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Biomedical subjects

S Kang

Publications and source records attributed to S Kang.

At least 19 recordsLinked to original sources
PubMed1992

Adrenal steroid receptor activation in rat brain and pituitary following dexamethasone: implications for the dexamethasone suppression test.

The dexamethasone suppression test (DST) has been used extensively to evaluate feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis by adrenal steroids. Nevertheless, it remains unclear at what level of the HPA axis and through which adrenal steroid receptor subtype dexamethasone exerts its inhibitory effect. Because adrenal steroid receptor activation is an important prerequisite for dexamethasone to affect cellular function, HPA axis tissues that exhibit evidence of receptor activation following dexamethasone administration are likely site(s) of action for this synthetic hormone to inhibit HPA axis activity. Therefore, type-I and type-II adrenal steroid receptor activation was assessed in the pituitary, hypothalamus, and hippocampus of intact and adrenalectomized rats after overnight exposure to various oral doses of dexamethasone. Results with dexamethasone were compared to similar studies using corticosterone, the endogenous glucocorticoid of the rat. All dexamethasone doses led to significant type-II receptor activation in the pituitary, whereas only an exceedingly high dexamethasone dose activated type-II receptors in the hippocampus and hypothalamus. Dexamethasone had little effect on type I receptors in any tissue at any dose. In contrast, corticosterone significantly activated type-I receptors in all tissues, whereas it activated type-II receptors in the brain and not the pituitary at physiological concentrations. Because dexamethasone activated pituitary type-II receptors at blood concentrations that did not activate type-II receptors in the brain, these results suggest that the DST in humans may primarily be a measure of type-II adrenal steroid receptor feedback inhibition at the level of the pituitary.

Adrenalectomy↗
PubMed1992

Central non-Pur.Pyr sequences in oligo(dG.dC) tracts and metal ions influence the formation of intramolecular DNA triplex isomers.

The effect of the central non-Pur.Pyr sequences in oligo(dG.dC) inserts on determining the type of intramolecular DNA triplex isomers formed in negatively supercoiled plasmids was investigated. Different triplex types (H-r3, H-r5, and H-y3), revealed by a combination of chemical probing and Maxam-Gilbert sequencing reactions, were adopted by the oligo(dG.dC) tracts depending on the length and composition of the central non-Pur.Pyr sequences (0, 3, or 5 base pairs) and the kind of metal ions. The H-r3 triplex conformer, one isomer of a Pur.Pur.Pyr structure, was formed in the (C)20 and (C)10GCG(C)10 inserts in plasmids in the presence of certain metal ions. Interestingly, H-r5, the other isomer of the Pur.Pur-Pyr triplex which had not been detected previously, was formed in a (C)9GAATT(C)9 insert in the presence of either Mg2+ or Ca2+. Alternatively, H-y3, one isomer of a Pyr.Pur.Pyr triplex, was formed in the (C)9GAATT(C)9 insert in the absence of metal ions. Thus, central non-Pur.Pyr sequences and metal ions play a role as determinants of the types of intramolecular triplexes formed; they also reduce the requirement of longer Pur.Pyr repeat sequences to form intramolecular triplexes. Furthermore, the effects of MgCl2 concentration and pH on the formation of triplex isomers were examined. The Pur.Pur.Pyr conformations (H-r3 and H-r5) may be the favored conformations in the cellular milieu, since they are stable at physiological pH and metal ion concentration.

Acetaldehyde↗
PubMed1992

Multiple primary cutaneous melanomas.

BACKGROUND: Development of multiple primary cutaneous melanomas is a well-recognized phenomenon. As with single primary melanoma, personal and family histories of melanoma and dysplastic nevi (DN) are considered important risk factors. The natural history and impact of regular follow-up evaluation of this entity were examined. METHOD: Through a search of the computerized data bank of the Pathology Department and the Melanoma Registry of the Pigmented Lesion Clinic at Massachusetts General Hospital, 41 patients with multiple cutaneous melanomas were identified. RESULTS: Mean (+/- standard error) age at first diagnosis was 49 +/- 2 years (range, 21-75 years). The male to female ratio was 2:1. The median number of primary melanomas was two (88%). Three patients had three and one had five. Melanoma types included superficial spreading (70%), nodular (8%), lentigo maligna (2%), and unclassified (10%), and in 7% the type was unknown. Nineteen (46%) patients had histologic and/or clinical evidence of DN. For the group with DN, the mean age at first diagnosis (44 +/- 3 years) was significantly less than that of patients without DN (54 +/- 3 years) (P less than 0.05). Family history of melanoma was found in 10 patients (24%). Multiple melanomas were diagnosed concurrently in 16 patients (39%), whereas in 25 (61%) diagnosis was sequential. For the latter group, the mean tumor thickness from the first (1.21 +/- 0.28 mm) to the second melanoma (0.51 +/- 0.08 mm) decreased significantly (P less than 0.05); the median time interval was 36 months (range, 2-372 months). CONCLUSION: These data confirm the need for complete skin examination for patients with newly diagnosed melanoma; and, with subsequent melanomas appearing as long as 31 years after the first melanoma, continued follow-up with complete skin examinations seems prudent.

Adult↗
PubMed1992

GC-rich flanking tracts decrease the kinetics of intramolecular DNA triplex formation.

The effect of the base composition of flanking sequences on DNA intramolecular triplex formation was investigated in negatively supercoiled plasmids. The rates of triplex formation at two oligopurine.oligopyrimidine inserts with interrupting sequences in plasmids containing AT- or GC-rich flanking sequences were compared as a function of temperature, pH, and negative superhelical density. The kinetics of the transition of linear B-DNA to triplex (also called H-DNA) were influenced by all of these factors; triplexes were formed slower in a GC-rich background than in an AT-rich background. However, at equilibrium, the same amounts of the triplexes in AT- or GC-rich contexts were formed, and the conformations adopted by (GAA)4TTCGC(GAA)4 showed the canonical intramolecular triplex as mapped with chemical probes. We propose that the GC-rich segments caused this effect by thermodynamically clamping the DNA inserts, since the dependence of kinetics on base composition disappeared in tetraalkylammonium ions which eliminate the dependence of helix-coil transitions on base composition. The dependence of the kinetics of intramolecular triplex formation on flanking sequences further strengthens the concept of the role of DNA as a dynamic participant in cellular events.

Base Sequence↗
PubMed1992

Lymphotropic papovavirus transforms hamster cells without altering the amount or stability of p53.

Expression of the early regions of several primate polyomaviruses (SV40, BKV, JCV, and LPV) in hamster cells induces transformation, manifested by the ability to grow in soft agar. Hamster cells transformed by SV40 contain complexes between the SV40 T antigen and the cellular tumor suppressor protein p53. We detected analogous complexes between p53 and the BKV T antigen in hamster cells transformed by the BKV early region, where the half life of p53 increased 16-fold. However, neither a LPV-transformed hamster fibroblast cell line [LPV-HE (F); K. K. Takemoto and T. Kanda, 1984, J. Virol. 50, 100-105] nor BHK-21 cells transformed by the LPV early region contained detectable complexes between the LPV T antigen and p53, nor was the stability of p53 in LPV transformed BHK-21 cells altered. Association between hamster p53 and the LPV T antigen expressed as glutathione S-transferase fusion protein could not be detected in vitro. These data indicate that alteration of the amount or stability of p53 is not required for transformation of hamster cells by LPV. However, as viruses such as SV40 and BKV whose T antigens bind p53 are oncogenic in hamsters, whereas LPV is not, the alteration of p53 amount or stability may be required for tumorigenesis.

Agar↗
PubMed1992

Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging: Part 1. Theory and data analysis methods.

Theory and novel data analysis methods of 17O inhalation measurements are presented for the calculation of CMRO2, regional cerebral blood flow (rCBF), the reflow (R), the arterial venous difference (AVD) and the partition coefficient (lambda). Several of the methods proposed for the determination of CMRO2 do not require measurements of regional cerebral blood flow and H2(17)O arterial concentration. All methods of analysis are based on the Kety-Schmidt approach.

Animals↗
PubMed1992

[Chemical constituents of Rhodiola kirilowii (Reg.) Reg].

Three compounds were isolated from the water-soluble part of alcohol extracts of rhizomes of Rhodiola kirilowii. Two of them were identified as salidroside and tyrosol, respectively by chemical and spectral analysis. beta-sitosterol was obtained from the petroleum extracts of the plant.

Drugs, Chinese Herbal↗
PubMed1992

Primary malignant melanoma of the external auditory canal: a case report with presentation as an aural polyp.

A case of primary cutaneous melanoma of the external auditory canal and a review of the literature are reported. This is the first reported case with microstaging of the tumor. The tumor presented as a polypoid obstructive lesion of the external ear canal. Although occurrence of melanoma in this location is extremely rare, differential diagnosis of an external ear canal polyp should be expanded to include primary malignant melanoma.

Biopsy↗
PubMed1991

Prognosis after initial recurrence of cutaneous melanoma.

We reviewed 231 patients who developed recurrent disease 1 to 218 months after surgical therapy for clinical stage I cutaneous melanoma. Metastatic lesions amenable to surgery, including visceral recurrences, were resected. Adjuvant systemic chemotherapy/immunotherapy or regional hyperthermic perfusion was added in patients with unresected disease. Local irradiation was employed for nonresectable brain or other isolated symptomatic metastases. The overall 5-year survival rate after initial recurrence was 36%. In patients with soft tissue or nodal recurrence, the 5-year survival rates were 49% and 38%, respectively; six (11%) of 53 patients whose initial recurrence was in a visceral organ achieved prolonged remission. Primary lesion anatomic site, thickness, pathologic type, and interval from initial therapy to recurrence were unrelated to survival. Significant prognostic factors included the site of initial metastasis, stage of primary disease, and the successful complete eradication of gross disease by surgical excision or intensive chemotherapy.

Adult↗
PubMed1991

Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

OBJECTIVE: The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. RESEARCH DESIGN AND METHODS: Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. RESULTS: The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). CONCLUSIONS: The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.

3-Hydroxybutyric Acid↗
PubMed1991

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

OBJECTIVE: To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. RESEARCH DESIGN AND METHODS: Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. RESULTS: The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and 68.9 +/- 3.5 from 2.5 h onward; and hexameric insulin 20.7 +/- 1.9 from 0 to 2 h, 45.6 +/- 5.0 from 2.5 to 5 h, and 70.6 +/- 6.3 from 5 h onward. CONCLUSIONS: Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.

Absorption↗
PubMed1991

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

OBJECTIVE: To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). RESEARCH DESIGN AND METHODS: Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. RESULTS: Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). CONCLUSIONS: Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Adult↗
PubMed1991

[The qualitative and quantitative analyses of protein with a novel fluorescence agent (EPQS) by fluorescent scanning on solid substrate].

We synthesized a new fluorescence agent, EPQS, which could be soluble in water and was stable in the analytical process. It was characteristic of good fluorescence parameters. Human serum albumin (HSA) was marked with EPQS and purified by the paper electrophoresis dialysis. We determined the fluorescent spectra and excitation spectra of the marked HSA, or EPQS on the cellulose acetate paper by RF-510 fluorescence spectrophotometer-thin-layer chromatoscanner. The former lambda ex = 370nm lambda em = 470nm; the latter lambda ex = 382nm lambda em = 476 nm. Then we touched different quantity of EPQS-HSA upon the cellulose acetate. The fluorescent scanning on the paper disclosed that the relationship between the quantity adopted and the fluorescence intensity is linear. These showed that the protein could be quickly determined qualitatively and quantitatively by this simple method, and EPQS was useful.

Chromatography, Thin Layer↗
PubMed1990

Comparison of insulin analogue B9AspB27Glu and soluble human insulin in insulin-treated diabetes.

Postprandial plasma glucose excursions and plasma levels of free insulin after subcutaneous bolus injection of a rapidly absorbed monomeric insulin analogue (B9AspB27Glu) or soluble human insulin ('Actrapid HM' U100) were studied in six insulin-treated diabetic subjects. 10 U actrapid or an equimolar amount of the analogue were injected, in random order with an interval of 1 week, immediately before a 500 kcal test meal. Basal insulin levels were similar on the 2 study days (mean 74.1 [SE 5.1] pmol/l, actrapid; 79.7 [13.0] pmol/l, analogue). After injection of actrapid plasma free insulin levels rose slowly, reaching a plateau by 105 min at 222 (19) pmol/l. Injection of the analogue resulted in a rapid early peak at 30 min (798 [112] pmol/l), and levels were significantly higher than those after actrapid between 15 and 210 min. The more physiological plasma insulin levels achieved with the analogue were accompanied by a substantial reduction in postprandial plasma glucose excursions; the integrated area under the incremental plasma glucose curve was 45% lower after the analogue than after actrapid.

Adult↗