Biomedical subjects

H Katsumata

Publications and source records attributed to H Katsumata.

At least 37 records · Page 2Linked to original sources

PubMed1999

Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene.

Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung disease predominantly found in Asian populations. Although its etiology is unknown, DPB is considered to be a multifactorial disease of whose susceptibility is determined by genetic predisposition unique to Asians. We and others have previously reported that the B*5401 allele of the human leukocyte antigen (HLA)-B gene or a closely linked gene in the HLA region on 6p21.3 is one of the major genetic factors in susceptibility to this disease. However, the association with B*5401 is not absolute and the contribution of other genetic or environmental factors should also be considered. Here, four candidate genes that are postulated to play a role in the pathophysiology of DPB, namely, RON-kinase, CYP3A4, motilin, and interleukin (IL)-8, were chosen, and association studies between microsatellite markers at these loci and DPB were conducted. We demonstrated the presence of a specific allele at the IL-8 locus was associated with the disease (c2 = 9.13; P = 0.0025; corrected P [Pc] < 0.05). Although further studies are needed to examine whether neutrophil accumulation in the airways of patients with DPB is controlled by a possible genetic variation of IL-8 or other chemokine genes located in the region 4q12-q13, our data suggest that genes other than those of the HLA system may also contribute to a genetic predisposition to DPB.

Asian People↗

PubMed1999

A novel LDLR mutation, H190Y, in a Utah kindred with familial hypercholesterolemia.

Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein (LDL) cholesterol levels early in childhood and very early coronary disease in both men and women. Treatment with multiple medications together with diet can normalize cholesterol levels in many persons with FH and prevent or delay the development of coronary atherosclerosis. Previously published blood cholesterol criteria greatly under-diagnosed new cases of FH among members of known families with FH and over-diagnosed FH among participants of general population screening. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To carry out molecular genetic diagnosis of the disease, we screened DNA samples for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor gene (LDLR). Novel point mutations were identified in the proband: a C-to-T transversion at nucleotide position 631, causing substitution of tyrosine for histidine at codon 190 in exon 4 of the LDLR gene. The mutant allele-specific amplification method was used to examine 12 members of the family recruited for the diagnosis. This method helped to unequivocally diagnose 7 individuals as heterozygous for this particular LDLR mutation, while excluding the remaining 5 individuals from carrier status with FH.

Adult↗

PubMed1999

Effects of cicletanine on the progression of renal failure in 5/6 nephrectomized hypertensive rats.

1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure of 5/6 nephrectomized spontaneously hypertensive rats with salt loading was examined. 2. All nephrectomized rats were randomly assigned to one of four groups and their diet was changed from a normal- to a high-salt (5.5% NaCl) diet for the next 10 weeks. Either 10 or 50 mg/kg per day cicletanine (low- and high-dose cicletanine, respectively) or 10 mg/kg per day trichlormethiazide were administered to rats during this period once a day. During the experimental period, urine volume, urinary excretion of sodium, protein, prostaglandin (PG) E2 and 6-keto-PGF1 alpha and systolic blood pressure (SBP) were measured every 2 weeks. 3. Systolic blood pressure was significantly reduced by the administration of trichlormethiazide and the higher dose of cicletanine, but not by the lower dose of cicletanine. 4. In contrast with changes to SBP, levels of serum creatinine in rats treated with both doses of cicletanine were significantly lower than in controls (0.57 +/- 0.12, 0.78 +/- 0.12 and 1.68 +/- 0.26 mg/dL for high- and low-dose cicletanine and control, respectively). 5. Urinary excretion of both PGE2 and 6-keto-PGF1 alpha were significantly increased in groups treated with high and low doses of cicletanine compared with control. In rats treated with trichlormethiazide, PGE2 and 6-keto-PGF1 alpha levels were significantly decreased compared with control. 6. In contrast with changes in SBP, marked glomerular sclerosis with hyalinosis found in the control group was not ameliorated by trichlormethiazide treatment. These changes were not observed in rats treated with low- and high-dose cicletanine, particularly those treated with the higher dose of cicletanine. 7. These data suggest that administration of cicletanine has a beneficial protective effect regarding the progression of renal failure, regardless of the level of blood pressure, through a direct and/or indirect action on the glomerulus.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Familial hypercholesterolemia in Utah kindred with novel 2412-6 Ins G mutations in exon 17 of the LDL receptor gene.

Familial hypercholesterolemia (FH) is a monogenic disorder associated with primary hypercholesterolemia. FH is characterized by autosomal co-dominant inheritance with strikingly elevated LDL-cholesterol, the presence of xanthoma and premature atherosclerosis. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To determine the genetic etiology of the lipoprotein abnormalities, we screened DNA samples from the family for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein receptor (LDLR) gene. Novel point mutations were identified in the proband: a one-base insertion of G to a five-G stretch at nucleotides 2412-6 (codons 783-785), causing a frameshift in exon 17 of the LDL receptor gene. The direct sequencing method was used to examine six members of the family recruited for the diagnosis. This method helped to unequivocally diagnose the five individuals as heterozygous for this particular LDL receptor mutation. This method also helped us to diagnose with FH, or to exclude from carrier status, three children between ages 6 and 11.

Child↗

PubMed1999

Familial hypercholesterolemia in Utah kindred with novel R103W mutations in exon 4 of the LDL receptor gene.

Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein cholesterol levels early in childhood and very early coronary disease in both men and women. Previously published blood cholesterol criteria greatly under-diagnosed new cases of FH among members of known families with FH and over-diagnosed FH among participants of general population screening. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To carry out molecular genetic diagnosis of the disease, we screened DNA samples for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein (LDL) receptor gene. Novel point mutations were identified in the proband: a C-to-T transversion at nucleotide position 369, causing substitution of Tryptophan for Arginine at codon 103 in exon 4 of the LDL receptor gene. The SSCP method was used to examine seven members of the family recruited for the diagnosis. This method helped to unequivocally diagnose only the proband as heterozygous for this particular LDL receptor mutation while excluding the remaining six individuals from carrier status with FH.

Adolescent↗

PubMed1998

Familial hypercholesterolemia kindred in Utah with novel C54S mutations of the LDL receptor gene.

In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To determine the genetic etiology of the lipoprotein abnormalities, we screened DNA samples for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein (LDL) receptor gene. Novel point mutations were identified in the proband: a T-to-A transversion at nucleotide position 223, causing substitution of Ser for Cys at codon 54 in exon 3 of the receptor gene. This amino acid replacement would disrupt one of the disulfide bonds necessary for maintenance of the secondary structure of the repeat at the N-terminal of the receptor, prevent correct folding of the receptor, and result in defective intracellular transport of the receptor.

Adult↗

PubMed1995

Status of patients who underwent uninephrectomy in adulthood more than 20 years ago.

We investigated the status of patients without systemic diseases who had undergone uninephrectomy for unilateral renal diseases in adulthood more than 20 years ago at Tokyo Denryoku Hospital. There were 21 participants (mean age +/- SD, 58.6 +/- 8.0 years) who fulfilled these criteria. The average interval since nephrectomy was 27.9 +/- 6.2 years. The mean current creatinine clearance was 88.5 +/- 21.2 mL/min/1.73 m2, which is 92.9% of that in healthy age- and sex-matched controls with two kidneys. The 24-hour urine protein excretion in these patients was only slightly higher than in the controls (214 +/- 190 mg v 119 +/- 62 mg, P = NS). Age at nephrectomy, length of time with a single kidney, or sex had little effect on the remnant renal functions. There was a positive correlation between current mean arterial pressure and serum creatinine (r = 0.44, P < 0.05). Patients who developed hypertension after uninephrectomy had a family history of hypertension more frequently than those with normotension (86% v 29%, P < 0.05). We conclude that (1) renal function after compensatory hyperfiltration of more than 20 years due to uninephrectomy for unilateral renal diseases in adulthood is well maintained, although hypertension has a considerable effect on the renal functions, and that (2) family history of hypertension plays a key role in determining the incidence of hypertension even in the uninephrectomized patients.

Adult↗

PubMed1995

C1Q complexes with beta-2-microglobulin and amyloid P-component in sera of patients with dialysis-associated amyloidosis.

We studied complexes composed of C1q and beta 2-microglobulin (C1q.beta 2M) or serum amyloid P-component (C1q.SAP) in the sera of 38 patients receiving hemodialysis (HD) and 20 healthy control subjects using an enzyme-linked immunoassay. We also compared complex levels in HD patients with and without symptoms of HD-associated amyloidosis (HA). Serum C1q-beta 2M levels were significantly higher in HD patients without HA than in healthy control subjects and significantly higher in HD patients with HA than in HD patients without HA. Serum C1q.SAP levels were significantly lower in patients with HA than in those without HA. These results suggest that C1q.beta 2M may contribute to HA.

Amyloidosis↗

PubMed1993

Two cases of Goodpasture's syndrome--clinicopathological studies and relapse.

The requirements for a diagnosis of Goodpasture's syndrome (GPS) include: (1) the presence of glomerulonephritis, (2) alveolar bleeding, and (3) the presence of anti-glomerular basement membrane (anti-GBM antibody). Among Japanese case, the 2 patients reported here were rare in that they satisfied all of these requirements. In case 1 (a 40-year-old male), the disease developed with initial signs of proteinuria and hematuria. The patient developed hemoptysis after hospitalization. The interval from onset to hospitalization was 38 days. The serum creatinine (CRN) level was 3.6 mg/dl on admission. The pathological findings were rated as full-circumferential, cellular crescentic nephritis, and the patient did not display oliguria. The renal and pulmonary impairments in this case were markedly improved by glucocorticoid (prednisolone PSL, 60 mg/day), cyclophosphamide therapy (50 mg/day) and plasma exchange (PE 10 times). In case 2 (a 58-year-old male), the initial signs developed as proteinuria and hematuria, followed by rapidly progressive renal functional deterioration and hemoptysis occurred. Compared to Case 1, the interval from onset to hospitalization was longer in Case 2 (125 days) and the CRN level was also higher (10.7 mg/dl). Case 2 was rated as full-circumferential, fibrous crescentic nephritis, and the patient was oliguric. Although the pulmonary impairment was reduced by pulse therapy and 10 PEs, recovery of renal function has not been achieved, still necessitating maintenance hemodialysis at present. In case 1, the disease relapsed at 4.5 years after remission, presenting with aggravated renal function and hemoptysis. In this case, low-dose PSL therapy had been discontinued at 3 months before the relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[A case of rheumatoid arthritis with immunotactoid glomerulopathy].

The patient was a 64-year-old female who had been treated by a local doctor for rheumatoid arthritis and hypertension for 10 years. Malaise and edema developed since July, 1990, and as proteinuria and renal dysfunction were noted, the patient was admitted to our hospital on November 2. On admission, BUN was 33mg/dl, creatinine was 2.5mg/dl, and proteinuria was about 3g/day. Renal biopsy was performed after admission. Light microscopy revealed nodular lobulation of glomeruli and occlusion of loops. Dylon staining was negative. Immunofluorescent study showed granular deposition of IgG, IgM, C3, C4, Clq in the glomerular basement membrane and mesangial area. Electron microscopy showed a large amount of electron dense deposits in the subendothelium and mesangial area and dense aggregation of tubular structure in the deposit, part of which exhibited a profile of fingerprint deposit. The tubular structures were classified into three major types, which were 120, 100, and 50nm in diameter. From these findings, a diagnosis of immunotactoid glomerulopathy was made. After renal biopsy, plasmapheresis and prednisolone were administered, and the patient has been managed conservatively to date.

Arthritis, Rheumatoid↗

PubMed1990

Effects of antihypertensive agents on blood pressure and the progress of renal failure in partially nephrectomized spontaneously hypertensive rats.

The purpose of this study was to investigate the effects of antihypertensive agents on blood pressure and the development of glomerular changes in salt-loaded, 5/6 nephrectomized spontaneously hypertensive rats (SHR). Thirty-two spontaneously hypertensive rats with 5/6 nephrectomy were divided into 4 groups: a control group (N = 8), and group treated with 10 mg/kg/day trichlormethiazide. (N = 8), 30 mg/kg/day captopril (N = 8), and 200 mg/kg/day nicardipine (N = 8). Each of these antihypertensive drugs was added to the drinking water for 10 weeks and the rats were given the drugs and a high-salt diet (5% NaCl). During the experiment, body weight and systolic blood pressure were measured every 2 weeks. At the end of the study, blood was collected for determination of serum creatinine, blood urea nitrogen, serum protein, serum sodium and potassium, and plasma renin activity and aldosterone concentration. Also renal tissues were obtained for light and electron microscopic examination at the end of the study. Systolic blood pressure in 5/6 nephrectomized SHR loaded with a high salt was significantly reduced by administration of trichlormethiazide (155 +/- 12 versus 204 +/- 12 mm Hg), but not by administration of either captopril or nicardipine. However, levels of serum creatinine were not significantly elevated in rats treated with captopril and nicardipine (control: 0.93 +/- 0.11 mg/dl, captopril: 0.62 +/- 0.01 mg/dl, nicardipine: 0.55 +/- 0.05 mg/dl). In contrast to changes in blood pressure, marked glomerular sclerosis with hyalinosis, which was found in the control group was not ameliorated by treatment with trichlormethiazide. However, these changes were not observed in rats treated with either captopril or nicardipine in spite of the absence of a prominent fall in blood pressure. These data suggest that captopril and nicardipine ameliorated glomerular injury regardless of the level of systolic blood pressure through the direct and/or indirect actions on the glomerulus.

Animals↗

PubMed1989

Differences in the effects of angiotensin converting enzyme inhibitors with or without a thiol group in chronic renal failure in rats.

1. We have investigated the effects of the non-renin-mediated actions of angiotensin converting enzyme inhibitors on the progression of chronic renal failure accelerated by hypertension. For this purpose, we studied the effects of captopril (a thiol-containing angiotensin converting enzyme inhibitor), enalapril (an angiotensin converting enzyme inhibitor without a thiol group) and cysteine (a thiol-containing amino acid which has no angiotensin converting enzyme-inhibitory action) in adriamycin-treated rats with deoxycorticosterone acetate-salt hypertension, in which the renin-angiotensin system was suppressed. 2. There were no significant differences in blood pressure between these groups and the control group [adriamycin-treated group with deoxycorticosterone acetate-salt loading, 206 +/- 7 mmHg (27.4 +/- 0.9 kPa) at week 10]. 3. Massive proteinuria occurred in all groups. At the end of the experiment (at week 10), urinary protein excretion was significantly reduced in the captopril and cysteine groups compared with the control group. No manifest improvements appeared in the enalapril group. 4. Levels of serum creatinine and blood urea nitrogen increased progressively. At week 10, the increases in the serum levels of creatinine were less in the captopril (87 +/- 16 mmol/l) and cysteine (80 +/- 19 mmol/l) groups than in the control group (124 +/- 27 mmol/l) (P less than 0.01). No marked differences were found between the control and enalapril groups. 5. Captopril and cysteine caused more than a three-fold reduction in the focal glomerulosclerosis score when compared with that in the control group, but enalapril did not decrease the score. The extent of tubulointerstitial change was parallel with the focal glomerulosclerosis score. 6. We conclude that the thiol group is possibly involved in the mechanism of the beneficial effects of some angiotensin converting enzyme inhibitors on the progression of chronic renal failure exacerbated by hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

The influence of dietary protein on the synthesis of vasoactive substances in subtotally nephrectomized spontaneously hypertensive rats.

The effects of dietary protein alterations on the synthesis of prostaglandins and kallikrein were examined in subtotally nephrectomized spontaneously hypertensive rats. Three diets containing 40, 24 and 8% protein were prepared. After subtotal nephrectomy, rats were given one of the three diets for the next 12 weeks. During the study, systolic blood pressure, urinary excretions of protein, 6-keto-prostaglandin F1 alpha, thromboxane B2 and kallikrein were measured every 2 weeks. Although the diets did not prevent the further elevation of systolic blood pressure, the rats on the low protein diet displayed lower serum creatinine levels and urinary protein levels. The urinary excretion of thromboxane B2 was unaffected by the amount of dietary protein, but the urinary excretion of 6-keto-prostaglandin F1 alpha was lower in the low protein diet group. Furthermore, the urinary excretion of kallikrein increased significantly in rats on high protein diet. These results suggest that manipulation of dietary protein may alter the natural course of renal failure induced by subtotal nephrectomy in spontaneously hypertensive rats.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Hormonal and renal responses to oral once-daily calcium entry blocker in normotensive and hypertensive persons.

A newly produced calcium entry blocker, KW3049 (Kyowa Hakko, Tokyo, Japan), which maintains its antihypertensive action for greater than 24 h, was administered orally once daily to 12 subjects (5 normotensive, 7 hypertensive) for 12 days. To elucidate its hypotensive efficacy and mechanisms of action, daily changes in blood pressure and heart rate, serial alterations in the renin-angiotensin system and sympathetic nervous system, and the renal hemodynamics were investigated. KW3049 caused a significant decrease in mean arterial pressure from 124 + 3 to 107 + 2 mm Hg, accompanied by a moderate increase in heart rate (+15%). The urine volume and urinary excretion of sodium were persistently increased in hypertensive subjects with improvement of the renal blood flow. The plasma renin activity and plasma and urinary norepinephrine (NE) increased significantly (p less than 0.05) on the sixth day and returned to baseline levels on the twelfth day. In addition to these renal and hormonal changes, the pressor responses to infused NE and angiotensin II were attenuated on the twelfth day after KW3049 administration. The above findings suggest that only once-daily administration of KW3049 is able to reduce the blood pressure without fluctuation, and its antihypertensive mechanisms are related to a natriuretic action and attenuation of pressor responses as well as to strong vasodilation.

Adult↗

PubMed1981