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Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 343 records · Page 19Linked to original sources
PubMed1996

Lack of response to dietary protein in pancreatic secretion by chronic deprivation of jejunal chyme in rats.

BACKGROUND: Exocrine pancreatic secretion is regulated by luminal factors, bile-pancreatic juice (BPJ), and food chyme. The effects of 10 days' chronic deprivation of luminal chyme on the stimulation of exocrine pancreatic secretion by dietary protein were examined in rats with or without BPJ in the jejunum. METHODS: The jejunum was deprived of ingested food by preparing a whole-jejunum blind loop. The BPJ was diverted by a common bile-pancreatic duct catheter and was returned to the upper jejunum (with BPJ) or ileum (without BPJ). RESULTS AND CONCLUSION: In rats with the ingested food and BPJ in the jejunum (control), secretion rates in terms of volume, protein, amylase, and trypsin increased more than twofold from the rates in the fasting state after a jejunal injection of peptic hydrolysate of casein. In contrast, the secretions were not increased by the protein injection in the rats deprived of jejunal chyme with or without BPJ in the jejunum. Even in the chyme-deprived group the protein and trypsin secretion of the fasting state was significantly higher in BPJ-diverted rats than in rats with BPJ. These results showed that chronic deprivation of the jejunal chyme impaired responses of the exocrine pancreas to dietary protein but not the hypersecretions of the pancreas by BPJ diversion.

Amylases↗
PubMed1996

[A case of plasma cell granuloma associated with cerebral infarction].

A 36-year-old male complained of double-vision and pain of left orbita. On admission, T1-weighted Gd-enhanced MR image of his head showed high intensity lesion in the left carvenous sinus, and his chest X-P showed multiple coin lesions. Microscopic findings of lung open biopsy specimen showed prolifelation of mature plasma cell in the granuloma and the patient was diagnosed as having plasma cell granuloma. Although the lung lesions had a tendency to spontaneous remission, we started the steroid pulse therapy and betamethasone (8 mg/day) therapy for intracranial lesion. Then the lung lesions vanished and we decreased the dose of betamethasone from 8 mg/day to 6 mg/day. As the results, the intracranial lesion of this patient expanded and left middle cerebral artery occluded, resulting in right hemiparesis and total aphasia. This is the first case report of plasma cell granuloma with a lesion in the central nervous system associated with cerebral infarction.

Adult↗
PubMed1996

[A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET].

We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-I antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We investigated cerebral blood flow, glucose and amino acid metabolism in this patient using positron emission tomography, and obtained the following three characteristic findings in the lesions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.

Animals↗
PubMed1996

[Removal of complete type of mediastinal goiter in thirty-six-year-old female--a case report].

A tumor 6 cm in diameter located in the anterior superior mediastinum was found in a 36-year-old female, initially detected on chest-X-ray film in mass screening. The tumor was positively shown by 201thallium chloride scintigram. It was removed, and rapid diagnosis by frozen section proved benign. Follicular adenoma, with no connection to the thyroid, was diagnosed. It was a complete type of mediastinal goiter. Considering quality of life (QOL) as a 36-year-old female, the approach is important. Right half collar incision and upper median sternotomy from the top to the 3rd intercostal space was performed. Because few difficulties were experienced in removing the tumor, this case suggested that the incision and approach has usefulness to keep QOL.

Adenoma↗
PubMed1996

[Optimal time of the day for measuring peak expiratory flow rates in patients with asthma].

Regular measurement of peak expiratory flow rate (PEF) has been recommended as an aid in the management of asthma, but the time of the day when PEF should be measured remains unclear. We therefore sought to determine the optimal time for measuring PEF in untreated patients with mild to moderate asthma. PEF was measured in 11 patients four times daily: on waking, around noon, in the evening, and at bedtime. Significant (p < 0.05) rhythms were detected by single cosinor analysis in all patients. Analysis by the population mean cosinor method showed that the mesor was 381 +/- 120 l/m, the amplitude was 52 +/- 21 l/m, and the acrophase was at 16:28 +/- 0:55. These data indicate that, in general, PEF is lowest at 4:30 a.m. and highest at 4:30 p.m. in patients with mild to moderate asthma. We conclude that PEF should be measured early in the morning and at 4:30 p.m. in such patients.

Adolescent↗
PubMed1995

MDM2 protein confers the resistance of a human glioblastoma cell line to cisplatin-induced apoptosis.

Induction of apoptosis in tumor cells is an important mechanism of chemotherapy-induced cell death. The tumor-suppressor gene p53 is required for the efficient activation of apoptosis following chemotherapy. However, the molecular mechanism regulating p53-associated apoptosis remains controversial. In this study, we show that the expression of both wild-type p53 and MDM2 (murine double minute 2) proteins was induced when cis-diamminedichloroplatinum (cisplatin) caused apoptosis in human glioblastoma U87-MG cells, which expressed neither wild-type p53 nor MDM2 protein prior to treatment. Overexpression of MDM2 in U87-MG cells transfected with human mdm2 expression vector conferred the resistance of tumor cell to cisplatin-induced apoptosis. In contrast, the treatment with mdm2 antisense oligonucleotide targeted against mdm2 mRNA increased the susceptibility of tumor cells to apoptosis. Changes in expression level of MDM2 protein, however, did not affect the expression of wild-type p53 protein. These findings suggest that MDM2 protein may act as a negative regulator of cisplatin-induced apoptosis, and moreover, may play an important role in the development of resistance to cisplatin in human tumors.

Apoptosis↗
PubMed1995

Intracoronary stenting of a coronary occlusion resulting from an aortic dissection.

Acute myocardial infarction secondary to aortic dissection may occur due to compression of the coronary arteries by a hematoma or extension of the dissection into the coronary arterial wall. We report a patient with this condition who was successfully treated by Palmaz-Schatz stenting, providing an alternative to thrombolysis or angioplasty.

Aortic Dissection↗
PubMed1995

Sequential changes in human Ito cells and their relation to postnecrotic liver fibrosis in massive and submassive hepatic necrosis.

To examine the relationship of Ito cells to postnecrotic liver fibrosis, liver specimens, obtained at autopsy from 17 patients with acute massive necrosis (AMN) and acute submassive hepatic necrosis (ASMN), were examined immunohistochemically. In normal adult livers, Ito cells positive for alpha-smooth muscle actin isoform (ASMA) were rarely seen, scattered along hepatic sinusoids. In contrast, in AMN the Ito cells in necrotic areas became strongly positive for ASMA. They were swollen with elongated cytoplasmic processes along collapsed sinusoidal walls. Around these ASMA-positive Ito cells, there were numerous infiltrated macrophages and lymphocytes present. There was no significant alteration of fibroblasts in the portal tracts. In the middle and late stages of ASMN, the spindle-shaped ASMA-positive Ito cells formed a continuous cellular network. New fibre formation was predominantly around them. In this immediate postnecrotic fibrosis, ASMA-positive stromal cells of Ito cell origin were distributed irregularly and were closely associated with reticulin and newly-formed collagen fibres. Regenerative nodules were surrounded by dense layers of ASMA-positive stromal cells. Throughout the stages of ASMN, portal fibroblasts remained negative for ASMA. We believe that Ito cells in necrotic areas show myofibroblastic transformation and play a central role in the postnecrotic liver fibrosis. Portal fibroblasts play no significant part in this type of fibrosis.

Actins↗
PubMed1995

Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man.

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.

Adult↗
PubMed1995

Urinary excretion of type IV collagen and laminin in the evaluation of nephropathy in NIDDM: comparison with urinary albumin and markers of tubular dysfunction and/or damage.

To clarify the diagnostic relevance of urinary type IV collagen (IV-C) and laminin in diabetic nephropathy, the excretion of these basement membrane proteins were determined by enzyme immunoassay in 172 non-insulin-dependent diabetic patients with different grades of nephropathy and 64 non-diabetic control subjects, and were evaluated in comparison with those of urinary albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin (alpha 1MG). These excretions were also compared between a group of non-diabetic renal disease (NDRD) patients (n = 24) and a subgroup of the diabetic patients studied (n = 76), whose urinary albumin excretion (UAE) varied within the ranges of micro- and macroalbuminuria. Of the diabetic patients studied, 49.7%, 53.4% and 32.4% had raised urinary albumin, NAG and alpha 1 MG excretion, respectively. In these patients, 54% and 53% exceeded the upper limit of normal for urinary IV-C and laminin. The level of IV-C and laminin excretion and the prevalence of their abnormal excretion showed a trend to increase with increasing grade of nephropathy, as assessed by UAE. In the normoalbuminuric [UAE < 20 mg/g creatinine (Cr)] stage, 28.3% and 26.3% patients had raised urinary IV-C and laminin excretion, respectively. In this stage, the excretion values for IV-C and laminin also rose significantly even when the UAE was < or = 10 mg/g Cr (P < 0.05 and P < 0.005, respectively). There was a close linear relationship between IV-C and laminin excretion (r = 0.73, P < 0.0001), together with their significant relationships with albumin, NAG and alpha 1MG excretion. The relationship of urinary IV-C and laminin with urinary NAG and alpha 1MG excretion remained significant even in normoalbuminuric patients. The normoalbuminuric patients with raised NAG and/or alpha 1MG excretion also had a higher prevalence of raised IV-C and laminin excretion than those with normal NAG and alpha 1MG excretion. The excretion values for IV-C and laminin, and the excretion ratios for IV-C/albumin and laminin/albumin were significantly higher in diabetic patients with evidence of incipient and clinical nephropathy than in NDRD patients, though the two patient groups had a comparable level of serum Cr and UAE. We conclude that the measurement of urinary IV-C and laminin may have potential for the evaluation of diabetic nephropathy. Furthermore, their determination might be helpful for distinguishing diabetic versus non-diabetic etiologies of altered renal function in diabetic patients.

Acetylglucosaminidase↗
PubMed1995

Proliferative activity in breast carcinoma evaluated by BrdU and PCNA. Correlation with expression of p53, c-erbB-2, estrogen receptor and P-glycoprotein.

The proliferative activity in 35 cases of breast carcinoma was evaluated by bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) and was compared with benign breast lesion. Overexpression of p53 and c-erbB-2 oncoprotein, presence of estrogen receptor (ER) and cellular localization of multidrug resistance gene product P-glycoprotein (P-gp) were immunohistochemically examined to investigate the relation with the proliferative activity and clinicopathologic characteristics. The mean BrdU labeling index (LI) was 12.6% and PCNA labeling rate (LR) was 33.5% in breast carcinomas, and good correlation was found between them. The proliferative activity of breast carcinomas was significantly higher than that of benign lesions. The BrdU LI correlated positively with tumor size, histologic grade, TNM stage and p53 immunoreactivity, and negatively with the presence of ER. PCNA LR correlated with histologic grade and expression of p53. p53 protein was demonstrated in 43% of the breast carcinomas and correlated with proliferative activity. The extent of p53 immunoreactivity on carcinoma cells was also related to BrdU LI. c-erbB-2 oncoprotein was demonstrated in 51% of the breast carcinomas and correlated with histologic grade. ER was found in 34% of the breast carcinomas and correlated negatively with histologic grade, lymph node metastasis and TNM stage. P-gp was observed in 49% of the breast carcinomas and no correlation was found with clinicopathologic characteristics. None of the benign lesions expressed p53 protein, c-erbB-2 oncoprotein and P-gp. BrdU is a reliable standard and a more useful tool for the evaluation of proliferative activity of breast tumors. High proliferative activity, overexpression of p53 protein and the absence of ER are considered as a high grade malignancy of breast carcinoma. Expression of c-erbB-2 oncoprotein and P-gp may be related to malignant transformation of breast tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Anti-A and/or anti-B is not detectable in some patients who underwent ABO-incompatible bone marrow transplantation.

BACKGROUND: Recently, anti-A and/or anti-B produced by B cells from donor marrow could not be detected for more than 20 weeks in some patients who had undergone ABO-incompatible bone marrow transplantation (BMT). STUDY DESIGN AND METHODS: Twelve to 72 weeks after 11 patients underwent ABO-incompatible BMT, titers of anti-A and anti-B were assayed, A and B antigens were identified by routine methods and flow cytometry, direct and indirect antiglobulin tests were performed, and the red cell antibody was eluted. RESULTS: In some patients who underwent ABO-incompatible BMT, anti-A and/or anti-B produced by the B cells from the donor marrow could not be detected after BMT when red cells taken from the patients before BMT carried the corresponding antigen--that is, when hematopoiesis had already changed the cells to the donor's type according to ABO blood typing. Furthermore, some blood samples from those patients gave positive results in direct antiglobulin tests. Blood typing of patients after BMT showed mixed-field agglutination. In one patient, the half-life of red cells assayed with 51Cr was 22.4 days (30.0 +/- 4.0 days for normal controls). CONCLUSION: Although many hypotheses could be considered to explain the present data, the possibility is proposed that anti-A and/or anti-B in the sera must have been consumed in some patients who underwent ABO-incompatible BMT. This may lead to problems such as difficulty of ABO typing, positive direct antiglobulin tests, and a relatively short life span of red cells.

ABO Blood-Group System↗
PubMed1995

Induction of pancreatic growth and proteases by feeding a high amino acid diet does not depend on cholecystokinin in rats.

We examined differences in pancreatic growth, enzyme content and enzyme concentration between rats fed diets containing normal (2.49 g nitrogen/kg diet) or high (7.46 g nitrogen/kg diet) levels of an amino acid mixture and those in rats fed diets containing normal and high levels of casein for 11 d. Rats fed these diets were injected with a potent cholecystokinin antagonist, MK-329 (2.5 mg/kg body wt.d) or with vehicle only. Pancreatic contents (units in pancreas per 100 g body wt) of protein, trypsinogen and chymotrypsinogen were greater in rats fed a high amino acid diet compared with those in rats fed a normal amino acid diet. Proportionate increases in protein and the serine proteases in pancreata of the high amino acid group relative to those of the normal amino acid group were comparable to those of the high casein group relative to the normal casein group. The pancreatic protease concentrations (units/g pancreas) of rats fed the high casein diet and treated with MK-329 were lower than in rats fed high casein but not treated with MK-329. This difference was not observed in rats fed the high amino acid diet. These results demonstrate that pancreatic growth and proteases are induced by dietary amino acids in rats, and the stimulatory effects of amino acids on exocrine pancreas do not depend on cholecystokinin.

Amino Acids↗
PubMed1995

Gastric acid-independent enhancement of exocrine pancreatic secretion by dietary protein in chronic bile-pancreatic juice diverted rats.

Diversion of bile-pancreatic juice (BPJ) causes exocrine pancreatic hypersecretion in a fasting state, and we demonstrated that a feeding of dietary protein stimulates further secretion of pancreatic enzymes in chronic BPJ-diverted rats. We determined that gastric acid secretion is associated with the stimulatory effect of dietary protein feeding on pancreatic secretion in the diverted rats. BPJ was diverted with a cannula of the common bile-pancreatic duct and returned to the upper ileum for 7 days. The BPJ-diverted rats were administered omeprazole (12 mg/kg body weight) orally and were fed a 25% casein, fat-free diet spontaneously under unrestrained conditions. The volume of BPJ was not changed after administration of omeprazole and feeding the diet. Total protein, amylase, and chymotrypsin secretions were not changed 1 h after omeprazole administration but increased gradually after feeding the diet. The secretion of these enzymes reached peak values 120-150 min after feeding, and these values were two- to threefold higher than those before feeding. We conclude that gastric acid secretion is not responsible for the stimulation of pancreatic secretion that occurs after feeding a dietary protein to chronic BPJ-diverted rats.

Amylases↗
PubMed1995

Clonal analysis of peripheral blood and haemopoietic colonies in patients with aplastic anaemia and refractory anaemia using the polymorphic short tandem repeat on the human androgen-receptor (HUMARA) gene.

The clonalities in white blood cells (WBC) of blood and nucleated bone marrow cells from patients with refractory anaemia and aplastic anaemia were examined by polymerase chain reaction (PCR) methods using the polymorphic short tandem repeat (STR) on the human androgen-receptor gene (HUMARA). Peripheral blood samples were obtained from 12 female patients, six with aplastic anaemia (AA) and six with refractory anaemia (RA). Peripheral blood was fractionated into granulocytes, lymphocytes, T lymphocytes and B lymphocytes. DNA was extracted from each fraction. Bone marrow samples were obtained from seven female patients (three with AA and four with RA). Sorted CD34 positive cells were cultured in a semisolid culture system. DNA was extracted from a 14-day haemopoietic colony. The clonal pattern was assessed using HUMARA gene STR polymorphism and the differential methylation pattern of nearby cytosine residues by PCR methods. Four of six (67%) AA and two of six (33%) RA patients had a monoclonal proliferating pattern in their granulocytes. The ratio of the numbers of minority colonies per majority colonies (m/M ratio) was examined for seven patients (three AA and four RA). In patients who had a clonal haemopoietic pattern in peripheral WBC the ratio was under 0.4 but not zero. In contrast, patients exhibiting a polyclonal pattern had an m/M ratio above 0.8. We concluded that some normal or heterogenous haemopoietic clones, not only MDS but also AA, may remain in the bone marrow, although almost all colonies were derived from a single pathogenic clone when the clonality pattern exhibited monoclonality in peripheral blood analysis.

Adult↗
PubMed1995

Effects of Ca2+ channel blockers on cortical hypoperfusion and expression of c-Fos-like immunoreactivity after cortical spreading depression in rats.

1. We examined the effects of two Ca2+ channel blockers, lomerizine (KB-2796) and flunarizine, on the cortical hypoperfusion (measured by hydrogen clearance and laser Doppler flowmetry methods) and cortical c-Fos-like immunoreactivity that follow KCl-induced cortical spreading depression in anaesthetized rats. Cortical spreading depression was induced by application of 1 M KCl for 30 s to the cortical surface, 3.0 mm posterior to the area of cerebral blood flow measurement. 2. In control rats, KB-2796 (0.3 and 1 mg kg-1, i.v.) dose-dependently increased cerebral blood flow significantly at 30 min and 15 min, respectively, after its administration. Flunarizine (1 mg kg-1, i.v.) significantly increased cerebral blood flow 15 min after its administration. In contrast, dimetotiazine (3 mg kg-1, i.v.), a 5-HT2 and histamine H1 antagonist, failed to affect cerebral blood flow significantly. 3. After KCl application to the cortex, cerebral blood flow monitored by the laser Doppler flowmetry method increased transiently, for a few minutes, then fell and remained approximately 20 to 30% below control for at least 60 min. Cerebral blood flow monitored by the hydrogen clearance method was also approximately 20 to 30% below baseline for at least 60 min after KCl application. KB-2796 (0.3 and 1 mg kg-1, i.v.) and flunarizine (1 and 3 mg kg-1, i.v.) administered 5 min before KCl application inhibited the cortical hypoperfusion that followed KCl application, but dimetotiazine (1 and 3 mg kg-1, i.v.) did not. 4. An indicator of neuronal activation, c-Fos-like immunoreactivity, was detected in the ipsilateral, but not in the contralateral frontoparietal cortex 2 h after KCl application. No c-Fos-like immunoreactivity was seen on either side of the brain in the hippocampus, thalamus, striatum or cerebellum. 5. KB-2796 (1 mg kg-1, i.v.) and flunarizine (3 mg kg-1, i.v.), but not dimetotiazine (3 mg kg-1, i.v.), significantly attenuated the expression of c-Fos-like immunoreactivity in the ipsilateral frontoparietal cortex. 6. These findings suggest that the inhibitory effects of KB-2796 and flunarizine on the cortical hypoperfusion and expression of c-Fos-like immunoreactivity induced by spreading depression are mediated via the effects of Ca(2+)-entry blockade, which may include an increase in cerebral blood flow and the prevention of excessive Ca2+ influx into brain cells. KB-2796 and flunarizine may prove useful as inhibitors of cortical spreading depression in migraine.

Animals↗
PubMed1995

Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase.

Halogenated gomisin J (a derivative of lignan compound), represented by the bromine derivative 1506 [(6R, 7S, S-biar)-4,9-dibromo-3,10-dihydroxy-1,2,11,12-tetramethoxy-6, 7-dimethyl-5,6,7,8- tetrahydrodibenzo[a,c]cyclo-octene], was found to be a potent inhibitor of the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) on MT-4 human T cells (50% effective dose, 0.1 to 0.5 microM). Gomisin J derivatives were active in preventing p24 production from acutely HIV-1-infected H9 cells. The selective indices (toxic dose/effective dose) of these compounds were as high as > 300 in some systems. 1506 was active against 3'-azido-3'-deoxythymidine-resistant HIV-1 and acted synergistically with AZT and 2',3'-ddC. 1506 inhibited HIV-1 reverse transcriptase (RT) in vitro but not HIV-1 protease. From the time-of-addition experiment, 1506 was found to inhibit the early phase of the HIV life cycle. A 1506-resistant HIV mutant was selected and shown to possess a mutation within the RT-coding region (at position 188 [Tyr to Leu]). The mutant RT expressed in Escherichia coli was resistant to 1506 in the in vitro RT assay. Some of the HIV strains resistant to other nonnucleoside HIV-1 RT inhibitors were also resistant to 1506. Comparison of various gomisin J derivatives with gomisin J showed that iodine, bromine, and chlorine in the fourth and ninth positions increased RT inhibitory activity as well as cytoprotective activity.

Antiviral Agents↗