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Biomedical subjects

K Kondo

Publications and source records attributed to K Kondo.

At least 541 records · Page 30Linked to original sources

GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients.

Clinical findings were compared with the results of molecular analysis in 16 Japanese patients from 10 unrelated families with the adult/chronic form of GM1 gangliosidosis. Age of onset ranged from 3 to 30 years. Major clinical manifestations were gait and speech disturbances caused by persistent muscle hypertonia. Dystonic postures and movements, facial grimacing, and parkinsonian manifestations were commonly seen. Cerebellar signs, myoclonus, severe intellectual impairment, dysmorphism, or visceromegaly were not observed. A common single-base substitution, 51Ile(ATC)----Thr(ACC), reported in a previous study of ours, was confirmed in 14 patients by the Bsu36I restriction site analysis; one was a compound heterozygote with another mutation (457Arg[CGA]----Gln[CAA]) and the others were homozygotes of this mutation. Clinically, the compound-heterozygous patient showed more severe neurological manifestations and a more rapid clinical course than those of homozygotes. The homozygotes showed considerable variations in the age of onset and subsequent clinical course. The 51Ile----Thr mutant allele expressed a significant amount of beta-galactosidase activity, whereas the 457Arg----Gln mutant allele expressed extremely low activity in human GM1 gangliosidosis fibroblasts. We conclude that these gene mutations causing different residual enzyme activities are related to the severity of clinical manifestations, but some other genetic or environmental factors contribute to clinical heterogeneity. The Bsu36I restriction site analysis was performed in 7 families and provided clear results for the diagnosis of heterozygotes as well as homozygotes of this specific clinical form of GM1 gangliosidosis. The technique is applicable to prenatal diagnosis and genetic counseling.

Adult↗

Sensory mother cell division is specifically affected in a Cyclin-A mutant of Drosophila melanogaster.

Cyclin proteins are one of the important components of the mechanism regulating mitosis in eukaryotic cells. We isolated a Drosophila Cyclin-A mutant in which the progenitor cells of the peripheral nervous system (the sensory mother cells) do not divide properly, causing the loss and other abnormalities of mechanosensory organs in the adult fly. Sequence analysis of the mutant genome reveals that a P element is inserted into the first intron of the Cyclin-A gene. A 13 kb wild-type genomic DNA containing the Cyclin-A transcription units rescued the mutant phenotype when introduced into the mutant fly. The regulation of cell type specific expression of the Cyclin-A gene is discussed.

Animals↗

Effects of eel atrial natriuretic peptide on NaCl and water transport across the intestine of the seawater eel.

Eel atrial natriuretic peptide inhibited the serosa-negative transepithelial potential difference and short-circuit current, accompanied by a decrease in NaCl and water absorption across the seawater eel intestine. Similar effects were obtained after treatment with N-terminally truncated eel atrial natriuretic peptide (5-27), indicating that N-terminal amino acids are not essential for the action of eel atrial natriuretic peptide. Although mammalian atrial natriuretic peptides also inhibited the short-circuit current, a 100-fold higher concentration was required to obtain the same effect as with eel atrial natriuretic peptide, indicating that eel atrial natriuretic peptide is 100 times as potent in eel intestine as the mammalian atrial natriuretic peptides. Similarly, in mammalian atrial natriuretic peptide, the four N-terminal amino acids had no significant effects. However, when the C-terminal tyrosine was removed, the potency of rat atrial natriuretic peptide was lowered. Compared with the effects of acetylcholine, serotonin and histamine, eel atrial natriuretic peptide was the most potent inhibitor, with 100% inhibition at 10(-7) M; 50% inhibition was obtained at 10(-2) M in acetylcholine, and 30% inhibition in serotonin (10(-5) M) and histamine (10(-3) M). These inhibitory effects of eel atrial natriuretic peptide were not diminished even in the presence of tetrodotoxin, and were mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate. Based on these results, structure-activity relationships of eel atrial natriuretic peptide and a possible mechanism of action of eel atrial natriuretic peptide are discussed.

Amino Acid Sequence↗

Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases.

In vitro erythroid differentiation of mouse erythroleukemia (MEL) cells was induced by combinations of topoisomerase and protein kinase inhibitors. Neither inhibitor alone exhibited inducing activity. Although inhibitors of topoisomerases I and II were equally effective in the synergistic induction of erythroid differentiation, only inhibitors of tyrosine kinases, not of serine/threonine kinases, exhibited synergistic activity. The erythroid differentiation induced by the combination of topoisomerase and protein tyrosine kinase inhibitors was distinguished from that induced by typical erythroid inducing agents such as DMSO or HMBA by (1) earlier hemoglobin accumulation in the cells and (2) insensitivity to specific inhibitors (dexamethasone and sodium orthovanadate) of MEL cell differentiation.

Acetamides↗

Relationship of QRST isointegral maps during simulated left bundle branch block to impairment of left ventricular function due to myocardial infarction.

The clinical usefulness of QRST isointegral maps for assessing left ventricular (LV) dysfunction due to myocardial infarction (MI) in patients with MI in the setting of simulated left bundle branch block (LBBB) was investigated. Isointegral maps were recorded during sinus rhythm and right ventricular pacing, which simulated LBBB, in 62 patients with MI and 26 patients without MI. An abnormal decrease in the QRST value in the isointegral map was assessed by the difference map that indicated a "-2 SD area" where the QRST integral value was less than the normal range (mean - 2 SD) calculated from 608 normal individuals. The isointegral maps during the two activation sequences were similar in patients with and without MI (r = 0.87 and 0.92, respectively). The sum of QRST integral values less than the normal range (sigma DM) during simulated LBBB correlated significantly with the asynergy index, derived from left ventriculographic data (r = 0.81, p < 0.01). LV dysfunction (asynergy index > or = 2) was diagnosed in simulated LBBB with a sensitivity of 81%, specificity of 77%, and diagnostic accuracy of 80% when the criterion that LV dysfunction is present if the number of lead points in the -2 SD area exceeds 4, and a sensitivity of 71%, specificity of 81%, and diagnostic accuracy of 74% if sigma DM exceeds 200 mVms was used. The findings demonstrate that isointegral maps may be useful in assessing LV dysfunction due to MI in patients with MI and LBBB in addition to detecting the presence and site of MI in these patients.

Adult↗

Small differences among body surface and epicardial QRST integral maps recorded during normal activation and experimentally simulated left bundle branch block or preexcitation in canine hearts.

QRST integral maps were constructed from 87-lead body surface electrocardiograms (ECGs) and from 45-lead epicardial electrograms during artificial pacing, which simulated left bundle branch block (LBBB) and Wolff-Parkinson-White syndrome in 12 dogs. Although the ECGs and electrograms differed in configuration for each conduction model, the body surface and the epicardial QRST integral maps showed only small differences. Correlation coefficients (r) and root mean square differences (rms) were calculated to assess quantitatively the similarities in the QRST integral maps among the different conduction models. Mean r values between the normal conduction and the left bundle branch block models were 0.95 in the body surface maps and 0.89 in the epicardial maps. Mean r values between the normal conduction and the Wolff-Parkinson-White ECG models were 0.97 in the body surface maps and 0.91 in the epicardial maps, and rms values were small enough. The small differences were also verified by the difference maps and by paired t tests. QRST integral maps on the epicardium and on the body surface were largely independent of altered activation sequences in both the left bundle branch block and the Wolff-Parkinson-White ECG models.

Animals↗

Case report: hypertension in Cushing's syndrome.

Pathogenesis of hypertension in Cushing's syndrome has remained controversial. A 56-year-old Japanese man with Cushing's syndrome due to adrenal carcinoma has been followed up for more than 6 years. During the followup period, left adrenalectomy and hemihepatectomy due to metastatic lesion were performed. Blood pressure, serum cortisol, and urinary excretion of 17-OHCS, as well as other routine biochemicals, have been measured periodically. These data revealed that there is a marked correlation between the levels of blood pressure and serum cortisol or urinary excretion of 17-OHCS. This finding suggests that cortisol production by tumor is a determinant factor in hypertension in Cushing's syndrome.

Adrenal Gland Neoplasms↗

Regulation of proliferation by vasopressin in aortic smooth muscle cells: function of protein kinase C.

AIM: To investigate the effect of arginine vasopressin-stimulated prostaglandin synthesis and the activation of protein kinase C on DNA synthesis in rat aortic smooth muscle cells. METHODS: The effects of arginine vasopressin on the release of arachidonic acid and the synthesis of prostaglandin (PG) E2 and prostacyclin (PGI2) were determined. The effects of 12-o-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C-activating phorbol ester, and of 1-oleoyl-2-acetylglycerol, a specific activator of protein kinase C, were evaluated in cultured rat aortic smooth muscle cells. The effects of arginine vasopressin and prostaglandins on the progression from the late G1 to the S phase of the cell cycle were evaluated by measuring the DNA synthesis, and the effects of TPA on them were evaluated. RESULTS: Arginine vasopressin dose-dependently stimulated arachidonic acid release. TPA and 1-oleoyl-2-acetylglycerol dose-dependently increased the vasopressin-induced arachidonic acid release. Vasopressin stimulated the synthesis of both PGE2 and PGI2. TPA increased the vasopressin-stimulated prostaglandin synthesis as well as the arachidonic acid release. Vasopressin, added at the G0/G1 phase of the cell cycle, stimulated DNA synthesis of aortic smooth muscle cells. Exogenous PGE2 and PGI2 inhibited the DNA synthesis and showed maximum inhibition when added at the late G1 phase. TPA alone, added at the late G1 phase, reduced the DNA synthesis stimulated by vasopressin at the G0/G1 phase to about 45%, but vasopressin alone, added at the late G1 phase, had little effect. However, with TPA pretreatment, vasopressin significantly suppressed the DNA synthesis by about 70%. Staurosporine, a protein kinase C inhibitor, reduced the suppression by TPA alone or by vasopressin with TPA pretreatment almost to the control level. Indomethacin, a cyclo-oxygenase inhibitor, reduced the suppression by vasopressin with TPA pretreatment almost to the level of TPA alone. CONCLUSIONS: These results suggest that arginine vasopressin has a suppressive effect on DNA synthesis in rat aortic smooth muscle cells by inhibiting progression from the late G1 into the S phase of the cell cycle through the synthesis of PGE2 and PGI2, and that protein kinase C acts as an amplifier of this mechanism.

Animals↗

Experimental infection of cynomolgus and African green monkeys with human herpesvirus 6.

Cynomolgus and African green monkeys were inoculated with human herpesvirus 6 (HHV-6). An antibody response was first observed 10 days and 5 days after inoculation of cynomolgus monkeys and African green monkeys, respectively, and was detectable for the duration of the experiment (33 days). HHV-6 DNA was first detected by the polymerase chain reaction in mononuclear cells of one cynomolgus monkey and one African green monkey 10 days after virus inoculation, and in a total of three of four cynomolgus monkeys (75%) and four of five African green monkeys (80%) later after inoculation. Furthermore, HHV-6 DNA was detected in the lymph nodes and spleen of monkeys killed 33 days after virus inoculation. A rash was observed on the trunk of one African green monkey 13 days after virus inoculation, otherwise the infection was asymptomatic. When mononuclear cells from both groups of monkeys were cultured in medium containing concanavalin A and interleukin 2, and infected with HHV-6 in vitro, virus replication was observed. The data suggest that HHV-6 infects these species of monkey and that this system could be useful as an animal model of HHV-6 infection.

Animals↗

Detection of locally recurrent colorectal cancer with radiolabeled monoclonal antibody H-15.

H-15 (HT-29-15) is an IgG1 mouse monoclonal antibody (mAb) to a cell surface antigen (molecular mass, 200,000 daltons) present on virtually all colorectal cancers and also in normal pancreatic ducts and bile ducts, but not in other normal tissues. The biological distribution and imaging characteristics of iodine-131 (131I)-labeled mAb H-15 were studied in 5 primary colorectal cancer patients and 9 patients with local recurrence of colorectal cancer. H-15 mAb labeled with 0.5-10 mCi of 131I was administered 7 to 8 days before surgery at 4 dose levels, ranging from 0.2 to 6 mg. Selective mAb H-15 localization to tumor tissues was demonstrated in 6 of 12 patients with antigen-positive tumors: in two patients, recurrent tumors were negative to H-15 mAb, although the primary tumors were positive. In six patients with positive radioimaging, tumor:normal tissue ratios ranged from 2.05 to 5.35 and tumor:serum ratios from 1.18 to 2.73. The clarity of images seems to correlate well with the latter ratios. Technetium-99 (99mTc)-albumin blood pool studies in selected cases showed that local recurrence of colorectal cancers was hypovascular, emphasizing the selective localization of mAb H-15 despite poor blood flow distribution in the tumors. The results altogether demonstrated that radioimmunodetection with 131I mAb H-15 is valuable for differentiating recurrent colorectal cancer from granuloma formation after surgery.

Adult↗

Nocturnal myoclonus observed in a patient with neuroleptic-induced akathisia.

An all-night polysomnogram was twice recorded in a patient with neuroleptic-induced akathisia (NIA). The polysomnogram revealed nocturnal myoclonus. After disappearance of akathisia by the administration of clonazepam, we recorded the second polysomnogram. At the second examination, sleep efficacy increased and the total number of nocturnal myoclonus decreased remarkably. The mean inter-movement interval of nocturnal myoclonus prolonged. These findings suggest a close relationship between the mechanisms of neuroleptic-induced akathisia and nocturnal myoclonus.

Adult↗

Incidence of Paneth cells in minute tubular adenomas and adenocarcinomas of the large bowel.

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis).

Adenocarcinoma↗

Human herpesvirus 6 (HHV-6) infection in the central nervous system.

Human herpesvirus 6 (HHV 6) was isolated from patients with exanthema subitum (ES) with a high frequency, and it is now believed that this virus causes ES as a primary infection in childhood. HHV 6 infection is highly prevalent in early childhood and this virus may infect infants through the saliva mainly from mother to child. HHV 6 has a tropism to CD4+ cells and destroys cells in vitro. Although children recover from ES without any sequelae, neurological symptoms associated with exanthema subitum are often observed, and we could detect HHV 6 in the cerebrospinal fluid of ES patients. This result suggests that HHV 6 may invade the central nervous system and cause neurological symptoms.

Antibodies, Viral↗

[A survey of intestinal parasites of the foreign laborers (Indonesians and Filipinos) in Ishikawa Prefecture].

A survey of intestinal parasites was conducted on 198 foreign workers aged 19-27 from Inodonesia and Philippines. They work for a private company in Ishikawa Prefecture as technical trainee. On the base of stool examination, 94 (71%) out of 133 Indonesians and 48 (74%) of 65 Filipinos had intestinal helminths and/or protozoan infections. The prevalence of Ascaris lumbricoides, Trichuris trichura and Hookworm was 4.5, 64.1, 10.6%, respectively. In addition, the positive rate of the cyst of Entamoeba coli, Endolimax nana, Blastocystis hominis and Giardia lumblia was 11.1, 5.6, 4.5 and 2.0%, respectively. No E. histolytica was found; however, counter current immunoelectrophoresis revealed that one out of 112 sera possessed the antibody against the antigen of HK-9 strain of E. histolytica. Sixty-three cases of trichuriasis were treated with mebendazole at a dose of 200 mg/day x 3 consecutive days. Re-examination revealed that 53 (85.5%) of them were cured.

Adult↗

Elevated ratio of late measles among subacute sclerosing panencephalitis patients in Karachi, Pakistan.

Subacute sclerosing panencephalitis (SSPE) in Western countries and Japan is found more often in early- than in late-measles sufferers. Recent SSPE findings in Karachi, however, present a different picture. Age at measles contraction was obtained and analyzed for 44 SSPE patients identified in Karachi between 1983 and 1988. The ratios of early- (< 2 years of age) and late- (> or = 2 years of age) measles sufferers among 36 of these patients who had experienced only one attack of measles were 0.33 and 0.67, respectively. This is in striking contrast to the predominance of early measles in the SSPE histories reported in Japan and an number of Western countries.

Age Factors↗

Progressive supranuclear palsy-like syndrome in two siblings of a consanguineous marriage.

Two siblings of a consanguineous marriage showed identical clinical features consisting of supranuclear vertical ophthalmoplegia, bradykinesia, rigidity, stooped posture, pseudobulbar palsy, and dementia, all beginning in the sixth decade. There was no history of encephalitis or of exposure to known chemicals. L-Dopa therapy was only partially and temporarily effective. Autopsy of one patient revealed extensive neurofibrillary degeneration with prominent involvement of the limbic system. There were no senile plaques or Lewy bodies. Under electron microscopy, there were paired helical filaments as well as 15-nm-wide straight tubules. The diffuse appearance of neurofibrillary tangles, predominant in the limbic system, and familial occurrence are unusual in progressive supranuclear palsy; these cases may, therefore, constitute a different, distinctive clinicopathologic disease.

Consanguinity↗

A synthesis of 2-substituted 2-aminoethanol derivatives having inhibitory activity against protein kinase C.

A series of 2-aminoethanol derivatives was synthesized and their inhibitory activities against protein kinase C were investigated. Among these compounds, 2-endo-hexadecylamino-5-norbornene-2- exo-methanol (4h) and 2-endo-hexadecylamino-5-norbornene-2,3-exo-dimethanol (4i) inhibited protein kinase C at the IC50 values of 2 x 10(-5) and 1 x 10(-5) M, respectively, but not protein kinase A at a concentration of 1 x 10(-3) M. The structure-activity relationships are discussed.

Animals↗

Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae.

The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action.

Amides↗