Biomedical subjects

K Nagashima

Publications and source records attributed to K Nagashima.

At least 199 records · Page 11Linked to original sources

PubMed1997

Blockage of mesenteric lymphatic flow in rats.

An experimental model of blockage of the mesenteric lymphatic flow (MLF) in rats was designed, and morphologic changes of mesenteric lymphatic vessels (MLV) and lymph nodes were investigated by mesenteric lymphangiography and histopathologic examination. Body weight in rats with blockage of MLF did not increase normally. Mesenteric lymphangiography revealed dilation of the MLV, reverse flow into the peripheral MLV, and leakage of contrast medium, resulting in chylous ascites. Remarkable dilation of the lymphatic sinuses and dilated and increased rough endoplasmic reticulum in lymphocytes in the mesenteric lymph nodes due to lymph stagnation were observed by light and electron microscopic examination, respectively.

Animals↗

PubMed1997

Establishment of a new continuous clear cell sarcoma cell line. Morphological and cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts.

Clear cell sarcoma (CCS), a rare tumour of deep soft tissues, often has a t(12; 22) (q13; q12) translocation that induces the formation of a hybrid EWS/ATF-1 gene. To investigate these alterations further, we established a new continuous cell line directly from a CCS taken from a 9-year-old girl. The cultures were characterized with respect to morphological, ultrastructural, immunohistochemical and karyotypical features and were tested by reverse transcription PCR (RT-PCR) for chimaeric EWS/ATF-1 transcripts. The continuous cell line, designated KAO, is tumorigenic in nude mice, and the resultant tumours resemble the primary CCS. The tumour cells and the cultured cells have melanosomes in their cytoplasm and are immunoreactive with the melanoma-specific antibody HMB45, but do not express S-100 protein. The cultured CCS cells have the t(12; 22)(q13; q12) translocation and express the hybrid EWS/ATF-1 gene. No transcripts of the hybrid gene were detected in a malignant cutaneous melanoma tested simultaneously. Although CCS and malignant melanoma are morphologically related, the present results suggest that their geneses differ at the chromosome and molecular levels. They also indicate that chromosome analysis and detection of fusion EWS/ATF-1 transcripts may be useful adjuvant tools for the diagnosis of CCS.

Activating Transcription Factor 1↗

PubMed1997

Lack of evidence for the transmission of JC polyomavirus between human populations.

Human polyomavirus JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically then persisting in renal tissue. Since JCV DNA can readily be detected from urine, it should be a useful tool with which to study the mode of virus transmission in humans. Based on this notion, we examined the extent to which JCV was transmitted from the American to Japanese populations in Okinawa Island, Japan. (A population of about 50 000 American soldiers and families have been stationed in Okinawa since 1945.) Four JCV types (A to D) were identified in American populations in U.S.A., whereas only type B was prevalent in elder Japanese in Okinawa who had reached adulthood by 1945. Thus, types A, C, and D served as indicators of the transmission of JCV from American to Japanese populations. We then examined whether types A, C, and D were detectable in Japanese in Okinawa aged 30-50 years who may have been in contact with Americans during childhood. However, all the 125 isolates from the younger Japanese population were type B without exception. From this finding, we concluded that JCV is rarely transmitted between human populations.

Adult↗

PubMed1997

Childhood bronchial mucoepidermoid tumors.

A very rare case of a childhood bronchial mucoepidermoid tumor is presented. A 4-year-old girl was hospitalized with prolonged pneumonia. Computed tomography of the chest showed a tumor with calcifications in the right upper lobe. Subsequently, the patient underwent right upper lobectomy. Histologically, the tumor was a low-grade mucoepidermoid tumor originating from the bronchus. Three years postoperatively there has been no evidence of disease. A review of the literature indicates that 30 cases of bronchial mucoepidermoid tumors in children have been reported. Symptoms result from associated bronchial obstruction. Children with recurrent or prolonged pneumonia should undergo aggressive diagnostic investigation by chest tomography or bronchoscopy. Appropriate therapy for childhood bronchial mucoepidermoid tumor is total resection of the lesion while sacrificing as little of the normal lung tissue as possible.

Airway Obstruction↗

PubMed1997

Induction of in vitro nuclear apoptosis activity coincides with the production of 50 kDa cytosolic protein.

Human monocytic leukemia U937 cells undergo apoptosis when cells are treated with the anticancer drug etoposide. To study the mechanism of drug-induced apoptosis, we used an in vitro apoptosis system with cytosol from etoposide-treated U937 cells. The cytosol from apoptotic U937 cells showed activity to induce morphologic changes and oligonucleosomal DNA fragmentation in isolated nuclei in vitro; both are typical features of apoptosis. We generated monoclonal antibodies to the proteins in the etoposide-treated U937 cytosol. We found that a 50 kDa protein, recognized by SN-1 monoclonal antibody, appeared in the cytosol of U937 cells, in accordance with its cell-free apoptosis activity. Z-Asp, an inhibitor of interleukin-1beta converting enzyme (ICE) family proteases, inhibited the appearance of the 50 kDa protein and the emergence of the cell-free apoptosis activity in the etoposide-treated U937 cytosol. These results indicate that the 50 kDa protein is produced by the activation of ICE family protease during apoptosis and suggest some roles of the protein in the development of apoptosis.

Journal Article↗

PubMed1997

A novel point mutation of thyroid hormone receptor beta gene in a family with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is characterized by variable tissue hyporesponsiveness to thyroid hormone caused by mutations of thyroid hormone receptor beta (TRbeta) gene. We found a novel point mutation of the TRbeta gene in a family (F123) with RTH, a transition of a guanine to adenine at nucleotide 1215, which replaced the normal Met-310 with Ile. This substitution was found in only one allele of affected family members. In vitro transcription and translation of this mutant TRbeta demonstrated a 12-fold reduction of the affinity for triiodothyronine (T3) compared with the wild type TRbeta. Thyroid function tests were similar to a previously reported RTH family (F99) who had a different mutation in the same codon (Thr 310).

Adolescent↗

PubMed1997

Relationship between aerobic power, blood volume, and thermoregulatory responses to exercise-heat stress.

To clarify the relationship between aerobic power (VO2max), blood volume (BV), and thermoregulatory responses to exercise-heat stress, we analyzed the cross-sectional relationship between the resting BV, plasma volume (PV), erythrocyte volume (EV), VO2max, forearm blood flow (FBF), and sweating responses during exercise in a hot environment (31 degrees C, 50% relative humidity). Twelve college-aged male subjects with a mean maximal oxygen uptake of 48 (range 42-59) mL.kg-1.min-1, a mean PV of 54 (range 42-72) mL.kg-1, a mean EV of 31 (range 23-43) mL.kg-1, and a mean BV of 85 (range 67-115) mL.kg-1 (measured by the Evans Blue dye dilution method) performed three sessions of 20-min cycle exercise at two levels of intensity (40% and 60% VO2max). The BV, PV and EV correlated positively with peak FBF (r = 0.596-0.711, P < 0.05), the increase of FBF in response to a unit rise in esophageal temperature (Tes; peak delta FBF/peak delta Tes) (r = 0.592-0.656, P < 0.05) and with total sweat loss (TSL) (r = 0.599-0.634, P < 0.05) during the exercise. The VO2max correlated with TSL during exercise at 40% VO2max (r = 0.578, P < 0.05), but not with peak FBF and peak delta FBF/peak delta Tes. The VO2max per lean body mass also showed a significant positive correlation with BV (r = 0.769, P < 0.01), PV (r = 0.706, P < 0.05), and with EV (r = 0.841, P < 0.001). The peak delta FBF/peak delta Tes was correlated positively with peak FBF (r = 0.597-0.830, P < 0.05-0.01) and negatively with peak Tes (r = 0.641-0.769, P < 0.05-0.01) during the exercise at the two levels. However, the chest sweat rate (CSR), TSL, and the increase of CSR in response to a unit rise in Tes (peak delta CSR/peak delta Tes) showed no correlation with peak Tes during the exercise at the two levels. These findings suggest that 1) heat dissipation responses during exercise were related more to blood volume than aerobic power and 2) skin blood flow was related more to body temperature than sweating responses during exercise under mild heat stress.

Adolescent↗

PubMed1997

Multiple hilar cysts of the liver in patients with alcoholic cirrhosis: report of three cases.

The present report concerns the clinicopathological study of three patients with alcoholic cirrhosis (a 40-year-old man, a 52-year-old woman and a 48-year-old man) who had multiple cysts along their intrahepatic bile ducts. The cysts were visible on gross examination of the liver and, in two cases, an enlargement of the cysts had been detected in abdominal computed tomography scans performed 1 year apart. Histologically, the cysts consisted of proliferating and dilated peribiliary glands. The cysts occasionally compressed the original bile ducts. The latter showed mucosal hyperplasia with antral-type gland metaplasia. Neoplastic changes and necroinflammation were not seen. Immunohistochemical assays revealed that the peribiliary glands and antral-type glands expressed not only cytokeratin and carbohydrate antigen 19-9, but also c-MET protein, the hepatocyte growth factor receptor which may be related, at least in part, to the cystic dilatation of the peribiliary glands.

Adult↗

PubMed1997

Osmoregulatory inhibition of thermally induced cutaneous vasodilation in passively heated humans.

We examined the effect of increased plasma osmolality (P(osm)) on cutaneous vasodilatory response to increased esophageal temperature (T(es)) in passively heated human subjects (n = 6). To modify P(osm), subjects were infused with 0.9, 2, or 3% NaCl infusions (Inf) for 90 min on separate days. Infusion rates were 0.2, 0.15, and 0.125 ml.min-1.kg body wt-1 for 0.9, 2, and 3% Inf, respectively, which produced relatively similar plasma volume expansion. Thirty minutes after the end of infusion, subjects immersed their lower legs in a water bath at 42 degrees C (room temperature 28 degrees C) for 60 min after 10 min of preheating control measurements. Passive heating without infusion (NI) served as time control to account for the effect of volume expansion. P(osm) (mosmol/kgH2O) values at the onset of passive heating were 289.9 +/- 1.4, 292.1 +/- 0.6, 298.7 +/- 0.7, and 305.6 +/- 0.6 after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively. The increases in T(es) (delta T(es)) at equilibrium during passive heating (mean delta T(es) during 55-60 min) were 0.47 +/- 0.08, 0.59 +/- 0.08, 0.85 +/- 0.13, and 1.09 +/- 0.12 degrees C after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively, which indicates that T(es) at equilibrium increased linearly as P(osm) increased. delta T(es) required to elicit cutaneous vasodilation (delta T(es) threshold for cutaneous vasodilation) also increased linearly as P(osm) increased as well as the delta T(es) threshold for sweating. The calculated increases in these thresholds per unit rise in P(osm) from regression analysis were 0.044 degree C for the cutaneous vasodilation and 0.034 degree C for sweating. Thus the delta T(es) thresholds for cutaneous vasodilation and sweating are shifted to higher delta T(es) along with the increase in P(osm), and these shifts resulted in the higher increase in T(es) during passive heating.

Adult↗

PubMed1997

Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia.

To test the hypotheses that plasma volume (PV) expansion 24 h after intense exercise is associated with reduced transcapillary escape rate of albumin (TERalb) and that local changes in transcapillary forces in the previously active tissues favor retention of protein in the vascular space, we measured PV, TERalb, plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure (Pi), and colloid osmotic pressure in leg muscle and skin and capillary filtration coefficient (CFC) in the arm and leg in seven men and women before and 24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P < 0.05) and COPp (26.1 +/- 0.8 to 24.3 +/- 0.9 mmHg, P < 0.05), although plasma albumin concentration was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11) and was correlated with the increase in PV (r = -0.69, P < 0.05). CFC increased in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 microl . 100 g-1 . min-1 . mmHg-1, P < 0. 05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0. 7 to 3.8 +/- 0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV regulation and that local transcapillary forces in the leg muscle may favor retention of albumin in the vascular space after exercise.

Adult↗

PubMed1997

Mechanism of posturally induced crackles as predictor of latent congestive heart failure.

We investigated the role of changes in pulmonary function in posturally induced crackles (PIC) in 76 patients with various heart diseases. Regional ventilation was evaluated by spirometric gated ventilation scanning using 133Xe in 23 of these patients and its relationship to PIC was analyzed. A change from the sitting to the supine position was associated with a significant decrease in the percent functional residual capacity (FRC, p < 0.01) and significant increases in closing volume (CV), CV/vital capacity (VC) and closing capacity (CC)/FRC (p < 0.01) in the PIC-positive subjects. CV, CV/VC and CC/FRC did not differ significantly between PIC-positive (n = 37) and PIC-negative (n = 39) subjects in the sitting position, but in the supine position, these values were significantly higher in the PIC-positive group than in the PIC-negative group (CV: p < 0.05, CV/VC and CC/FRC: p < 0.01). These results suggest that airway closure was markedly increased in PIC-positive subjects in the supine position compared with PIC-negative subjects. Regional ventilation (V) was assessed in the sitting and the supine position from right lateral images divided into 9 segments from the base to the apex of the lung using spirometric gated ventilation scanning. There was no significant difference in regional ventilation in the sitting position between PIC-negative (n = 11) and PIC-positive (n = 12) subjects; in the supine position, regional ventilation decreased significantly at the base in the PIC-positive group. Findings suggest that PIC at the base of the lungs may be related to airway closure at the base of the lungs in the supine position in PIC-positive subjects.

Adult↗

PubMed1997

Clival chordoma presenting as acute esotropia due to bilateral abducens palsy.

A case involving a 14-year-old girl having clival chordoma with symptoms of diplopia, acute esotropia, and bilateral abducens palsy is reported. Magnetic resonance imaging revealed a clival tumor invading the posterior edges of the bilateral cavernous sinuses. After removal of the tumor, no ocular manifestations were noted. The importance of acute esotropia as a sign indicating a possible brainstem mass is emphasized.

Abducens Nerve↗

PubMed1997

Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation.

Most cases of congenital nephrogenic diabetes insipidus (NDI) are inherited in an X-linked manner, which is due to the mutations of the vasopressin type 2 receptor (V2R) gene. However, recent reports have presented female NDI patients with heterozygote V2R gene mutations. The mechanism of inheritance was thought to be skewed X-inactivation. We present a family with congenital NDI. Three male members were diagnosed with NDI, and examination of their V2R gene revealed a G inserted at nucleotide 804 of the open reading frame. Three female individuals display different degrees of symptoms of NDI, and all of them possess both the normal and abnormal genes. The X-inactivation patterns of the female members were investigated via the detection of methylated trinucleotide repeat in the human androgen receptor gene. The grandmother showed extremely skewed methylation of one X chromosome, and the mother revealed moderately skewed methylation. The daughter of the grandmother's sister, who has no symptoms of NDI, showed random methylation. The highly skewed X-inactivation pattern of the grandmother suggests that her NDI phenotype is caused by dominant methylation of the normal allele of V2R gene.

Adult↗

PubMed1997

Relationship between concentration of serum leptin and fetal growth.

The serum leptin concentration reflects the amount of adipose tissue in the body. Although fat deposition in the fetus in the third trimester markedly increases, the role of leptin during pregnancy has not been clarified. In the present study, whether or not the serum leptin concentration correlates with growth in utero was investigated, in addition to how leptin levels change in the first few days after birth. One hundred sixteen Japanese infants were divided into term (n = 91) and preterm groups (n = 25). Term infants were divided into 3 subgroups: birth weight appropriate for gestational age (AGA) (n = 44), birth weight large for gestational age (LGA) (n = 28), and birth weight small for gestational age (SGA) (n = 19). Longitudinal changes in the concentration of serum leptin after birth were examined in 48 infants. The serum leptin concentration was determined by RIA. No significant difference in leptin levels between cord sera and infants' sera obtained within the first 6 h of life (n = 28) was observed. Within the first 6 h of life, the concentration of serum leptin in LGA infants (12.8 +/- 10.2 ng/mL) and SGA infants (1.6 +/- 1.1 ng/mL) was significantly higher and lower, respectively, than that in the AGA infants (4.4 +/- 3.0 ng/mL) (P < 0.01). A significant positive correlation was found between the leptin concentration within 6 h of life and birth body weight (r = 0.59, P < 0.01). After birth, the concentration of leptin in LGA and AGA infants significantly decreased to the level in SGA infants within 72 h [corrected] of delivery (P < 0.05). After 72 h [corrected] of life, no significant differences in the concentration of leptin were observed among the three groups, and low levels continued to 7 days of age. These findings indicate that serum level of leptin correlates with fetal body weight gain.

Adult↗

PubMed1997

Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM.

One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes. It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 alpha cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1 alpha gene for mutations in Japanese subjects with IDDM. Ten exons and flanking introns of the HNF-1 alpha gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products. Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM. A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1 alpha was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age. A frameshift mutation of P291 fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age. A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1 alpha was found in a subject with sudden-onset IDDM at 20 years of age. None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes). These results indicate that the HNF-1 alpha gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1 alpha-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.

Adolescent↗

PubMed1997

A rat model of Parkinson's disease induced by Japanese encephalitis virus.

In Fischer rats infected with Japanese encephalitis virus (JEV) at 13 days after birth and sacrificed 12 weeks later, the major pathological changes resembled those found in Parkinson's disease. Specifically there was neuronal loss with gliosis which was confined mainly to the zona compacta of the substantia nigra, with a notable absence of lesions in the cerebral cortex and cerebellum. Changes were bilateral being most severe in the central part of the zona compacta. Immunohistochemical studies with anti-tyrosine hydroxylase (TH) demonstrated that the number of TH-positive neurons was significantly decreased in the substantia nigra compared to controls, while comparable numbers of TH-positive neurons were found in the basal ganglia in both JEV-treated rats and age-matched controls. JEV-infected rats showed marked bradykinesia, with significant behavioral improvement being observed following administration of L-DOPA. Immunohistochemical studies failed to detect JEV antigens in any region of the rat brain and the JEV genome was undetectable in the substantia nigra and the cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). The findings suggest that JEV infection of rats under the conditions described may serve as a model of virus induced Parkinson's Disease.

Animals↗

PubMed1997

[Mechanism of neuronal damage in AIDS].

Neurologic problems in AIDS are usually caused by opportunistic infections or secondary malignancy of the central nervous system (CNS), but brain damage occurs primarily as the result of HIV infection in CNS. In one of the typical opportunistic virus infections of CNS, progressive multifocal leukoencephalopathy (PML), oligodendroglial cells which maintain and support myelin sheaths are specifically attacked by JC virus. As the consequence, demyelination occurred, which could well explain the neuronal deficits. In contrast, in HIV the viral target cells are not neuronal cells, but infiltrating macrophages in CNS. Thus, the indirect injury such as HIV-related neurotoxic substances and macrophage-released cytokines would be augmented to induce diffuse neuronal damage in HIV infected brains. Recent discovery of co-receptor, chemokine receptor (CCR5) which is expressed in macrophages, may give a clue to understand the mechanism of HIV encephalopathy more precisely.

AIDS Dementia Complex↗

PubMed1997

Assembly of JC virus-like particles in COS7 cells.

JC virus lacks an appropriate cell line to support virus replication. The establishment of a JC pseudovirus assembly system could play an alternative role for a virus culture system. COS7 cells and a transfer vector, pcDL-SR alpha 296, were used to express JC viral structural genes. VP231-SR alpha, which encodes VP2/VP3 and VP1, but lacks 137 bp of the 5'-terminus of agnogene, showed both efficient nuclear migration and quantitative expression of the major capsid protein VP1. JC pseudovirus assembly was observed in the nucleus of VP231-SR alpha transfected cells. Evidence of JC pseudovirus assembly is presented. The further utilization of this system, which includes a study for the viral morphogenesis, serological diagnosis, as well as the potential application for gene transfer vector, is discussed.

Animals↗