsid (NC) domain of the Gag protein of human immunodeficiency virus type 1 (HIV-1), we changed cysteine to serine in either of the two motifs or both by site-directed mutagenesis. Viral infectivity was lost by any of the mutations, but their effects appeared differently in the respective mutants. Northern blot analysis showed that the first finger mutant was far less efficient (approximately 10% of the wild type) in genomic RNA encapsidation and that the dual mutant of both fingers completely failed to encapsidate the RNA. In contrast, the second finger mutant retained its ability for RNA encapsidation with an efficiency similar to that of the wild type. Immunoblot analysis of the lysates of CD4-positive M8166 cells transfected with the mutant proviral DNAs showed that the processing of Gag precursors was delayed in two mutant viruses having alterations in the first finger sequence, whereas the processing of the second finger mutant appeared to be normal. On the other hand, immunoblot analysis of the virus particles showed that the second finger mutant particles contained some proteins that were thought to be degradation products of p24CA. Electron microscopic observation showed that all particles of these mutant viruses were morphologically alike except that they had a slightly larger diameter than that of the wild type. These results indicate that these finger motifs of HIV-1 NC protein do not function equivalently. Namely, the first finger is primarily responsible for RNA encapsidation and the second is required for stabilization of virus particles.

Amino Acid Sequence↗