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Biomedical subjects

H Kobayakawa

Publications and source records attributed to H Kobayakawa.

At least 19 recordsLinked to original sources

Induction of irreversible glomerulosclerosis in the rat by repeated injections of a monoclonal anti-Thy-1.1 antibody.

The present experiment demonstrated that an irreversible glomerulosclerosis could be induced in the rat through repeated intravenous administrations of OX-7 (a monoclonal anti-Thy-1.1 antibody). Rats were injected with 0.2 mg of affinity-purified OX-7 at 1-week intervals for a period of 4 weeks. Glomerular damage was periodically examined at light-microscopic level. Thirty-five days after the initial injection (7 days after the final injection), capillary aneurysms and expansion of the mesangial areas with hypercellularity were frequently observed. Similar glomerular damage was also observed in rats 7 days after they received a single injection of either 1.0 or 0.2 mg of OX-7. After repeated injections, 112 days from the initial administration (84 days after the final injection), approximately 60% of the glomeruli had expanded mesangial areas with an apparent increase in the mesangial matrix. The result contrasts sharply with that obtained from a single injection of OX-7 in that more than 85% of the glomeruli showed no abnormalities 84 days after the injection. This chronic model, as a result of repeated injections of the antibody, could serve as a potential for further investigation of the mechanisms involved in the development of chronic glomerulonephritis.

Animals

[The use of a metallic stent in 32 patients with benign prostatic hypertrophy. Preliminary results and 3 months of follow-up].

A prospective noncontrolled study of the safety and potential efficacy of the metallic stent was performed on 32 patients with benign prostatic hypertrophy. Mean age was 76.6 years (range, 56-98 years), and mean prostatic volume was 24.2 cm3. The patients were selected on the basis of a quantitative symptom score (QSS), uroflowmetry measurements, and residual urine volume (RU). Nineteen patients had urinary retention and remaining 13 patients had moderate symptoms and signs of prostatism. Placing the stent was successfully done in 31 patients (97%). It took 15 minutes to place the stent using transabdominal and/or endorectal sonography. After 3 months, 27 patients (87%) showed improved QSS. In patients with dysuria, maximum flow rate (MFR) and RU before treatment were 6.9 +/- 1.7 ml/sec and 112.3 +/- 61.8 ml, respectively. After treatment, they improved to 12.3 +/- 2.7 ml/sec and 12.7 +/- 6.7 ml, respectively. On the other hand, all patients who had urinary retention were able to urinate just after treatment, and MFR and RU were 12.9 +/- 3.6 ml/sec and 24.4 +/- 43.3 ml, respectively. Evaluation on the basis of improvement in MFR and reduction in RU showed that the stent was effective in 71% of total patients (22 out of 31 patients), 94% of the patients with urinary retention (17 out of 18 patients). The overall clinical efficacy of this stent was 68% (21 patients). There were no major complications such as urge incontinence and urinary tract infection during follow-up. Although proximal migration of the stent was observed in 6 patients, the stent could be taken out and replaced in 4 patients. From the above results, we conclude that the metallic stent is useful for the treatment of prostatism and urinary retention.

Aged

Mechanism of dialysis-induced hypotension.

Dialysis-induced hypotension, the sharp decrease in blood pressure occurring during hemodialysis, remains one of the most difficult problems associated with hemodialysis even today. However, there is yet no established theory to explain the mechanism triggering dialysis-induced hypotension. This review attempts to offer a consistent and cohesive source of information on the hemodynamics during dialysis-induced hypotension, and then analyzes etiologic factors in such hypotension reported by various investigators. Finally, three hypotheses concerning the mechanism of dialysis-induced hypotension including our own are introduced.

Humans

Effects of excess factor D on early- and late-phase activation of the complement cascade.

The present study was undertaken to examine the effects of excess factor D build-up in the body of end-stage renal disease (ESRD) patients upon the activation of the alternative pathway and the terminal pathway in the fluid phase. First, to clarify the effect of excess factor D on the alternative pathway, purified factor D from an ESRD patient was added to normal serum and the changes in concentrations of C3a-des-Arg and C5a-des-Arg were investigated. The results showed that once the serum factor D level reached a concentration corresponding to 15 micrograms/ml in the serum of the ESRD patient, the C3a-des-Arg and C5a-des-Arg levels had climbed to about 1.7-fold the concentration in normal serum. Next, in order to clarify the effect of excess factor D on the terminal pathway, purified factor D was added to normal serum, and the changes in C5b6 generation were examined. The results indicated that as the factor D level increased in the serum, the C5b6 level rose gradually also; and when the factor D concentration reached 15 micrograms/ml, the C5b6 generation had risen to approximately 1.5-fold the level in normal serum. The present results therefore suggest that factor D build-up in ESRD patients provides a uremic toxin that can cause abnormal activation of the whole complement cascade.

Complement Activating Enzymes

[Renal sodium handling and renal dopaminergic activity in overweight normotensive subjects].

Recently, we reported that the blunted natriuretic ability related to an attenuation of renal dopaminergic activity might play an important role in the hypertensive mechanisms of overweight patients with essential hypertension. On the other hand, the interrelationships between obesity, blood pressure and renal sodium handling in normotensives (NT) have not been clear. The purpose of the present study is to reveal the role of renal dopaminergic activity on renal sodium handling in overweight NT. The study consisted of 52 hospitalized NT receiving a regular diet containing 200mEq of sodium, 75mEq of potassium, 2400kcal/day, who were divided into two groups of 31 non-obese (NNT) and 21 obese (ONT) subjects. NNT was categorized as the body mass index (BMI) less than, and ONT as the BMI equal to or more than, 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance. During the clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) and urinary excretion of free dopamine (uDA) were determined. There were no significant differences in age, HR, Ccr or UNaV between the two groups. Higher MAP and lower FENa) were observed in ONT than in NNT, but the differences in these parameters were not statistically significant. However, FENa in ONT was significantly lower than in MAP-and Ccr-matched NNT. In addition, FENa correlated negatively with BMI in ONT, unlike in NNT. MAP was correlated positively with FENa, and a similar tendency was found between MAP and FEP in NNT, but not in ONT. On the other hand, there was no significant correlation between BMI and uDA in either NNT or ONT. This result was different from our previous data in patients with essential hypertension (EHT) in which BMI correlated with uDA positively in non-obese EHT and negatively in obese EHT. These findings suggest that blunted natriuretic ability may exist in ONT, and the role of renal dopaminergic activity related to the attenuated natriuretic ability in ONT may be less important than in obese EHT.

Adult

[The coefficient of variation of RR intervals (CVRR) on electrocardiogram in patients with essential hypertension with reference to aging, hemodynamics and sympatho-adrenomedullary function].

To evaluate the significance of parasympathetic nerve activity in essential hypertension, we measured the coefficients of variation of RR intervals (CVRR) on electrocardiogram and examined the relationships between CVRR and aging, hemodynamics and sympatho-adrenomedullary function in normotensive subjects (NT) and in patients with essential hypertension (EHT). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA), plasma adrenaline concentration (pAd) and CVRR resting in a supine position were simultaneously measured in 37 NT (33.8 +/- 2.0 years) and 47 mild-to-moderate EHT (51.3 +/- 1.5 years). In both NT and EHT, significantly negative correlations between CVRR and age (NT: r = -0.54, p less than 0.001, EHT: r = -0.41, p less than 0.005) were observed, however, CVRR correlated with neither MAP, HR nor pAd. CVRR tended to correlate negatively with pNA (r = -0.27, p less than 0.1) in NT, unlike in EHT. The mean value of CVRR in EHT (n = 10, age: 38.3 +/- 1.6 years, CVRR: 3.61 +/- 0.37%) was significantly (p less than 0.005) lower than in age-matched NT (n = 10, age: 38.3 +/- 2.5 years, CVRR: 5.76 +/- 0.45%). These results indicate that the parasympathetic tone suggested by CVRR may be related to aging and sympathetic nerve activity, and that parasympathetic function might be impaired in EHT.

Adolescent

[Shy-Drager syndrome: its autonomic function, alpha 2 receptor density and mechanism of postprandial hypotension].

The autonomic function, platelet alpha 2 receptor (alpha 2R) density, and mechanism of postprandial hypotension were examined in a 58-year-old man with Shy-Drager syndrome (SDS). His chief complaints were orthostatic syncope and impotence. His blood pressure was kept within normal limits in a supine position, but severe hypotension and fainting occurred when he assumed an upright posture. There were diminished sweating response to warm stress, abnormal pupil reactions to drugs, lack of blood pressure elevation at phase IV during the Valsalva maneuver, and a lack of pressor response to hyperventilation and cold stress. The plasma norepinephrine levels (pNE) were very low in a supine position at rest and in a head-up tilt position. Severe blood pressure fall (hypotension) associated with a lack of pNE elevation occurred during an oral glucose tolerance test (oGTT). Platelet alpha 2R density increased and the pressor response to infused norepinephrine (NE-R) was pronounced. The heart rate response to injected atropine was clearly attenuated. The coefficient of the R-R interval variation in the ECG (CVRR), which may reflect parasympathetic activity, was markedly low at rest. In addition, a decrease in a head-up tilt position and increase during oGTT also resolved. These results indicate that a dysfunction of the parasympathetic and sympathetic nervous systems and the up-regulation in the alpha 2R system that leads to an increase in alpha 2R density in SDS are involved in this disease and that the mechanism of postprandial hypotension in SDS may be different from that in normal elderly subjects.

Atropine

[Correlations between the coefficient of variation of RR intervals and sympathetic nerve activity following superior tilting in normotensive subjects and in patients with essential hypertension].

The relationship between changes in sympathetic nerve activity and those in parasympathetic tone with a change in position was investigated in patients with essential hypertension using the coefficient of variation of RR intervals on electrocardiograms (CVRR). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA) and CVRR were measured in a supine position at rest and 20 min after having the head tilted 60 degrees superiorly in 10 normotensives (NT: 51.9 +/- 3.0 yrs) and 7 essential hypertensive patients (EHT: 51.0 +/- 2.8 yrs). After changing the position, CVRR decreased significantly in the NT, but not in the EHT; whereas, significant increases of both HR and pNA without significant changes in MAP were shown in both groups. A significant negative correlation between percentage changes in CVRR (% delta CVRR) and pNA (% delta pNA) were observed in the NT, but not in the EHT. However, there was no relationship of % delta CVRR to % delta MAP or to % delta HR in either group. It was suggested from the changes in CVRR that suppression of the parasympathetic tone, which occurs in the NT group corresponding to sympathetic augmentation to present a decrease in blood pressure with a change in position, may be impaired in the EHT group.

Blood Pressure

The role of Na,K-ATPase inhibitor on pressor responsiveness in patients with benign essential hypertension.

To clarify the role of Na,K-ATPase inhibitor in the enhanced pressor response to infused noradrenaline (NA-R) in patients with benign essential hypertension (EHT), NA-R, plasma noradrenaline concentration (PNA), and blood ionized calcium (Ca2+) were investigated before and after intravenous injection of ouabain in 15 normotensive subjects (NT) and 13 EHT. NA-R was enhanced by ouabain in both NT and EHT. The augmentation of NA-R following ouabain injection (delta NA-R) and % delta NA-R were significantly lower in EHT than in NT. Following ouabain injection, no significant change in PNA and blood Ca2+ was observed in both NT and EHT. NA-R negatively correlated with PNA and blood Ca2+, which were estimated just prior to noradrenaline infusion, before ouabain injection as well as after. After ouabain, the regression line between NA-R and PNA or blood Ca2+ shifted toward higher NA-R level in NT, unlike in EHT. These results suggest that an exogenous Na,K-ATPase inhibitor brings about a blunted enhancement of NA-R in EHT consistent with the presence of an endogenous Na,K-ATPase inhibitor in EHT.

Adult

Effectiveness of push/pull hemodiafiltration using large-pore membrane for shoulder joint pain in long-term dialysis patients.

Long-term hemodialysis (HD) patients complaining of shoulder joint pain were treated by HD and by push/pull HDF using high-flux synthetic membranes with large pores (Asahi PAN 20CX2) for 2 weeks. The results showed no significant difference in Kt/Vurea between HD and push/pull HDF. Nevertheless, reduction of the plasma beta 2-microglobulin was greater during push/pull HDF than during HD. These findings can be explained by far more convective flux in push/pull HDF than in HD: nearly 30 L during push/pull HDF vs. 3 L during HD. In the present study, there was no alleviation of the shoulder joint pain during HD treatment, whereas marked relief of the symptom was found during push/pull HDF treatment. Since the two treatment modalities differ simply in their efficiency in removing larger molecular weight substances, the joint pain alleviation effected by push/pull HDF could well be ascribed to elimination of an unknown larger molecular weight substance causing this symptom. However, a considerable amount of beta 2-microglobulin was removed both by HD and push/pull HDF. Therefore, the substance causing the joint pain might be larger than beta 2-microglobulin.

Female

Beta-2-microglobulin generation rate and clearance rate in maintenance hemodialysis patients.

We analyzed the rebound pattern of plasma beta 2-microglobulin (beta 2-m) concentration from 4 h after completion of hemodiafiltration until the start of the next treatment according to the one-pool beta 2-m kinetic model so as to determine beta 2-m generation rate and whole-body beta 2-m clearance. Next, we obtained the whole renal beta 2-m clearance as the product of renal creatinine clearance and the glomerular sieving coefficient of beta 2-m. Then, extrarenal beta 2-m clearance was calculated as the difference between whole-body beta 2-m clearance and whole renal beta 2-m clearance and renal beta 2-m clearance due to tubular absorption was taken to be the difference between whole renal beta 2-m clearance and renal beta 2-m clearance due to urinary excretion. The results showed that the higher the patients' plasma beta 2-m concentration was, the lower was the whole-body beta 2-m clearance. Moreover, in the present study, an inverse correlation was found between the following respective factors: plasma beta 2-m concentration and whole renal beta 2-m clearance; plasma concentration and renal clearance due to tubular absorption; plasma concentration and renal clearance due to urinary excretion. However, there was no correlation between plasma beta 2-m concentration and extrarenal beta 2-m clearance. The findings indicate that the variation of plasma beta 2-m concentration with the individual patient is solely attributable to the variation in residual renal function in terms of beta 2-m elimination.

Adult

Comparison of various treatment modes in terms of beta 2-microglobulin removal: hemodialysis, hemofiltration, and push/pull HDF.

The beta 2-microglobulin clearance increased as the convective transport was added during hemodialysis to perform hemodiafiltration (HDF), suggesting that a convective transport type artificial kidney is more effective for beta 2-microglobulin removal. Actually, the decrease in the plasma beta 2-microglobulin level per treatment was more pronounced in hemofiltration and push/pull HDF than in hemodialysis. In the present study, no significant fluctuation in the pretreatment level of beta 2-microglobulin was shown by serial treatment by hemodialysis, whereas an obvious decreasing trend of it was indicated in serial treatment of either push/pull HDF or hemofiltration. Moreover, our study indicated that the ratio of posttreatment beta 2-microglobulin level in relation to its pretreatment level increases as the treatment by hemofiltration or push/pull HDF is repeated.

Amyloid

Effects of L-carnitine administration on short-chain fatty acid (acetic acid) and long-chain fatty acid metabolism during hemodialysis.

The purpose of the study is to investigate the effects of L-carnitine on the exogenous acetate metabolism during hemodialysis together with the triglyceride and free fatty acid metabolism. Sixteen chronic renal failure patients on acetate dialysis were orally administered 1,200 mg of L-carnitine chloride per day for 12 weeks. Plasma triglyceride concentrations at 30 and 60 min following initiation of hemodialysis were significantly lower than before hemodialysis, while the plasma concentrations of free fatty acid at the same points into hemodialysis were significantly higher than before hemodialysis, whether L-carnitine chloride was being given or not. This is attributed to the enhanced degradation of triglyceride and the increased generation of the free fatty acid with heparin administration during hemodialysis. The L-carnitine chloride treatment did not affect the plasma triglyceride concentrations at 30 and 60 min into hemodialysis, whereas the free fatty acid concentrations at the same points into hemodialysis were significantly lower after L-carnitine chloride administration commenced than before it. This is attributed to the fact that fatty acid oxidation was enhanced following the L-carnitine chloride treatment. Compared to before the drug administration, the whole body clearance of exogenous acetate was significantly increased after the drug was given, and the plasma acetate level during hemodialysis fell accordingly. This is attributed to the fact that with L-carnitine chloride administration, the amount of accumulated acyl-CoA in the cytosol decreased and consequently the citrate cycle function increased.

Acetates

Attenuated renal production of dopamine in patients with low renin essential hypertension.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Adolescent

Interrelationship between plasma ionized calcium, plasma noradrenaline (NA) and pressor response to infused NA in patients with essential hypertension.

We evaluated the role of calcium metabolism on plasma noradrenaline concentration (pNA) and pressor response to infused noradrenaline (NA-R) in patients with mild-to-moderate essential hypertension (EHT). Mean arterial pressure (MAP), plasma ionized calcium (pCa2+), and NA-R were measured at the basal condition in 17 EHT and after the administration of calcium antagonist, nifedipine (60mg, t.i.d., for 4 weeks) in 9 EHT. Under basal condition, pCa2+ correlated positively with pNA and negatively with NA-R in EHT. Following nifedipine therapy, persistent reductions of MAP and NA-R, a transient increase in pNA and a sustained increase of urinary excretion of calcium were observed. On the other hand, no significant change in pCa2+ was found during the therapy. Percent change in MAP following 4 weeks of nifedipine administration correlated positively with pCa2+ and pNA before the therapy. In addition, change in NA-R by nifedipine therapy correlated positively with the basal values of pCa2+ and PNA and negatively with NA-R before the treatment. A significant negative correlation between NA-R and pNA was observed following nifedipine therapy as well as the basal state. However, the slope of the regression line between NA-R and pNA decreased significantly after the treatment as compared to the basal state. These results suggest that calcium metabolism relating sympathetic nerve activity and NA-R may contribute to the hypertensive mechanism in EHT. The hypotensive effects of nifedipine may be caused partly by the attenuation of sympathetic nerve activity and NA-R.

Blood Pressure

[A case of bilateral testicular tumor].

A case of bilateral germ cell tumor of the testis is reported. In 1988, a 36-year-old male presented with painless swelling of left scrotal contents. Right orchiectomy and retroperitoneal lymph node dissection for embryonal carcinoma had been performed 5 years earlier. Left orchiectomy was performed and its histological finding was seminoma and embryonal carcinoma. Evaluations including CT scan and Ga scintigraphy revealed no metastasis. Postoperatively, the patient was treated with PVB therapy. Previous reports of bilateral germ cell testicular tumor were reviewed, and the age distribution, interval, and histological classification of these cases are discussed.

Adult

[A case of bowenoid papulosis of the penis].

A 44-year-old man, who was seen for further examination of macroscopic hematuria, was found to have black eruptions on the penis and the scrotum. These eruptions appeared benign clinically, but on histological examination they showed the features of Bowen's disease. These eruptions were diagnosed as Bowenoid papulosis and were successfully treated with 5-FU cream. Twenty five cases of Bowenoid papulosis observed in men have been reported in Japan. Although Bowenoid papulosis is characterized by the histopathologic conditions of Bowen's disease, the lesions of Bowenoid papulosis differ clinically from those of Bowen's disease in several respects: onset at earlier average age, multiplicity of lesion, lack of associated symptoms, smaller size of the lesion, clinical morphologic features and possible spontaneous regression.

Adult