Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 91 records · Page 5Linked to original sources

PubMed1997

Gastric myoelectrical activity in patients with diabetes. Role of glucose control and autonomic nerve function.

OBJECTIVE: Gastric myoelectrical activity was studied in diabetic patients using electrogastrography (EGG) to elucidate the relationship between glucose control, diabetic autonomic neuropathy (AN), and gastrointestinal motility. RESEARCH DESIGN AND METHODS: Cutaneous EGG was recorded during 1 h of fasting and 1 h after the ingestion of a standard meal in 57 diabetic patients and 10 healthy subjects. EGG was measured in 12 diabetic patients after glycemic control for 4 weeks. Diabetic patients were also studied with respect to the presence of gastrointestinal symptoms and AN. RESULTS: The percentage of dominant electrical frequency (DF) in normal range (the percentage ratio between the power at 2.4-3.6 cycles/min [cpm] and at 1-10 cpm) was significantly lower in patients with AN than in either the control subjects or the patients without AN (P < 0.01). The dominant frequency instability coefficient (DFIC) was significantly higher in patients with and without AN than in the control subjects (P < 0.01). The postprandial-to-fasting power ratio (PR) was the lowest in patients with AN (P < 0.01). Multiple regression analysis revealed that HbA1c levels were independently associated with the DFIC (R2 = 0.099, P = 0.0170) and that AN and HbA1c levels were independently associated with the PR (R2 = 0.378, P < 0.0001) in diabetic patients. The percentage of normal DF increased and the DFIC decreased significantly after glycemic control in 12 diabetic patients (P = 0.0409; P = 0.0096, respectively). CONCLUSIONS: There appears to be an association between improvement in gastric myoelectrical activity and autonomic nerve function. Abnormalities of gastric myoelectrical activity may be partly ameliorated via the improvement of autonomic nerve function, which accompanies glycemic control.

Adult↗

PubMed1997

A case of renin-producing juxtaglomerular tumor: effect of ACE inhibitor or angiotensin II receptor antagonist.

We report a case of a renin-producing juxtaglomerular cell tumor and the effects of angiotensin-converting enzyme (ACE) inhibitor captopril or angiotensin II receptor antagonist TCV-116. A 19-year-old female visited our clinic because of hypertension (162/122 mmHg). Plasma renin activity (PRA) was 25 ng/ml/h and plasma aldosterone concentration (PAC) was 880 pg/ml. Abdominal sonography revealed a low echoic tumor in the center of the right kidney. The mass was shown to have isodensity on a computed tomography scan, iso- or slightly lower intensity on T1-weighted magnetic resonance imaging (MRI), and low intensity on T2-weighted MRI. Renal angiography disclosed a hypovascular tumor. Plasma renin activity was not decreased in response to oral administration of captopril (50 mg) or TCV-116 (4 mg), which is associated with a marked decrease in PAC and blood pressure. The average of the mean blood pressure determined by an ambulatory monitoring system every hour for 24 h was lowered from 118 +/- 10.6 (SD) to 85 +/- 11.4 mmHg by TCV-116. Plasma renin activity did not show any difference between the right and left renal vein. Removal of the tumor successfully decreased PRA to 0.3 ng/ml/h and PAC to 33 pg/ml, resulting in a decrease in 24-h average of the mean blood pressure to 78 +/- 16.9 mmHg. The tumor was well capsulated and stained with an antibody against mouse renin. In the tumor, but not normal tissues, renin mRNA was detected at 1.6 kb using rat renin cDNA. The content of active renin in the tumor amounted to 182 micrograms/g tissue, which is 109 times higher than that in normal tissue. The plasma- or tumor-inactive renin concentration was 3.6- or 1.8-fold the active renin concentration, respectively. These results suggest that the juxtaglomerular tumor had an MRI image of iso- to low intensity on T1 and low intensity on T2, and that renin secretion from the tumor may be due mainly to the constitutive pathway and angiotensin II receptor antagonist, as well as to ACE inhibitors, and may be very effective for lowering the blood pressure.

Administration, Oral↗

PubMed1997

[Effects of long-term administration of alfacalcidol on bone mass and bone metabolism in patients with primary osteoporosis--comparison with calcium preparations].

Long-term administration of active vitamin D3 can reduce the loss of bone mass and the incidence of fractures in Japanese whose intake of calcium (Ca) is low. In a crossover study, we examined the safety and efficacy of 1 alpha (OH)D3 and combination therapy with a Ca preparation. We measured bone mass, the incidence of fractures and bone metabolism in 33 elderly patients with a high risk of fracture (mean age: 77.5 %/- 7.8 (SD) years). Subjects were randomly assigned to receive calcium lactate alone for 12 months after 12 months of combination therapy with 1 alpha (OH)D3 (1 microgram/day) (A-C group, 17 patients) or to take calcium lactate alone for 12 months and then undergo 12 months of combination therapy with 1 alpha(OH)D3 (C-A group, 16 patients). These subjects were followed for 24 months. In the A-C group, the bone mineral density (BMD) of the lumbar spine (L2-4 BMD) measured 6 months after the start of 1 alpha (OH)D3 administration was 3% higher than the baseline value. In the C-A group, L2-4 BMD measured 6 months after the start of calcium lactate administration had decreased by approximately 2%. The rate of decrease was the same 12 months after the start of administration. The differences in L2-4 BMD between the two groups 6 and 12 months after the start of administration were significant (p = 0.023 and p = 0.005, respectively). In the A-C group, the mean BMD of the distal one-third radius measured 6 months after the start of administration had increased by 5%, but the increase was 1% when measured 12 months after the start of administration. In the C-A group, there were no such changes. The incidence of vertebral fracture during combination therapy with 1 alpha(OH) D3 and Ca preparations in the A-C group was significantly lower than that in the C-A group (chi square test, p < 0.05). The serum Ca level in the C-A group gradually increased, as measured 6 and 12 months after the start of combination therapy with 1 alpha(OH) D3 and Ca preparations, although these changes were within the reference range. There was no hypercalciuria. Serum intact parathyroid hormone levels had decreased from 26.5 +/- 11.3 pg/ml and 30.7 +/- 10.3 pg/ml to 19.8 +/- 9.7 pg/ml and 25.5 +/- 9.6 pg/ml in the A-C group and the C-A group, respectively, by 6 months after the start of administration. The rate of decrease was significantly higher in the A-C group (p = 0.004). These findings suggest that long-term administration of 1 alpha(OH)D3 is safe even when combined with administration of Ca preparations, and that this agent inhibits parathyroid function, and thus prevents loss of bone mass and reduces the incidence of vertebral fracture.

Aged↗

PubMed1997

[Acquisition of resistance to anticancer agents by overproduction of target enzymes].

Antimetabolic anticancer agents possess their own target enzymes: that of methotrexate is dihydrofolate reductase; 5-fluorouracil and ZD1604, thymidylate synthase; hydroxyurea, ribonucleotide reductase; 2'-deoxycoformycin, adenosine deaminase; N-(phosphonacetyl)-L-aspartate, aspartate transcarbamylase. Overproduction of each target enzyme has been observed with various animal and human cell lines which acquired resistance to all these agents. These facts suggest that this is a common mechanism for resistance to these agents. Most of these resistant cells showed amplification of the corresponding genes in double minute chromosome or homogeneously stained region of the chromosome. The relation between the degree of resistance and those of enzyme overproduction, the expression and amplification of the gene coding for each enzyme protein in various resistant cell lines are demonstrated and discussed.

Animals↗

PubMed1997

Coronary artery bypass grafting of Takayasu's disease with calcified aorta and subclavian artery obstruction.

The lesions of Takayasu's disease, which may involve the aorta and major arterial branches, may pose technical difficulties during coronary artery bypass grafting (CABG). Because the aorta is often thick and calcified, the coronary arterial lesion is often located near the coronary orifice, and the internal thoracic arteries may not be suitable for grafting due to the lesions in the subclavian arteries. A 63-year-old man with a known history of Takayasu's disease was referred to our department with chest pain complaint. Coronary angiography revealed obstruction of the left main coronary artery. CT scan showed that he had a thickened and calcified aorta. Aortography showed that both subclavian arteries had obstructive disease. Instead of using ordinary arterial grafts or vein grafts, a piece of prosthetic patch carrying saphenous vein grafts was sewn to the ascending aorta to construct the proximal anastomosis of CABG. Distal anastomosis was made on the left anterior descending artery and the obtuse marginal branch in the usual fashion. The patient showed uneventful recovery, and a postoperative coronary angiogram showed patent grafts and uncomplicated ventricular performance. This technique is useful when the aorta is not suitable for vein graft anastomosis and arterial grafts are not available as in this case with aortitis reported in the paper.

Aorta↗

PubMed1996

Angiotensin-converting enzyme gene polymorphism is associated with carotid arterial wall thickness in non-insulin-dependent diabetic patients.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the ACE gene has been shown to be associated with cardiovascular disease in healthy subjects as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM). We investigated the relationship between the ACE gene polymorphism and the wall thickness of both carotid and femoral arteries in NIDDM patients. METHODS AND RESULTS: We measured the intimal plus medial thickness (IMT) of both carotid and femoral arteries using high-resolution B-mode ultrasonography in 288 Japanese NIDDM patients (160 men, 128 women). No significant differences among the three genotypes were found with respect to age, sex, duration of diabetes, body mass index, blood pressure, plasma glucose, hemoglobin AIC, total cholesterol, triglycerides, HDL cholesterol, or cigarette-years. Plasma ACE levels were strongly associated with I/D polymorphism, with an additive effect of the D alleles. The carotid IMT of the patients carrying the D allele (DD+ID genotype) was significantly higher than that of the patients not carrying the D allele (II genotype) (P = .037), whereas the femoral IMT was not affected by the I/D polymorphism. Multiple regression analysis demonstrated that the risk factors for carotid IMT of patients with NIDDM were age, non-HDL cholesterol, and D allele of the ACE gene (R2 = .155, P < .0001). CONCLUSIONS: The D allele of the ACE gene may be a risk factor for the development of wall thickening of the carotid but not the femoral artery in NIDDM patients.

Adolescent↗

PubMed1996

Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation.

We studied bovine subjects that exhibited a moderate uncompensated anemia with hereditary spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Based on the results of SDS-PAGE, immunoblotting, and electron microscopic analysis by the freeze fracture method, we show here that the proband red cells lacked the band 3 protein completely. Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C --> T substitution resulting in a nonsense mutation (CGA --> TGA; Arg --> Stop) at the position corresponding to codon 646 in human red cell band 3 cDNA. The proband red cells were deficient in spectrin, ankyrin, actin, and protein 4.2, resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the proband red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Total deficiency of band 3 also resulted in defective Cl-/HCO3- exchange, causing mild acidosis with decreases in the HCO3- concentration and total CO2 in the proband blood. Our results demonstrate that band 3 indeed contributes to red cell membrane stability, CO2 transport, and acid-base homeostasis, but is not always essential to the survival of this mammal.

Animals↗

PubMed1996

Changes in markers, receptors and adhesion molecules expressed on murine hemopoietic stem cells after a single injection of 5-fluorouracil.

Cytokines play a crucial role in the differentiation and proliferation of hemopoietic cells, and it has recently been found that adhesion molecules play crucial roles not only in differentiation and proliferation, but also in the homing and other functions of hemopoietic cells. We have very recently established a new method for purifying pluripotent hemopoietic stem cells (P-HSC) in mice by injecting 5-fluorouracil (5-FU). The P-HSC were found to be low-density, lineage marker-negative (Lin-), CD71- and major histocompatibility complex class I(high). In the present study, we analyze changes in the expression of various HSC markers (Sca-1 and CD34), receptors (c-kit and interleukin-6 receptor [IL-6R]) and adhesion molecules (very late activation antigen-4 [VLA-4], lymphocyte function-associated antigen-1 [LFA-1], and CD44) after 5-FU injection. The percentage of Sca-1+ cells increases after 5-FU treatment, reaching a maximum on day 3, whereas the percentage of IL-6R+ cells decreases, reaching a minimum on day 3. The percentage of CD34+ cells does not change after 5-FU treatment. The percentages of both c-kit(low) and c-kit(high) cells decrease, reaching a minimum on day 3 after 5-FU treatment, whereas the percentage of c-kit- cells reciprocally increases, reaching a maximum on day 3. However, there is no change in the expression of adhesion molecules (VLA-4, LFA-1 and CD44) on the P-HSC.

Animals↗

PubMed1996

Early results of a reinforced biosynthetic ovine collagen vascular prosthesis for small arterial reconstruction.

The efficacy of a reinforced biosynthetic ovine collagen (RBOC) vascular prosthesis developed for small arterial reconstruction was assessed by examining 30 grafts in 29 patients with arteriosclerosis obliterans. The operative procedures performed were femorofemoral bypass in 2 patients, above-knee femoropopliteal bypass in 28 patients, and below-knee femoropopliteal bypass in 1 patient. Femoropopliteal bypass was simultaneously performed in two patients undergoing femorofemoral bypass using one or two grafts. The indications for surgery were intermittent claudication in 27 patients and to salvage the limb in 2 patients. The longest follow-up period was 49 months, and there were six graft failures, occurring 1, 1, 9, 17, 17, and 23 months after implantation, respectively; caused by compression of the graft from outside in two, infection in one, anastomotic intimal hyperplasia in one, and unknown factors in two. Thus, the primary cumulative patency rate for above-knee femoropopliteal bypass at 3 years was 83.7%, and the secondary patency rate was 91.2%. No aneurysmal change was observed. Moreover, the RBOC was able to be used without preclotting, and its handling and suturing characteristics were satisfactory. Our findings suggest that this vascular prosthesis may be an acceptable alternative for above-knee femoropopliteal bypass.

Aged↗

PubMed1996

Cytokine-induced selective increase of high-molecular-weight bFGF isoforms and their subcellular kinetics in cultured rat hippocampal astrocytes.

Cytokines such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF) are probable factors responsible for up-regulation of basic fibroblast growth factor (bFGF) expression in reactive astrocytes following brain damage, however the effect of these cytokines on the expression of each bFGF-isoform has not been elucidated. Western blot analysis revealed the expression of 18, 22 and 24-kD bFGF isoforms in cultured rat hippocampal astrocytes, and the expression of high molecular weight (HMW)-isoforms (22 and 24-kD isoforms) but not of 18-kD isoform was selectively increased by cytokines. Immunofluorescent analysis demonstrated that bFGF content in the cytoplasm of astrocytes is initially increased by cytokines followed by nuclear targeting and localization in agreement with the previous evidence that HMW-isoforms possess a nuclear targeting signal. The present results suggest the important role of HMW-bFGF isoforms in the response of nervous tissue to injury.

Animals↗

PubMed1996

Hepatocyte growth factor levels in bone marrow plasma of patients with leukaemia and its gene expression in leukaemic blast cells.

Hepatocyte growth factor (HGF) has been known as a multiple function factor, which also stimulates early haematopoiesis. In this study, we found that HGF was expressed at both the RNA and protein levels in acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). In patients with AML (n = 20) and CML (n = 5), bone marrow plasma HGF concentrations were 20.44 +/- 6.26 (mean +/- s.e.) ng ml-1 and 7.17 +/- 0.53 ng ml-1 respectively. These were significantly higher (P < 0.01) than the value for normal subjects (n = 26): mean 0.92 +/- 0.09 ng ml-1. Constitutive HGF production was observed in freshly prepared leukaemic blast cells from three patients with high HGF levels of bone marrow plasma. Expression of HGF mRNA was correlated with bone marrow plasma HGF levels. After complete remission was obtained in six patients, bone marrow plasma HGF levels were significantly decreased. In contrast, the HGF mRNA was less abundantly expressed in acute lymphoid leukaemia (ALL). In patients with ALL (n = 5), bone marrow plasma HGF concentration (0.69 +/- 0.14 ng ml-1) remained low within the value for normal subjects. These results suggest that some populations of myeloid lineage cells have the ability to produce HGF.

Adult↗

PubMed1996

Phosphorus intake regulates intestinal function and polyamine metabolism in uremia.

This study found that 5/6-nephrectomized uremic rats showed secondary hyperparathyroidism as reflected by an increase in their serum parathyroid hormone (PTH) level in association with a decrease in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]. These changes recovered partially upon phosphorus restriction. Calcium absorption and gene expression of calbindin-D9k were decreased in uremia and were also improved by phosphorus restriction. In uremia, intestinal spermidine/spermine N1-acetyltransferase activity was decreased, while ornithine decarboxylase (ODC) activity and its gene expression were potentiated. Enhancement of c-fos and c-jun gene expressions was also observed in uremia. These phenomena suggest that the intestinal villus may proliferate in uremia. Phosphorus restriction prevented increases in the expression of ODC, c-fos and c-jun observed in uremia. Since phosphorus restriction caused a rise in the serum 1,25-(OH)2D level, the role of 1,25-(OH)2D in uremia-induced intestinal dysfunction was examined. A single injection of 1,25-(OH)2D3 to uremic rats caused an increase in the steady-state calbindin-D9k mRNA level, and decreases in steady state c-fos and ODC mRNA levels, suggesting that the deficiency of 1,25-(OH)2D3 is responsible for intestinal dysfunction in uremia. In conclusion, altered polyamine metabolism caused by 1,25-(OH)2D deficiency is intimately involved in intestinal dysfunction and the development of the proliferative state of the intestinal villus in uremia.

Absorption↗

PubMed1996

Amyloid goiter: radiological study in a case presenting hypothyroidism.

We report herein a case of amyloid goiter associated with rheumatoid arthritis in which hypothyroidism was observed. A 52-year-old housewife who had suffeed from rheumatoid arthritis for 15 years was referred to our hospital because of general fatigue. On admission, a large goiter was observed. Laboratory data showed primary hypothyroidism. Renal biopsy and gastric mucosa biopsy showed amyloid deposition of AA-type. Thyroid biopsy showed massive amyloid involvement. Although the findings of iodine-123 scintigraphy, technetium-99m pertechnetate scintigraphy, computed tomography and magnetic resonance image studies were similar to those for goiter associated with chronic thyroiditis, tallium-201 chloride scintigraphy gave a differing result, demonstrating absent uptake at 3 hours in this case. Replacement therapy with levothyroxine relieved the symptoms. This case was unusual in that amyloid goiter presented clinically as hypothyroidism. Absence of tallium-201 chloride uptake at 3 hours may be a diagnostic specificity for amyloid goiter in differentiating its hypothyroidism from that caused by chronic thyroiditis.

Amyloid↗

PubMed1996

Reduced activity of anabolizing enzymes in 5-fluorouracil-resistant human stomach cancer cells.

The mechanism of resistance to 5-fluorourcil (5-FU) was studied with NUGC-3/5FU/L, a human stomach cancer cell line which had acquired resistance as a consequence of repeated 5-day exposures to stepwise-increasing concentrations of 5-FU in vitro. NUGC-3/5FU/L was 200-fold and over 16-fold resistant to 96-h and 1-h exposures to 5-FU, respectively. NUGC-3/5FU/L incorporated less 5-FU into RNA, indicating resistance to the RNA-directed action of 5-FU. On the other hand, NUGC-3/5/5FU/L also showed resistance to in situ thymidylate synthase (TS) inhibition by 5-FU. Polymerase chain reaction-single-strand conformation polymorphism analysis of TS cDNA and a FdUMP ligand binding assay showed that quantitative and qualitative alterations of TS are not responsible for this resistance. In contrast, the ability to metabolize 5-FU to its active metabolites, FUTP and FdUMP, was reduced in NUGC-3/5FU/L. We found that not only the activities of uridine phosphorylase/kinase and orotate phosphoribosyl-transferase (OPRT), but also the level of phosphoribosyl pyrophosphate, a cosubstrate for OPRT, were significantly lower in NUGC-3/5FU/L than in the parent NUGC-3. These results indicated that resistance to 5-FU in NUGC-3/5FU/L is due to reduced activities of 5-FU-anabolizing enzymes, but not to an alteration of TS. 2'-Deoxyinosine effectively enhanced TS inhibition by 5-FU in the resistant cells, thus markedly sensitizing them to 5-FU.

Antimetabolites, Antineoplastic↗

PubMed1996

Case of a parathyroidectomized patient observed longitudinally by ultrasonography. Relationship between the growth rates and 1,25-dihydroxyvitamin D3 receptor contents in the parathyroid glands.

Parathyroid glands enlarge gradually with the progression of secondary hyperparathyroidism. The significance of down-regulation of the 1,25-dihydroxyvitamin D receptor (VDR) in parathyroid glands has been emphasized. Here we report a case in whom the relationship between the growth rates of the parathyroid glands and their VDR content was examined. A 36-year-old man, who had been hemodialyzed for 8.8 years because of chronic renal failure due to chronic glomerulonephritis, developed severe secondary hyperparathyroidism. The first ultrasonographic examination of the parathyroid glands, performed 10 months before parathyroidectomy, revealed that the sizes of the right upper (RU) and left upper (LU) glands were 10 x 8 x 5 and 14 x 10 x 9 mm3, respectively, although the right lower (RL) and left lower (LL) glands were not detected. The second ultrasonographic examination performed 5 days before PTX revealed that the RU gland had enlarged up to 24 x 12 x 10 mm3, while the LU gland remained unchanged at 16 x 9 x 8 mm3. At this time, the sizes of the RL and LL glands were determined only in the longitudinal section to be 10 x 5 and 4 x 3 mm2, respectively. In the excised specimens, the sizes and weights of the RU and RL glands were 25 x 10 x 9 mm3 and 1,950 mg and 17 x 10 x 8 mm3 and 1,160 mg, respectively, while those of the LU and LL glands were 16 x 10 x 7 mm3 and 850 mg and 9 x 8 x 7 mm3 and 350 mg, respectively. Histopathologic study demonstrated that the RU and RL glands exhibited nodular hyperplasia, while the LU and LL glands exhibited diffuse hyperplasia. Using a ligand binding assay, the VDR content of the rapidly growing RU and RL glands were significantly reduced to 32.6 +/- 9.6 and 32.7 +/- 5.2 fmol/mg protein, respectively, as compared to that of the LU gland with no significant proliferating activity (111.8 +/- 0.8 fmol/mg protein). It is of great interest that the smallest LL gland, which showed some proliferating potential in spite of a histologic pattern of diffuse hyperplasia, has a VDR content of 41.0 +/- 2.6 fmol/mg protein. In summary, it was implied from this case that the VDR content in the parathyroid gland might reduce as the growth rate of the parathyroid gland increases and, furthermore, that the VDR content seems to depend to some degree on the histopathologic pattern rather than on gland weight.

Adult↗

PubMed1996

Hemoglobin types, erythrocyte membrane skeleton and plasma iron concentration in calves with poikilocytosis.

The pathogenesis of poikilocytosis in calves was investigated. Nine calves 1 to 2 months old exhibiting poikilocytosis (poikilocytic calves), were examined. The proportion of poikilocytes in their blood was more than 70% in two calves (severely poikilocytic), while it averaged 30% in the remaining seven calves (moderately poikilocytic). All of the polikilocytic calves exhibited mild anemia. The concentration of plasma iron in 8 of them was 20-30% of that in normal calves, but it increased as the calves aged. The polikilocyte count in moderately poikilocytic calves decreased in proportion to the increase of the plasma iron concentration, though a high poikilocyte count was observed in a severely poikilocytic calf even after the plasma iron concentration reached the normal level. Column chromatography of a hemoglobin preparation from all the calves examined revealed 5 distinct peaks. Three peaks were embryonic, fetal and adult hemoglobins, respectively. The other peaks were tentatively designated Hb-2 and Hb-3, respectively. The amount of Hb-2 in the two severely poikilocytic calves was about three times that in the other calves including those moderately poikilocytic, and it decreased as the calves aged. The decrease of Hb-2 in one severely poikilocytic calf was related to a reduction of the proportion of poikilocytes in its peripheral blood. There was no significant difference in age-dependent changes of hemoglobin types between moderately poikilocytic calves and normal calves. Furthermore, SDS-PAGE analysis of red cell membrane revealed that protein 4.2 consisted of two polypeptides in the two severely poikilocytic, and three moderately poikilocytic calves, while it consisted of a single polypeptide in the remaining calves examined. These results indicated that the abnormalities of hemoglobin composition and protein 4.2 in the erythrocyte membrane observed in the severely poikilocytic calves might be responsible for the morphological changes in the erythrocytes, whereas iron deficiency was thought to be the predominant cause of poikilocytosis in the moderately poikilocytic calves.

Anemia↗

PubMed1996

Expression of CD45-restricted form B in (NZW x BXSB) F1 and MRL/Mp-lpr/lpr mice.

Expression of CD45RB on CD4+ or CD8+ cells in combination with TCRV beta usages (V beta 6, V beta 8.1, V beta 8.2, V beta 11 and V beta 17a) in normal mouse strains (BALD/c and C57BL/6) was compared with autoimmune-prone strains (NZW x BXSB) F1 and MRL/lpr) at young and old ages. The frequencies, and also the numbers of CD45RB- cells in CD4+ T cells with various TcR repertoires was significantly less in the autoimmune-prone stains at old ages, while, in normal control strains, they remained unchanged. Furthermore, CD4+/CD45RB- cells are CD44high and CD62L (L- selectin).low These findings suggest that most T cells, especially CD4+ T cells, in old W/BF1 and old MRL/lpr mice, were activated and this may reflect the elevation of autoantibodies and the progress of autoimmune status in aged autoimmune-prone mice. This will be discussed in relation to the progress of the autoimmune diseases.

Aging↗

PubMed1996

Evaluation of the efficiency of targeting of antitumor drugs: simulation analysis based on pharmacokinetic/pharmacodynamic considerations.

Antitumor drugs can be classified into two groups; cell cycle phase nonspecific (type I) and specific (type II) drugs. The cytotoxic activity of type I drugs depends on the time-concentration product (AUC), whereas that of type II drugs is time-dependent. Therefore, not only the AUC in the target organ, but also the exposure time is an important factor for evaluating the efficiency of any delivery system for antitumor drugs. In the present study, we examined the factors governing the cytotoxicity of drugs in tumors based on a hybrid perfusion model. It is suggested that the increase in tumor tissue binding of drug results in an increased unbound drug mean residence time (MRTT,U), leading to the increased activity of type II drugs. In contrast, the cytotoxic activity of type I drugs is unaffected by the alteration in the tissue binding since the intracellular AUC defined for unbound drugs (AUCT,U) is unaffected by the extent of drug binding. We also found that the symmetrical increase in the permeability-surface area products (PS) for drug influx (PSinf) and efflux (PSeff) across the tumor plasma membrane results in the unaltered and reduced antitumor activity for the type I and type II drugs, respectively, due to the unaltered AUCT,U and to the reduced MRTT,U. The kinetic analysis suggests that the increase in PSinf/PSeff ratio results in the increased cytotoxic activity of both type I and type II drugs. Collectively, optimization of the antitumor activity can be attained by increasing the tissue binding for type II drugs and by increasing PSinf and/or by decreasing PSeff type I and type II drugs. The present simulation study was carried out by considering the pharmacodynamic features of antitumor drugs and was a method of predicting how the antitumor activity may change on altering each process (tissue binding and membrane permeability for the influx and efflux processes) which governs the characteristics of drug distribution to tumors.

Antineoplastic Agents↗