Biomedical subjects
Publications and source records attributed to T Baba.
Culture media from human fibroblasts pretreated with culture media from activated normal human monocytes partially inhibited the activation of monocytes. Molecular weight of the major inhibitory factor in these culture media was very close to that of human fibroblast interferon. However, an immunoadsorption experiment using monoclonal antibody to human fibroblast interferon failed to adsorb this inhibitory factor.
A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.
The possibility of an impaired hepatic de-esterification of enalapril to enalaprilat due to hepatic dysfunction was assessed in seven patients with compensated liver cirrhosis and 10 normal control subjects. The peak serum concentration and time to the peak serum concentration of enalaprilat, as well as the suppression of serum angiotensin converting enzyme activity, following a single oral dose of enalapril maleate (10 mg) were not different in the two groups. The elimination half-life of enalaprilat was related to renal function. The results suggest that hepatic biotransformation of the drug may not be disturbed in a clinically significant manner in patients with moderate hepatic dysfunction due to compensated liver cirrhosis.
We isolated a temperate phage which carried the cytotoxin gene (ctx) from a cytotoxin (CTX)-producing Pseudomonas aeruginosa strain, PA158. The phage, phi CTX, had a head with a hexagonal outline and a contractile tail with tail fibres. The phage genome was a linear double-stranded 35.5 kb DNA with single-stranded cohesive ends (cos). The attP, cos and ctx genes were all located very close to one another within a 2.3 kb segment on the phage genome in the order given (in the circular form). phi CTX converted CTX non-producing P. aeruginosa strains into CTX producers. A single copy of phi CTX DNA was integrated at the same site on the host chromosome (attB) in every lysogen, including PA158. However, the amount of CTX produced in these lysogens varied from strain to strain and was less than that in PA158.
A new system for selective low density lipoprotein apheresis with an automated regenerating column using dextran-sulfate (DS) as ligand was evaluated for six months in a 13-year-old boy homozygous for familial hypercholesterolemia. Two columns each containing 150 ml of DS cellulose were alternately used after rinsing with a regenerating solution. The patient could well tolerate the volume in the system. The values of plasma total cholesterol decreased by 79.4 +/- 4.9% of the pretreatment levels after a total of 5l plasma apheresis, while those of high density lipoprotein cholesterol did not change. Although the values of CH50 decreased, no adverse reaction was seen during the period of treatment. It was concluded that the present apheresis system was highly efficacious and safe for children homozygous for the mutant LDL receptor gene.
An extreme dwarf 10-year-old boy was described. His clinical features resemble those of isolated GH deficiency type 1A, but the Southern blot analysis showed no gross deletion in the GH structural gene. Endocrinological evaluations showed severe GH and PRL deficiencies, and mild TSH deficiency. The simultaneous deficiencies of anterior pituitary hormones in our patient resemble those of the Snell and Ames dwarf mice and suggest a common etiology. The evolutionary and embryological similarities between GH and PRL imply that mutations at a gene which controls GH and PRL production in somatotropes and lactotropes or at a gene of which product affects the embryological development from a common ancestral cell in the anterior pituitary gland may be a primary defect in our patient.
Mutations which cause poor growth at a low temperature, which affect aspects of protein secretion, and which map in or around secY (prlA) were characterized. The prlA1012 mutant, previously shown to suppress a secA mutation, proved to have a wild-type secY gene, indicating that this mutation cannot be taken as genetic evidence for the secA-secY interaction. Two cold-sensitive mutants, the secY39 and secY40 mutants, which had been selected by their ability to enhance secA expression, contained single-amino-acid alterations in the same cytoplasmic domain of the SecY protein. Protein export in vivo was partially slowed down by the secY39 mutation at 37 to 39 degrees C, and the retardation was immediately and strikingly enhanced upon exposure to nonpermissive temperatures (15 to 23 degrees C). The rate of posttranslational translocation of the precursor to the OmpA protein (pro-OmpA protein) into wild-type membrane vesicles in vitro was only slightly affected by reaction temperatures ranging from 37 to 15 degrees C, and about 65% of OmpA was eventually sequestered at both temperatures. Membrane vesicles from the secY39 mutant were much less active in supporting pro-OmpA translocation even at 37 degrees C, at which about 20% sequestration was attained. At 15 degrees C, the activity of the mutant membrane decreased further. The rapid temperature response in vivo and the impaired in vitro translocation activity at low temperatures with the secY39 mutant support the notion that SecY, a membrane-embedded secretion factor, participates in protein translocation across the bacterial cytoplasmic membrane.
The mode of inactivation of cis-diamminedichloroplatinum (II) (DDP) in the bloodstream by sodium thiosulfate (STS) was investigated experimentally and clinically by a bioassay system using the phytohemagglutinin stimulation assay of human peripheral blood mononuclear cells. Active DDP in the plasma of dogs after 3 mg/kg of DDP injection, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. In 6 patients with hepatic malignancies who were treated with hepatic artery infusion of 3 mg/kg DDP and systemic STS, active DDP in the plasma was not detectable in the concurrent presence of STS at molar ratios of more than 500. Severe DDP toxicity in these patients was completely protected. The results indicate that an inactivation of DDP in the bloodstream after DDP injection and, further, an effective protection against DDP toxicity can be achieved by the concurrent presence of STS at molar ratios of more than 500 in the plasma of these patients.
The pharmacokinetics of intraperitoneal cisplatin (DDP) administered with simultaneous intravenous sodium thiosulfate (STS) were investigated by a bioassay system using the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM). Active DDP in the plasma, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. However, the peak level of active DDP in the peritoneal cavity was not significantly decreased. Fourteen patients with intraperitoneal carcinoma were treated with intracavitary DDP chemotherapy in combination with STS in this setting. Of 8 patients with malignant ascites who were evaluable for response, 4 patients experienced complete disappearance of ascites and the remaining 4 patients responded with apparent decrease in the volume of their ascites. No serious drug-associated toxicity was encountered.
Expression of actin was examined in a cultured rat embryonic cell line 3Y1 and transformed cell lines that originated from 3Y1. An alpha-actin in addition to cytoplasmic beta- and gamma-actins was detected in 3Y1 by two-dimensional gel electrophoresis. This alpha-actin was hardly detected at all in the transformants induced by Rous sarcoma virus, v-H-ras oncogene or adenovirus type 12, while the alpha-actin was retained in the transformed cell lines induced by N-methyl-N'-nitro-N-nitrosoguanidine or in SV40, which are cell lines of relatively low malignancy. Western and Northern blot analyses established that this alpha-actin was a smooth muscle alpha-isoform. An immunofluorescence study revealed that smooth muscle alpha-actin in 3Y1 cells is present in stress fibers. Thus, smooth muscle alpha-actin is also a component of actin stress fibers, as beta- and gamma-actins are in 3Y1 cells. An alteration in the expression of this actin isoform may be related to phenotypical changes accompanying transformation.
The relationship between blood pressure and progression of nephropathy was studied (the mean follow-up period of 32.6 +/- 17.9 (S.D.) months in 20 Type 2 (non-insulin-dependent) diabetic patients with clinical nephropathy (proteinuria greater than 0.5 g/day) and preserved renal function (serum creatinine level less than 150 mumol/liter). Fifteen hypertensive patients under antihypertensive treatment were divided into 2 groups: those with the mean diastolic blood pressure greater than or equal to 90 mmHg and/or the mean systolic blood pressure greater than or equal to 150 mmHg during the follow-up period were designated as Group A (n = 6) and the remainders as Group B (n = 9). Five normotensive patients without any anti-hypertensive treatment throughout the follow-up period served as a control group (Group C). The decline rate in GFR was significantly greater (p less than 0.05) in Group A (1.15 +/- 0.39 (S.E.) ml/min/month) than those in Groups B (0.33 +/- 0.08 ml/min/month) and C (0.40 +/- 0.09 ml/min/month), respectively. The decline rate in GFR showed significant positive correlations both with systolic (rS = 0.553, p less than 0.05) and diastolic (rS = 0.493, p less than 0.05) blood pressures in the 15 hypertensive patients. The age, initial glomerular filtration rate, duration of diabetes and mean HbA1c level during the observation period were comparable in Groups A, B and C, respectively. The results indicate that an uncontrolled hypertension is associated with a rapid progression of kidney impairment in Type 2 diabetic patients with overt nephropathy, as has been suggested in Type 1 (insulin-dependent) diabetic patients.
We investigated whether medial arterial calcification (MAC) impairs O2 supply to the exercising foot in diabetic patients with foot lesions. Transcutaneous O2 tension (tcPO2) was monitored at the dorsum of the foot before and after bicycle exercise in 11 diabetic patients with peripheral ischemic vascular disease (PIVD) with or without concomitant existence of MAC, 10 patients with MAC but without PIVD, 10 diabetic control subjects, and 6 nondiabetic control subjects. The mean preexercise tcPO2 level was comparable in these four groups. However, tcPO2 decreased significantly with exercise in feet with PIVD (mean +/- SE -17.9 +/- 2.7%, P less than 0.01, n = 11), regardless of presence or absence of vascular calcification. On the other hand, the value increased significantly with exercise in feet with MAC but without PIVD (21.2 +/- 3.5%, P less than 0.01, n = 10) and in those of diabetic control subjects (14.9 +/- 3.6%, P less than 0.01), respectively. The tcPO2 remained unchanged in the feet of nondiabetic control subjects (1.7 +/- 1.1%). The results suggest that MAC is not associated with reduced O2 supply to the exercising foot in diabetic patients.
The effect of intravenous and intracarotid administration of adenosine triphosphate (ATP) on the regional blood flow of glioma patients has been examined by means of positron emission tomography. Intracarotid administration of ATP at a dose of 0.52 to 1.3 micrograms/kg/min selectively increased the blood flow in the tumor by 26.2% +/- 10.5% (mean +/- standard deviation). The side effects observed were tolerable. In contrast, intravenous administration of ATP failed to increase tumor blood flow. It is suggested that intracarotid administration of ATP may serve to selectively enhance the delivery of anticancer agents to malignant brain tumors.
To clarify the influence of Transcatheter Arterial Embolization (TAE) on the stomach, endoscopic examination was carried out before and after TAE. Forty-six TAE were performed in 27 patients with primary hepatoma. New gastric lesions, erosions and ulcers, were developed in 25 of 46 TAE. There was no significant relationship between the incidence of the lesions in the cases with esophageal varices (15/24) and the cases without (10/22) and there was no significant relationship between the incidence of the lesions after the first TAE (12/22) and after the second TAE (5/14). Period between the first and the second TAE had no statistical influence on the lesions after the second TAE. Hepatic functions (Child's classification; Rmax, K, R15 of ICG; serum total protein; serum albumin; total bilirubin; prothrombin time; hepaplastin test) before TAE were not statistically related to the appearance of the gastric lesions following TAE (Table 1). On the other hand, the cases which showed apparent effects of TAE including 0.2 time decrease of AFP had the more gastric lesions (P less than 0.05) (Table 2). The cases with upper abdominal pain after TAE had more gastric lesions (24/38) than the cases without (2/8) (P less than 0.05). But the cases undergone TAE with high possibility of the influx of gelatin sponge pieces, lipiodol or anticancer agents into the supplying vessels for the stomach did not exhibit significant incidence of the lesions (Table 3). Thus, when TAE is followed by a 0.2 time decrease in AFP, it is necessary to pay more attention to the gastric lesions. The prophylactic administration of H2 antagonist before or just after TAE did not seem useful to prevent the gastric lesions. These findings suggest that the influx of gelatin sponge pieces, lipiodol or anticancer agents to the stomach does not always cause gastric ulcer or erosion.
It is known that PG is often associated with AOS. However, there have been no reports on long term follow-up of PG associated with AOS. We experienced a case of a 16 year old female who suffered from PG and AOS. The onset of both diseases occurred at the same time. On admission, many pustules and ulcers were found on the extremities. There was no finding of vasculitis in histopathological examinations. Development of skin lesions of PG coincided with the progress of AOS. But, AOS was progressive even when the patient was free of skin eruptions. It was concluded that the activity of PG was not always parallel to that of AOS.
The macrophage disappearance reaction (MDR) was induced when muramyl dipeptide (MDP) was injected intraperitoneally into guinea pigs bearing macrophage-rich peritoneal exudate cells. Heparin could inhibit the MDR induced by MDP. In the present study, we tested the effect of the immunosuppressive agent cyclosporine A (CsA) on MDR. The MDR was significantly suppressed in guinea pigs given 20 or 100 mg/kg of CsA, although 5 mg/kg of CsA had no effect. The number of macrophages elicited by liquid paraffin was significantly reduced in guinea pigs given with 20 or 100 mg/kg of CsA, but not in those given 5 mg/kg of CsA. These results indicate that CsA could directly affect macrophages in vivo, through a relatively high dose was required. Cyclosporine A (CsA), a cyclic peptide of 11 amino acids, is a fungal metabolite with potent immunosuppressive properties. Numerous experimental and clinical trials have demonstrated its effectiveness in organ transplantation. It has been suggested that primary target cells of CsA were T-lymphocytes, and macrophages were not directly affected. However, recent studies in an in vitro system have shown that some functions of macrophage are affected by CsA. These include chemotaxis (Drath & Kahan, 1983), interleukin-1 generation (Bunjes et al., 1981), prostaglandin E production (Whisler et al., 1984) and procoagulant activity (Carlsen et al., 1985). However, the effect of CsA on macrophages has not been elucidated in vivo. The macrophage disappearance reaction (MDR) is an in vivo manifestation of cell-mediated immunity and/or delayed type hypersensitivity (Sonozaki et al., 1975). Furthermore, our previous study demonstrated a possibility that MDR was an in vivo manifestation of macrophage activation (Ochiya et al., 1982). Muramyl dipeptide (MDP; N-acetyl-muramyl-L-alanyl-D-isoglutamine), a synthetic analogue of water soluble components of bacterial cell wall peptidoglycans, is known to have the ability to activate macrophages (Nagao et al., 1979). In the present study, attempts were made to induce MDR by MDP and the effect of CsA on the MDR was studied.
The role of the Harderian gland (HG) in the production of immunoglobulin, especially IgA, was investigated. Lacrimal immunoglobulin almost disappeared after surgical removal of the HG and immunoglobulin produced by HG cells was detected in saliva but not in the trachea. Immunoglobulin production occurred in HG cell culture in vitro and it consisted mostly of IgA; the production of IgM and IgG was very low. These findings indicate that lacrimal IgA is produced locally in the HG and lacrimal IgG and IgM are mostly transported from the blood.
We investigated 31 cases of cutaneous malignant lymphoma diagnosed by skin biopsy during about 11 years at the University of Tsukuba Hospital. The specific eruption was occurred in 17.7% of all malignant lymphomas at the hospital. The skin was primarily affected in 5.8% of all malignant lymphomas including Hodgkin disease, and in 6.9% excluding Hodgkin disease. We divided 31 cases into 3 groups; Group A is the primary cutaneous lymphoma, and Group B and C are the secondary cutaneous lymphoma. The skin lesions of Group B share the major part. On the other hand, that of Group C is minimal and transient. The differences between group A/B and group C were the high frequency of epidermotropism. The T cell dominance, the widespread eruption and the variety of the eruptions for one case in Group A/B. Group A differed from group B/C by the specific plaque, and from Group B by the high frequency of Pautrier's microabscess. B cell lymphomas did not show dermal-epidermotropism as well as epidermotropism.