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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 523 records · Page 29Linked to original sources
PubMed1985

Clinical application of monoclonal antibodies to small cell lung cancer.

Monoclonal antibodies to small cell lung cancer (SCLC) were produced by fusion of P3X63/AgU1 mouse myeloma cells with spleen cells from BALB/c mice immunized against intact cells of SCLC tumors grown in BALB/c athymic nude mice. The antibody TFS-2 demonstrated "pancarcinoma" reactivity showing binding to non-small cell lung cancer (NSCLC) and carcinomas derived from other organs such as stomach, pancreas, and colon. This antibody failed to react with a variety of normal tissues including lung, bone marrow, spleen, stomach, colon, and pancreas. TFS-2 showed complement-mediated cytolysis of target cells. TFS-2 had no significant effects on hematopoietic stem cells. This antibody will serve as a powerful tool for the in vitro removal of tumor cells from bone marrow, thus facilitating high-dose chemotherapy of SCLC with autologous bone marrow transplantation. In contrast, TFS-4 monoclonal antibody reacted specifically with SCLC but not with NSCLS tumors. This antibody can distinguish SCLC from NSCLC tumors in histologic diagnosis at transbronchial biopsy, and in cytological identification of tumor cells in malignant effusion, and in infiltrated bone marrow. Radiolabeled TSF-4 specifically accumulated into SCLC tumors that were implanted subcutaneously into athymic nude mice. Thus, the antibody will be useful not only for diagnosis of lung cancer but also for targeting anti-tumor agents.

Animals↗
PubMed1985

[Clinical experience in renal transplantation].

In Shiga Prefecture, 378 chronic renal failure patients were registered at the end of 1981. In 1982, the Kidney Transplantation Group, composed of the department of Urology and the 1st division of Surgery, was organized in our hospital and 10 living related renal transplantations and 8 cadaver renal transplantations were performed between July 1982 and October 1984. As immunosuppressants, azathioprine, mizoribine, cyclosporine, prednisolone, methylprednisolone and ALG were used. Azathioprine was used mainly for living transplantation and cyclosporine mainly for cadaver transplantation. ALG was used only for the initial 3 living transplantations. Mizoribine was sometimes used in combination with azathioprine to reduce the dose of azathioprine and reduce its severe side effects. Seven episodes of acute rejection were experienced and all episodes were remitted by methylprednisolone pulse therapy. There were 20 major post-transplant complications in 13 recipients and among them 2 pulmonary infections were fetal (1 from aspergillus infection and 1 from cytomegalovirus infection). The 10 living related kidney transplantation recipients are all well and none have undergone hemodialysis. Three of the 8 cadaver renal transplantation are well without hemodialysis. One patient could not obtain diuresis. In addition to our experience of renal transplantation, the preoperative scheduled blood transfusion with combination of azathioprine administration, was briefly discussed.

Adolescent↗
PubMed1985

Reduced hepatic clearance of propranolol induced by chronic carbon tetrachloride treatment in rats.

Effect of liver injury induced by chronic treatment with carbon tetrachloride for 1 to 4 months on hepatic clearance of propranolol was investigated in male Wistar rats. Plasma propranolol level after i.v. and p.o. dosing (1.0 mg/kg) was always higher in the rats which were treated for 2 and 4 months than in control (sham-injected) rats. The chronic treatment reduced hepatic clearance of propranolol significantly, yielding only approximately 30 to 50% of the control clearance value. Distribution volume of this drug was also significantly reduced by the chronic treatment but seemed to be less sensitive to the treatment than the hepatic clearance. Accordingly, the elimination rate constant was decreased slightly in the rats treated longer than 2 months. The chronic treatment for 2 and 4 months also reduced intrinsic hepatic clearance substantially. The hepatic clearance estimated for both these control and chronically treated rats was significantly dependent on the liver blood flow. Furthermore, propranolol was eliminated much more slowly in the injured liver of the rat which was treated for 2 or 4 months than in the control liver when perfused in in vitro technique. It is, therefore, suggested that the metabolic dysfunction induced by chronic treatment with carbon tetrachloride may be directly related to substantial changes in anatomical arrangement of the hepatic circulation (portasystemic shunting), which may be due to a fibrosis of the tissue.

Animals↗
PubMed1985

[Clinical study of children with sterile vesicoureteral reflux].

A clinical study of 5 children (3 boys and 2 girls) with primary sterile vesicoureteral reflux is presented. Their ages ranged from 8 to 11 years old. During the same period, we saw 14 children (6 boys and 8 girls) with primary infected vesicoureteral reflux. Their ages ranged from 1 to 13 years old. There were several distinctions between these two reflux groups. Manifestations of the infected reflux group were mainly fever attacks, while those of the sterile reflux group were hypertension, proteinuria and enuresis. The duration from onset to diagnosis was longer in the sterile reflux group because their manifestations did not appear to be severe especially in cases of enuresis. The grade of reflux tended to be more advanced in sterile reflux group. The renal scarrings were identified in all involved kidneys in the sterile reflux, while in 65.2% in the infected reflux group. It is difficult to detect sterile reflux early because the manifestations are not related with urinary tract infection. Recently, reflux nephropathy is a subject of frequent discussion and end stage of reflux nephropathy has been sporadically reported. Therefore, an effort should be made for early detection of sterile reflux. Based on our experiences as well as review of the literature, possible clues to detect sterile reflux are abnormal voiding patterns, such as nocturnal enuresis, incontinence, frequency and so on.

Adolescent↗
PubMed1984

Difference in hepatic uptake kinetics of aspirin and salicylamide in rats.

Immediately after intraportal administration to rats, the ratio of liver to plasma concentrations for total aspirin was close to unity, whereas that for total salicylamide ranged from about 3 to 7. The hepatic accumulation of salicylamide appeared to be capacity-limited because the ratio decreased with increases in the dose. In vitro experiments with isolated hepatocytes indicated that aspirin was slowly transported into the hepatocytes by an apparently linear process only, while salicylamide was taken up very rapidly by both saturable and apparently linear transport processes. The cell to medium concentration ratio estimated for the initially net transported component of the unchanged drug was significantly larger with salicylamide, which give ratios from 3.5 to 19, than with aspirin which gave an almost constant value lower than 2 despite wide variations in the initial concentration. For the capacity-limited uptake process of salicylamide, the kinetic parameters were estimated as Vmax = 0.325 nmole X (mg cellular protein)-1 X sec-1 and Km = 201 microM. Among various metabolic inhibitors, 2,4-dinitrophenol (50 microM) inhibited the uptake of salicylamide most extensively. The present comparison of the in vivo and in vitro data for aspirin with those for salicylamide confirmed the previously reported difference in the hepatic first-pass effect of these two drugs.

2,4-Dinitrophenol↗
PubMed1984

Sarcoid granulomas metabolize 25-hydroxyvitamin D3 in vitro.

Sarcoid granulomas metabolized 25-hydroxyvitamin D3 to two unidentified metabolites during in vitro incubation. A two-step high pressure liquid chromatography system revealed two unique elution positions of these sarcoid-derived metabolites that exactly comigrated with the elution positions of 5(Z)-19-nor-10-oxo-25(OH)D3 and 5(E)-19-nor-10-oxo-25(OH)D3, respectively. These unique metabolites did not bind specifically to a protein receptor for 1,25(OH)2D3.

Biopsy↗
PubMed1984

Effect of vitamin E on platelet aggregation in diabetes mellitus.

Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E in platelets was significantly reduced in diabetics compared with age matched controls. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane production and aggregation which relate to the development of vascular complications.

Blood Platelets↗
PubMed1984

Development of morphologic heterogeneity of hepatocyte mitochondria in the mouse.

The ultrastructure of mitochondria in periportal and perihepatic hepatocytes from newborn, 5-, 10-, and 20-day-old, and adult male ddY mice was analyzed by quantitative electron microscopy. In newborn and 5- and 10-day-old animals, the axial ratio (length per diameter), surface to volume ratio (area of the outer membrane per unit mitochondrial volume), and volume density were not significantly different between periportal and perihepatic cells. In 20-day-old and adult animals, the surface to volume ratio was greater in perihepatic cells than periportal cells, and the volume density was greater in periportal cells than perihepatic cells. The axial ratio became greater in perihepatic cells than periportal cells in adult animals. However, there were no differences in the surface density of the outer membrane, and of the inner membrane and cristae between the cells of both zones in all age groups examined. When the data were expressed as volume and area per cell, the patterns of subacinar distribution and age-related changes differed from the patterns seen in the volume and surface density data mainly in adult animals. This difference was generally caused by the marked increase in hepatocyte volume between 20 days of age and adulthood, especially in perihepatic cells. The results show that differences between mitochondria in periportal cells and those in perihepatic cells in the shape (the axial and surface to volume ratios), volume density, and area of the outer membrane per cell, evident in adult animals, are not present in newborn animals but arise during postnatal development.

Animals↗
PubMed1984

Receptor-mediated endocytosis of glucagon in isolated mouse hepatocytes.

The binding of glucagon to the cell surface and the pathway of intracellular transport of the hormone in isolated mouse hepatocytes were studied by autoradiography, colloidal gold-labeled glucagon (Au-glucagon), and biochemical methods. In cells incubated with 1251-glucagon at 4 degrees C, the label was mainly localized to the plasma membrane even after 60 min of incubation. At 20 degrees C, the labeled ligand was internalized by the cells and the amount of internalized ligand increased with time of incubation. At 37 degrees C, the ligand was rapidly internalized and found to be associated with coated or uncoated vesicles. Au-glucagon experiments revealed clearly the process of internalization of glucagon. Au-glucagon bound to the plasma membrane was transported to coated regions and then internalized into vesicles via coated pits. Biochemical results supported these findings from autoradiography and Au-glucagon experiments. Thus, glucagon is internalized by hepatocytes via receptor-mediated endocytosis.

Animals↗
PubMed1984

pKa determination of verapamil by liquid-liquid partition.

The pKa of verapamil was determined by measuring the partition coefficient of verapamil between n-heptane and aqueous buffer solution at various pH values. The magnitude of the effects of ionic strength or temperature on the pKa of verapamil was in agreement with those reported previously. The estimated pKa of verapamil in human plasma was 8.75. The pKa of 2,4,6-trimethylpyridine measured by means of the present partition method was in good agreement with that determined by UV spectrophotometry.

Hydrogen-Ion Concentration↗
PubMed1984

Visual fixation of caloric nystagmus with special reference to a new index.

The effects of visual fixation upon caloric nystagmus were computed in each parameter as a measure. The percentage reduction established with slow-phase velocity best distinguished normal from abnormal visual fixation at the line of 60%. However, if a +/- 5% safety margin is taken into account, 11 of 176 ears showed false-negatives. The number of nystagmus beats in normals decreased markedly during the period of fixation. In abnormals, the number of nystagmus beats increased definitely during the fixation period. Based on this fact, the product of slow-phase velocity multiplied by the number of nystagmus beats was assessed as the fixation-suppression index. As a result, 11 ears showing false-negative slow-phase velocity decreased to 2 ears. Thus, this modified fixation-suppression index seems to be an appropriate parameter to separate normal from abnormal fixation-suppression of caloric nystagmus.

Adult↗
PubMed1984

Salivary excretion of urea in dogs.

The salivary excretion of urea was investigated by collecting parotid saliva (Pr) and mandibular-sublingual saliva (MS) separately in beagle dogs. (1) After intravenous administration of urea (1.5 g/kg), urea concentrations in both Pr and MS were well correlated to but were lower than those in plasma. Urea concentrations in MS were significantly lower than those in Pr (p less than 0.05), indicating that there was glandular difference in salivary excretion of urea. (2) This glandular difference was not explained by Matin's equation, even if all variation factors in this equation were considered. (3) At relatively low salivary flow rates, the increase in saliva/plasma urea concentration ratio (S/P ratio) for both Pr and MS was found in the experiments for endogenous urea. (4) At relatively low salivary flow rates, glandular difference was observed in the S/P ratios of sodium ion. (5) Salivary clearance of urea was highly dependent on salivary flow rate under stimulated condition for salivation, and mean value of the salivary clearance of urea was about 20% of its total body clearance.

Absorption↗
PubMed1984

Effect of hypothermia and ether anesthesia on the dispositions of creatinine and urea in mice.

Hypothermal mice were used under the anesthetized condition with ether to clarify the effect of diminished blood circulation on the dispositions of creatinine and urea which are considered to pass through the water-filled pores of biological membranes easily. The total body clearance of each chemical was considerably decreased in hypothermal mice compared with normal mice. This was considered to be caused by the decrease of glomerular filtration rate. The whole-body autoradiograms obtained following intravenous administration of 14C-urea and the rate of muscular blood flow showed that the transfer of urea from blood to muscle was apparently delayed by the decrease of muscular blood flow rate. However, the transfer of creatinine to muscle was not influenced by the change of muscular blood flow rate. This difference between creatinine and urea might be related to the higher permeability of muscular cell membrane to urea than to creatinine.

Anesthesia↗
PubMed1984

Disposition of salicylic acid in analbuminemic rats.

To clarify the role of albumin in the dispositions of drugs by in vivo experiment, analbuminemic rats were used and plasma-level analyses and whole-body autoradiography following intravenous administration of 14C-salicylic acid were carried out. The distribution volume of salicylic acid in analbuminemic rats (650 +/- 33 ml/kg) was remarkably larger than that in normal rats (180 +/- 3 ml/kg) (p less than 0.01). Whole-body autoradiograms demonstrated that transfer of salicylic acid from the blood to the liver, muscle and brain, especially to the liver, may be increased in analbuminemic rats. The increased distribution may be explained by the lack of plasma albumin, since the distribution of salicylic acid depends in part on plasma albumin binding. The total body clearance of salicylic acid in analbuminemic rats (12.2 +/- 1.4 ml/min/kg) was about 3.2 times that in normal rats (3.8 +/- 0.1 ml/min/kg) (p less than 0.01), suggesting that metabolic clearance and/or renal clearance is enhanced in analbuminemic rats. Increased extraction by the liver and/or the kidney due to increased free fraction in total (bound and unbound) plasma salicylic acid assumed to be responsible for this result.

Animals↗