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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 433 records · Page 24Linked to original sources

Biologic and biochemic properties of recombinant platelet factor 4 demonstrate identity with the native protein.

Platelet factor 4 (PF4) is a 70 amino acid protein released from the alpha-granules of platelets after activation. The exact biologic function of this protein is unknown. We have constructed an expression vector for recombinant PF4 (rPF4) in the T7-based promoter vector pT7-7 to better study the relationship between PF4 structure and function. The protein was expressed in Escherichia coli and purified to homogeneity by heparin-agarose affinity chromatography and reverse-phase high-performance liquid chromatography. Purity of protein was confirmed by immunoblot analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which resulted in a single component with a molecular weight of 8,000 daltons. The amino acid composition and sequence of the N-terminal 20 residues showed that rPF4 is identical to PF4 prepared from human platelets (hPF4), except for an N-terminal initiating methionine residue. Immunoblots revealed that rPF4 and hPF4 bound polyclonal anti-hPF4 equally well, while chemotaxis experiments demonstrated similar potencies as neutrophil attractants. Dose-dependent neutrophil chemotactic responses and competitive studies with polyclonal anti-hPF4 antiserum further demonstrate similar chemotactic properties of the two PF4 species. In conclusion, our data show that this recombinant protein and the native protein appears to have similar immunologic, heparin-binding, and chemotactic properties. The chemotactic properties of hPF4 appear to be entirely intrinsic to the protein and not due, in part, to any contaminating protein. Furthermore, our expression vector should prove useful for the construction of recombinant forms of PF4 to investigate structure/function relationships of this biologically important protein.

Amino Acid Sequence↗

A case of infantile acute monocytic leukemia caused by vertical transmission of the mother's leukemic cells.

A case of infantile acute monocytic leukemia (AMoL), which was probably transmitted from a pregnant woman with leukemia to her unborn infant, is presented. A woman had AMoL when her third infant was born. This infant, who was a boy, also suffered from AMoL when he was 20 months of age. The infant's leukemic cells had the same cytochemical and immunophenotypic patterns as the mother's leukemic cells. By cytogenetic analysis, the majority of the infant's leukemic marrow cells had the 46,XX karyotype and showed no Y body by quinacrine staining. Moreover, the phenotype for human major histocompatibility system, HLA-A, HLA-B, and HLA-DR of the infant's leukemic cells was consistent with that of the mother's lymphocytes. Thus, the infant's leukemic clone was found to be identical to the mother's leukemic clone. His lymphocytes could not react with the mother's leukemic cells or his own leukemic cells in mixed lymphocyte culture, suggesting that the HLA homozygosity of the mother may have played a role in inducing immunologic tolerance to the immigrated leukemic cells in the infant. This is the first report of an infantile leukemia transmitted from a mother with leukemia, supposedly through the placenta.

Adult↗

[Measurement of plasma free cortisol, estradiol, testosterone and prednisolone by direct radioimmunoassay of ultrafiltrate and its clinical application].

The authors aimed at developing a simplified method for the measurement of plasma free (unbound) steroids with ultrafiltration using Grace MPS device, and its clinical application. In this method, the movement of free steroids from plasma into ultrafiltrate was monitored with [14C]glucose added to the plasma. Plasma free steroids (cortisol, testosterone, estradiol and prednisolone) were measured as follows: Plasma was incubated with [14C]glucose (1.2 X 10(4) dpm/5 microliters) for 30 min at 37 degrees C. A 0.5 ml of aliquot was transferred to MPS device containing a single YMT membrane, and centrifuged at 1100 x g, at 37 degrees C, for 30 min in a 45 degree fixed angle head with the special temperature controller. After centrifugation, [14C] in 30 microliters of plasma and ultrafiltrate were counted. For the calculation of plasma free level, steroid concentration of ultrafiltrate measured directly by radioimmunoassay (RIA) was multiplied by the ratio of [14C]glucose (dpm) in plasma to [14C]glucose (dpm) in ultrafiltrate. For RIA of cortisol, testosterone and estradiol, commercially available kits were used, and for prednisolone, anti-prednisolone antibody developed in our laboratory was utilized. Since plasma free cortisol level showed a parallel increase with rise in temperature, strict temperature control during ultracentrifugation was required. On the other hand, the duration of centrifugation and the sample volume applied to MPS did not show any significant effect on the estimated values. Intraassay and interassay variations were 4.4% and 6.1% in free cortisol, 6.3% and 8.7% in free testosterone, 8.5% and 9.2% in free estradiol, and 8.8% and 9.9% in free prednisolone, respectively. The correlations between the plasma free steroid levels obtained by ultrafiltration (y) and equilibrium dialysis (x) were as follows, respectively: free cortisol; y = 1.16x + 0.017 (r = 0.95, n = 10), free testosterone; y = 1.17x-0.027 (r = 0.92, n = 10), free estradiol; y = 1.33x + 8.55 (r = 0.98, n = 12), free prednisolone; y = 1.03x + 1.00 (r = 0.98, n = 7). The mean plasma free cortisol levels and percent free fractions (%FF) were 1.16 +/- 0.40 (+/- SD) micrograms/dl and 10.9 +/- 3.0% in 10 control patients, 4.4 +/- 1.6 micrograms/dl and 15.6 +/- 3.3% in 8 patients with Cushing's syndrome, and 1.45 +/- 0.48 micrograms/dl and 5.9 +/- 2.4% in 11 normal pregnant women (10-40 weeks of pregnancy), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Secretion and clinical significance of atrial natriuretic peptide in patients with muscular dystrophy.

The plasma concentration of atrial natriuretic peptide was measured in patients with muscular dystrophies to study its relationship with congestive heart failure. In patients with Duchenne muscular dystrophy, the plasma atrial natriuretic peptide concentration was 35.5 +/- 3.3 pg/mL (mean +/- SE), which was higher than that in age-matched normal subjects (9.8 +/- 0.6 pg/mL). It increased with progression of disability and showed significant correlations with the cardiothoracic ratio and the ratio of the preejection period to the left ventricular ejection time. In patients with other types of muscular dystrophy, the plasma atrial natriuretic peptide concentration showed no significant change. Immunohistochemical examination demonstrated many atrial natriuretic peptide-positive cells in atrial muscle of an autopsied patient, indicating preservation of the peptide until the end stage. These findings suggest that measurement of the plasma atrial natriuretic peptide concentration is useful for evaluating heart failure in patients with Duchenne muscular dystrophy.

Adolescent↗

Management of tracheal lesions in Hurler syndrome.

Hurler syndrome is a rare mucopolysaccharide storage disease that becomes clinically apparent during early childhood as mucopolysaccharide deposits form in skeletal and soft tissues. Progressive mucopolysaccharide deposition in the oropharynx and tracheal connective tissues leads to airway obstruction if untreated. Tonsillectomy, adenoidectomy, and tracheostomy have been utilized to provide symptomatic relief of upper airway obstruction. Treatment of tracheal lesions by laser excision is a recent innovative method for the management of airway obstruction in children with Hurler syndrome. We describe two boys with Hurler syndrome whose mucopolysaccharide tracheal lesions were excised by utilization of the carbon dioxide laser.

Child↗

Elevated soluble interleukin-2 receptor levels in patients with active multiple sclerosis.

The level of soluble interleukin-2 receptor (sIL-2R) was quantitated with enzyme-linked immunosorbent assay in serum and cerebrospinal fluid obtained from 24 patients with multiple sclerosis and 10 patients with other neurological disorders in whom immunological mechanisms are unlikely to participate. The sIL-2R level in the serum and cerebrospinal fluid of patients with multiple sclerosis in relapse was significantly higher compared with patients with multiple sclerosis in remission and with controls. The sIL-2R level, especially in the cerebrospinal fluid, showed higher sensitivity and specificity than other clinical parameters including the cerebrospinal fluid IgG ratio, peripheral lymphocyte CD4/CD8 ratio, cerebrospinal fluid myelin basic protein and oligoclonal bands. Our data suggest that measurement of the sIL-2R level may be useful in evaluating disease activity in patients with multiple sclerosis.

Adult↗

Pro-thyrotropin-releasing hormone concentrations in the brain of ataxic mice.

Concentrations of pro-thyrotropin-releasing hormone (pro-TRH) were studied in the brain of the Weaver ataxic mouse, the Purkinje cell degenerative mouse (pcd-ataxic mouse), the Staggerer ataxic mouse and the C3H mouse. The brain tissue was dissected into 7 parts, e.g., hypothalamus, cerebrum, thalamus, striatum, brain stem, cerebellum and cervical spinal cord. Pro-TRH concentrations in each part of the brain were measured by radioimmunoassay. Pro-TRH concentrations in the brain of Weaver ataxic mice, pcd-ataxic mice and Staggerer ataxic mice were significantly higher in the thalamus, brain stem, cerebellum and cervical spinal cord. Pro-TRH concentrations in the hypothalamus, striatum and cerebrum of ataxic mice did not differ from those of controls. The elution profile of acetic acid extracted cerebellum of ataxic mice on Sephadex G-50 was identical to that of synthetic pro-TRH. These findings suggest that changes in pro-TRH concentrations in the brain may play a pathophysiological role in ataxic mice.

Animals↗

The effects of topical diazoxide on hair follicular growth and physiology of the stumptailed macaque.

Diazoxide, an anti-hypertensive agent, has diverse pharmacologic effects; hypertrichosis, hyperglycemia associated with suppression of insulin release, and elevation of serum levels of androgens. Taking advantage of the hypertrichotic side effects of diazoxide, we examined the effect of topical application of the drug on hair regrowth in the bald frontal scalp of stumptailed macaques (Macaca arctoides); we also monitored systemic side effects. Using 7 adult stumptails, we applied diazoxide (5% solution in a vehicle) topically on the bald frontal scalp, once a day, 5 days per week. Two of seven macaques had vehicle alone applied. Hair growth was monitored by photographic recording (once every month) and by sequential analysis of folliculograms from biopsied skin (once every 4 months). We also examined body weight, hematology, blood pressure, heart rate, serum levels of testosterone and dihydrotestosterone, and glucose tolerance for a 4-month period. All 5 diazoxide-treated animals showed thickening and maintenance of the frontal hair during the entire treatment period (16 months). Analysis of folliculograms showed progressive enlargement of hair follicular size and acceleration of its cyclic growth from telogen to anagen phase and prolongation of anagen phase in all treated animals. Controls showed no consistent progressive changes of follicular growth. None of the animals treated with diazoxide showed abnormal changes in physical growth, cardiovascular function, serum levels of androgens, glucose tolerance (including insulin levels), or hematology.

Alopecia↗

Magnesium concentration in brains from multiple sclerosis patients.

Magnesium (Mg) concentrations were studied in the brains of 4 patients with definite multiple sclerosis (MS) and 5 controls. The magnesium contents were determined by inductively coupled plasma emission spectrometry in autopsy samples taken from 26 sites of central nervous system tissues, and visceral organs such as liver, spleen, kidney, heart and lung. The average Mg content in the CNS tissues, as well as visceral organs except for spleen, of MS patients showed a significantly lower value than that seen in control cases. The most marked reduction of Mg content was observed in CNS white matter including demyelinated plaques of MS samples. Whether or not these significantly lower Mg contents found in CNS and visceral organs of MS patients may play an essential role in the demyelinating process remain unclear, requiring further studies on MS pathogenesis from the point of metal metabolism.

Adult↗

Effects of demethylchlortetracycline phototoxicity on the structure and functions of rat liver mitochondria.

The phototoxic effects of demethylchlortetracycline (DMCT) with UVA radiation on isolated rat liver mitochondria were studied. DMCT at concentration of 21.5 microM with 5.53 x 10(-2) J cm-3 of UVA was found to be a potent uncoupler of oxidative phosphorylation. DMCT alone also uncoupled mitochondria but at higher concentrations (105 microM). ATPase activity was remarkably induced in mitochondria exposed to DMCT (21.5 microM) plus UVA (120% of DNP-stimulated ATPase activity). Content of ATP in such mitochondria when measured after addition of ADP was much smaller than that in control mitochondria. Ultrastructurally, mitochondria treated either with DMCT (21.5 microM) or with UVA alone stayed in the condensed configuration. On the other hand, uncoupled mitochondria treated with DMCT plus UVA became swollen and were changed into the orthodox configuration.

Animals↗

[Five cases of listeriosis in the elderly].

We reported five cases of listeriosis (sepsis and meningitis) in the elderly in our hospital during the last 4 years, where no cases of listeriosis had been found. These 5 cases had diabetes mellitus, lung cancer, chronic respiratory failure, gastric ulcer and aplastic anemia respectively as their underlying diseases. At the onset of listeriosis, 3 cases received corticosteroid and 3 cases received H2-blocker. 2 patients were cured and 3 patients died. Three autopsy cases had meningitis or meningoencephalitis and 2 cases of these autopsy cases had granulomatous changes in these spleens. In serotypes of Listeria monocytogenes (L. monocytogenes), 4 cases were 4b and 1 cases was 1b. All 5 strains were resistant to 3rd generation cephems. Wide uses of 3rd generation cephems and H2-blocker may be one of the reasons for the recent increase of listeriosis. Ingestion of contaminated food is the pathogenetic mechanism for initiating L. monocytogenes infections. And following the change of eating habits and the increase of imported foods, food-born listeriosis may increase. We suppose the increase of L. monocytogenes infections and must give attention to L. monocytogenes infections.

Age Factors↗

Inhibition of osteoclast recruitment at a local site by 1-hydroxyethylidene-1,1-bisphosphonate (HEBP).

We hypothesized that bisphosphates, a class of antiosteolytic drugs that affect bone cells, may block localized bone modeling in the middle ear. Prior studies have shown that transmitted pressure in the middle ear leads to osteoclastic bone resorption. Catheters were surgically implanted into the middle ear cavity (bulla) of 31 Mongolian gerbils. The animals were then divided into two groups, one subset receiving a bisphosphonate, and the other receiving no drug. Positive air pressure was applied to one middle ear, and the other side served as a control. At the end of the experimental period, tissue specimens were obtained, and histomorphometric evaluation of the ventral bullae was performed. Significant differences in osteoclast surface, osteoclast number, and mean individual osteoclast profile area led us to conclude that administration of the bisphosphonate used at the dose studied inhibits localized recruitment and activation of osteoclasts.

Air Pressure↗

Changes in the pharmacokinetics of plasma total and free prednisolone during daily and intermittent regimens.

To determine the pharmacokinetic changes of prednisolone associated with differing therapy regimens, we studied 15 patients with various diseases who were treated with daily doses of prednisolone and were then placed on an intermittent regimen, [administration for 4 consecutive days (on-day period), followed by 3 days cessation (off-day period)]. The mean duration of the study and the mean total dosage were 1.6 months and 2.4 g in the daily period, respectively, and 4.7 months and 3.5 g in the intermittent period, respectively. Blood was drawn for 6 h after iv administration of 20 mg prednisolone (average, 0.36 mg/kg). Plasma total and free prednisolone concentrations were measured by RIA. On-day and off-day tests were performed during the same week. The mean MCR of both total and free prednisolone decreased significantly in the daily and on-day periods compared with the pretreatment values. The decreased MCR during the on-day period was restored to the pretreatment level during the off-day period. A similar trend was observed in the changes in half-life, prolongation in the daily and on-day periods compared with the pretreatment value, and restoration to the pretreatment level during the off-day period. These alterations were not associated with the total duration or the total dosage of prednisolone administered. The results indicate that the pharmacokinetic parameters of prednisolone may periodically change during the intermittent regimen, and that off-day and on-day parameters are similar to those before therapy and during the daily period, respectively.

Adolescent↗

Adipose tissues and vitamin E.

1. Vitamin E content in the adipose tissue was examined in rats with and without vitamin E deficiency. With the progression of vitamin E depletion, the more rapid decrease in tocopherol concentration was observed in brown adipose tissue (BAT) than in white adipose tissue (WAT), and the rate of decrease of tocopherol was approximately three times faster in BAT than in WAT. After the intramuscular administration of 10 mg/kg of all-rac-tocopheryl acetate twice a week for two weeks to vitamin E-deficient rats, a similar pattern of increase was observed in the tocopherol concentrations of BAT and WAT, although the rate of increase was slower in WAT than in BAT. 2. Changes of tocopherol concentration in BAT and WAT were investigated in normo-nourished rats with hyperlipemia produced by the intramuscular injection of Triton WR-1339 for 7 days. A marked increase in tocopherol concentration was observed in both BAT and WAT in the late period of hyperlipemia, with the increase being greater in WAT. 3. The fatty acid composition of adipose tissue was compared between rats with and without vitamin E deficiency. No significant differences were observed in BAT and WAT between the two groups. 4. The glucose uptake of WAT was not altered in vitamin E-deficient rats when compared with control rats.

Adipose Tissue↗

A new depsipeptide antibiotic, variapeptin.

A culture similar to Streptomyces variabilis was found to produce a novel cyclic hexadepsipeptide antibiotic named variapeptin. Variapeptin is structurally related to azinothricin, A83586C, and citropeptin. The antibiotic was active against Gram-positive bacteria and showed cytotoxic activity against mammalian cells.

Amino Acid Sequence↗

[Current status and therapeutic strategy for hepatocellular carcinoma].

It is reported that the number of hepatocellular carcinoma (HCC) in Japan is increasing and this is mainly due to the increase of HBsAg negative HCC patients with history of blood transfusion. However 80% of HCC patients are positive for HBV related serum markers. HBV DNA is detected by PCR method in 15% of HBsAg negative HCC patients with other HBV marker. These findings indicated that at least 40% of HCC patients in Japan are closely related to HBV infection. Several hypotheses on the mechanism of carcinogenesis by HBV have been proposed, however none of these has yet to be established. The type C hepatitis virus (HCV) reported by Chiron Co. is thought to be the majority of viruses which cause chronic non A non B hepatitis in Europe, United States and also Japan. The rate of anti-HCV in HBsAg negative HCC patients is about 70% in Japan. As strategies for HCC, the following 3 steps should be established; 1) prophylaxis against infection, 2) prevention of progression of liver cirrhosis, and 3) early detection of HCC. Though the role of hepatitis virus in hepatocarcinogenesis has not yet been established, it is thought that HBV and HCV are responsible for about 85% of HCC patients in terms of the development of liver cirrhosis which frequently associates with HCC. A marked decrease of HCC in Japan is forthcoming through the establishment of prophylaxis against HBV and HCV infection.

Adult↗

Demonstration that spleen green hemeprotein is identical to granulocyte myeloperoxidase.

The biochemical, spectroscopic, enzymatic, and redox properties of spleen myeloperoxidase, a peroxidase formerly called "spleen green hemeprotein," and granulocyte myeloperoxidase were compared by electrophoresis, amino-terminal amino acid sequences, optical and EPR spectroscopy, steady-state enzyme kinetics, and oxidation-reduction potential. The spleen enzyme exhibits properties indistinguishable from those of the granulocyte enzyme. We conclude that the spleen enzyme is indeed identical to granulocyte myeloperoxidase.

Amino Acid Sequence↗