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Biomedical subjects

J Patel

Publications and source records attributed to J Patel.

At least 19 recordsLinked to original sources
PubMed1997

Utility of square-wave gratings to assess perioral spatial acuity.

PURPOSE: The usefulness of square-wave gratings to assess perioral spatial resolution acuity was evaluated. MATERIALS AND METHODS: A psychophysical tracking procedure was used to estimate the threshold groove width for discriminating orientation (horizontal or vertical) of square-wave gratings pressed into the skin. Ten positionally matched sites on the two sides of the face of 36 right-handed, healthy young adults were studied. Commercially available gratings provided alternating ridge- and-groove stimuli with element widths from 0.35 to 3.0 mm. RESULTS: Thirty-three of the 36 subjects could discriminate orientation at all six sites on the vermilion (threshold width averaged 1.06 mm for grooves and for ridges). Thresholds were lower on the mid-portion of the lower vermilion than on the mid-portion of the upper vermilion (P < .05). Moreover, thresholds were lower on the right side of the vermilion than on the left side (P < .02). In contrast to the vermilion, only 25 and 30 subjects could discriminate orientation on the left and right hairy upper lip, respectively; and two or fewer subjects, at each of 12 sites on the chin and cheeks. CONCLUSIONS: Clinical use of small square-wave gratings with ridge and groove widths of 3 mm or smaller is limited to the vermilion. Moreover, baseline values are needed for individual patients to minimize false-positive diagnoses of sensory impairment. The size required of coarser gratings to test other perioral sites may preclude their use for evaluation of discrete, suspect skin areas.

Adolescent↗
PubMed1997

Prediction of outcome after perinatal asphyxia.

Perinatal asphyxia at term remains a significant cause of infant death and neurodevelopmental impairment, probably causing 20% of all cases of cerebral palsy. This review examines indicators that can help determine the prognosis after suspected asphyxia in term infants, including obstetric information, clinical examination, and diagnostic methods based on neurophysiology, neuroimaging, and biochemistry. New data confirm that many frequently used indicators are generally not specific predictors, while simple electroencephalographic methods, magnetic resonance spectroscopy, and magnetic resonance imaging can have high positive predictive values even when used quite soon after birth.

Asphyxia Neonatorum↗
PubMed1997

ICAM-1 expression in corneal epithelium of a patient with vernal keratoconjunctivitis: case report.

Recent reports have demonstrated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) on the epithelium in various allergic diseases and inflammatory conditions, including the bronchial epithelium of patients with allergic asthma, conjunctival epithelium of allergic patients after allergen-specific challenge, and corneal epithelium of rejected corneal allografts. We investigated the presence of ICAM-1 expression on the corneal epithelium from a patient with vernal keratoconjunctivitis (VKC). Immunohistochemical staining of the diseased cornea demonstrated abundant ICAM-1 expression on the corneal epithelium. Immunoreactive ICAM-1 appeared to localize primarily to the cells of the basal and middle layers of the corneal epithelium. No staining was detected on the ocular surface epithelium. The normal, healthy cornea demonstrated no significant ICAM-1 expression on any of the epithelial layers, similar to that previously reported. To the best of our knowledge, this is the first report of ICAM-1 expression on the corneal epithelium from a patient with VKC.

Adult↗
PubMed1997

The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps.

Colorectal cancers continue as the second most common cause of death from cancer in the United States. Only a few prospective, randomized clinical trials have been performed to evaluate the potential preventive effects of dietary fiber or calcium in patients with an increased risk for the development or recurrence of colorectal cancer. We designed and conducted a double-blinded, placebo-controlled randomized trial involving supplementation of fiber and calcium intake and measurements of [3H]thymidine labeling index (LI) percentages in rectal mucosal biopsies obtained from patients with resected colorectal adenomas to examine the potential mechanisms by which dietary interventions might reduce colorectal cancer risk. We performed a randomized, double-blinded, Phase II study, using a factorial design to measure the effects of supplemental dietary wheat bran fiber (2.0 or 13.5 g/day) and calcium carbonate (250 or 1500 mg/day elemental calcium) supplementation on [3H]thymidine LI percentages in rectal mucosal crypts and 24-h in vitro outgrowth cultures. Measurements were made at baseline randomization (i.e., after a 3-month placebo run-in period using 2.0 g of wheat bran fiber plus 250 mg of calcium carbonate) and after 3 and 9 months on treatment in 100 randomized participants who had a history of colon adenoma resection. Neither the wheat bran fiber nor the calcium carbonate supplements significantly reduced [3H]thymidine LI percentages in rectal mucosal crypts (total or compartmental analysis) or 24-h in vitro outgrowth cultures at either 3 or 9 months of daily supplementation in the 93 evaluable participants. We conclude that 9 months of high-dose wheat bran fiber and calcium carbonate supplementation in study participants with a history of recently resected colorectal adenomas does not have a significant effect on cellular proliferation rates in rectal mucosal biopsies, comparing 3- and 9-month results to baseline results. Ultimately, there is great need for the evaluation of these two different nutrient interventions in the setting of Phase III studies wherein adenomatous polyp recurrence, rather than a rectal mucosal biomarker, serves as the primary end point.

Adenomatous Polyps↗
PubMed1996

Randomized, double-blinded, placebo-controlled study of effect of wheat bran fiber and calcium on fecal bile acids in patients with resected adenomatous colon polyps.

BACKGROUND: Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. PURPOSE: We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. METHODS: In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. RESULTS: All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. CONCLUSIONS: High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. IMPLICATION: Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.

Adenomatous Polyposis Coli↗
PubMed1996

Novel phosphonium salts display in vitro and in vivo cytotoxic activity against human ovarian cancer cell lines.

Phosphonium salts are part of a class of lipophilic cationic molecules that accumulate preferentially in mitochondria and inhibit the growth of human and rodent carcinoma cells in vitro and in animal models. The delocalized cations tested previously such as dequalinium have exhibited considerable cross resistance against multiple drug-resistant cells expressing gp 170. In order to overcome this cross resistance, we have developed two novel phosphonium salts which contain haloalkyl moieties with potential protein alkylating capabilities. 3-Chloropropyltris(4-dimethylaminophenyl)phosphonium chloride (APPCL) and 3-iodopropyltris(4-dimethylaminophenyl)phosphonium iodide (APPI) are more lipophilic than other phosphonium salts described to date. By comparing the 50% inhibitory concentration (IC50) values for the A2780 human ovarian carcinoma parental line to a multiple drug-resistant variant (A2780-DR), the degree of cross resistance (IC50 for A2780-DR/IC50 for A2780 Parental) were found to be 494 for doxorubicin, but only 2.7 for APPCL. Similarly, the degree of cross resistance using a cisplatin-resistant variant (IC50 for A2780-CR/IC50 for A2780 Parental) was 30 for cisplatin, but only 2.2 for APPCL. APPCL is also active in vitro against UCI 101 (IC50 = 80 nM), an ovarian carcinoma line isolated from a patient who had failed chemotherapy with taxol, doxorubicin, and high-dose cisplatin. The cytotoxicity of APPI was comparable to that of APPCL with an IC50 ranging from 16.7 to 83.0 nM for a panel of seven cell lines. When administered intraperitoneally at a total dose of 46 mg/kg over 15 days, APPCL increased the median lifespan of nude mice bearing UCI 101, from a control value of 48.0 to 92.5 days (P < 0.0061). The median survival of the APPI-treated mice was 55 days. A total of 37.5% of the APPCL-treated group and 12.5% of the APPI-treated group were long-term survivors: sacrifice of these mice on Day 180 and subsequent histology showed no evidence of disease. Exposure to APPCL and APPI caused mitochondrial damage to UCI 101 cells at sublethal doses in vitro, as shown by morphological damage observed with transmission electron microscopy. APPCL appears to decrease the uptake of rhodamine 123 by mitochondria, suggesting that mitochondria may be significant targets or initial reservoirs for this agent. In conclusion, APPI and APPCL show promising anticancer activity against a variety of human ovarian carcinoma cell lines warranting further investigation.

Animals↗
PubMed1996

Lactic acid is the factor in blood cell extracts which enhances the ability of CMP-NANA to sialylate gonococcal lipopolysaccharide and induce serum resistance.

In previous work, a factor which enhances the ability of cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) to sialylate gonococcal lipopolysaccharide (LPS) was liberated at 4 degrees C in diffusates from high M(r) fractions of blood cell sonicates. The diffusates also contained CMP-NANA and converted serum susceptible gonococci to resistance. The enhancer has now been separated from CMP-NANA and material absorbing at 260 nm by HPLC on mu Bondapak-10 NH2. Resistance inducing activity was found only in fractions containing CMP-NANA and recovery was poor (about 25%). However, addition of enhancer fractions to CMP-NANA substantially increased its resistance inducing activity. Blood cell sonicates dialysed at 18-20 degrees C released enhancer in diffusates. These were ultrafiltered (nominal cut off 3000 Da) and fractionated on Biogel P2 which removed saccharides and most material absorbing at 260 nm. Over 90% of a fraction which was enhancer-active in nanogram quantities was identified by nuclear magnetic resonance (NMR) spectroscopy and gas chromatography/mass spectometry (GC/MS) as lactic acid. A fraction with similar properties was obtained from a different batch of diffusate by fractionation on Dowex 1. Authentic lithium L-lactate in nanogram quantities enhanced LPS sialyation by CMP-NANA and increased its serum resistance inducing activity. These results have important implications for gonococcal pathogenicity.

Blood Cells↗
PubMed1996

Calcium-dependent enhancement of depletion-activated calcium current in Jurkat T lymphocytes.

We have obtained evidence that the Ca(2+)-selective current activated by Ca2+ store depletion (Ca2+ release-activated Ca2+ current; Icrac) in Jurkat T lymphocytes is augmented in a time-dependent manner by Ca2+ itself. Whole cell patch clamp experiments employed high cytosolic Ca(2+)-buffering conditions to passively deplete Ca2+ stores. Rapidly switching to nominally Ca(2+)-free extracellular buffer instantaneously reduced Icrac measured at -100 mV to leak current level. Unexpectedly, readmission of 2 mM Ca2+ instantaneously restored only 38 +/- 5% (mean +/- SEM, n = 9) of the full Icrac amplitude. The remainder reappeared in a monotonic time-dependent manner over 10 to 20 sec. Rapid vs. slow intracellular Ca2+ chelators did not alter this process, and inorganic Icrac blockers did not regenerate it, arguing against an intracellular site of action. The effect was specific to Ca2+: introduction of the permeant ions, Ba2+ or Sr2+, failed to invoke time-dependent Icrac reappearance. Moreover, equimolar substitution of Ba2+ for Ca2+ initially produced Ba2+ current of similar magnitude to the full Ca2+ current, but the Ba2+ current decayed monotonically to < 50% of its initial amplitude in < 20 sec. Conversely, return to Ca2+ produced a time-dependent increase in Icrac to its larger Ca2+ permeation level. Thus Ca2+ appears to selectively promote a reversible transition of Icrac that results in larger current flux, and at least partially explains the selectivity of this current for Ca2+ over other divalent ions.

Animals↗
PubMed1996

Gabapentin for the treatment of hemifacial spasm.

Pharmacologic therapy for hemifacial spasm is often limited by the paucity of effective medications and problems with side effects. Gabapentin is a novel antiepileptic drug that is generally well tolerated. Its anticonvulsant effect is independent of gamma-aminobenzoic acid (GABA) receptor mechanisms. We report a patient with hemifacial spasm who responded well to gabapentin therapy. Gabapentin may be a useful alternative medical therapy to currently used drugs.

Acetates↗
PubMed1996

Limited role for nitric oxide in mediating cerebrovascular control of newborn piglets.

AIMS: To investigate the effects of the nitric oxide (NO) synthase inhibitor L-nitro-arginine methyl ester (L-NAME) on cerebral blood flow, and its response to alterations in arterial carbon dioxide tension (CBF-CO2 reactivity). METHODS: Cerebral blood flow was measured six times at varying arterial carbon dioxide tension (PaCO2) using the intravenous 133Xenon clearance technique in eight mechanically ventilated piglets of less than 24 hours postnatal age. After the third measurement L-NAME was administered as a bolus (20 mg/kg) and subsequently infused (10 mg/kg/hour). RESULTS: PaCO2 ranged between 2.7-8.9 kPa. Cerebral blood flow decreased by 14.0% (95% confidence interval 1.9-27.4) after L-NAME. CBF-CO2 reactivity was 18.4% per kPa (95% CI 14.1-22.2) before L-NAME and 15.2%/kPa (95% CI 11.1-19.3) afterwards; the difference between the CBF-CO2 reactivities was 3.2%/kPa (95% CI -0.4-6.8): these were not significantly different. CONCLUSIONS: Inhibition of nitric oxide synthesis reduces cerebral blood flow no more than a 0.5-1.0 kPa fall in PaCO2. Nitric oxide is not an important mediator of CBF-CO2 reactivity.

Animals↗
PubMed1995

The effect of nitrogen dioxide exposure on the release of surfactant isolated from neonatal rabbit type II pneumocytes in culture.

Nitrogen dioxide (NO2) is a well-known environmental air toxin, produced from a variety of sources, including cigarette smoke. Because of the growing knowledge of the harmful effects of passive smoking on children, we decided to study the effect of NO2 exposure on the release of surfactant from isolated neonatal type II pulmonary epithelial cells. After isolation from 1 to 4 day old rabbits, type II epithelial cells were allowed to adhere for 18 hours, washed, media changed, and were exposed to either 5% CO2 in room air or NO2, 5 ppm, for 2 hours (all results mean +/- sd; comparisons, paired t-test). There was no difference in cell number or viability prior to exposure. Cells exposed to NO2 had an increase in LDH release [LDH activity in media/(LDH in media+cells) x 100], air 12.6 +/- 2.2%, NO2 21.7 +/- 3.7%, (p < 0.05). NO2-exposed cells also had an increase in total phospholipid (microgram/cell culture dish) in media compared to air exposed, air 170.13 +/- 7.54, NO2 195.15 +/- 11.2, (p < 0.05). 3H-choline incorporation as a precursor to disaturated phosphatidylcholine (DSPC) was also conducted during exposure to either air or NO2. Incorporation of 3H-choline into surfactant lipid was increased in media from cells after NO2 exposure compared to air, 58.23 +/- 15.16 air, 76.81 +/- 19.86 NO2 (cpm/microgram protein; p < 0.05). These results show that 2 hours of 5 ppm NO2 exposure is associated with an increase in release of surfactant from neonatal type II cells in culture.

Animals↗
PubMed1995

A prodrug approach to increasing the oral potency of a phenolic drug. Part 2. Pharmacodynamics and preliminary bioavailability of an orally administered O-(imidomethyl) derivative of 17 beta-estradiol.

The O-saccharinylmethyl prodrug of 17 beta-estradiol was about nine times as potent, based on 50% effective dose (ED50) values, as 17 beta-estradiol when each was given as an oral dose to ovariectomized rats. Similarly, a significant lowering of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at 24 h was observed when an ED50 dose of the prodrug was given but not when an equimolar dose of 17 beta-estradiol was given orally. However, when given intravenously, there was no difference in potency between the two drugs. In the bioavailability studies, a significantly longer half-life (approximately 5-7 times) for 17B-estradiol was observed when the prodrug was given orally than when 17 beta-estradiol was given orally or when the prodrug or 17 beta-estradiol were given intravenously. This result was consistent with an observed five-fold enhancement in the oral bioavailability of 17 beta-estradiol when the prodrug was given.

Administration, Oral↗
PubMed1995

Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro.

BACKGROUND/AIMS: Helicobacter pylori is associated with neutrophil infiltrates, although the mechanism of their recruitment is only partially defined. The aim of the study was to determine if Kato III, a human gastric epithelial cell line, expressed cytokines and the intercellular adhesion molecule 1 (ICAM-1), which could contribute to the initiation of inflammation during infection with H. pylori. METHODS: Kato III cells were stimulated with H. pylori and were examined for evidence of infection, cytokine production, and the expression of ICAM-1. RESULTS: The expression of interleukin 8 messenger RNA and immunoreactive protein by Kato III cells was significantly increased over constitutive levels within 3 hours of infection with H. pylori. Infected Kato III supernatants activated neutrophils as evidenced by increased CD11b/CD18 and decreased L-selectin that could be blocked by anti-interleukin 8. In contrast, Campylobacter jejuni, lipopolysaccharide, killed H. pylori, and supernatants from cultures of H. pylori did not increase interleukin 8. Interleukins 2 and 6; interferons alfa, beta, and gamma; and tumor necrosis factor were not produced by resting or H. pylori-stimulated Kato III cells. In addition to producing interleukin 8, Kato III constitutively expressed surface ICAM-1, which acts as an intercellular adhesion molecule for neutrophils. CONCLUSIONS: Our results indicate that H. pylori stimulates the gastric epithelium to initiate inflammation and neutrophil recruitment and activation.

Base Sequence↗
PubMed1995

Biphasic inhibition of stimulated endogenous dopamine release by 7-OH-DPAT in slices of rat nucleus accumbens.

1. Fast cyclic voltammetry was used to investigate the effect of 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative D3 receptor agonist, on electrically stimulated endogenous dopamine release in slices of rat nucleus accumbens. 2. 7-OH-DPAT inhibited single pulse stimulated dopamine release in a concentration-dependent manner with a maximum inhibition of 95.5%. Analysis of concentration-response curves to 7-OH-DPAT showed that they were biphasic, with the high affinity component contributing 18.0% to the total inhibition and the low affinity component 77.5%. 7-OH-DPAT exhibited a 560 fold selectivity between the high and low affinity components (0.015 nM compared to 8.4 nM). 3. Concentration-response curves to the non-selective D2/D3 agonist, apomorphine, were monophasic. The maximum inhibition was 93.1% and the EC50 value 82 nM. 4. The selective D2 antagonist, haloperidol (30 nM), antagonized the low affinity component of the concentration-response cuve to 7-OH-DPAT whilst the high affinity component was essentially unaffected. The pKB values calculated for the high and low affinity components were 7.89 and 9.45 respectively. 5. In conclusion, these results demonstrate that 7-OH-DPAT inhibits stimulated dopamine release by acting at two different sites. Furthermore, the results are consistent with the hypothesis that the high and low affinity components of the concentration-response curve to 7-OH-DPAT may reflect activation of functional D3 and D2 release-regulating autoreceptors respectively. However, the possibility that the biphasic nature of the curve may reflect different subtypes of the D2 receptor cannot be excluded.

Animals↗
PubMed1995

Elevation of maternal alpha-fetoprotein in systemic lupus erythematosus: a controlled study.

OBJECTIVE: To determine if maternal alpha fetoprotein (AFP) is elevated in lupus pregnancy and, if so, whether it is associated with treatment or outcome. METHODS: Maternal serum AFP values were obtained once during Weeks 16.3 to 31.7 in 54 pregnancies followed prospectively. AFP was measured by the Maryland State Health Department, who reported the AFP level and a corrected value, multiple of the median (AFP MOM), adjusted for weight, gestational age, and insulin dependent diabetes. Controls were 1001 consecutive samples measured by the same laboratory. RESULTS: AFP MOM was higher in lupus pregnancies (1.425 +/- 0.73 vs 1.169 +/- 0.50, p = 0.001), as were the unadjusted AFP levels (lupus 68.26 +/- 42.2, control 52.49 +/- 27.25, p = 0.001). Of lupus pregnancies 7.4 vs 2.6% of control pregnancies had an abnormal AFP MOM (p = 0.06). The 4 patients with abnormal AFP-MOM, using the 2.3 cutoff, were taking more prednisone (27.25 +/- 18.54 mg vs 10.85 +/- 12.29 mg, p = 0.02), were more likely to have delivered preterm (31.50 +/- 36.31 weeks, p = 0.02), and were more likely to have a high anticardiolipin (aCL) antibody during the pregnancy (p = 0.03). CONCLUSION: AFP is higher in lupus than in control pregnancies, without any increase in neural tube or other birth defects. An abnormal maternal serum AFP level is associated with higher prednisone dose, preterm delivery and aCL. Patients and obstetricians need to be aware that an elevated maternal AFP in lupus pregnancy is not necessarily due to a birth defect, and may be predictive of preterm delivery.

Adult↗
PubMed1995

Comparison of fixation disparity curve variables measured with the Sheedy Disparometer and the Wesson Fixation Disparity Card.

BACKGROUND: Previous studies suggest differences in the fixation disparity curves obtained with the Sheedy Disparometer and the Wesson Fixation Disparity Card, the two most commonly used methods for measuring fixation disparity. In one study the investigators proposed that the differences do not exist for subgroups divided by phoria. The purpose of this paper is to try to clarify this issue by use of two large sets of data. METHODS: Dissociated phorias were measured by the von Graefe method. Fixation disparity curves were plotted using the Disparometer and the Wesson card. RESULTS: Type I fixation disparity curves were most common with the Wesson card. Type II curves were found more often with the Disparometer than with the Wesson card. The x-intercepts were shifted in the base-in (BI) direction with the Wesson card compared to the Disparometer. The y-intercepts were shifted in the exo direction with the Wesson card compared to the Disparometer. The differences were statistically significant regardless of whether the dissociated phoria was exo or eso. The slope of the fixation disparity curve was steeper with the Wesson card than with the Disparometer. The difference was statistically significant for exophores but not for esophores. The differences between results obtained with the two instruments are not consistent from one subject to another as shown by high standard deviations of the differences. CONCLUSIONS: The fixation disparity curves measured with these two instruments are different. Fixation disparity parameters obtained from one of these instruments cannot be used with normative findings from the other.

Evaluation Studies as Topic↗
PubMed1994

Deletions within the DNA recognition subunit of M.EcoR124I that identify a region involved in protein-protein interactions between HsdS and HsdM.

The DNA recognition subunit (HsdS) of type I restriction endonucleases can be divided into domains by means of amino acid identity between subunits from the same family. It has been proposed that DNA-protein interactions occur within the variable domains of the subunit and that protein-protein interactions involve the conserved domains. We have constructed a number of deletion mutants of HsdS that have allowed us to investigate protein-protein interactions. Using a combination of a "competitive" complementation assay and the ability of HsdM to "solubilize" HsdS, we have defined a region within the central conserved domain of HsdS that is responsible for HsdS-HsdM interaction. Computer analysis of amino acid identity between the N-terminal half and the C-terminal half of HsdS identifies a region (repeated in both conserved domains), one copy of which overlaps the region we have identified as essential for HsdS-HsdM interactions, which may be responsible for such protein-protein interactions.

Amino Acid Sequence↗