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Biomedical subjects

H Akama

Publications and source records attributed to H Akama.

At least 37 records · Page 2Linked to original sources
PubMed1999

[MPO-ANCA positive rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis during treatment with D-penicillamine].

We present here a case of MPO-ANCA positive rapidly progressive glomerulonephritis (RPGN) after 34 months of D-penicillamine (D-PC) therapy for rheumatoid arthritis (RA). A 27-year-old Japanese woman was diagnosed as having RA in June 1994 at our out-patient clinic. Oral D-PC administration was initiated at a dose of 100 mg per day in January 1995. In August 1997, proteinuria, hematuria, renal insufficiency, and anemia developed. D-PC was withdrawn promptly, and prednisolone 5 mg per day was started. The patient was admitted to our hospital in September. On admission, anti-neutrophil cytoplasmic antibody against mycloperoxidase (MPO-ANCA) was strongly positive in the serum. Renal biopsy showed glomerulonephritis with cellular crescent formation in 60% of the glomeruli observed. Immunofluorescence examinations revealed deposits of granular IgG, IgA, C 1 q, and C 3 in the mesangium. The patient was treated with steroid pulse therapy along with administration of anti-coagulation and anti-platelet agents under the diagnosis of MPO-ANCA positive D-PC-induced RPGN. The renal function was gradually recovered and MPO-ANCA disappeared. Since RPGN is potentially a fatal disease, frequent monitoring of renal function and discontinuation of D-PC are required. In case MPO-ANCA becomes positive, prompt and correct diagnosis of the renal disorder could lead to a good prognosis as in this case. The present case may provide some important immunological insights into medical procedures to treat D-PC-induced RPGN and MPO-ANCA related glomerulonephritis.

Adult↗
PubMed1998

Volume expansion fails to normally activate neural pathways in the brain of conscious rabbits with heart failure.

Immunohistochemical detection of the protein, Fos, was used to identify neurons in the brain activated following a volume load in conscious rabbits with doxorubicin-induced congestive cardiomyopathy. The plasma expander, Haemaccel, was infused intravenously into rabbits for 60 min and significantly increased right atrial pressure, blood pressure and heart rate. The rabbits were perfusion fixed 90 min after the start of the infusion and the distribution of Fos-positive cell nuclei was examined. Compared to control rabbits with heart failure, there was a small significant increase in the number of Fos-positive cell nuclei in the organum vasculosum of the lamina terminalis following volume expansion. In other regions of the brain that were studied in detail, there were no significant increases in Fos production. These included the parvocellular paraventricular nucleus (PVN) of the hypothalamus, the midbrain periaqueductal gray, the nucleus tractus solitarius (NTS), area postrema and the ventrolateral medulla (VLM). In the supraoptic nucleus and the magnocellular PVN, no Fos-positive cell nuclei were present as expected. The median preoptic nucleus, the bed nucleus of the striae terminalis and the diagonal band of Broca contained some Fos but there was no marked difference between volume expanded and control animals. In the anterior cortical and medial subnuclei of the amygdala there was a high concentration of Fos but there was no consistent difference between the two groups. The present findings in heart failure rabbits suggest that most brain regions are not activated sufficiently by the stimulus to elicit Fos expression. The results are in accord with findings showing that sympathetic reflexes initiated by volume expansion are attenuated in heart failure.

Animals↗
PubMed1998

Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold.

A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.

Alcohol Oxidoreductases↗
PubMed1998

[A patient with acute sarcoidosis associated with fever, polyarthritis, and erythema nodosum: a typical of Löfgren's syndrome].

A 26-year-old female was admitted to Aoyama Hospital in February 1996, for evaluation of abnormal chest shadows and polyarthritis. She visited our clinic in December 1995 with complaints of fever, fatigue, and polyarthralgia which lasted for 3 weeks. Two weeks later she developed erythema nodosum on her lower legs with the exacerbation of polyarthritis. Erythrocyte sedimentation rate was 108 mm/hr and CRP 4.9 mg/dl. A chest radiograph showed hilar lymphadenopathy and multiple nodular shadows in both lung fields. On admission, she had arthritis of the shoulders and knees, erythema nodosum on her lower extremities, and keloid-like skin lesion on her left knee. Thoracoscopic lung biopsy of nodular lesion and skin biopsy of keloid-like lesion revealed noncaseating granuloma of epithelioid cells with lymphocytes, macrophages, and giant cells, confirming the diagnosis of sarcoidosis. She was cured in three months, and was well and free of the symptoms thereafter. Löfgren's syndrome is acute sarcoidosis, characterized by arthritis, erythema nodosum, and bilateral hilar lymphadenopathy. This syndrome is common in Europe and is closely related to HLA-B8 and DR-3. The frequency of HLA-B8 and DR-3 in Japanese is almost 0%, explaining the rare onset of this syndrome in Japan. Our case is the second report of typical Löfgren's syndrome in Japan, although the patient did not have these HLA loci.

Acute Disease↗
PubMed1998

Acute sympathetic hyperfunction in overlapping syndromes of systemic lupus erythematosus and polymyositis.

A 20-year-old woman with arthralgia, serositis, thrombocytopenia, proteinuria, muscle weakness, elevated creatinine kinase, and positive anti-Sm antibody was diagnosed as having polymyositis and systemic lupus erythematosus (SLE). She had persistent high temperature, sinus tachycardia, hyperhidrosis, mydriasis, visual disturbance, hallucination, and loss of consciousness. Levels of plasma adrenaline, noradrenaline, and dopamine and cerebrospinal fluid interleukin (IL)-6 and IL-8 were all high. A diagnosis of sympathetic hyperfunction accompanied by central nervous system (CNS) involvement in SLE was made parenteral. Pulse administration of high dose corticosteroid therapy was effective. This is the first reported case of a connective tissue disease with CNS involvement manifesting as sympathetic hyperfunction with high plasma catecholamine levels.

Acute-Phase Reaction↗
PubMed1998

[Alkaline phosphatase (ALP) activity in rheumatoid arthritis (RA): its clinical significance and synthesis of ALP in RA synovium].

Increased concentration of serum alkaline phosphatase (ALP) is a common feature in rheumatoid arthritis (RA), although its origin remains unclear. The aim of this study is to analyze the origin and clinical significance of the elevated ALP value in RA. In 123 RA and 63 age- and sex-matched OA (osteoarthropathy) patients, concentrations of total ALP and its isozymes in serum and synovial fluid were studied. Serum CRP, Fe, ferritin, and Cu values were examined, respectively. The expression of ALP as protein was also investigated by using an enzymehistochemical and an immunohistochemical staining methods. Serum ALP values were elevated in 37.4% of RA (245.2 +/- 91.2 IU/L), and significantly higher than those of OA (192.3 +/- 45.2 IU/L: P < 0.01, RA v.s. OA). The serum CRP, and ferritin values each had a relation with the serum ALP activity. Fluid ALP concentration of RA was 110.3 +/- 40.1 IU/L, and that of OA, 83.6 +/- 15.0 IU/L (P < 0.05), respectively. In RA, a predominant isozyme was liver-type one both in the sera (91%) and the synovial fluid (59%). However, this result means that bone-type one was more abundant in the synovial fluids (41%) than those in the sera (9%). An enzymehistochemical and an immunohistochemical studies revealed that ALP was positive in a perivascular area, sublining cells, and a part of vascular endothelium in RA. In contrast, the synovial tissue from OA and a healthy patient exhibited only a weak staining. In RA, a positive correlation between the elevation of serum ALP and the disease activity was confirmed. Furthermore, we elucidated that ALP is produced in RA synovium.

Adult↗
PubMed1998

[Lupus cystitis and peritonitis successfully treated with intravenous cyclophosphamide pulse therapy: a case report].

The patient, a 35-year-old woman, had been diagnosed as SLE since she developed butterfly rash, arthritis and hair loss with positive antinuclear antibody, anti-DNA antibody, and LE cells in 1989, and treated with daily 20 mg prednisolone (PSL). She had been suffering from nausea, vomiting and waterly diarrhea since 1992. In June 1995, she noted pollakisuria and sense of residual urine, followed by dysuria and nocturia in October. She was admitted to our hospital in January 1996 with progressive gastrointestinal and urinary symptoms. Computerized tomography (CT) depicted thickening of the wall of intestine and bladder, diminished volume of bladder, and bilateral hydronephrosis and hydroureter. Biopsy of the bladder revealed erosion of mucosa and moderate infiltration with inflammatory cells. The diagnosis of lupus cystitis and peritonitis was made and she was initially given intravenous methylprednisolon pulse therapy (500 mg/day) for 3 days, and then switched to 100 mg of daily intravenous PSL. She responded partially to this regimen, but gradually developed gastrointestinal and urinary symptoms again when PSL was tapered down to 70 mg/day. Therefore, monthly intravenous cyclophosuphamide pulse therapy was started. With this therapy, her bladder and bowel symptoms improved, and then the thickness of her bladder and intestinal wall, and the bladder volume normalized. Five months after institution of therapy, PSL was successfully tapered down to 30 mg/day and she was discharged. Intravenous cyclophosphamidepulse therapy is a choice of treatment for steroid-resistant lupus cystitis and peritonitis.

Adult↗
PubMed1997

Preferential changes in hepatosplanchnic hemodynamics in patients with borderline hypertension.

To investigate changes in systemic and regional hemodynamics during the development of human hypertension, we simultaneously measured cardiac index (CI) by the indocyanine green (ICG) dye dilution method, hepatosplanchnic blood flow (HBF) by the ICG clearance method using a two-compartment model, and renal blood flow (RBF) by the p-aminohippurate clearance method in patients with borderline and essential hypertension. In patients with borderline hypertension (BH, n = 27), HBF (435 +/- 15 ml/min/m2) and HBF/CI (16 +/- 1%) were significantly (p < 0.05) lower than in age-matched normotensive controls (528 +/- 21 and 19 +/- 1, respectively, n = 21), while CI, RBF and RBF/CI were similar. In patients with essential hypertension (EH, n = 32), HBF, RBF, and RBF/CI were all significantly (p < 0.01) lower than in the control subjects. Hepatosplanchnic vascular resistance (HVR) in patients with BH was preferentially increased, while total peripheral resistance (TPR) and renal vascular resistance (RVR) remained in the normal range. In patients with EH, TPR, HVR, and RVR were all increased. These results indicate that hemodynamic changes in patients with BH do not occur uniformly among the various regional circulations and suggest that hemodynamic changes in the hepatosplanchnic region precede those in other organ circulations during the development of human hypertension.

Adolescent↗
PubMed1997

Sclerosing cholangitis associated with hypereosinophilic syndrome.

A 15-year-old male with hypereosinophilic syndrome was admitted to our hospital because of general malaise and abnormal liver function tests. Endoscopic retrograde cholangiopancreatography demonstrated bile duct changes consistent with primary sclerosing cholangitis. The patient's liver profile tests returned to normal after treatment with prednisolone and ursodeoxycholic acid. In this case, eosinophils might have played an important role in the pathogenesis of the bile duct lesion.

Adolescent↗
PubMed1996

Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 secretion.

Type II complement protein C2 deficiency is characterized by a selective block in C2 secretion. The Type II C2 null allele (C2Q0) is linked to two major histocompatibility haplotypes (MHC) that differ from the MHC of the more common Type I C2 deficiency. To determine the molecular basis of Type II deficiency the two Type II C2Q0 genes were isolated and transfected separately into L-cells. Subsequent molecular biology, biosynthetic, and immunofluorescence studies demonstrated that C2 secretion is impaired in Type II C2 deficiency because of different missense mutations at highly conserved residues in each of the C2Q0 alleles. One is in exon 5 (nucleotide C566 --> T; Ser189 --> Phe) of the C2Q0 gene linked to the MHC haplotype A11,B35,DRw1,BFS, C4A0B1. The other is in exon 11 (G1930 --> A; Gly444 --> Arg) of the C2Q0 gene linked to the MHC haplotype A2,B5, DRw4,BFS,C4A3B1. Each mutant C2 gene product is retained early in the secretory pathway. These mutants provide models for elucidating the C2 secretory pathway.

Alleles↗
PubMed1996

Two cases of malignant pheochromocytoma treated with cyclophosphamide, vincristine and dacarbazine in a combined chemotherapy.

Two patients with malignant pheochromocytoma were treated with a combination chemotherapy regimen consisting of cyclophosphamide vincristine, and dacarbazine (CVD). With the first few cycles of the treatment, one patient, a 29-year-old man had a marked improvement of clinical symptoms and decreases in tumor size and catecholamine levels in plasma and urine. He had been in a clinically stable condition for 18 months but died 34 months after starting of this treatment because the CVD regimen became ineffective and rapid growth of the metastatic tumors occurred. The other patient, a 35-year-old man showed no significant change in tumor size but decreases in hormonal levels in response to CVD regimen. The patient has been in clinically stable condition in a follow-up of 24 months. The combined chemotherapy with CVD appears to be effective for advanced malignant pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1995

Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung.

The small-complement C5 activation fragment, C5a, is a potent phlogistic molecule that, on binding to the C5a Receptor (C5aR), mediates contraction of smooth muscle, enhances vascular permeability, and promotes leukocyte functions such as directed chemotaxis, degranulation, mediator release, and production of superoxide anions. Although C5aR expression has traditionally been thought to be limited primarily to myeloid blood cells, including neutrophils, monocytes, macrophages, and eosinophils, we report here that C5aR is expressed by liver and lung cells as well as by cells in several other tissues. By Northern blot analysis, it was determined that mouse liver, baboon liver, human liver, and the human hepatoma-derived cell line HepG2 express a normal size (2.3 kb) C5aR mRNA; in HepG2 cells, the quantity of C5aR mRNA was comparable to that contained in dbcAMP-differentiated U937 cells. HepG2 cells were demonstrated to express the C5aR on their cell surface by flow cytometric and immunofluorescence analyses as well as by 125I-C5a binding assays. The binding data indicated that HepG2 cells express a single class of C5aR with a Kd of 1.18 nM and approximately 28,000 receptors per cell. In vivo expression of C5aR in human liver cells was demonstrated by in situ hybridization and immunohistochemistry analyses. Northern blot analysis of murine and baboon organs shows that, in addition to the liver, other tissues express C5aR mRNA in significant quantities, including the spleen, lung, heart, kidney, and intestine. Moreover, mice treated with LPS show a large increase in C5aR mRNA in all these tissues except the intestine. Immunostaining of human lung tissue demonstrated that bronchial and alveolar epithelial cells, as well as vascular smooth muscle and endothelial cells, also express the C5aR. Collectively, these data indicate that the C5aR is expressed in several different types of cells in liver and lung, and in yet undetermined cell types in spleen, heart, intestine, and kidney. Furthermore, these data suggest that the C5a anaphylatoxin mediates previously unrecognized functions by binding to tissue cells that express the C5aR.

Amino Acid Sequence↗
PubMed1995

Human complement protein C2. Alternative splicing generates templates for secreted and intracellular C2 proteins.

Alternative splicing of the primary transcript for human complement protein C2 generates templates for translation of a secreted (C2 long) protein and an intracellular (C2 short) form in liver, bronchoalveolar macrophages, and fibroblasts. The approximate ratio of C2 long to C2 short mRNA is 2:1. The C2 short mRNA does not contain the 396-base pair encompassed by exons 2 and 3 of the full-length C2 long and thus lacks codons for the 5 carboxyl-terminal residues of the signal peptide. Synthesis of C2 in cells transfected with full-length RNA corresponding to each of the transcripts show that C2 long is secreted within a half-time of approximately 1 h and that C2 short is not secreted. Cell-free biosynthesis in the presence of microsomes demonstrate that this intracellular C2 protein (70 kDa) is apparently capable of traversing the membrane of the endoplasmic reticulum. Though the function of the intracellular C2 protein is unknown, it is abundant in all cell types that express the C2 gene.

Alternative Splicing↗
PubMed1995

Renal dopamine spillover rate using 3H-dopamine radiotracer technique as an index of renal dopaminergic nerve activity.

Renal and total dopamine (DA) spillover rates at rest were measured in 25 conscious rabbits with chronically implanted renal vein catheters. Renal DA spillover rate was calculated from veno-arterial difference in plasma free DA concentrations across the kidney corrected by the fractional extraction of infused 3H-DA. Plasma free DA concentrations were 11.0 +/- 2.7 pg/ml in the artery and 14.3 +/- 3.6 in the renal vein. Renal and total DA spillover rates were 0.51 +/- 0.08, 2.61 +/- 0.30 ng/min, respectively, both of which were significantly (p < 0.001) lower than the respective norepinephrine (NE) spillover rates (renal: 16.3 +/- 1.4, total: 39.6 +/- 1.7). The fractional extraction of 3H-DA across the kidney (55 +/- 3%) and the total DA clearance (285 +/- 31 ml/min) were both significantly (p < 0.05) higher than that of 3H-NE (45 +/- 3) and the total NE clearance (198 +/- 9), respectively. The ratio of renal to the total spillover rate of DA (0.23 +/- 0.05) was significantly (p < 0.05) lower than that of NE (0.41 +/- 0.04). These results demonstrate that DA is released into plasma within the kidney and suggest that the measurement of renal DA spillover rate using 3H-DA radiotracer technique is useful to detect resting renal dopaminergic nerve activity.

Animals↗
PubMed1995

Effect of dexamethasone on plasma free dopamine: dopaminergic modulation in hypertensive patients.

To investigate the peripheral dopaminergic modulation in the pathogenesis of human hypertension, we examined the responses of plasma free dopamine (DA) to dexamethasone (Dx) administration, which is suggested to activate dopaminergic activity. We administered Dx 2 mg intravenously to patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls (NT). Plasma free DA was increased significantly in all groups and the responses were more remarkable in PA than in EH and NT. Plasma epinephrine (E) showed a gradual increase while plasma norepinephrine (NE) tended to decrease in all groups. The responses of both plasma DA and E were completely blocked by 250 mg of alpha-methyl-p-tyrosine, a tyrosine hydroxylase (TH) inhibitor, suggesting that Dx may stimulate peripheral dopaminergic activity by increasing catecholamine synthesizing enzyme (probably TH) activities. These data suggest that DA itself plays an inherent role in the sympathoadrenal regulation rather than only as a precursor of NE and that dopaminergic hyperresponses may be involved in the pathophysiology of PA.

Adult↗
PubMed1995

Plasma free dopamine: physiological variability and pathophysiological significance.

Dopamine (DA) is the most abundant catecholamines in human plasma and exists mostly in the sulfo-conjugated form (DA sulfate), a biologically inactive metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its physiological significance. However, PDA, when measured with a highly sensitive radioenzymatic method, showed quite different features from norepinephrine and epinephrine in some types of clinical hypertension, lower in essential hypertension and higher in primary aldosteronism and pheochromocytoma. There was a weak but significant correlation between the values of PDA and DA sulfate measured in the same specimens, but DA sulfate was more susceptible to impaired renal function. Upright posture, high salt diets and an intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, induced a slight but significant increase in PDA in normal and hypertensive subjects. An intravenous dexamethasone (2 mg) caused a gradual increase in PDA over 150 min after medication, which was completely blocked by concomitant administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The responses of PDA to both high salt diets and MCP were blunted in salt-sensitive patients with uncomplicated essential hypertension. The results suggest that DA is not only a precursor of norepinephrine biosynthesis but also plays an inherent role as an active neurotransmitter in the peripheral sympathoadrenal system, and that PDA is a sensitive marker of peripheral dopaminergic activity, which may operate to modulate the cardiovascular and endocrine functions and participate in the pathogenesis of some types of hypertension.

Dexamethasone↗