Mannose-Presenting "Glyco-Colicins" Convert the Bacterial Cell Surface into a Multivalent Adsorption Site for Adherent Bacteria.

Biofilm formation is integral to the pathogenesis of numerous adherent bacteria and contributes to antimicrobial resistance (AMR). The rising threat of AMR means the need to develop novel nonbactericidal antiadhesion approaches against such bacteria is more urgent than ever. Both adherent-invasive (AIEC, implicated in inflammatory bowel disease) and uropathogenic (UPEC, responsible for ∼80% of urinary tract infections) adhere to terminal mannose sugars on epithelial glycoproteins through the FimH adhesin on their type 1 pilus.

Expanding the scope of the successive ring expansion strategy for macrocycle and medium-sized ring synthesis: unreactive and reactive lactams.

New methods are described that expand the scope of the Successive Ring Expansion (SuRE) with respect to synthetically challenging lactams. A protocol has been developed for use with 'unreactive' lactams, enabling SuRE reactions to be performed on subsrates that fail under previously established conditions. Ring expansion is also demonstarted on 'reactive' lactams derived from iminosugars for the first time.

Strain-Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion.

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide-alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide- and strained alkyne-functionalized Förster resonance energy transfer (FRET) dye pairs.

Oral hypoglycaemic agents: the first thirty years.

A series of 1,333 patients with non-insulin dependent diabetes (NIDDM) treated with oral hypoglycaemic agents (OHAs) between 1956 and 1988 is described. In addition there were 137 patients with insulin dependent diabetes (IDDM). When last on OHAs 51% of the patients with NIDDM were free from symptoms and satisfactorily controlled; 262 patients are known to have died, 223 have had to be changed to insulin and in 41 patients it has been possible to stop OHAs as no longer being needed, usually owing to better dietary compliance.

Diabetes in the United Kingdom: a personal series.

A personal series of 6780 patients with diabetes mellitus is reported. Of these 1410 were thought to have insulin-dependent (Type 1) diabetes and 4926 non-insulin-dependent (Type 2) diabetes. Among the former, 128 patients were only diagnosed when in severe ketoacidosis or coma.

Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle.

Acromegaly is associated with an increased cardiac morbidity and mortality, but it is not clear whether this is the result of increased incidence of hypertension and coronary heart disease or of a specific disease of heart muscle. Thirty four acromegalic patients were studied by non-invasive techniques. Seven of these patients had raised plasma concentrations of growth hormone at the time of study; three were newly diagnosed and had not received any treatment.

Acromegaly.

A personal series of 256 cases of acromegaly/gigantism seen over a 20-year period from 1963 is described. The insidious nature of the condition resulted in delay in diagnosis which was often made by a doctor when seeing the patient for an unrelated problem. Other features which commonly led to the diagnosis being made were headache, change in appearance, carpal tunnel syndrome, amenorrhoea and diabetes.

Peripheral lactate and oxygen metabolism in man: the influence of oral glucose loading.

We investigated the influence of oral glucose loading (100 g) on glucose, lactate, and oxygen metabolism by deep (mainly muscle) and superficial (mainly skin and adipose tissue) forearm tissues. In normal men aged 19 to 32 years (mean +/- SE, 24 +/- 1), basal arterialized venous-deep venous (A-DV) and arterialized venous-superficial venous (A-SV) plasma glucose concentration differences were 4.1 +/- 1.

Basal glucose homeostasis with and without fixed concentrations of glucagon and insulin.

The aim of this study was to investigate the extent to which the basal steady state could be maintained with fixed concentrations of glucagon and insulin. To this end, arterial plasma glucose concentrations and peripheral glucose uptake (using the forearm technique) were compared in healthy men (age 19 to 23 years) in the normal postabsorptive state and after suppression of endogenous pancreatic secretion. Two groups (A and B), each consisting of four men, were studied.

Acromegalic heart disease: influence of treatment of the acromegaly on the heart.

In a series of 256 patients with acromegaly, 10 had evidence of heart disease for which no explanation apart from the acromegaly could be found. Heart disease presented with effort dyspnoea, cardiac failure, palpitation, ECG changes or cardiomegaly. Initial chest radiographs showed cardiac enlargement in seven patients.

The influence of graded hyperglycemia with and without physiological hyperinsulinemia on forearm glucose uptake and other metabolic responses in man.

We studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (+/- SE) basal serum insulin levels (14 +/- 2 microU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 +/- 1 mg/dl) to 146 +/- 1 and 202 +/- 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.

Relationship among peripheral glucose uptake, oxygen consumption, and glucose turnover in postabsorptive man.

To assess the importance of glucose uptake by muscle in determining total glucose utilization in the basal state, forearm glucose uptake (FGU), reflecting mainly skeletal muscle metabolism, and glucose turnover using [3-3H]glucose were studied simultaneously in 17 postabsorptive normal men. Mean +/- SE glucose disappearance was 2.36 +/- 0.

Neurological aspects of insulinomas.

Neurological involvement occurred in every one of a series of 30 patients with an insulinoma. The episodic nature of the hypoglycaemia caused symptoms and signs to fluctuate and often led to delay in diagnosis (mean length of history was 3 years). The commonest feature at first presentation was confusion (20 instances), but as the illness evolved, coma (16 instances) and convulsions (8 instances) became more frequent.

Pancreatic cancer and diabetes mellitus.

In a series of 6,500 patients with diabetes mellitus there were 37 cases of primary carcinoma of the pancreas which significantly exceeded the expected number for the patient years at risk in both males and females (p less than 0.01). There was no evidence that pancreatic cancer was more common in patients with long-standing diabetes.

Peripheral glucose uptake in young men with myocardial infarction.

Forearm glucose uptake (FGU) was studied during 100 g oral glucose tolerance tests (GTT) in nonobese, nondiabetic men who had suffered a myocardial infarction (MI) at or before the age of 40, and the results compared with the response in age-matched normal men. In the MI group the rise in both glucose and insulin concentrations after glucose loading was similar to that in normal subjects, although in the former, peak levels tended to be slightly higher. Concomitant FGU, however, was significantly greater in the MI group than in control subjects in the period 0-90 min and in the test as a whole (0-180 min).

Circulating IgG antibody to protamine in patients treated with protamine-insulins.

Sera from patients with different types of protamine-insulin were assayed for IgG antibody to protamine. A high prevalence of circulating antibody was found in patients treated with either bovine isophane insulin (26 out of 28 patients; 26 of whom also had antibodies to insulin), or bovine protamine zinc insulin (27 out of 30 patients; all 30 had antibodies to insulin). In sera from 24 patients treated with highly purified porcine isophane insulin, protamine antibody was detected in nine; circulating insulin-antibody was detected in 12 patients, eight of whom had protamine-antibody; in the 12 patients with no detectable antibody to insulin, antibody to protamine was detected in only one (x2 = 8.

Comparison of peripheral glucose uptake after oral glucose loading and a mixed meal.

Forearm glucose uptake (FGU) and other metabolic responses were studied in six normal men for three hours after a 75-g oral glucose load and a mixed meal containing 75 g carbohydrate. After the meal the rise in arterial glucose levels was considerably less than that following the oral glucose load but the overall insulin responses from 0 to 180 minutes were not statistically different. Although the initial rise in FGU was more gradual after the meal, the subsequent elevation was more sustained and, at the termination of the study, exceeded significantly that seen after the oral glucose load.