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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 469 records · Page 26Linked to original sources

A double embedding technique for the electron microscopic analysis of the liver acinus.

A double embedding technique allowing accurate and systematic sampling of zones of the hepatic acinus by electron microscopy was developed. The method involved the primary embedding of large (10 mm x 30 mm x 0.5 mm) liver slices and the preparation of 10 micrometers thick tissue sections by means of a rotary microtome with a steel knife. Veins 20--40 micrometers in diameter, the landmarks of the hepatic acinus, were localized by light microscopy, dissected from surrounding tissue and reembedded for ultramicrotomy. The method facilitated the systematic evaluation of hepatocyte ultrastructure in each zone of the microcirculatory unit of the liver, the hepatic acinus.

Animals↗

Effects of osmotic gradients on water and solute transport: in vivo studies in rat duodenum and ileum.

We examined effects of luminal osmolality on net water and solute movements in rat duodenum and ileum. Solutions of sodium chloride (permeating solute) or mannitol (nonpermeating solute) at hypo-, iso-, or hyperosmotic concentrations were recirculated through in situ segments. Luminal osmolality increased towards that of plasma with hyposmotic solutions of both solutes. With isosmotic solutions, luminal osmolality did not change with sodium chloride, but increased with mannitol. With hyperosmotic solutions, luminal osmolality always decreased toward that of plasma with sodium chloride; with mannitol, however, decreases were significant only when initial concentrations were above 400 mosmol/kg. The decrease in osmolality of hyperosmotic sodium chloride resulted from sodium absorption and water secretion. Thus, both hypo- and hyperosmotic solutions of sodium chloride adjusted toward isomolality with plasma by the usual mechanisms of water and solute movement. With mannitol, however, osmotic adjustment of hypertonic luminal contents was restricted or even absent due to movement of sodium down its concentration gradient and reduced hydraulic conductivity of the gut.

Animals↗

National Childhood Encephalopathy Study: an interim report.

Data from the first year of the National Childhood Encephalopathy Study were reviewed to see whether any relation was apparent between pertussis vaccination and brain disease. Three hundred and eighty-seven cases of encephalitis and other specified neurological conditions in which the children were admitted to hospital were reported, of which 267 satisfied the study criteria. Control children were matched for age with the index cases, and medical and immunisation histories were reviewed. Few of the index cases had been vaccinated within 28 days before admission to hospital, so that no close association between vaccination and brain disease existed in most cases. The number of children who had recently been immunised was too small for any statistically useful conclusion to be reached about the risk associated with pertussis vaccine. The study is continuing.

Brain Diseases↗

A comparison of the activities of the products of the two genes for elongation factor Tu.

The two species of Elongation Factor Tu coded for by the tufA and tufB genes were synthesized in UV-irradiated E coli infected by transducing phages bearing the separate genes. Both proteins interact similarly with EFTs, GDP, and phe-tRNA. Although the phe-tRNA.EFTu.GMP.PNP complex containing the tufA gene product binds somewhat more tightly to ribosomes, both proteins promote the complete process of binding phe tRNA to ribosomes at similar rates.

Coliphages↗

Multimodal outpatient group treatment for the psychiatrically disabled.

Outpatient clinics gradually accumulate patients with longstanding disabilities. The traditional treatment approach is to see such patients in brief, intermittent, individual visits. Staff generally dislikes treating such patients and patients may, in part, maintain their symptoms in order to maintain ties with a nurturing institution. The experience with an alternative approach, weekly group meetings using a number of helping modalities, is described. Although no panacea, the approach appears to provide a reasonably effective, efficient, and enjoyable way of helping chronically disabled patients.

Adult↗

Functional covalent complex between elongation factor Tu and an analog of lysyl-tRNA.

Complex formation between elongation factor Tu, GTP, and Nepsilon-bromoacetyl-Lys-tRNA results in the cross-linking of the protein and the modified Lys-tRNA. The efficiency of affinity labeling is greater than 50%. In the presence of unmodified Lys-tRNA, the amount of crosslinking is greatly decreased. There is no covalent reaction with elongation factor Tu in the absence of complex formation. Substantial purification of the crosslinked ternary complex can be achieved by gel filtration at low Mg2+ concentration and passage through nitrocellulose filters. The crosslinked complex exhibits message-dependent binding to ribosomes which is accompanied by the hydrolysis of the associated GTP, as shown by both filter assays and gel filtration profiles. The crosslinked complex therefore appears to function normally except for its inability to dissociate. These experiments demonstrate that the ternary complex is the true intermediate in the binding of aminoacyl-tRNA to the ribosomes.

Affinity Labels↗

Facilities and diagnostic criteria in sexually transmitted disease clinics in England and Wales.

A study was conducted to collect information from consultants about the facilities and diagnostic criteria used in clinics for sexually transmitted diseases in England and Wales. Most of the information was obtained by personal interview with a response rate of 92%. Half the clinics were open for 10 hours or less a week, the mean length of time for all clinics was 14 1/2 hours a week. Eighty per cent of clinics had a full or part-time contact-tracing service. All the clinics had microscopical and serological services and almost all (99%) had cultural facilities. The policy concerning the most efficient use of these facilities is discussed.

England↗

Induction of cytochrome P-450 in a selective subpopulation of hepatocytes.

The objective of this study was to determine whether the inductive effect of phenobarbital (PB) on liver cytochrome P-450 was the result of the action of this drug on all or some hepatocytes. For this purpose, a light (cell band I) and a heavy (cell band II) subpopulation of hepatocytes were separated from rat liver in a continuous density gradient. To determine the location of these hepatocytes in tissue, [14C]bromobenzene, which binds covalently to centrilobular hepatocytes, was administered. The specific activity (14C dpm/mg protein) was greater in cells of band I than in cells of band II, suggesting a predominant contribution of centrilobular hepatocytes to the lighter cell band. Microsomes were separated from each cell subpopulation after 3 days of PB administration and cytochrome P-450 was measured. Although a fivefold increment in cytochrome P-450 content of light hepatocytes was noted, the content of heavy hepatocytes was similar to that of the respective subpopulation in controls. Concomitantly, PB administered for 3 days induced the smooth endoplasmic reticulum of centrilobular hepatocytes only, as revealed by electron microscopy of whole tissue. These results indicated that PB induces cytochrome P-450 in a selective subpopulation of hepatocytes, most likely located near the terminal hepatic venule.

Animals↗

Follow-up of patients with tuberculosis treated in a general hospital program. Treatment largely as outpatients by community physicians.

As of December 1975, there had been 5 to 8 1/2 years of observation on 263 patients with bacteriologically proven tuberculosis who were initially admitted to a general hospital and were treated largely as outpatients by community physicians from July 1967 through December 1970. Ten patients died during hospitalization, and 253 were released to therapy as outpatients. Although smears or cultures of sputum remained positive at discharge in 136 (54 percent) of the 253 patients, no new infections were subsequently detected among their contacts. During initial therapy, 24 patients died of causes other than tuberculosis. Of the remaining 229 patients, the original 18-month treatment was successful in 197 (86 percent). The treatment failed initially in 11 patients, eight of whom represented relapses from previous therapy. During long-term follow-up of the 229 patients, there were only six relapses (3 percent) after the initial success. An overall rate of successful treatment of 92 percent (211/229) was achieved in the program, with 18 failures of treatment (8 percent); ie, 11 patients were lost to supervision, four died of tuberculosis, and in three, treatment was never successful.

Aged↗

Bile secretion and liver cell heterogeneity in the rat.

The contribution of hepatocytes of different acinar zones to bile salt transport and to the secretion of the BSNDF was studied in the rat. Changes in the removal of 14C-taurocholate from blood, in the biliary secretion of taurocholate, and in canalicular flow were determined after damage of the periportal (acinar zone 1) or centrilobular (acinar zone 3) areas by allyl alcohol or bromobenzene, respectively. The extent of cell necrosis was quantitated by light microscopy, and the quality of the intracellular damage was assessed by electron microscopy. After either periportal or centrilobular damage, surviving cells responded to an intravenous infusion of taurocholate by secreting bile salts into bile at a rate similar to controls. However, following the administration of 14C-taurocholate at high concentrations and as a single bolus, the rate of removal of this isotope from blood was slower than in controls. Both experiments suggested that periportal and centrilobular hepatocytes had the capability for bile salt transport. Consequently, since the concentration of bile salts in sinusoidal blood at each zone determines the relative contribution of hepatocytes to bile salt transport, periportal cells probably transport the largest amount of bile salts reaching the acinus. Canalicular bile flow, on the other hand, decreased following centrilobular cell damage, and this was associated with a high concentration of bile salts in bile. This suggested that at bile salt loads near physiological concentrations, the predominant contribution of centrilobular hepatocytes is to the secretion of the BSNDF.

Animals↗

Acinar distribution of liver cell regeneration after selective zonal injury in the rat.

Liver cell regeneration after selective zonal injury induced by bromobenzene (acinar zone III damage) and allyl alcohol (acinar zone I damage) was examined in the context of the simple liver acinus. The zonal distribution of necrosis and inflammation was assessed by light microscopy and the volume fraction of necrosis was quantitated at the times of maximal damage. The acinar distribution of hepatocytic [6-3H]thymidine incorporation was determined autoradiographically at 24, 36, 48, 60, 72, and 96 hr after the administration of the toxicants. The mitotic index for each acinar zone was calculated at the time of peak thymidine incorporation after each drug and then at 12-hr intervals for the next 24 hr. Autoradiographic data indicated that the relative contributions of acinar zones II and III to [6-3H]thymidine incorporation were greater after zone III damage (bromobenze), whereas the relative contribution of acinar zone I was greater after allyl alcohol (zone I) damage. This was observed despite the greater degree of damage seem after bromobenzene than after allyl alcohol (volume fractions of necrosis were 26.4 and 10.1%, respectively). Moreover, the acinar distribution of mitosis indicated an increased centrizonal mitosis after centrizonal damage, and an increased periportal mitosis after periportal damage. Thus, the contribution of each acinar zone to liver cell regeneration depends on the acinar location of damage.

Allyl Compounds↗