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parasites and many are pathogenic to human beings. ¾ Pseudomonadaceae → Spirillaceae ¾ Enterobacteriaceae → Bacteroidaceae ¾ Corynebacteriaceae → Bacillaceae ¾ Lactobacillaceae → Neisseriaceae

 Results

Alkaline phosphatase activity : Reddish brown

Nuclei : Green.

α-Naphthyl Acetate Method for Nonspecific Esterase

This method employs α-naphthyl acetate as the substrate,

the enzyme releases α-naphthol during the hydrolysis

of the substrate. The α-naphthol is then coupled with a

suitable diazonium salt to produce an insoluble azo dye at

the site of enzyme activity.

Preparation of Solutions

a. Substrate solutions

α-naphthyl acetate 50 mg

Acetone 5 mL

b. Buffer solution

Sodium dihydrogen orthophosphate 2.75 g

Distilled water 100 mL

c. Sodium nitrite solution

Sodium nitrite 400 mg

Distilled water 10 mL

d. Pararosanilin HCl - Stock solution

Pararosanilin hydrochloride 2 g

2 N-hydrochloric acid 50 mL

e. Distilled water.

Preparation of Incubating Medium

Solution (A) 0.25 mL

Solution (B) 7.25 mL

Solution (C) 0.8 mL

Solution (D) 0.8 mL

A volume of 0.4 mL of solution C and D is mixed together

and allowed to stand before adding to incubating medium.

The pH should be 5.8 to 6.1.

Method

a. Incubate smears at 37°C for 20 minutes.

b. Wash in water.

c. Counterstain in 2% methyl green (chloroform extracted).

d. Wash well in water.

e. Dehydrate, clear and mount.

Results

Esterase : Reddish brown

Nuclei : Green.

Diaminobenzidine Method for Peroxidase

Preparation of Incubating Solution

3:3 - diaminobenzidine tetrahydrochloride 5 mg

Tris buffer (pH 7.6) 10 mL

1% hydrogen peroxide 0.1 mL

Cytology 817

Method

a. Rinse fixed smears in distilled water.

b. Transfer to incubating solution for 5 minutes at room

temperature.

c. Rinse in 3 changes of distilled water.

d. Dehydrate clear and mount in DPX.

Result

Peroxidase—fine brownish granules.

Peroxidase Stain

Fixative—95% ethanol : 90 mL

 40% Formaldehyde (HCHO): 10 mL

Preparation of Solutions

To 30 mL of 30% ethanol, add 0.9 g of Benzidine, mix well

and then add 3 mL of zinc sulfate (3.8%). A precipitate is

formed then add 3 mg of sodium acetate and 4.5 mL of INNaOH (4 g in 100 mL). The pH should be 6. Filter and store

at room temperature.

Method

a. Fix the smear with fixative for one minute.

b. Wash gently with tap water and soak out the excess

water.

c. Take 5 mL of staining solution and 3 drops of 3%

hydrogen peroxide, mix well and cover the slide for

30 sec at 20°C.

d. Wash the slide in running tap water for 10 seconds.

e. Counterstain with dituted Giemsa’s stain for 2 minutes.

f. Wash with tap water then dried and mounted in DPX.

Results

Peroxidase positive seen as green granules.

Oil Red O Method for Lipids

It is a useful preliminary method to indicate two major

lipid classes. For detailed morphology oil red O method is

used with Mayer’s hemalum.

Preparation of Solution

The working solution is prepared an hour in advance by

mixing three parts of a stock solution of oil red O (saturated

in 99% isopropanol) with two parts of distilled water and

filtering just before use.

Method

Fix the smears in formalin vapor for 5 minutes and wash in

running tap water for 10 minutes.

a. Rinse in 60% isopropanol.

b. Stain for 15 minutes in Oil Red O.

c. Differentiate in 60% isopropanol until a delipidized

control section appears colorless.

d. Wash in water and counterstain nuclei with Mayer’s

hemalum for 3 minutes.

e. Wash well in water.

f. Rinse in distilled water and mount in glycerin jelly.

Results

Unsaturated hydrophobic lipids and mineral

Oil stain : Red

Phospholipids stain : Pink

IMMUNOPEROXIDASE STAINING FOR

C YTO AND HISTOPATHOLOGY

Introduction

This is an immunohistochemical technique, aimed at

the specific histological localization of particular tissue

antigens by immunological method. These techniques

are being increasingly used for diagnostic histology. The

immunoperoxidase test which makes use of specific antibodies conjugated with horse radish peroxidase or alkaline

phosphatase enzymes are nowadays commonly used for

histochemical detection of various antigenic markers.

Direct method: The primary antibody conjugated with

enzyme, is used to react with the antigenic sites. The combined antibody-antigen complex with enzyme is developed

with specific substrate. Tissues/smears are examined under

light microscope to detect the substrate color at the antigenic

site.

Indirect method: It is more sensitive and commonly used.

The specific primary antibody is applied directly to the

tissues/smears. This is followed by the second antibody

(antispecies specific IgG) conjugated with enzyme. The

color of the reaction is developed by using specific substrate

and examined under light microscope.

Material

Peroxidase conjugated with antirabbit immunoglobulins

(Igs), PBS (pH 7.2/0.2M), DAB (3.3 Diamino benzidine-4

HCl), normal swine serum, hydrogen peroxidase, antigen

specific antibody raised in rabbit.

Indirect Method

1. Dewaxed paraffin sections are hydrated in usual

manner. Where prefixed smears are used, these are

washed with buffered distilled water.

818 Concise Book of Medical Laboratory Technology: Methods and Interpretations 2. Endogenous peroxidase activity is blocked with a fresh

3% solution of hydrogen peroxide in distilled water for

10–30 minutes or with acid alcohol for 15 minutes.

For Cryostat, use acid alcohol or phenylhydrazine

(5 × 103M) for 15–30 minutes.

3. Wash twice with phosphate buffer saline *(pH 7.2, 0.2M).

4. Expose sections/smears to normal swine serum diluted

1:5 with buffer at 22o

C, 5–10 minutes. Excess NSS/NGS

is removed, without washing prior to stage 4.

5. Sections/smears are treated with optimally diluted

primary rabbit antiserum at 22oC, 15–30 minutes or

24–48 hours at 4oC with highly diluted antiserum.

6. Treat sections/smears with horseradish peroxidase

labeled swine/antirabbit IgG 1:20-1:100 for 15–30

minutes at 22oC.

7. Wash twice with phosphate buffer saline* (pH 7.2). The

end product is revealed with a freshly made solution

of 0.05%, 3, 3-diaminobenzidine tetrahydrochloride

(DAB) in 0.01% H2O2 in wash buffer.

Sections/smears are counterstained with a weak hematoxylin, dehydrated, cleared in xylene and mounted in

DPX for the DAB or PDP reactions (brown to dark brown).

Aqueous mountants, e.g. glycerin gelatine, are used for the

carbazole reaction (red).

Solution A

(Sodium dihydrogen orthophosphate)

NaH2PO4. 2H2O—31.2 g for 1 liter.

Solution B

Disodium hydrogen phosphate

Na2HPO4. 2H2O—31.6 g for 1 liter.

Working solution:

Solution A 70 mL + Solution B 180 mL. Make the volume

up to 1 liter and dissolve 5.7 g NaCl in a liter and filter

before use.

Immunofluorescence

Principle

It is a histochemical or cytochemical technique for in

situ detection and localization of specific intracellular

antigens. Specific antibodies conjugated with fluorescent

dyes, such as fluorescein or rhodamine, are used to trace

the specific antigenic areas on the tissue smear or section.

This can be visualized under the fluorescent microscope,

as bright purple green/red color fluorescence.

Direct Immunofluorescence

In this method, conjugated antiserum is added directly to

the tissue sections or viable cell suspension.

Indirect Immunofluorescence

It is more sensitive and commonly used. The unlabeled,

specific antibody is applied directly to the tissue smears/

sections, followed by a second antibody treatment, i.e.

antispecies specific Ig conjugated with fluorescein or

rhodamine and examined under UV-microscope. Due to

the use of second antibody, the sensitivity and specificity

of the reaction is highly improved.

Material

FITC/antihuman Igs conjugate, phosphate buffer saline

(PBS), specific antibody, glycerol buffer, fluorescent

microscope. Smear or section of tissue.

Method

1. Reasonably diluted antibody put on the antigen slide

fixed in methanol for half an hour at room temperature

in moisture chamber.

2. Wash the slide twice in PBS pH 7.2. All washes are

carried out on a magnetic stirrer.

3. Incubate slides for 30 minutes with 1:20 diluted

FITC (Fluoroscein isothiocynate) conjugated with

Igs in PBS/pH 7.2* containing 0.01%. Evans blue

as counterstain at room temperature in a moisture

chamber.

4. Wash the slide twice in PBS pH 7.2.

5. Mount the slide with 90% glycerol buffer pH 8.6.

6. Examine the slide under UV-microscope. The antigen

positive areas of the cell will show purple green

fluorescence, whereas the negative area would appear

brick red.

AUTOMATION IN CYTOLOGY

A programable cytocentrifuge from WESCOR is available,

which can be used to prepare slide from any body fluid.

With the help of cytocentrifuge sample cells, one can

safely and quickly deposit a monolayer of cells on to a

microscope slide for staining or any other processing.

This can be used on any of the body fluids, such as CSF,

urine, synovial fluid, aspirates, washes, etc. and can be

programed as per the requirements.

* PBS (Phosphate buffer saline) pH 7.2/0.2 M

* PBS preparation described earlier.

27

Microbiology and Bacteriology

C H A P T E R

In the following pages maximum stress is laid on diagnostic

bacteriology.

CLASSIFICATION

Protophyta

Schizomycetes (Bacteria and related forms)

Actinomycetales

These members form elongated cells and have a tendency

to branch, produces spores, not all are pathogenic to man

¾ Actinomycetaceae

¾ Mycobacteriaceae

¾ Nitrobacteriaceae.

Eubacteriales

This represents the true bacteria forms, classifiable as

bacilli, cocci, or vibrios. Their staining reaction can either

be gram-positive or gram-negative. Some are motile and

possess peritrichous flagella. They multiply by binary

fission. Widely distributed they can be saprophytes,

parasites and many are pathogenic to human beings.

¾ Pseudomonadaceae → Spirillaceae

¾ Enterobacteriaceae → Bacteroidaceae

¾ Corynebacteriaceae → Bacillaceae

¾ Lactobacillaceae → Neisseriaceae

¾ Micrococcaceae → Brucellaceae.

Spirochetales

These are slender, spiral shaped cells, aflagellate but move

by flexing or whirling and spinning. Stainable by special

stains only, they are free-living and include saprophytic

and parasitic forms.

¾ Treponemataceae.

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