Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 361 records · Page 20Linked to original sources

PubMed1995

Ethanol inhibition of Ca2+ and Na+ currents in the guinea-pig heart.

The effects of ethanol on L-type Ca2+ and fast Na+ currents (ICa and INa, respectively) were examined using the whole-cell patch-clamp experiments on guinea-pig ventricular cells. At a clinically relevant concentration of 24 mM, ethanol slightly but significantly shortened the action potential duration, and reduced the ICa by 7 +/- 4% (mean +/- S.D.). This concentration of ethanol did not affect INa, but a lethal concentration of ethanol (80 mM) significantly inhibited INa by 13 +/- 5%. The voltage dependence of INa activation was not affected by ethanol, whereas the inhibitions of ICa by 80 mM ethanol and INa by 240 mM were both accompanied by a several mV shift in the channel availability curve toward more negative potentials, suggesting that the channels in the inactivated state are more susceptible to ethanol. The ICa inhibition by ethanol at clinically relevant concentrations could contribute to a negative inotropic effect, action potential shortening and development of arrhythmias, while the pathophysiological significance of ethanol inhibition of INa seems less important.

Action Potentials↗

PubMed1995

Computer-assisted pathology of intraepithelial adenocarcinoma and related lesions: 3-D distribution, structural aberration and discrimination.

To discriminate among intraepithelial neoplasms, we have been relying on tissue microscopy, but pathologists' subjectivity sometimes impairs diagnosis. Even an individual pathologist is sometimes unable to reproduce exactly his or her own previous diagnosis. Are various atypical lesions classifiable in a reproducible way, and if they are, how? The reliability of a diagnosis will be strengthened if we can define the "natural" categories inherent in cells and tissues. Morphometry and statistical analysis using a computer can provide answers. Atypia, a morphological feature of carcinoma, is essentially multivariate. Quantification of a tissue feature requires reducing it to a set of ten or more quantities, including size, shape and position of the nucleus, nucleolus, and the cell itself. The grade of aberration from the norm can be assessed only by a synthetic approach, using a computer for multivariate cluster analysis. This classification has been attempted in adenocarcinoma and related lesions of the lung and pancreas. The categories thus established are reproducible, because the lesions fall into divisions according to their forms. We can also examine the organ distribution of intraepithelial neoplasms by three dimensional (3-D) computer-assisted mapping. To reach a higher level of reliability, as many meaningful features as possible should be taken into account. Particularly, we emphasize the significance of architectural pattern as a biomarker for intraepithelial glandular neoplasms. Computer-aided 3-D structural analysis visualizes the basic skeleton of these neoplasms around which the cells adhere. Instead of the dichotomous tree pattern of normal glands, the tumors basically harbor a 3-D network, tubular or porous, which increasingly deviates from the norm along with the transition from adenoma to well to moderately to poorly differentiated adenocarcinoma. This structural aberration, if recognizable on 2-D sectional images, will serve as a surrogate endpoint biomarker for glandular tumors.

Algorithms↗

PubMed1995

Coexpression of epsilon, G gamma and A gamma globin mRNA in embryonic red blood cells from a single copy beta-YAC transgenic mouse.

We utilized reverse transcription polymerase chain reaction (RT-PCR) to amplify epsilon, G gamma and A gamma globin cDNAs from single red blood cells isolated from a day-10 transgenic fetus harboring a single copy of the human beta-YAC. A detailed structural analysis of the beta-YAC showed a single copy of each beta-like globin gene is present and linked to the locus control region (LCR). RNase protection analysis of RNA isolated from erythroid tissues from day-8 to day-16 of development and the adult stage showed proper developmental switching of the beta-like globin gene expression. Using epsilon / gamma and G gamma / A gamma primer sets in separate RT-PCR reactions on RNA from single day-10 red blood cells we observed an intercellular variation in the epsilon and gamma RT-PCR products that may be indicative of a change in the LCR preference from the epsilon gene promoter to the gamma gene promoter during switching. We also found that the majority of the red blood cells examined contain all three globin mRNA species. These observations suggest that either the LCR is capable of interacting simultaneously with more than one globin gene promoter or alternatively, the LCR may interact with only one promoter at any given time, but its interaction oscillates between promoters (flip-flop mechanism) resulting in expression of more than one gene from a single beta-globin locus.

Animals↗

PubMed1995

Japanese encephalitis virus nonstructural protein NS3 has RNA binding and ATPase activities.

Sequence data suggest that Japanese encephalitis virus (JEV) protein NS3 is a multifunctional protein with sequence motifs characteristic of a protease and a helicase. To examine the functions of JEV-NS3, a fusion protein of NS3 in Escherichia coli was generated. Analysis by Western blot using monospecific rabbit antisera generated against the fusion protein (anti-MBJEN3) showed that NS3 was localized in the membrane fraction of JEV-infected cells and the particulate fraction of bacteria extracts. The addition of anti-MBJEN3 sera reduced JEV-specific RNA synthesis activity in a in vitro system. In addition, NS3 was shown to exhibit RNA binding and ATPase activities, suggesting this protein has an important role in viral RNA replication in virus-infected cells.

Adenosine Triphosphatases↗

PubMed1995

Identification of hibernating myocardium by dobutamine stress echocardiography: comparison with thallium-201 reinjection imaging.

The aim of this study was to determine the diagnostic value of dobutamine stress echocardiography (DSE) in the identification of hibernating myocardium and to compare its predictive accuracy with that of thallium-201 reinjection (RI) imaging. The subjects were 26 patients with wall motion abnormalities related to stenosed coronary arteries. DSE predicted postrevascularization improvement in 31 of 33 segments that were considered to be hibernating and identified 8 of 10 nonhibernating segments. In contrast, thallium-201 scintigraphy predicted all 33 hibernating segments when a post-RI myocardial thallium uptake in ischemic areas of > or = 50% of the maximum count in normal segments was used as a positive marker of myocardial viability. However, thallium studies predicted only 30 of 33 hibernating segments when thallium redistribution (RD) was used as a marker of viability in delayed or RI images. Among the 10 nonhibernating segments, an uptake of < 50% was observed in 4 segments and negative thallium-201 RD was observed in 5 segments. The sensitivity, specificity, and predictive values (PV) of DSE were 94%, 80%, positive PV 94%, and negative PV 80%, respectively. In contrast, the sensitivity, specificity, and PV of thallium-201 RI imaging were 100%, 40%, 85%, and 100% with uptake > or = 50% and 91%, 50% 86%, and 63% with RD, respectively. These results suggest that DSE may be useful for identifying hibernating myocardium and could therefore be helpful in selecting candidates for coronary revascularization.

Adult↗

PubMed1995

An analysis of lidocaine block of sodium current in isolated human atrial and ventricular myocytes.

Lidocaine is a Na+ channel blocker that is highly effective for the treatment of ventricular tachyarrhythmias, but is largely ineffective against atrial arrhythmias. If is not known if this differential efficacy is the result of differences in lidocaine inhibition of atrial v ventricular Na+ channels. The purpose of the present study was to characterize lidocaine block of Na+ channels in human atrium and ventricle. We used the whole cell voltage clamp technique with low external and internal Na+ concentrations (5 mM) to study the Na+ current (INa) in single human atrial and ventricular cells isolated enzymatically from specimens obtained during surgery. We found that tonic block of peak INa by lidocaine (200 microM, holding potential = -140 mV, 0.1 Hz, at 17 degrees C) was not voltage dependent in either cell type. Reduction of maximal peak Na+ conductance in 41 atrial cells (19.8 +/- 2.7%) and nine ventricular cells (22.6 +/- 1.7%) was virtually identical. The rate of onset of block development was determined during depolarization to either -80 mV or -20 mV. The time course of onset of block was described by a single exponential at -80 mV and by a double exponential at -20 mV. When the rate of block onset during a single conditioning depolarization was compared to that which developed during conditioning by a train of brief pulses (3 ms, 30 Hz), onset was faster during the pulse train. The results were nearly identical for atrial and ventricular INa. The time constants of recovery from block following either single pulse or multiple-pulse conditioning did not differ. These data suggest that lidocaine binds to both the activated and inactivated states of the human cardiac Na+ channel. Using an analytical method based upon the Guarded Receptor Hypothesis, we calculated apparent rate constants describing lidocaine's interaction with the three primary states of the human Na+ channel (resting, activated and inactivated). Rate constants were similar to those reported for other mammalian species. Our results demonstrate that lidocaine block of INa is virtually identical for human atrial and ventricular cells; thus additional mechanisms must be invoked to explain the differential efficacy of lidocaine against ventricular as compared to atrial dysrhythmias.

Adolescent↗

PubMed1995

Involvement of beta-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and alpha-melanocyte-stimulating hormone, in rats.

The present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 micrograms/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.

Animals↗

PubMed1995

Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on yawning, stereotypy, and body temperature in rats.

7-OH-DPAT ((+/-)-2-(dipropylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene) was recently identified as a dopamine receptor agonist having a > 100-, 1,000- and > 10,000-fold higher affinity for dopamine D3 than for D2, D4 and D1 receptors, respectively. Quinpirole (LY 171555) has also been reported to have a 113-fold greater affinity for dopamine D3 receptors than for D2 receptors. Therefore, we investigated the effects of these putative dopamine D3 receptor agonists on yawning, stereotypy and rectal temperature in rats (N = 424). 7-OH-DPAT and quinpirole administered subcutaneously (SC) at respective low doses of 10-250 micrograms/kg and 25-500 micrograms/kg elicited yawning behavior. The yawning induced by these agents was blocked by spiperone (0.5 mg/kg, SC) and scopolamine (0.5 mg/kg, SC) but was increased by intraperitoneal (IP) administration of pindolol (20 mg/kg). The yawning was also potentiated after treatment with reserpine. 7-OH-DPAT and quinpirole at respective high doses of 0.25 mg/kg (SC) and 0.5 mg/kg (SC) evoked slight stereotypy such as sniffing and licking, and this effect was enhanced by a selective dopamine D1 receptor agonist, SK&F 38393 (1-phenyl-2,3,4,5,-tetrahydro-(1H)-3-benzazepine-7,8-diol). 7-OH-DPAT (0.5 mg/kg, SC) and quinpirole (0.5 mg/kg, SC) decreased, but SK&F 38393 (10 mg/kg, SC) increased body temperature. However, the hyperthermia induced by SK&F 38393 was interestingly enhanced by 7-OH-DPAT and quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Status of patients who underwent uninephrectomy in adulthood more than 20 years ago.

We investigated the status of patients without systemic diseases who had undergone uninephrectomy for unilateral renal diseases in adulthood more than 20 years ago at Tokyo Denryoku Hospital. There were 21 participants (mean age +/- SD, 58.6 +/- 8.0 years) who fulfilled these criteria. The average interval since nephrectomy was 27.9 +/- 6.2 years. The mean current creatinine clearance was 88.5 +/- 21.2 mL/min/1.73 m2, which is 92.9% of that in healthy age- and sex-matched controls with two kidneys. The 24-hour urine protein excretion in these patients was only slightly higher than in the controls (214 +/- 190 mg v 119 +/- 62 mg, P = NS). Age at nephrectomy, length of time with a single kidney, or sex had little effect on the remnant renal functions. There was a positive correlation between current mean arterial pressure and serum creatinine (r = 0.44, P < 0.05). Patients who developed hypertension after uninephrectomy had a family history of hypertension more frequently than those with normotension (86% v 29%, P < 0.05). We conclude that (1) renal function after compensatory hyperfiltration of more than 20 years due to uninephrectomy for unilateral renal diseases in adulthood is well maintained, although hypertension has a considerable effect on the renal functions, and that (2) family history of hypertension plays a key role in determining the incidence of hypertension even in the uninephrectomized patients.

Adult↗

PubMed1995

Detection of muscle layer invasion with submillimeter pixel MR images: staging of bladder carcinoma.

Conventional magnetic resonance (MR) images used for the pelvic organs generally have a pixel size of 1.3 mm x 1.3 mm. We obtained images with a higher resolution than conventional images, and evaluated the usefulness of this type of image in staging urinary bladder carcinoma. Twenty-six patients having either transurethral resection of bladder tumor (TUR-BT) or cystectomy were retrospectively studied. T2-weighted images of the bladder were acquired with a 20 cm field-of-view, a matrix size of 224 x 224 (pixel size: 0.9 mm x 0.9 mm), and a slice thickness of 7 mm using a 0.5 T system. MR appearances of the carcinoma were divided into the following five categories: no abnormality found on the inner surface of the bladder wall (0), high signal layer or protrusion without breakage of the wall (I), partial disruption of the wall (II), transmural disruption of the wall (III), and complete disruption with mass formations in the perivesicular region (IV). These findings were correlated with the TNM pathologic staging determined from each tissue specimen. A prediction for muscle layer invasion was calculated by selecting pathologic stage pT2 and MR category III as a boundary measure. The accuracy was 96.2%, the sensitivity 100.0%, and the specificity 91.7%. The results obtained indicate that submillimeter pixel MR imaging shows promise as a noninvasive method for the preoperative staging of bladder cancers.

Aged↗

PubMed1995

DNA rearrangements in Japanese facioscapulohumeral muscular dystrophy patients: clinical correlations.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder in which the disease locus has been mapped to chromosome 4q35-qter. In most patients, the DNA rearrangements associated with FSHD have been found in the EcoRI fragment detected by the p13E-11 probe, and deletions of the 3.2 kb repeat units within the fragment are thought to cause the disease. To examine FSHD-associated DNA rearrangements in the Japanese population, we performed Southern blot analysis of the genomic DNA, using the p13E-11 and pFR-1 probes, in 158 Japanese individuals, including 38 FSHD patients from 19 families. We found that all but one (a possible affected recombinant) of the Japanese FSHD patients (97.4%) had specific smaller (< 28 kb) EcoRI fragments which cosegregated with the disease; this included four patients who had severe inflammatory changes in the muscle and eight patients with de novo DNA rearrangements. We found no FSHD patient who had a fragment larger than 28 kb. By contrast, only two of 35 Japanese controls (5.7%) had EcoRI fragments smaller than 28 kb. Our patients showed anticipation, i.e. decreased size of the EcoRI fragment in parallel with earlier onset of the disease (r = 0.531, P = 0.003, with younger age at onset in children (17.8 +/- 7.0) than their affected parents (31.5 +/- 14.8) (P = 0.019). However, since each family had a specific small EcoRI fragment associated with the disease, the differing clinical severity within a family cannot be explained by the size of the fragment alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Dual modulation by l-leucovorin and recombinant human interferon alpha 2a of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4.

We investigated the dual modulation by l-leucovorin (LV) and recombinant human interferon-alpha 2a (IFN-alpha 2a) of 5-fluorouracil (5-FU) antitumor activity against human colon carcinoma cells (Co-4) using a nude mouse system. 5-FU was administered intraperitoneally (IP) at 10 or 90 mg/kg. 5-FU (10 mg/kg) was administered daily for 10 days, and 90 mg/kg was administered once. LV was administered IP 1 and 0 h before 5-FU treatment at 200 mg/kg. IFN-alpha 2a was administered subcutaneously (SC) daily for 14 days at 60,000 IU/mouse. When 5-FU was administered at 10 or 90 mg/kg with these two modulators, the antitumor effect was increased significantly, with T/C ratios of 18.1 and 6.1, respectively. These modulatory effects were assessed as synergistic, without associated severe side effects or death during the experimental period. LV augmented the antitumor activity of 5-FU through increment of thymidylate synthetase (TS) inhibition, and IFN-alpha 2a showed a modulatory effect in elevating the intratumoral concentration of fluorouridine without change in TS inhibition. These results suggest that 5-FU antitumor activity against human colon carcinoma could be significantly potentiated without severe side effects by these two modulators, which possess different modes of action.

Animals↗

PubMed1995

Engraftment of immune-deficient mice with primitive hematopoietic cells from beta-thalassemia and sickle cell anemia patients: implications for evaluating human gene therapy protocols.

Permanent correction of genetic deficiencies of the hematopoietic system requires gene transfer into stem cells and long-term lineage specific expression after autologous transplantation. However, progress to develop gene therapy protocols has been hampered by the absence of in vivo assays that detect genetically deficient human hematopoietic stem cells and their diseased differentiated progeny. The establishment of systems to transplant human cells into immune-deficient SCID mice provides such an assay. We report that primitive bone marrow cells from beta-thalassemia major and sickle cell anemia patients engraft immune-deficient mice, giving rise to high levels of human erythroid and myeloid cells in response to treatment with human cytokines. The bone marrow of transplanted mice contained the entire erythroid lineage from BFU-E to mature erythrocytes expressing human gamma, beta or beta s-globin. Moreover, human erythroid cells from mice transplanted with sickle cell anemia bone marrow showed characteristic sickling under reducing conditions in an in vitro assay. This model provides a powerful in vivo system that can be used to evaluate the efficiency of globin gene transfer into primitive human hematopoietic cells, lineage-specific expression in mature erythrocytes, and ultimately correction of the cellular defect found in the erythroid lineage.

Anemia, Sickle Cell↗

PubMed1995

Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins.

To investigate the involvement of peripheral-type benzodiazepine receptors (PBR) in heme metabolism, we examined the interaction of [55Fe]heme with PBR. Transfection of the cloned mouse PBR-isoquinoline carboxamide-binding protein (PBR/IBP) cDNA into monkey kidney Cos-1 cells resulted in a 2.5-fold increase in [55Fe]hemin binding sites, concomitant with the increase in [3H]PK11195 binding sites, as compared with those seen in antisense PBR/IBP cDNA-transfected cells. The binding of hemin to the transfected receptors exhibited a relatively high affinity with a Kd of 12 nM, and was inhibited by several benzodiazepine ligands, including PK11195, Ro 5-4864, diazepam and protoporphyrin IX. When mouse liver mitochondria were incubated with [55Fe]hemin, the binding to PBR had a Kd of 15 +/- 1.8 nM. The Bmax of [55Fe]hemin binding to the mitochondria was 6.88 +/- 0.76 pmol/mg of protein, a value consistent with that of [3H]PK11195 binding, with a lower affinity. Coproporphyrinogen III, a precursor porphyrin produced in the cytosol, is translocated into mitochondria, then is converted to protoporphyrinogen IX; this conversion decreased in the presence of benzodiazepine ligands. To examine whether this decrease was related to a decrease in the binding of coproporphyrinogen to the mitochondria, the effects of benzodiazepines on the binding of coproporphyrinogen were examined. As the binding was dose-dependently inhibited by PK11195, Ro 5-4864, and diazepam, porphyrins are likely to be endogenous ligands for PBR. We propose that PBR play a role in the intracellular transport of porphyrins and heme.

Animals↗

PubMed1995

Loss of immunostaining of the RBP-J kappa transcription factor upon F9 cell differentiation induced by retinoic acid.

RBP-Jkappa is a novel type of transcriptional regulatory protein that does not contain any known DNA-binding motif. We raised anti-RBP-Jkappa monoclonal antibodies (K0043 and T6709) to investigate the roles of RBP-Jkappa in cell differentiation. These antibodies stained nuclei of undifferentiated embryonic stem cells and F9 cells but not those of the other differentiated cell lines tested so far although the RBP-Jkappa protein is expressed at similar levels. Interestingly, differentiated F9 cells lost the immunostaining reaction with the anti-RBP-Jkappa monoclonal antibodies. Biochemical subcellular fractionation study showed that the majority of RBP-Jkappa was localized in nuclei of F9 cells and that there are at least two forms of the RBP-Jkapppa protein in the nuclei of undifferentiated F9 cells, a free form and a chromatin-bound form. Upon induction of F9 cell differentiation, free nuclear RBP-Jkappa disappeared concomitantly with the loss of immunostaining, suggesting that the anti-RBP-Jkapppa antibodies cannot recognize chromatin-bound RBP-Jkappa. Since there is no evidence to indicate covalent modification of RBP-Jkappa, we assume that chromatin-bound RBP-Jkappa interacts with a large number of proteins which block the exposure of RBP-Jkappa epitopes to the monoclonal antibodies.

3T3 Cells↗

PubMed1995

Ionotropic mechanisms involved in postsynaptic inhibition by the endothelins of ganglionic transmission in dog cardiac sympathetic ganglia.

We investigated the effects of endothelin-1 and endothelin-3 (ET-1, ET-3) on the ganglionic transmission of cardiac sympathetic ganglia in vivo by the direct administration of agents to the ganglia through the right subclavian artery while monitoring the heart rate (HR) as an indicator of the ganglionic function in spinal dogs. The positive chronotropic responses to dimethylphenylpiperazinium (DMPP) and McN-A-343 administered to the ganglia were similarly inhibited by ET-1 (0.05-0.2 microg) and ET-3 (0.5-2 microg), but ET-1 was approximately 10 times more potent than ET-3. The inhibition induced by ETs was antagonized by endothelin ETA receptor antagonist BQ-123 (20 microg). This inhibition was unaffected by pretreatment with indomethacin given intravenously (i.v.), ruling out the possible involvement of endogenous prostaglandins production. The voltage-sensitive Ca2+ channel antagonist nifedipine had no effect on inhibition. However, the inhibition was antagonized by pretreatment with the low conductance Ca2+-activated potassium channel antagonists, such as apamin (20 microg intraarterially, i.a.), scyllatoxin (10 mug i.a.) and D-tubocurarine (0.6 mg i.a.). On the other hand, the voltage-sensitive K+ channel antagonist 4-aminopyridine (4-AP), ATP-dependent K+ channel antagonist, glibenclamide, and high-conductance Ca2+-activated K+ channel antagonists iberiotoxin and charybdotoxin failed to affect the inhibition by ETs. The results suggest that ETs inhibit the nicotinic and muscarinic ganglionic transmission through the ETA receptor-operated low-conductance Ca2+-activated potassium channel at postganglionic sites.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1995

In vivo antitumor activity of hexamethylmelamine against human breast, stomach and colon carcinoma xenografts.

We have evaluated the antitumor activity of Altretamine (hexamethylmelamine, HMM) on human carcinoma xenografts serially transplanted in nude mice. Five human breast carcinoma xenografts, MX-1, T-61, MCF-7, R-27 and Br-10, were inoculated subcutaneously into female nude mice. Two human stomach carcinoma xenografts, SC-1-NU and St-4, and three human colon carcinoma xenografts, Co-3, Co-4 and Co-6, were inoculated subcutaneously into male nude mice. One pellet of 17 beta-estradiol (0.1 mg/mouse) was inoculated subcutaneously in the mice transplanted with MCF-7 when the tumors were inoculated. HMM was administered per os daily for 4 weeks. MX-1 and T-61 tumors regressed completely after treatment with HMM at a dose of 75 mg/kg (the maximum tolerated dose: MTD) for MX-1 and 25 mg/kg for T-61. Br-10 was sensitive, whereas MCF-7 and R-27 were resistant to HMM at its MTD. HMM exerted the most potent antitumor effect against T-61. Against MX-1, it exerted an antitumor effect equivalent to that of cisplatin or cyclophosphamide. In addition, this agent was effective against all stomach and colon carcinoma xenografts, in particular St-4 (T/C% = 10.7: the mean tumor weight of treated group/the mean tumor weight of control group) and Co-3 (T/C% = 31.5%) which are insensitive to presently available agents. HMM seems worthy of further clinical investigation as a candidate agent to treat breast, stomach, colon and other carcinomas.

Altretamine↗

PubMed1995

Persistence of chronic mood disorders: a 2 year follow-up.

Chronic mood disorder patients who remain frequent and long-term users of psychiatric facilities constitute a major clinical concern today. A 2 year naturalistic prospective follow-up study was conducted on a cohort (n = 40) randomly extracted out of 335 such patients. Longitudinal data involving semi-structured interviews, observer-rated scales and self-report measures were available for 37 patients (93%). While three (8%) remitted completely, the cohort on the average showed no statistically significant change in the severity of depression, social adjustment or global functions during the 2 years under observation. Two baseline features that characterized ameliorated patients were the absence of panic disorder and lower level of education.

Adult↗