Biomedical subjects
Publications and source records attributed to H Kohno.
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The pathogenesis and clinical progress of chondromalacia patellae have not been well studied in experimental models. We, therefore, studied the patellar subluxation produced experimentally in rabbit knees. In this model, sequential changes of the patellar cartilage were followed by simple X-rays, CT, macroscopic, histologic and scanning electron microscopic examinations up to 32 weeks. Pathological changes extending from horizontal fissures in the middle to the deep layers of the patellar cartilage and thinning of the subchondral bone were found at about six weeks after operation. The early changes of chondromalacia patellae were mostly what is called the basal degeneration, which was presumably attributed to the shearing stress on the articular cartilage. The sequential changes were not very remarkable; none of the rabbits developed OA changes by thirty-two weeks after operation. From these findings, we have that the cartilaginous changes in chondromalacia patellae progress very slowly which probably result from the vigorous repair by the cartilage and also from the acquisition of adaptability on the patellofemoral joint.
A rare case of primary malignant lymphoma of the skull was reported. A 74-year-old woman was admitted to our hospital complaining of a growing mass in her forehead where she had had minor trauma one month previously. On admission, neurological findings were normal and an elastic hard tumor (6 x 6 x 2 cm) was found in the right frontal region. Computed tomography (CT) showed a large soft tissue mass in the subcutaneous tissue and a small mass in the ethmoid sinus, with erosion at the inner and outer tables of the frontal bone. Magnetic resonance imaging revealed a low intensity area in the bone marrow beneath the tumor. Right carotid angiography showed that the tumor was fed by branches of the ophthalmic artery in the arterial phase and stained in the capillary phase. Partial excision of the tumor was performed, but the affected bone was left because of her advanced age, even though thinning and spicular formation of the frontal bone were observed beneath the tumor in places. Pathological examination showed the tumor to be a malignant lymphoma of non-Hodgkin and diffuse mixed type. Postoperatively, systemic examinations were performed by 99mTechnetium-MDP bone scanning, 67Gallium citrate scanning, bone marrow puncture, and CT scanning, without any evidence of systemic lymphoma. The patient received postoperative chemotherapy with Cyclophosphamide, Doxorubicin HCl, Vindesine Sulfate, Prednisolone, and complete remission has been achieved for the 8 months since the operation.
Further therapeutical investigations are necessary to obtain a satisfactory survival rate of patients by improving the conventional methods of the treatment of osteosarcoma. Our working hypothesis is that an estrogenic hormonal influence is available for the effective treatment of osteosarcoma. An attempt was made to clarify this idea using experimentally induced hamster osteosarcoma. Male and female Syrian golden hamsters were used. Small amounts of minced tumor pieces were transplanted into hamsters subcutaneously. The levels of the circulating estradiol (E2) and alkaline phosphatase (ALPase) in blood were determined after the transplantation. An estrogen receptor (ER) on tumor cells was also demonstrated. Hamsters with an increased level of serum E2 were likely to have a smaller size of primary tumors and a smaller number of nodes in the lung metastasis. These tumor cells were successfully shown to be positive for ER stain. This suggests that E2 treatment may possibly control the osteosarcoma-condition.
In order to clarify the role of renal dopaminergic activity in renal sodium-water metabolism, the effects of oral administration of L-DOPA (400 mg), were studied on blood pressure (BP), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary volume (UV), urinary excretion of sodium and lithium (UNa and ULi) in 11 normal subjects (N) and 32 patients with essential hypertension (EH). EH were divided into the salt sensitive (SS) and non salt-sensitive (NSS) groups by response of mean blood pressure (10% increase) after administration of NaCl. The change of UNa, PRA, and PAC after administration of NaCl were lower in SS than in NSS. After administration of L-DOPA, BP falled and UV, UNa, FENa, FELi and Ccr increased in both N and EH. The change of these factors were greater in SS as compared with those in NSS. These results suggest that in SS patients the suppression of water-sodium handling in the kidney might be due to depression of renal dopaminergic activity. Renal dopaminergic activity may play an important role in the pathogenesis of EH.
To investigate the regulation mechanism of the uptake of iron and heme iron by the cells and intracellular utilization of iron, we examined the interaction between iron uptake from transferrin and hemopexin-mediated uptake of heme by human leukemic U937 cells or HeLa cells. U937 cells exhibited about 40,000 hemopexin receptors/cell with a dissociation constant (Kd) of 1 nM. Heme bound in hemopexin was taken up by U937 cells or HeLa cells in a receptor-mediated manner. Treatment of both species of cells with hemopexin led to a rapid decrease in iron uptake from transferrin in a hemopexin dose-dependent manner, and the decrease seen in case of treatment with hemin was less than that seen with hemopexin. The decrease of iron uptake by hemopexin contributed to a decrease in cell surface transferrin receptors on hemopexin-treated cells. Immunoblot analysis of the transferrin receptors revealed that the cellular level of receptors in U937 cells did not vary during an 8-h incubation with hemopexin although the number of surface receptors as well as iron uptake decreased within the 2-h incubation. After 4 h of incubation of the cells with hemopexin, a decrease of the synthesis of the receptors occurred. Thus, the down-regulation of transferrin receptors by hemopexin can be attributed to at least two mechanisms. One is a rapid redistribution of the surface receptor into the interior of the cells, and the other is a decrease in the biosynthesis of the receptor. 59Fe from the internalized heme rapidly appeared in non-heme iron (ferritin) coincidently with the induction of heme oxygenase. The results suggest that iron released from heme down-regulates the expression of the transferrin receptors and iron uptake.
This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide(ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, alpha-human ANP (alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of alpha-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of alpha-hANP increased plasma cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by alpha-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by alpha-hANP in normal subjects and patients with essential hypertension, was increased by MC. These results suggest that the hypotensive effect of alpha-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.
A novel and sensitive enzyme immunoassay (immune-complex-transfer enzyme immunoassay) for antihuman T cell leukemia virus type 1 IgG (anti-HTLV-1 IgG) in human serum using recombinant gag(14-139)-env-(197-295) hybrid protein is described. Anti-HTLV-1 IgG in test serum was reacted with dinitrophenyl biotinyl bovine serum albumin-recombinant gag-env hybrid protein conjugate. The complex formed was trapped onto polystyrene balls coated with affinity-purified antidinitrophenyl group IgG. After washing to eliminate nonspecific IgG in the test serum, the complex was eluted from the polystyrene balls with dinitrophenyl-L-lysine and transferred to polystyrene balls coated with streptavidin. After washing, anti-HTLV-1 IgG in the complex trapped onto the streptavidin-coated polystyrene balls was reacted with antihuman IgG gamma-chain Fab'-peroxidase conjugate. Peroxidase activity bound to the streptavidin-coated polystyrene balls was assayed by fluorometry. By transfer of the complex, the nonspecific binding of nonspecific human IgG was considerably reduced, and the detection limit of anti-HTLV-1 IgG in serum was lowered 30-300-fold compared with that by Western blotting, gelatin particle agglutination, and the conventional enzyme immunoassay, in which a recombinant gag-env hybrid protein-coated polystyrene ball was incubated with test serum and, after washing, with antihuman IgG gamma-chain Fab'-peroxidase conjugate. Usefulness of the immune-complex-transfer enzyme immunoassay was demonstrated using 271 serum samples.
In order to investigate whether or not transferrin is involved in the uptake of 67Ga by inflamed liver (acute inflammatory tissues) the uptake of 67Ga by the liver of mice treated with carbon tetrachloride (CCl4) was studied. The serum GPT value reached its maximum on the 1st day after the CCl4 treatment. The uptake of 67Ga by the liver also reached its maximum on the 1st day after the CCl4 treatment and the amount uptaken into inflamed liver was about 6 times that uptaken into normal liver. On the other hand, the uptake of 125I-transferrin into inflamed liver on the 1st day after CCl4 treatment was only about 1.6 times that into normal liver. Moreover, cold Fe3+ decreased the uptake of 67Ga by normal liver but increased the uptake of 67Ga by inflamed liver. These results show that transferrin plays an important role in the uptake of 67Ga by normal liver but not by inflamed liver, i.e. 67Ga in the transferrin-unbound form is preferentially taken up by inflamed liver.
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Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of four HTLV-related and seven HTLV-unrelated EOFL, were investigated with respect to the immunohistochemical and clinical features. HTLV-related EOFL were of T-cell phenotype and were associated with a poorer prognosis than HTLV-unrelated EOFL, most of which were of B-cell origin. The appearance of giant cells with cerebriform nuclei was helpful in identifying HTLV-related EOFL. The relatively high incidence of T-cell type EOFL in our series was considered to be related to the high percentage of HTLV carriers in our district, an area endemic for adult T-cell leukemia-lymphoma.
During the past 8 years, estrogen receptors (ERs) in the cytosol of hepatocellular carcinoma (HCC) were assayed in 66 unselected patients without preceding treatments on whom radical hepatic resection was performed. Twenty-six patients had ERs of 0.9 to 13.4 fmol/mg protein with a mean dissociation constant of 7.8 x 10(-10) M. The remaining 40 patients had no detectable amount of the receptor. There were no substantial differences between the ER-positive and ER-negative groups in preoperative clinical and laboratory data such as sex, age, alcohol abuse, underlying liver disease, and hepatic functions. Large tumors were more common in the ER-negative group and therefore the incidence of major hepatic resection was significantly higher in this group. Histopathologic studies revealed no substantial differences between the two groups. Operative mortality rate was 11.5% in the ER-positive and 12.5% in the ER-negative group. Excluding eight operative deaths, the rate of tumor recurrence in the residual liver and long-term survival rate were identical for the two study groups. The current results may indicate that the presence or absence of ERs in human HCC does not correlate to either biologic or pathologic characteristics of this tumor, but the true role of ERs in human HCC remains to be elucidated.
Five families with familial inherited TSH deficiency, reported to date, were examined for the TSH beta gene at the nucleotide level. The first family carries a single base substitution in the 29th codon which lies in the so-called CAGYC region; GCA (glycine) is replaced by AGA (arginine). This substitution induces conformational changes of the beta-polypeptide which make it unable to associate with the alpha-subunit. This mutation generates a new cleavage site for a restriction endonuclease MaeI, a new marker that can be used for DNA diagnosis. The second and third families were found to carry the same nucleotide substitution. Also, all three families were associated with an additional single base substitution in intron 2 as a polymorphic change, suggesting that these three families may have originated from the same single founder from Shikoku Island in Japan. The nucleotide sequence from the fourth and fifth families showed no alterations in the TSH beta gene from the about -200 basepair up-stream region to the polyadenylation site.
Several reports indicate that urinary hGH excretion is significantly lower in patients with either partial (PGHD) or complete GH deficiency (CGHD) than in normal but short children (NSC) or normal children (NC). However, there is an overlap between the NSC and NC groups and the PGHD group. Using a highly sensitive sandwich enzyme immunoassay, we investigated whether the measurement of urinary hGH can clearly separate the PGHD and CGHD groups from the NSC and NC groups. In addition, we measured the urinary excretion of synthetic methionyl-hGH (met-hGH) in PGHD and CGHD after sc injections of 2 and 4 IU and im injections of 4 IU in an attempt to determine the optimal replacement dose. Total 24-h urinary hGH excretion in each patient examined for 2 consecutive days varied from 1 day to the next. There were no differences in urinary hGH excretions between the NSC group and the NC group. The lower values for daily urinary hGH excretion in the NSC group overlapped some of the higher values in the PGHD group. However, when the mean urinary hGH level of both days was used, the 24-h urinary hGH excretion clearly separated the PGHD (5.5 +/- 2.3 ng/day; range, 1.3-9.2; n = 21) and CGHD (1.9 +/- 0.9 ng/day; range, 0.6-3.6; n = 14) groups from the NSC (12.8 +/- 3.1 ng/day; range, 9.3-17.5; n = 10) and NC (14.6 +/- 3.1 ng/day; range, 10.6-19.0; n = 6) groups without any overlap. A mean urinary hGH value less than 9.0 ng/day during a 2-day collection strongly suggested GH deficiency. Ten of 16 patients with PGHD and CGHD who received 2 IU met-hGH, sc, had urinary hGH levels within the range of the mean +/- SD in NSC. These patients received daily sc 0.097 +/- 0.024 IU/kg hGH injections. These results suggest that the measurement of 24-h urinary hGH excretion is noninvasive, accurate, and useful for the screening of GH deficiency. The mean value on 2 days of 24-h urinary hGH excretion for the screening of GH deficiency is estimated to be less than 9.0 ng/day. The optimal dose of GH as therapy for GH deficiency is demonstrated as daily sc injection of 0.1 IU/kg hGH, 0.7 IU/kg/week. To convert international units of met-hGH to milligrams, divide by 2.4.
Nine analogs based on a structure of Tyr-D-Arg-Phe-X (X = alkylamides or alkylhydrazide containing electron-withdrawing atoms or groups) were newly synthesized and their biological properties were examined by the opioid receptor binding properties of mu-, delta- and kappa-receptors, guinea-pig ileum (GPI) assay and analgesic activity in the tail pinch test after subcutaneous administration in mice. Analogs with X = NHCF2CF3, Sar-ol, or NH(CH2)2CN showed potent activities in the GPI and analgesic assays and high affinity for mu-receptor. An analog with X = taurinamide was found to possess 4-fold higher mu-receptor selectivity than that of [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAGO). The receptor binding properties of previously reported analogs [Chem. Pharm. Bull., 33, 1528 (1985); ibid., 33, 4865 (1985); ibid., 36, 4834 (1988)] were also examined for overall discussion of the structure-activity relationships of this series of tripeptide amides.
Five [D-Ala2, D-Leu55]enkephalin (DADLE) analogs containing fluorinated Tyr1 or Phe4 residue, that is, [Phe(2F)4] (I), [Phe(3F)4] (II), [Phe(4F)4] (III), [Tyr(3F)1] (IV) and [Tyr(2F)1] (V), were synthesized by the solid phase method and their opioid receptor affinities were examined. Affinity profiles of five derivatives for the mu- and delta-receptor were similar to those of DADLE, and the affinity for kappa-receptor was zero or negligible.
Brain damage in the early stage of experimental head injury was studied under electron microscope, especially with respect to the permeability of the blood brain barrier and damage to nerve fibers. Lightly anesthetized rabbits were treated by intravenous injection of horseradish peroxidase (150-250 mg/kg) and were subjected to occipital impacts with a pendulum impactor. The animals were then perfused with a 2.5% glutaraldehyde mixture. Small blocks of the brain were sampled, incubated, postfixed, and embedded in Epon. These sections were observed under an electron microscope without staining. The authors' criteria of concussion have been previously published. There were three nonconcussion, 11 nonlethal concussion and seven lethal concussion animals. All cases of lethal concussion showed subarachnoid hemorrhage (SAH) in the brainstem and 57% of them showed microscopic parenchymal perivascular hemorrhages in the brainstem. Fifty-five percent of the nonlethal concussion cases showed SAH in the brainstem with a little parenchymal hemorrhage. The nonconcussion cases showed no hemorrhagic change except contusions and/or SAH of the cerebellum. Hemorrhagic changes were frequently seen in the cerebrum and cerebellum of nonlethal and lethal concussion cases without correlation to the severity of concussion. Under electron microscope, nonconcussion cases showed mild splitting of myelins. In nonlethal concussion cases, swelling of perivascular astrocytic feet was seen to a moderate degree in the cerebrum, pons, and medulla oblongata and damage to axons and myelins were mainly seen in the pons and medulla oblongata. Many cored dense bodies containing peroxidase were diffusely recognized in vascular endothelial cells. In lethal concussion cases, beside findings seen in nonlethal concussion, intravascular peroxidase was seen to leak from the intravascular space through an opened tight junction to the extracellular space, axons and neurophils.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of the autonomic nervous system and the endocrine system to cold exposure were investigated. The subjects were all males, between 41 and 69 years of age. Seventy subjects with the vibration syndrome and vibration-induced white finger (VWF(+) group), 70 subjects with the vibration syndrome without VWF (VWF(-) group) and 70 healthy subjects (control group) were individually matched according to age. The subjects remained in a cold room at 7 C for 30 minutes. Catecholamines, cyclic nucleotides, thyroid hormones, ACTH and cortisol were measured before and during cold exposure. The VWF(+) group and the VWF(-) group had larger % increases of plasma norepinephrine, cyclic AMP, cyclic GMP, T3 and T4 levels than the control group. These findings indicate that the responses of the autonomic nervous system and the thyroid system to cold exposure are greater in the subjects with the vibration syndrome.